Field Investigation of the Surface-deposited Radon Progeny as a Possible Predictor of the Airborne Radon Progeny Dose Rate

PubMed Central

Sun, Kainan; Steck, Daniel J.; Field, R. William

2009-01-01

The quantitative relationships between radon gas concentration, the surface-deposited activities of various radon progeny, the airborne radon progeny dose rate, and various residential environmental factors were investigated through actual field measurements in 38 selected Iowa houses occupied by either smokers or nonsmokers. Airborne dose rate was calculated from unattached and attached potential alpha energy concentrations (PAECs) using two dosimetric models with different activity-size weighting factors. These models are labeled Pdose and Jdose, respectively. Surface-deposited 218Po and 214Po were found significantly correlated to radon, unattached PAEC, and both airborne dose rates (p < 0.0001) in nonsmoking environments. However, deposited 218Po was not significantly correlated to the above parameters in smoking environments. In multiple linear regression analysis, natural logarithm transformation was performed for airborne dose rate as the dependent variable, as well as for radon and deposited 218Po and 214Po as predictors. An interaction effect was found between deposited 214Po and an obstacle in front of the Retrospective Reconstruction Detector (RRD) in predicting dose rate (p = 0.049 and 0.058 for Pdose and Jdose, respectively) for nonsmoking environments. After adjusting for radon and deposited radon progeny effects, the presence of either cooking, usage of a fireplace, or usage of a ceiling fan significantly, or marginal significantly, reduced the Pdose to 0.65 (90% CI 0.42–0.996), 0.54 (90% CI 0.28–1.02) and 0.66 (90% CI 0.45–0.96), respectively. For Jdose, only the usage of a ceiling fan significantly reduced the dose rate to 0.57 (90% CI 0.39–0.85). In smoking environments, deposited 218Po was a significant negative predictor for Pdose (RR 0.68, 90% CI 0.55–0.84) after adjusting for long-term 222Rn and environmental factors. A significant decrease of 0.72 (90% CI 0.64–0.83) in the mean Pdose was noted, after adjusting for the radon and radon progeny effects and other environmental factors, for every 10 increasing cigarettes smoked in the room. A significant increase of 1.71 in the mean Pdose was found for large room size relative to small room size (90% CI 1.08–2.79) after adjusting for the radon and radon progeny effects as well as other environmental factors. Fireplace usage was found to significantly increase the mean Pdose to 1.71 (90% CI 1.20–2.45) after adjusting for other factors. PMID:19590273

Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells

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

Rithidech, K.N.; Rusek, A.; Reungpatthanaphong, P.

2010-05-28

The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-{kappa}B) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory [i.e., tumor necrosis factor-alpha (TNF-{alpha}), interleukin-1beta (IL-1{beta}), and IL-6] and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min{sup -1}, the dose and dose rates found during solar particle events in space. As amore » reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of {sup 137}Cs {gamma} rays (10 mGy min{sup -1}). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or {sup 137}Cs {gamma} rays, delivered at 10 mGy min{sup -1}, was similar. Although statistically significant levels of NF-{kappa}B activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student's t-test, p < 0.05 or < 0.01) were induced by either dose rate, these levels varied over time for each protein. Further, only a dose rate of 5 mGy min{sup -1} induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.« less

Method for the prediction of the effective dose equivalent to the crew of the International Space Station

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Tomi, Leena; Sihver, Lembit; Sato, Tatsuhiko; Richardson, Richard B.; Lewis, Brent J.

2014-03-01

This paper describes a methodology for assessing the pre-mission exposure of space crew aboard the International Space Station (ISS) in terms of an effective dose equivalent. In this approach, the PHITS Monte Carlo code was used to assess the particle transport of galactic cosmic radiation (GCR) and trapped radiation for solar maximum and minimum conditions through an aluminum shield thickness. From these predicted spectra, and using fluence-to-dose conversion factors, a scaling ratio of the effective dose equivalent rate to the ICRU ambient dose equivalent rate at a 10 mm depth was determined. Only contributions from secondary neutrons, protons, and alpha particles were considered in this analysis. Measurements made with a tissue equivalent proportional counter (TEPC) located at Service Module panel 327, as captured through a semi-empirical correlation in the ISSCREM code, where then scaled using this conversion factor for prediction of the effective dose equivalent. This analysis shows that at this location within the service module, the total effective dose equivalent is 10-30% less than the total TEPC dose equivalent. Approximately 75-85% of the effective dose equivalent is derived from the GCR. This methodology provides an opportunity for pre-flight predictions of the effective dose equivalent and therefore offers a means to assess the health risks of radiation exposure on ISS flight crew.

Dose estimation for astronauts using dose conversion coefficients calculated with the PHITS code and the ICRP/ICRU adult reference computational phantoms.

PubMed

Sato, Tatsuhiko; Endo, Akira; Sihver, Lembit; Niita, Koji

2011-03-01

Absorbed-dose and dose-equivalent rates for astronauts were estimated by multiplying fluence-to-dose conversion coefficients in the units of Gy.cm(2) and Sv.cm(2), respectively, and cosmic-ray fluxes around spacecrafts in the unit of cm(-2) s(-1). The dose conversion coefficients employed in the calculation were evaluated using the general-purpose particle and heavy ion transport code system PHITS coupled to the male and female adult reference computational phantoms, which were released as a common ICRP/ICRU publication. The cosmic-ray fluxes inside and near to spacecrafts were also calculated by PHITS, using simplified geometries. The accuracy of the obtained absorbed-dose and dose-equivalent rates was verified by various experimental data measured both inside and outside spacecrafts. The calculations quantitatively show that the effective doses for astronauts are significantly greater than their corresponding effective dose equivalents, because of the numerical incompatibility between the radiation quality factors and the radiation weighting factors. These results demonstrate the usefulness of dose conversion coefficients in space dosimetry. © Springer-Verlag 2010

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.

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.

Radiation exposure in the remote period after the Chernobyl accident caused oxidative stress and genetic effects in Scots pine populations

NASA Astrophysics Data System (ADS)

Volkova, Polina Yu.; Geras'Kin, Stanislav A.; Kazakova, Elizaveta A.

2017-02-01

Even 30 years after the Chernobyl accident, biological effects of irradiation are observed in the chronically exposed Scots pine populations. Chronic radiation exposure at dose rates above 50 mGy•yr-1 caused oxidative stress and led to the increase of antioxidants concentrations in these populations. Genetic variability was examined for 6 enzymes and 14 enzymatic loci of 6 Scots pine populations. Dose rates over 10 mGy•yr-1 caused the increased frequency of mutations and changes in genetic structure of Scots pine populations. However, the same dose rates had no effect on enzymatic activities. The results indicate that even relatively low dose rates of radiation can be considered as an ecological factor which should be taken into account for ecological management and radiation protection of biota species.

Passive dosimetry aboard the Mir Orbital Station: internal measurements.

PubMed

Benton, E R; Benton, E V; Frank, A L

2002-10-01

Passive radiation dosimeters were exposed aboard the Mir Orbital Station over a substantial portion of the solar cycle in order to measure the change in dose and dose equivalent rates as a function of time. During solar minimum, simultaneous measurements of the radiation environment throughout the habitable volume of the Mir were made using passive dosimeters in order to investigate the effect of localized shielding on dose and dose equivalent. The passive dosimeters consisted of a combination of thermoluminescent detectors to measure absorbed dose and CR-39 PNTDs to measure the linear energy transfer (LET) spectrum from charged particles of LET infinity H2O > or = 5 keV/micrometers. Results from the two detector types were then combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Contrary to expectations, both dose and dose equivalent rates measured during May-October 1991 near solar maximum were higher than similar measurements carried out in 1996-1997 during solar minimum. The elevated dose and dose equivalent rates measured in 1991 were probably due to a combination of intense solar activity, including a large solar particle event on 9 June 1991, and the temporary trapped radiation belt created in the slot region by the solar particle event and ensuing magnetic storm of 24 March 1991. During solar minimum, mean dose and dose equivalent rates were found to vary by factors of 1.55 and 1.37, respectively, between different locations through the interior of Mir. More heavily shielded locations tended to yield lower total dose and dose equivalent rates, but higher average quality factor than did more lightly shielding locations. However, other factors such as changes in the immediate shielding environment surrounding a given detector location, changes in the orientation of the Mir relative to its velocity vector, and changes in the altitude of the station also contributed to the variation. Proton and neutron-induced target fragment secondaries, not primary galactic cosmic rays, were found to dominate the LET spectrum above 100 keV/micrometers. This indicates that in low earth orbit, trapped protons in the South Atlantic Anomaly are responsible for the major fraction of the total dose equivalent. c2002 Elsevier Science Ltd. All rights reserved.

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.

Radiation dose rate affects the radiosensitization of MCF-7 and HeLa cell lines to X-rays induced by dextran-coated iron oxide nanoparticles.

PubMed

Khoshgard, Karim; Kiani, Parvaneh; Haghparast, Abbas; Hosseinzadeh, Leila; Eivazi, Mohammad Taghi

2017-08-01

The aim of radiotherapy is to deliver lethal damage to cancerous tissue while preserving adjacent normal tissues. Radiation absorbed dose of the tumoral cells can increase when high atomic nanoparticles are present in them during irradiation. Also, the dose rate is an important aspect in radiation effects that determines the biological results of a given dose. This in vitro study investigated the dose-rate effect on the induced radiosensitivity by dextran-coated iron oxide in cancer cells. HeLa and MCF-7 cells were cultured in vitro and incubated with different concentrations of dextran-coated iron oxide nanoparticles. They were then irradiated with 6 MV photons at dose rates of 43, 185 and 370 cGy/min. The MTT test was used to obtain the cells' survival after 48 h of irradiations. Incubating the cells with the nanoparticles at concentrations of 10, 40 and 80 μg/ml showed no significant cytotoxicity effect. Dextran-coated iron oxide nanoparticles showed more radiosensitivity effect by increasing the dose rate and nanoparticles concentration. Radiosensitization enhancement factors of MCF-7 and HeLa cells at a dose-rate of 370 cGy/min and nanoparticles' concentration of 80 μg/ml were 1.21 ± 0.06 and 1.19 ± 0.04, respectively. Increasing the dose rate of 6 MV photons irradiation in MCF-7 and HeLa cells increases the radiosensitization induced by the dextran-coated iron nanoparticles in these cells.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes.

PubMed

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes

PubMed Central

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications. PMID:28078052

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.

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.

Comparison of Data on Mutation Frequencies of Mice Caused by Radiation with Low Dose Model

NASA Astrophysics Data System (ADS)

Manabe, Yuichiro; Bando, Masako

2013-09-01

We propose low dose (LD) model, the extension of LDM model which was proposed in the previous paper [Y. Manabe et al.: J. Phys. Soc. Jpn. 81 (2012) 104004] to estimate biological damage caused by irradiation. LD model takes account of cell death effect in addition to the proliferation, apoptosis, repair which were included in LDM model. As a typical example of estimation, we apply LD model to the experiment of mutation frequency on the responses induced by the exposure to low levels of ionizing radiation. The most famous and extensive experiments are those summarized by Russell and Kelly [Proc. Natl. Acad. Sci. U.S.A. 79 (1982) 539], which are known as ``mega-mouse project''. This provides us with important information of the frequencies of transmitted specific-locus mutations induced in mouse spermatogonia stem-cells. It is found that the numerical results of the mutation frequency of mice are in reasonable agreement with the experimental data: the LD model reproduces the total dose and dose rate dependence of data reasonably. In order to see such dose-rate dependence more explicitly, we introduce the dose-rate effectiveness factor (DREF). This represents a sort of dose rate dependent effect, which are to be competitive with proliferation effect of broken cells induced by irradiation.

EFFECTS OF WEST NILE VIRUS DOSE AND EXTRINSIC INCUBATION TEMPERATURE ON TEMPORAL PROGRESSION OF VECTOR COMPETENCE IN CULEX PIPIENS QUINQUEFASCIATUS

PubMed Central

ANDERSON, SHERI L.; RICHARDS, STEPHANIE L.; TABACHNICK, WALTER J.; SMARTT, CHELSEA T.

2010-01-01

Culex pipiens quinquefasciatus were fed blood containing either 7.0 ± 0.1 logs plaque-forming units (pfu)/ml (high dose) or 5.9 ± 0.1 logs pfu/ml (low dose) of West Nile virus and held at extrinsic incubation temperatures (EIT) of 28°C or 25°C. Approximately 20 mosquitoes per dose were collected after incubation periods (IP) of 4, 6, 8, and 12 days postinfection (dpi). Infection rates were influenced by EIT and virus dose but not by IP. Body titer was significantly higher for mosquitoes fed the high dose and held at 28°C at the later IPs (6, 8, and 12 dpi). However, leg titer was significantly higher for mosquitoes at the later IPs but did not differ between EITs or doses. Because infection rates varied with EIT and dose, there is likely a midgut infection barrier influenced by these factors that is not influenced by IP. Dissemination rates were influenced by all 3 factors consistent with the presence of a midgut escape barrier. Dissemination rate, body titer, and leg titer were dependent on IP, indicating the need to investigate multiple time points in vector competence studies to elucidate critical events in infection and dissemination. PMID:20402358

Effects of West Nile virus dose and extrinsic incubation temperature on temporal progression of vector competence in Culex pipiens quinquefasciatus.

PubMed

Anderson, Sheri L; Richards, Stephanie L; Tabachnick, Walter J; Smartt, Chelsea T

2010-03-01

Culex pipiens quinquefasciatus were fed blood containing either 7.0 +/- 0.1 logs plaque-forming units (pfu)/ml (high dose) or 5.9 +/- 0.1 logs pfu/ml (low dose) of West Nile virus and held at extrinsic incubation temperatures (EIT) of 28 degrees C or 25 degrees C. Approximately 20 mosquitoes per dose were collected after incubation periods (IP) of 4, 6, 8, and 12 days postinfection (dpi). Infection rates were influenced by EIT and virus dose but not by IP. Body titer was significantly higher for mosquitoes fed the high dose and held at 28 degrees C at the later IPs (6, 8, and 12 dpi). However, leg titer was significantly higher for mosquitoes at the later IPs but did not differ between EITs or doses. Because infection rates varied with EIT and dose, there is likely a midgut infection barrier influenced by these factors that is not influenced by IP. Dissemination rates were influenced by all 3 factors consistent with the presence of a midgut escape barrier. Dissemination rate, body titer, and leg titer were dependent on IP, indicating the need to investigate multiple time points in vector competence studies to elucidate critical events in infection and dissemination.

Dose and dose rate effects of whole-body proton-irradiation on lymphocyte blastogenesis and hematological variables: part II

NASA Technical Reports Server (NTRS)

Pecaut, Michael J.; Gridley, Daila S.; Smith, Anna L.; Nelson, Gregory A.

2002-01-01

The goal of part II of this study was to evaluate functional characteristics of leukocytes and circulating blood cell parameters after whole-body proton irradiation at varying doses and at low- and high-dose-rates (LDR and HDR, respectively). C57BL/6 mice (n=51) were irradiated and euthanized at 4 days post-exposure for assay. Significant radiation dose- (but not dose-rate-) dependent decreases were observed in splenocyte responses to T and B cell mitogens when compared to sham-irradiated controls (P<0.001). Spontaneous blastogenesis, also significantly dose-dependent, was increased in both blood and spleen (P<0.001). Red blood cell counts, hemoglobin concentration, and hematocrit were decreased in a dose-dependent manner (P<0.05), whereas thrombocyte numbers were only slightly affected. Comparison of proton- and gamma-irradiated groups (both receiving 3 Gy at HDR) showed a higher level of spontaneous blastogenesis in blood leukocytes and a lower splenocyte response to concanavalin A following proton irradiation (P<0.05). There were no dose rate effects. Collectively, the data demonstrate that the measurements in blood and spleen were largely dependent upon the total dose of proton radiation and that an 80-fold difference in the dose rate was not a significant factor. A difference, however, was found between protons and gamma-rays in the degree of change induced in some of the measurements.

Radiation dosimetry measurements with real time radiation monitoring device (RRMD)-II in Space Shuttle STS-79

NASA Technical Reports Server (NTRS)

Sakaguchi, T.; Doke, T.; Hayashi, T.; Kikuchi, J.; Hasebe, N.; Kashiwagi, T.; Takashima, T.; Takahashi, K.; Nakano, T.; Nagaoka, S.;

On the use of quality factors and fluence to dose rate conversion in human radiation exposures

NASA Technical Reports Server (NTRS)

Sondhaus, C. A.

1972-01-01

It is shown that various combinations of numbers and factors arrive at estimates of dose and dose effectiveness from values of fluence; but as yet it has not been possible to use biological data with the same degree of precision to estimate the physical data. It would seem that the most reasonable way to use the human data that exist is to apply them as far as possible to the human animal as a whole.

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.

Cocaine self-administration under variable-dose schedules in squirrel monkeys.

PubMed

Panlilio, Leigh V; Thorndike, Eric B; Schindler, Charles W

2006-06-01

Squirrel monkeys self-administered cocaine under a variable-dose schedule, with the dose varied from injection to injection. As in earlier studies with rats, post-injection pauses varied as a monotonic function of dose, allowing a cocaine dose-effect curve to be obtained during each session. These curves were shifted by pretreatment with dopamine antagonists, demonstrating that this procedure may provide an efficient means of evaluating treatments that affect drug self-administration. However, drug intake eventually became "dysregulated" after extensive training (100-300 sessions), with relatively short pauses following all doses. Dose-sensitivity was restored by adding a 60-s timeout period after each injection, suggesting that dysregulation occurred because the monkeys developed a tendency to self-administer another injection before the previous injection had been adequately distributed. Finally, when the response requirement under the variable-dose schedule was increased from 1 to 10, both the post-injection pause and the rate of responding following the pause ("run rates") were found to vary with dose. The dose-dependency of run rates suggests that post-injection pauses reflect not only motivational factors, such as satiety, but also the direct effects of cocaine on leverpressing.

Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate.

PubMed

Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J; Ravelli, Raimond B G

2011-05-01

Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50-250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e(-)Å(-2) s(-1) or higher) combined with poor thermal contact between the grid and cryo-holder. Secondary radiolytic effects are likely to play a role in dose-rate effects. Stroboscopic data collection combined with an improved understanding of the effects of dose and dose rate will aid single-particle cryo-electron microscopists to have better control of the outcome of their experiments.

Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate

PubMed Central

Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J.; Ravelli, Raimond B. G.

2011-01-01

Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50–250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e−Å−2 s−1 or higher) combined with poor thermal contact between the grid and cryo-holder. Secondary radiolytic effects are likely to play a role in dose-rate effects. Stroboscopic data collection combined with an improved understanding of the effects of dose and dose rate will aid single-particle cryo-electron microscopists to have better control of the outcome of their experiments. PMID:21525648

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

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

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

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s −1 . At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution of diffracted intensitymore » within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ∼1.5–2 compared with those observed at conventional dose rates. Improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

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

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s –1. At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution ofmore » diffracted intensity within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ~1.5–2 compared with those observed at conventional dose rates. As a result, improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE PAGES

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.; ...

2017-10-13

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s –1. At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution ofmore » diffracted intensity within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ~1.5–2 compared with those observed at conventional dose rates. As a result, improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE PAGES

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.; ...

2017-10-13

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s −1 . At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution of diffracted intensitymore » within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ∼1.5–2 compared with those observed at conventional dose rates. Improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Effect of Remediation Parameters on in-Air Ambient Dose Equivalent Rates When Remediating Open Sites with Radiocesium-contaminated Soil.

PubMed

Malins, Alex; Kurikami, Hiroshi; Kitamura, Akihiro; Machida, Masahiko

2016-10-01

Calculations are reported for ambient dose equivalent rates [H˙*(10)] at 1 m height above the ground surface before and after remediating radiocesium-contaminated soil at wide and open sites. The results establish how the change in H˙*(10) upon remediation depends on the initial depth distribution of radiocesium within the ground, on the size of the remediated area, and on the mass per unit area of remediated soil. The remediation strategies considered were topsoil removal (with and without recovering with a clean soil layer), interchanging a topsoil layer with a subsoil layer, and in situ mixing of the topsoil. The results show the ratio of the radiocesium components of H˙*(10) post-remediation relative to their initial values (residual dose factors). It is possible to use the residual dose factors to gauge absolute changes in H˙*(10) upon remediation. The dependency of the residual dose factors on the number of years elapsed after fallout deposition is analyzed when remediation parameters remain fixed and radiocesium undergoes typical downward migration within the soil column.

Shielding from Solar Particle Event Exposures in Deep Space

NASA Technical Reports Server (NTRS)

Wilson, John W.; Cucinotta, F. A.; Shinn, J. L.; Simonsen, L. C.; Dubey, R. R.; Jordan, W. R.; Jones, T. D.; Chang, C. K.; Kim, M. Y.

1999-01-01

The physical composition and intensities of solar particle event exposures or sensitive astronaut tissues are examined under conditions approximating an astronaut in deep space. Response functions for conversion of particle fluence into dose and dose equivalent averaged over organ tissue, are used to establish significant fluence levels and the expected dose and dose rates of the most important events from past observations. The BRYNTRN transport code is used to evaluate the local environment experienced by sensitive tissues and used to evaluate bioresponse models developed for use in tactical nuclear warfare. The present results will help to the biophysical aspects of such exposure in the assessment of RBE and dose rate effects and their impact on design of protection systems for the astronauts. The use of polymers as shielding material in place of an equal mass of aluminum would prowide a large safety factor without increasing the vehicle mass. This safety factor is sufficient to provide adequate protection if a factor of two larger event than has ever been observed in fact occurs during the mission.

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

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.

LAND AND WATER USE CHARACTERISTICS AND HUMAN HEALTH INPUT PARAMETERS FOR USE IN ENVIRONMENTAL DOSIMETRY AND RISK ASSESSMENTS AT THE SAVANNAH RIVER SITE

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

Jannik, T.; Karapatakis, D.; Lee, P.

2010-08-06

Operations at the Savannah River Site (SRS) result in releases of small amounts of radioactive materials to the atmosphere and to the Savannah River. For regulatory compliance purposes, potential offsite radiological doses are estimated annually using computer models that follow U.S. Nuclear Regulatory Commission (NRC) Regulatory Guides. Within the regulatory guides, default values are provided for many of the dose model parameters but the use of site-specific values by the applicant is encouraged. A detailed survey of land and water use parameters was conducted in 1991 and is being updated here. These parameters include local characteristics of meat, milk andmore » vegetable production; river recreational activities; and meat, milk and vegetable consumption rates as well as other human usage parameters required in the SRS dosimetry models. In addition, the preferred elemental bioaccumulation factors and transfer factors to be used in human health exposure calculations at SRS are documented. Based on comparisons to the 2009 SRS environmental compliance doses, the following effects are expected in future SRS compliance dose calculations: (1) Aquatic all-pathway maximally exposed individual doses may go up about 10 percent due to changes in the aquatic bioaccumulation factors; (2) Aquatic all-pathway collective doses may go up about 5 percent due to changes in the aquatic bioaccumulation factors that offset the reduction in average individual water consumption rates; (3) Irrigation pathway doses to the maximally exposed individual may go up about 40 percent due to increases in the element-specific transfer factors; (4) Irrigation pathway collective doses may go down about 50 percent due to changes in food productivity and production within the 50-mile radius of SRS; (5) Air pathway doses to the maximally exposed individual may go down about 10 percent due to the changes in food productivity in the SRS area and to the changes in element-specific transfer factors; and (6) Air pathway collective doses may go down about 30 percent mainly due to the decrease in the inhalation rate assumed for the average individual.« less

SU-F-I-40: Impact of Scan Length On Patient Dose in Abdomen/pelvis CT Diagnosis

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

Park, I; Song, J; Kim, K

Purpose: To analysis the impact of scan length on patient doses in abdomen/pelvis CT diagnosis of each hospital. Methods: Scan length of 7 hospitals from abdomen/pelvis CT diagnosis was surveyed in Korea. Surveyed scan lengths were additional distance above diaphragm and distance below pubic symphysis except for standard scan range between diaphragm and pubic symphysis. Patient dose was estimated for adult male and female according to scan length of each hospital. CT-Expo was used to estimate the patient dose under identical equipment settings (120 kVp, 100 mAs, 10 mm collimation width, etc.) except scan length. Effective dose was calculated bymore » using tissue weighting factor of ICRP 103 recommendation. Increase rate of effective dose was calculated comparing with effective dose of standard scan range Results: Scan lengths of abdomen/pelvis CT diagnosis of each hospital were different. Also effective dose was increased with increasing the scan length. Generally increasing the distance above diaphragm caused increase of effective dose of male and female, but increasing the distance below pubic symphysis caused increase of effective dose of male. Conclusion: We estimated the patient dose according to scan length of each hospital in abdomen/pelvis CT diagnosis. Effective dose was increased by increasing the scan length because dose of organs with high tissue weighting factor such as lung, breast, testis were increased. Scan length is important factor on patient dose in CT diagnosis. If radiologic technologist interested in patient dose, decreasing the unnecessary scan length will decrease the risk of patients from radiation. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI13C0004).« less

Surface applicator calibration and commissioning of an electronic brachytherapy system for nonmelanoma skin cancer treatment.

PubMed

Rong, Yi; Welsh, James S

2010-10-01

The Xoft Axxent x-ray source has been used for treating nonmelanoma skin cancer since the surface applicators became clinically available in 2009. The authors report comprehensive calibration procedures for the electronic brachytherapy (eBx) system with the surface applicators. The Xoft miniature tube (model S700) generates 50 kVp low-energy x rays. The new surface applicators are available in four sizes of 10, 20, 35, and 50 mm in diameter. The authors' tests include measurements of dose rate, air-gap factor, output stability, depth dose verification, beam flatness and symmetry, and treatment planning with patient specific cutout factors. The TG-61 in-air method was used as a guideline for acquiring nominal dose-rate output at the skin surface. A soft x-ray parallel-plate chamber (PTW T34013) and electrometer was used for the output commissioning. GafChromic EBT films were used for testing the properties of the treatment fields with the skin applicators. Solid water slabs were used to verify the depth dose and cutout factors. Patients with basal cell or squamous cell carcinoma were treated with eBx using a calibrated Xoft system with the low-energy x-ray source and the skin applicators. The average nominal dose-rate output at the skin surface for the 35 mm applicator is 1.35 Gy/min with +/- 5% variation for 16 sources. The dose-rate output and stability (within +/- 5% variation) were also measured for the remaining three applicators. For the same source, the output variation is within 2%. The effective source-surface distance was calculated based on the air-gap measurements for four applicator sizes. The field flatness and symmetry are well within 5%. Percentage depth dose in water was provided by factory measurements and can be verified using solid water slabs. Treatment duration was calculated based on the nominal dose rate, the prescription fraction size, the depth dose percentage, and the cutout factor. The output factor needs to be measured for each case with varying shapes of cutouts. Together with TG-61, the authors' methodology provides comprehensive calibration procedures for medical physicists for using the Xoft eBx system and skin applicators for nonmelanoma skin cancer treatments.

The effects of proton radiation on the prothrombin and partial thromboplastin times of irradiated ferrets

PubMed Central

Krigsfeld, Gabriel S.; Sanzari, Jenine K.; Kennedy, Ann R.

2013-01-01

Purpose To determine whether proton radiation affects coagulation. Material and methods Ferrets were exposed to solar particle event-like proton radiation at doses of 0, 25, 100, or 200 centigray (cGy), and dose rates of 50 cGy/minute (high dose rate or HDR) or 50 cGy/hour (low dose rate or LDR). Plasma was isolated from blood collected prior to radiation exposure and at 3–7 h post-radiation. Prothrombin time (PT) assays and activated partial thromboplastin time (aPTT) assays were performed as were mixing studies to determine the coagulation factors involved. Results HDR and LDR exposure led to statistically significant increases in PT values. It was determined that the HDR-induced increase in PT was due to Factor VII, while Factors II, V, and VII contributed to the LDR-induced increase in PT values. Only acute LDR exposure caused an increase in aPTT values, which remained elevated for 48 h post-irradiation (which was the latest time assayed in these studies). Mixing studies revealed that Factor IX contributed to the increased aPTT values. A majority of the animals exposed at the LDR had an International Normalized Ratio approaching or surpassing 2.0. Conclusions PT/aPTT assays resulted in increased clotting times due to different coagulation factors, indicating potential radiation-induced coagulopathy. PMID:22221163

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

Rectal Bleeding After High-Dose-Rate Brachytherapy Combined With Hypofractionated External-Beam Radiotherapy for Localized Prostate Cancer: The Relationship Between Dose-Volume Histogram Parameters and the Occurrence Rate

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

Okamoto, Masahiko, E-mail: masaoka@showa.gunma-u.ac.jp; Ishikawa, Hitoshi; Ebara, Takeshi

2012-02-01

Purpose: To determine the predictive risk factors for Grade 2 or worse rectal bleeding after high-dose-rate brachytherapy (HDR-BT) combined with hypofractionated external-beam radiotherapy (EBRT) for prostate cancer using dose-volume histogram analysis. Methods and Materials: The records of 216 patients treated with HDR-BT combined with EBRT were analyzed. The treatment protocols for HDR-BT were 5 Gy Multiplication-Sign five times in 3 days or 7 Gy Multiplication-Sign three, 10.5 Gy Multiplication-Sign two, or 9 Gy Multiplication-Sign two in 2 days. The EBRT doses ranged from 45 to 51 Gy with a fractional dose of 3 Gy. Results: In 20 patients Grade 2more » or worse rectal bleeding developed, and the cumulative incidence rate was 9% at 5 years. By converting the HDR-BT and EBRT radiation doses into biologic effective doses (BED), the BED{sub 3} at rectal volumes of 5% and 10% in the patients who experienced bleeding were significantly higher than those in the remaining 196 patients. Univariate analysis showed that a higher rectal BED{sub 3-5%} and the use of fewer needles in brachytherapy were correlated with the incidence of bleeding, but BED{sub 3-5%} was found to be the only significant factor on multivariate analysis. Conclusions: The radiation dose delivered to small rectal lesions as 5% is important for predicting Grade 2 or worse rectal bleeding after HDR-BT combined with EBRT for prostate cancer.« less

Effect of dose rate on residual γ-H2AX levels and frequency of micronuclei in X-irradiated mouse lymphocytes.

PubMed

Turner, H C; Shuryak, I; Taveras, M; Bertucci, A; Perrier, J R; Chen, C; Elliston, C D; Johnson, G W; Smilenov, L B; Amundson, S A; Brenner, D J

2015-03-01

The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

Radon Release and Its Simulated Effect on Radiation Doses.

PubMed

Orabi, Momen

2017-03-01

One of the main factors that affect the uncertainty in calculating the gamma-radiation absorbed dose rate inside a room is the variation in the degree of secular equilibrium of the considered radioactive series. A component of this factor, considered in this paper, is the release of radon (Rn) from building materials to the living space of the room. This release takes place through different steps. These steps are represented and mathematically formulated. The diffusion of radon inside the material is described by Fick's second law. Some of the factors affecting the radon release rate (e.g. covering walls, moisture, structure of the building materials, etc.) are discussed. This scheme is used to study the impact of radon release on the gamma-radiation absorbed dose rate inside a room. The investigation is carried out by exploiting the MCNP simulation software. Different building materials are considered with different radon release rates. Special care is given to Rn due to its relatively higher half-life and higher indoor concentration than the other radon isotopes. The results of the presented model show that the radon release is of a significant impact in some building materials.

Exisulind in combination with celecoxib modulates epidermal growth factor receptor, cyclooxygenase-2, and cyclin D1 against prostate carcinogenesis: in vivo evidence.

PubMed

Narayanan, Bhagavathi A; Reddy, Bandaru S; Bosland, Maarten C; Nargi, Dominick; Horton, Lori; Randolph, Carla; Narayanan, Narayanan K

2007-10-01

Nonsteroidal anti-inflammatory drugs mediate anticancer effects by modulating cyclooxygenase-2 (COX-2)-dependent and/or COX-2-independent mechanism(s); however, the toxicity issue is a concern with single agents at higher doses. In this study, we determined the combined effect of celecoxib, a COX-2 inhibitor, along with exisulind (sulindac sulfone/Aptosyn) at low doses in prostate cancer. We used a sequential regimen of N-methyl-N-nitrosourea + testosterone to induce prostate cancer in Wistar-Unilever rats. Following carcinogen treatment, celecoxib and exisulind individually and their combination at low doses were given in NIH-07 diet for 52 weeks. We determined the incidence of prostatic intraepithelial neoplasia, adenocarcinomas, rate of tumor cell proliferation, and apoptosis. Immunohistochemical and Western blot analysis were done to determine COX-2, epidermal growth factor receptor (EGFR), Akt, androgen receptor, and cyclin D1 expression. Serum prostaglandin E2 and tumor necrosis factor-alpha levels were determined using enzyme immunoassay/ELISA assays. The rats that received celecoxib in combination with exisulind at low doses showed a significant decrease in prostatic intraepithelial neoplasia and adenocarcinomas as well as an enhanced rate of apoptosis. An overall decrease in COX-2, EGFR, Akt, androgen receptor, and cyclin D1 expression was found associated with tumor growth inhibition. Reduced serum levels of COX-2 protein, prostaglandin E2, and tumor necrosis factor-alpha indicated anti-inflammatory effects. A strong inhibition of total and phosphorylated form of EGFR (Tyr(992) and Tyr(845)) and Akt (Ser(473)) was significant in rats given with these agents in combination. In this study, we show for the first time that the combination of celecoxib with exisulind at low doses could prevent prostate carcinogenesis by altering key molecular events.

Doses of external exposure in Jordan house due to gamma-emitting natural radionuclides in building materials.

PubMed

Al-Jundi, J; Ulanovsky, A; Pröhl, G

2009-10-01

The use of building materials containing naturally occurring radionuclides as (40)K, (232)Th, and (238)U and their progeny results in external exposures of the residents of such buildings. In the present study, indoor dose rates for a typical Jordan concrete room are calculated using Monte Carlo method. Uniform chemical composition of the walls, floor and ceiling as well as uniform mass concentrations of the radionuclides in walls, floor and ceiling are assumed. Using activity concentrations of natural radionuclides typical for the Jordan houses and assuming them to be in secular equilibrium with their progeny, the maximum annual effective doses are estimated to be 0.16, 0.12 and 0.22 mSv a(-1) for (40)K, (232)Th- and (238)U-series, respectively. In a total, the maximum annual effective indoor dose due to external gamma-radiation is 0.50 mSv a(-1). Additionally, organ dose coefficients are calculated for all organs considered in ICRP Publication 74. Breast, skin and eye lenses have the maximum equivalent dose rate values due to indoor exposures caused by the natural radionuclides, while equivalent dose rates for uterus, colon (LLI) and small intestine are found to be the smallest. More specifically, organ dose rates (nSv a(-1)per Bq kg(-1)) vary from 0.044 to 0.060 for (40)K, from 0.44 to 0.60 for radionuclides from (238)U-series and from 0.60 to 0.81 for radionuclides from (232)Th-series. The obtained organ and effective dose conversion coefficients can be conveniently used in practical dose assessment tasks for the rooms of similar geometry and varying activity concentrations and local-specific occupancy factors.

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.

Benefits of High-dose Steroid + Hespander + Mannitol Administration in the Treatment of Bell's Palsy.

PubMed

Furukawa, Takatoshi; Abe, Yasuhiro; Ito, Tsukasa; Kubota, Toshinori; Kakehata, Seiji

2017-02-01

Large-scale investigations have not been recently conducted on the efficacy of high-dose steroid administration of prednisolone (PSL) for Bell's palsy. We compared treatment results between normal-dose steroid (PSL 60 mg/d) and high-dose steroid (PSL 200 mg/d) + Hespander + Mannitol administration. We also investigated the recovery rate for antiviral agents. Retrospective case review. Tertiary referral center. A total of 675 patients with Bell's palsy who had grade V and grade VI on the House-Brackmann (HB) scale were treated in our department between 1995 and 2014. These patients could be divided into a normal-dose group and high-dose group. We separately assessed treatment outcomes for HB grade V patients and HB grade VI patients. Logistic regression analysis was also performed to investigate factors that can impact treatment outcomes, i.e., sex, age, days to start of treatment, PSL dosage, and antiviral drug administration. Recovery rates were significantly better in the high-dose steroid + Hespander + Mannitol group in comparison with the normal-dose steroid group for HB grade V (100% versus 77.7%) and HB grade VI (92.5% versus 68.2%). Additional effects of antiviral agents were only shown in the normal-dose group. Significant factors for treatment outcomes were PSL 200 mg/d administration and early initiation of treatment. Insignificant factors were sex, age, and the antiviral agent. We showed the high-dose steroid + Hespander + Mannitol administration produced significantly better outcomes than normal-dose steroid administration in the treatment of patients with Bell's palsy.

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

Factors Influencing the Cardiovascular Response to Subanesthetic Ketamine: A Randomized, Placebo-Controlled Trial

PubMed Central

Li, Shijia; Lord, Anton; Colic, Lejla; Krause, Anna Linda; Batra, Anil; Kretzschmar, Moritz A; Sweeney-Reed, Catherine M; Behnisch, Gusalija; Schott, Björn H; Walter, Martin

2017-01-01

Abstract Background The increasing use of ketamine as a potential rapid-onset antidepressant necessitates a better understanding of its effects on blood pressure and heart rate, well-known side effects at higher doses. For the subanesthetic dose used for depression, potential predictors of these cardiovascular effects are important factors influencing clinical decisions. Since ketamine influences the sympathetic nervous system, we investigated the impact of autonomic nervous system-related factors on the cardiovascular response: a genetic polymorphism in the norepinephrine transporter and gender effects. Methods Blood pressure and heart rate were monitored during and following administration of a subanesthetic dose of ketamine or placebo in 68 healthy participants (mean age 26.04 ±5.562 years) in a double-blind, randomized, controlled, parallel-design trial. The influences of baseline blood pressure/heart rate, gender, and of a polymorphism in the norepinephrine transporter gene (NET SLC6A2, rs28386840 [A-3081T]) on blood pressure and heart rate changes were investigated. To quantify changes in blood pressure and heart rate, we calculated the maximum change from baseline (ΔMAX) and the time until maximum change (TΔMAX). Results Systolic and diastolic blood pressure as well as heart rate increased significantly upon ketamine administration, but without reaching hypertensive levels. During administration, the systolic blood pressure at baseline (TP0Sys) correlated negatively with the time to achieve maximal systolic blood pressure (TΔMAXSys, P<.001). Furthermore, women showed higher maximal diastolic blood pressure change (ΔMAXDia, P<.001) and reached this peak earlier than men (TΔMAXDia, P=.017) at administration. NET rs28386840 [T] carriers reached their maximal systolic blood pressure during ketamine administration significantly earlier than [A] homozygous (TΔMAXSys, P=.030). In a combined regression model, both genetic polymorphism and TP0Sys were significant predictors of TΔMAXSys (P<.0005). Conclusions Subanesthetic ketamine increased both blood pressure and heart rate without causing hypertensive events. Furthermore, we identified gender and NET rs28386840 genotype as factors that predict increased cardiovascular sequelae of ketamine administration in our young, healthy study population providing a potential basis for establishing monitoring guidelines. PMID:29099972

The acute physiological and mood effects of tea and coffee: the role of caffeine level.

PubMed

Quinlan, P T; Lane, J; Moore, K L; Aspen, J; Rycroft, J A; O'Brien, D C

2000-05-01

The objective of this study was to determine the effect of caffeine level in tea and coffee on acute physiological responses and mood. Randomised full crossover design in subjects after overnight caffeine abstention was studied. In study 1 (n = 17) the caffeine level was manipulated naturalistically by preparing tea and coffee at different strengths (1 or 2 cups equivalent). Caffeine levels were 37.5 and 75 mg in tea, 75 and 150 mg in coffee, with water and no-drink controls. In study 2 (n = 15) caffeine level alone was manipulated (water, decaffeinated tea, plus 0, 25, 50, 100, and 200 mg caffeine). Beverage volume and temperature (55 degrees C) were constant. SBP, DBP, heart rate, skin temperature, skin conductance, and mood were monitored over each 3-h study session. In study 1, tea and coffee produced mild autonomic stimulation and an elevation in mood. There were no effects of tea vs. coffee or caffeine dose, despite a fourfold variation in the latter. Increasing beverage strength was associated with greater increases in DBP and energetic arousal. In study 2, caffeinated beverages increased SBP, DBP, and skin conductance and lowered heart rate and skin temperature compared to water. Significant dose-response relationships to caffeine were seen only for SBP, heart rate, and skin temperature. There were significant effects of caffeine on energetic arousal but no consistent dose-response effects. Caffeinated beverages acutely stimulate the autonomic nervous system and increase alertness. Although caffeine can exert dose-dependent effects on a number of acute autonomic responses, caffeine level is not an important factor. Factors besides caffeine may contribute to these acute effects.

Application of real-time radiation dosimetry using a new silicon LET sensor

NASA Technical Reports Server (NTRS)

Doke, T.; Hayashi, T.; Kikuchi, J.; Nagaoka, S.; Nakano, T.; Sakaguchi, T.; Terasawa, K.; Badhwar, G. D.

1999-01-01

A new type of real-time radiation monitoring device, RRMD-III, consisting of three double-sided silicon strip detectors (DSSDs), has been developed and tested on-board the Space Shuttle mission STS-84. The test succeeded in measuring the linear energy transfer (LET) distribution over the range of 0.2 keV/micrometer to 600 keV/micrometer for 178 h. The Shuttle cruised at an altitude of 300 to 400 km and an inclination angle of 51.6 degrees for 221.3 h, which is equivalent to the International Space Station orbit. The LET distribution obtained for particles was investigated by separating it into galactic cosmic ray (GCR) particles and trapped particles in the South Atlantic Anomaly (SAA) region. The result shows that the contribution in dose-equivalent due to GCR particles is almost equal to that from trapped particles. The total absorbed dose rate during the mission was 0.611 mGy/day; the effective quality factor, 1.64; and the dose equivalent rate, 0.998 mSv/day. The average absorbed dose rates are 0.158 mGy/min for GCR particles and 3.67 mGy/min for trapped particles. The effective quality factors are 2.48 for GCR particles and 1.19 for trapped particles. The absorbed doses obtained by the RRMD-III and a conventional method using TLD (Mg(2)SiO(4)), which was placed around the RRMD-III were compared. It was found that the TLDs showed a lower efficiency, just 58% of absorbed dose registered by the RRMD-III.

The predictive factors of α1-D/A adrenoceptor antagonist, naftopidil, dose increase therapy for male lower urinary tract symptoms caused by benign prostatic hyperplasia: INFORM study.

PubMed

Tanuma, Yasushi; Tanaka, Yoshinori; Takeyama, Ko; Okamoto, Tomoshi

2017-01-01

We evaluated the predictive factors which affect the efficacy of naftopidil 50 mg/day therapy and dose increase therapy to administration of 75 mg/day after an initial dose of 50 mg/day. A total of 92 patients with male lower urinary tract symptoms/benign prostatic hyperplasia were administrated naftopidil 50 mg/day for 4 weeks (50 mg therapy). At week 4, the patients were divided into an effective and an ineffective group (Group E and Group I, respectively). For further 4 weeks, the dosage of naftopidil was increased to 75 mg/day in all patients. At week 8, the patients of Group E and Group I were divided into an effective and an ineffective group (Group EE, Group EI, Group IE, and Group II, respectively). Postvoid residual (PVR) urine volume at baseline was a predictive factor for efficacy of 50 mg therapy. In Group E, change in International Prostate Symptom Score storage symptoms subscore from baseline to week 4 was a predictive factor for efficacy of this dose increase therapy. In Group I, change in maximum flow rate from baseline to week 4 was a predictive factor for efficacy of this dose increase therapy. The short term of naftopidil 50 mg therapy was ineffective for the patients who had large PVR. The predictive factor of this dose increase therapy might be a dynamic variable in 50 mg/day of dose period, but not a baseline variable at the time of 75 mg/day dosage starts.

Ion recombination and polarity correction factors for a plane-parallel ionization chamber in a proton scanning beam.

PubMed

Liszka, Małgorzata; Stolarczyk, Liliana; Kłodowska, Magdalena; Kozera, Anna; Krzempek, Dawid; Mojżeszek, Natalia; Pędracka, Anna; Waligórski, Michael Patrick Russell; Olko, Paweł

2018-01-01

To evaluate the effect on charge collection in the ionization chamber (IC) in proton pencil beam scanning (PBS), where the local dose rate may exceed the dose rates encountered in conventional MV therapy by up to three orders of magnitude. We measured values of the ion recombination (k s ) and polarity (k pol ) correction factors in water, for a plane-parallel Markus TM23343 IC, using the cyclotron-based Proteus-235 therapy system with an active proton PBS of energies 30-230 MeV. Values of k s were determined from extrapolation of the saturation curve and the Two-Voltage Method (TVM), for planar fields. We compared our experimental results with those obtained from theoretical calculations. The PBS dose rates were estimated by combining direct IC measurements with results of simulations performed using the FLUKA MC code. Values of k s were also determined by the TVM for uniformly irradiated volumes over different ranges and modulation depths of the proton PBS, with or without range shifter. By measuring charge collection efficiency versus applied IC voltage, we confirmed that, with respect to ion recombination, our proton PBS represents a continuous beam. For a given chamber parameter, e.g., nominal voltage, the value of k s depends on the energy and the dose rate of the proton PBS, reaching c. 0.5% for the TVM, at the dose rate of 13.4 Gy/s. For uniformly irradiated regular volumes, the k s value was significantly smaller, within 0.2% or 0.3% for irradiations with or without range shifter, respectively. Within measurement uncertainty, the average value of k pol , for the Markus TM23343 IC, was close to unity over the whole investigated range of clinical proton beam energies. While no polarity effect was observed for the Markus TM23343 IC in our pencil scanning proton beam system, the effect of volume recombination cannot be ignored. © 2017 American Association of Physicists in Medicine.

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

PubMed Central

Vaiserman, Alexander M.

2010-01-01

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

MODELING THE VARIATIONS OF DOSE RATE MEASURED BY RAD DURING THE FIRST MSL MARTIAN YEAR: 2012–2014

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

Guo, Jingnan; Wimmer-Schweingruber, Robert F.; Heber, Bernd

2015-09-01

The Radiation Assessment Detector (RAD), on board Mars Science Laboratory’s (MSL) rover Curiosity, measures the energy spectra of both energetic charged and neutral particles along with the radiation dose rate at the surface of Mars. With these first-ever measurements on the Martian surface, RAD observed several effects influencing the galactic cosmic-ray (GCR) induced surface radiation dose concurrently: (a) short-term diurnal variations of the Martian atmospheric pressure caused by daily thermal tides, (b) long-term seasonal pressure changes in the Martian atmosphere, and (c) the modulation of the primary GCR flux by the heliospheric magnetic field, which correlates with long-term solar activitymore » and the rotation of the Sun. The RAD surface dose measurements, along with the surface pressure data and the solar modulation factor, are analyzed and fitted to empirical models that quantitatively demonstrate how the long-term influences ((b) and (c)) are related to the measured dose rates. Correspondingly, we can estimate dose rate and dose equivalents under different solar modulations and different atmospheric conditions, thus allowing empirical predictions of the Martian surface radiation environment.« less

Investigation of Risk Factors Affecting Lactate Levels in Japanese Patients Treated with Metformin.

PubMed

Yokoyama, Shota; Tsuji, Hideyuki; Hiraoka, Sachiko; Nishihara, Masayuki

2016-01-01

Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia. 290 outpatients receiving various doses of metformin at our hospital were enrolled between March and July 2014. Serum electrolytes, Cre (creatinine), BUN (blood urea nitrogen), UA (uric acid), HbA1c (hemoglobin A1c), and lactate levels were investigated. Lactate levels did not significantly differ between the elderly (≥75 years) and non-elderly (<75 years) groups. Patients in the elderly group had a significantly lower daily metformin dose and estimated glomerular filtration rate (eGFR), compared with the non-elderly group (both p<0.005). Between with and without hyperlactemia groups, no significant differences were observed in either Cre or age. On the other hand, patients with hyperlactemia had a significantly higher dose of metformin than those without hyperlactemia (p<0.05). In this study, we found that old age and mildly impaired kidney function were not associated with increased lactate levels, and that a higher dose of metformin may be an independent risk factor for elevated lactate levels in Japanese patients.

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.

SU-F-T-461: Dosimetric Evaluation of Indigenous Farmer Type Chamber FAR65- GB for Reference Dosimetry of FFF MV Photon Beam

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

Patwe, P; Mhatre, V; Dandekar, P

Purpose: Indigenous Farmer type chamber FAR 65 GB is a reference class 0.6 cc ion chamber. It can be used for dosimetric evaluation of photon and high energy electron beams. We studied dosimetric characteristics of the chamber for 6MV and 10MV Flattening filter free FFF photon beams available on trueBEAM STx Linac. Methods: The study was carried out on trueBEAM STx Linac having 6 and 10 MV FFF photon beam with maximum dose rate 1400 and 2400 MU per min respectively. The dosimetric device to be evaluated is Rosalina Instruments FAR 65-GB Ion Chamber with active volume 0.65 cc, totalmore » active length 23.1cm, inner diameter of cylinder 6.2mm, wall thickness 0.4mm, inner electrode diameter 1mm. Inner and outer electrodes are made from Aluminium 2.7 gm per cc and graphite 1.82 gm per cc respectively. The ion chamber was placed along central axis of beam at 10cm depth and irradiated for 10cm × 10cm field size at SAD of 100 cm in plastic phantom. We studied Precision, Dose Linearity, Dose Rate dependence, directional dependence, Recombination effect. Recombination effect was determined using standard two-voltage method. Results: 1. Measurements were reproducible std deviation of 0.0105 and type A uncertainty 0.003265 under same set of reference conditions 2. Chamber exhibit dose linearity over a wider dose range. 3. Chamber shows dose rate independence for all available dose rate range. 4. Response of chamber with the angle of incidence of radiation is constant. 5. Recombination correction factors were 1.01848 and 1.02537 for dose rate 1400 and 2400 MU per min resp. Conclusion: Our study reveals that the chamber is prone to saturation effect at dose rate of 2400 MU per min. FAR 65-GB can be used for reference dosimetry of FFF MV photon beam with proper calculation of recombination effect.« less

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.

Organ Dose-Rate Calculations for Small Mammals at Maralinga, the Nevada Test Site, Hanford and Fukushima: A Comparison of Ellipsoidal and Voxelized Dosimetric Methodologies.

PubMed

Caffrey, Emily A; Johansen, Mathew P; Higley, Kathryn A

2015-10-01

Radiological dosimetry for nonhuman biota typically relies on calculations that utilize the Monte Carlo simulations of simple, ellipsoidal geometries with internal radioactivity distributed homogeneously throughout. In this manner it is quick and easy to estimate whole-body dose rates to biota. Voxel models are detailed anatomical phantoms that were first used for calculating radiation dose to humans, which are now being extended to nonhuman biota dose calculations. However, if simple ellipsoidal models provide conservative dose-rate estimates, then the additional labor involved in creating voxel models may be unnecessary for most scenarios. Here we show that the ellipsoidal method provides conservative estimates of organ dose rates to small mammals. Organ dose rates were calculated for environmental source terms from Maralinga, the Nevada Test Site, Hanford and Fukushima using both the ellipsoidal and voxel techniques, and in all cases the ellipsoidal method yielded more conservative dose rates by factors of 1.2-1.4 for photons and 5.3 for beta particles. Dose rates for alpha-emitting radionuclides are identical for each method as full energy absorption in source tissue is assumed. The voxel procedure includes contributions to dose from organ-to-organ irradiation (shown here to comprise 2-50% of total dose from photons and 0-93% of total dose from beta particles) that is not specifically quantified in the ellipsoidal approach. Overall, the voxel models provide robust dosimetry for the nonhuman mammals considered in this study, and though the level of detail is likely extraneous to demonstrating regulatory compliance today, voxel models may nevertheless be advantageous in resolving ongoing questions regarding the effects of ionizing radiation on wildlife.

Characterisation of a MOSFET-based detector for dose measurement under megavoltage electron beam radiotherapy

NASA Astrophysics Data System (ADS)

Jong, W. L.; Ung, N. M.; Tiong, A. H. L.; Rosenfeld, A. B.; Wong, J. H. D.

2018-03-01

The aim of this study is to investigate the fundamental dosimetric characteristics of the MOSkin detector for megavoltage electron beam dosimetry. The reproducibility, linearity, energy dependence, dose rate dependence, depth dose measurement, output factor measurement, and surface dose measurement under megavoltage electron beam were tested. The MOSkin detector showed excellent reproducibility (>98%) and linearity (R2= 1.00) up to 2000 cGy for 4-20 MeV electron beams. The MOSkin detector also showed minimal dose rate dependence (within ±3%) and energy dependence (within ±2%) over the clinical range of electron beams, except for an energy dependence at 4 MeV electron beam. An energy dependence correction factor of 1.075 is needed when the MOSkin detector is used for 4 MeV electron beam. The output factors measured by the MOSkin detector were within ±2% compared to those measured with the EBT3 film and CC13 chamber. The measured depth doses using the MOSkin detector agreed with those measured using the CC13 chamber, except at the build-up region due to the dose volume averaging effect of the CC13 chamber. For surface dose measurements, MOSkin measurements were in agreement within ±3% to those measured using EBT3 film. Measurements using the MOSkin detector were also compared to electron dose calculation algorithms namely the GGPB and eMC algorithms. Both algorithms were in agreement with measurements to within ±2% and ±4% for output factor (except for the 4 × 4 cm2 field size) and surface dose, respectively. With the uncertainties taken into account, the MOSkin detector was found to be a suitable detector for dose measurement under megavoltage electron beam. This has been demonstrated in the in vivo skin dose measurement on patients during electron boost to the breast tumour bed.

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

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.

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.

Predictive factors for the methotrexate treatment outcome in ectopic pregnancy: A comparative study of 400 cases.

PubMed

Bonin, Lucie; Pedreiro, Cécile; Moret, Stéphanie; Chene, Gautier; Gaucherand, Pascal; Lamblin, Géry

2017-01-01

We sought to evaluate the global success rate of intramuscular methotrexate for the treatment of ectopic pregnancy, identify factors predictive of treatment success or failure, and study methotrexate tolerability in a large patient cohort. For this single-center retrospective observational study, we retrieved the records of all women who had a clinically or echographically confirmed ectopic pregnancy with a Fernandez score <13 and who were treated according to a 1mg/kg intramuscular single-dose methotrexate protocol. Medical treatment failure was defined by an obligation to proceed to laparoscopy. Needing a second injection was not considered to be medical treatment failure. Between February 2008 and November 2013 (69 months), 400 women received methotrexate for ectopic pregnancy. The medical treatment protocol was effective for 314 patients, i.e., an overall success rate of 78.5%. A single methotrexate dose was sufficient for 63.5% of the women and a second dose was successful for 73.2% of the remaining women. The medical treatment success rate fell as initial hCG levels climbed. The main factors associated with methotrexate failure included day (D) 0, D4 and D7 hCG levels, pretherapeutic blood progesterone, hematosalpinx at D0 and pain at D7. Early favorable kinetics of hCG levels was predictive of success. Methotrexate treatment was successful in 90% of women who had D0 hCG <1000IU/l. Methotrexate tolerability was good, with only 9% of the women reporting non-severe adverse effects. The fertility rate with delivery after medical treatment for ectopic pregnancy was 80.7%. In this study, we showed that an initial hCG value <1000IU/l and favorable early HCG kinetics were predictive factors for the successful medical treatment of ectopic pregnancy by methotrexate, and hematosalpinx and pretherapeutic blood progesterone >5ng/ml at diagnosis were predictive of its failure. We also confirmed good tolerability for single-dose methotrexate protocols. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

[Intermediary effectiveness of procaine and procaine metabolites following oral administration].

PubMed

Kaemmerer, K; Kietzmann, M

1989-01-01

The influence of orally administrated procaine hydrochloride and of its metabolites diethylaminoethanol, monoethylaminoethanol and ethanolamine on specific intermediary processes in rats was tested. While the animals got procaine hydrochloride in a single dose or via food the incorporation rate of amino acids in protein was measured in homogenisates of liver tissue by the incorporation of a mixture of 14C-amino acids. Procaine hydrochloride, the commercial product K. H. 3, as well as diethylaminoethanol, monoethylaminoethanol and ethanolamine increased the amino acid incorporation rate in a dose and time dependent mode, while p-aminobenzoic acid remained without any effect. The dose of procaine hydrochloride inducing a maximal reaction was in the range of 50 to 100 mg/kg b. w. (250 to 500 mg/kg food). The minimal active dose was nearly at 10 mg/kg b. w. Paying regard to a metabolic factor of 10 the effective dose-range is nearly the dose used in experience with human beings to influence geriatric complaints. In the study described here haematoporphyrine (a component of the commercial product K. H. 3, not absorbed) shows no specific intermediary effect. May be it promotes the intestinal absorption of procaine hydrochloride by protection against intestinal hydrolysis. The intermediary effect of procaine hydrochloride is to measure on cellular or subcellular level without compatibility to the activity as a local anaesthetic. With regard to other intermediary effects mentioned in the literature like growth promotion or inhibition of monoamine oxidase activity, it is discussed whether the increase of the hepatic amino acid incorporation rate is corresponding to geriatric experiences made with procaine hydrochloride.

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.

In-flight radiation measurements on STS-60

NASA Technical Reports Server (NTRS)

Badhwar, G. D.; Golightly, M. J.; Konradi, A.; Atwell, W.; Kern, J. W.; Cash, B.; Benton, E. V.; Frank, A. L.; Sanner, D.; Keegan, R. P.;

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

A dose assessment method for arbitrary geometries with virtual reality in the nuclear facilities decommissioning

NASA Astrophysics Data System (ADS)

Chao, Nan; Liu, Yong-kuo; Xia, Hong; Ayodeji, Abiodun; Bai, Lu

2018-03-01

During the decommissioning of nuclear facilities, a large number of cutting and demolition activities are performed, which results in a frequent change in the structure and produce many irregular objects. In order to assess dose rates during the cutting and demolition process, a flexible dose assessment method for arbitrary geometries and radiation sources was proposed based on virtual reality technology and Point-Kernel method. The initial geometry is designed with the three-dimensional computer-aided design tools. An approximate model is built automatically in the process of geometric modeling via three procedures namely: space division, rough modeling of the body and fine modeling of the surface, all in combination with collision detection of virtual reality technology. Then point kernels are generated by sampling within the approximate model, and when the material and radiometric attributes are inputted, dose rates can be calculated with the Point-Kernel method. To account for radiation scattering effects, buildup factors are calculated with the Geometric-Progression formula in the fitting function. The effectiveness and accuracy of the proposed method was verified by means of simulations using different geometries and the dose rate results were compared with that derived from CIDEC code, MCNP code and experimental measurements.

Exclusive low-dose-rate brachytherapy in 279 patients with T2N0 mobile tongue carcinoma

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

Bourgier, Celine; Coche-Dequeant, Bernard; Fournier, Charles

2005-10-01

Purpose: To evaluate the therapeutic results obtained with {sup 192}Ir low-dose-rate interstitial brachytherapy in T2N0 mobile tongue carcinoma. Patients and Methods: Between December 1979 and January 1998, 279 patients with T2N0 mobile tongue carcinoma were treated by exclusive low-dose-rate brachytherapy, with or without neck dissection. {sup 192}Ir brachytherapy was performed according to the 'Paris system' with a median total dose of 60 Gy (median dose rate, 0.5 Gy/h). Results: Overall survival was 74.3% and 46.6% at 2 and 5 years. Local control was 79.1% at 2 years and regional control, respectively, 75.9% and 69.5% at 2 and 5 years (Kaplan-Meiermore » method). Systematic dissection revealed 44.6% occult node metastases, and histologic lymph node involvement was identified as the main significant factor for survival. Complication rate was 16.5% (Grade 3, 2.9%). Half of the patients presented previous and/or successive malignant tumor (ear-nose-throat, esophagus, or bronchus). Conclusion: Exclusive low-dose-rate brachytherapy is an effective treatment for T2 tongue carcinoma. Regional control and survival are excellent in patients undergoing systematic neck dissection, which is mandatory in our experience because of a high rate of occult lymph node metastases.« less

Quality factor and dose equivalent investigations aboard the Soviet Space Station Mir

NASA Astrophysics Data System (ADS)

Bouisset, P.; Nguyen, V. D.; Parmentier, N.; Akatov, Ia. A.; Arkhangel'Skii, V. V.; Vorozhtsov, A. S.; Petrov, V. M.; Kovalev, E. E.; Siegrist, M.

1992-07-01

Since Dec 1988, date of the French-Soviet joint space mission 'ARAGATZ', the CIRCE device, had recorded dose equivalent and quality factor values inside the Mir station (380-410 km, 51.5 deg). After the initial gas filling two years ago, the low pressure tissue equivalent proportional counter is still in good working conditions. Some results of three periods are presented. The average dose equivalent rates measured are respectively 0.6, 0.8 and 0.6 mSv/day with a quality factor equal to 1.9. Some detailed measurements show the increasing of the dose equivalent rates through the SAA and near polar horns. The real time determination of the quality factors allows to point out high linear energy transfer events with quality factors in the range 10-20.

Biphasic and monophasic repair: comparative implications for biologically equivalent dose calculations in pulsed dose rate brachytherapy of cervical carcinoma

PubMed Central

Millar, W T; Davidson, S E

2013-01-01

Objective: To consider the implications of the use of biphasic rather than monophasic repair in calculations of biologically-equivalent doses for pulsed-dose-rate brachytherapy of cervix carcinoma. Methods: Calculations are presented of pulsed-dose-rate (PDR) doses equivalent to former low-dose-rate (LDR) doses, using biphasic vs monophasic repair kinetics, both for cervical carcinoma and for the organ at risk (OAR), namely the rectum. The linear-quadratic modelling calculations included effects due to varying the dose per PDR cycle, the dose reduction factor for the OAR compared with Point A, the repair kinetics and the source strength. Results: When using the recommended 1 Gy per hourly PDR cycle, different LDR-equivalent PDR rectal doses were calculated depending on the choice of monophasic or biphasic repair kinetics pertaining to the rodent central nervous and skin systems. These differences virtually disappeared when the dose per hourly cycle was increased to 1.7 Gy. This made the LDR-equivalent PDR doses more robust and independent of the choice of repair kinetics and α/β ratios as a consequence of the described concept of extended equivalence. Conclusion: The use of biphasic and monophasic repair kinetics for optimised modelling of the effects on the OAR in PDR brachytherapy suggests that an optimised PDR protocol with the dose per hourly cycle nearest to 1.7 Gy could be used. Hence, the durations of the new PDR treatments would be similar to those of the former LDR treatments and not longer as currently prescribed. Advances in knowledge: Modelling calculations indicate that equivalent PDR protocols can be developed which are less dependent on the different α/β ratios and monophasic/biphasic kinetics usually attributed to normal and tumour tissues for treatment of cervical carcinoma. PMID:23934965

Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal

PubMed Central

van Gorp, Freek; Duffull, Stephen; Hackett, L Peter; Isbister, Geoffrey K

2012-01-01

AIMS To describe the pharmacokinetics and pharmacodynamics (PKPD) of escitalopram in overdose and its effect on QT prolongation, including the effectiveness of single dose activated charcoal (SDAC). METHODS The data set included 78 escitalopram overdose events (median dose, 140 mg [10–560 mg]). SDAC was administered 1.0 to 2.6 h after 12 overdoses (15%). A fully Bayesian analysis was undertaken in WinBUGS 1.4.3, first for a population pharmacokinetic (PK) analysis followed by a PKPD analysis. The developed PKPD model was used to predict the probability of having an abnormal QT as a surrogate for torsade de pointes. RESULTS A one compartment model with first order input and first-order elimination described the PK data, including uncertainty in dose and a baseline concentration for patients taking escitalopram therapeutically. SDAC reduced the fraction absorbed by 31% and reduced the individual predicted area under the curve adjusted for dose (AUCi/dose). The absolute QT interval was related to the observed heart rate with an estimated individual heart rate correction factor (α = 0.35). The heart rate corrected QT interval (QTc) was linearly dependent on predicted escitalopram concentration [slope = 87 ms/(mg l–1)], using a hypothetical effect-compartment (half-life of effect-delay, 1.0h). Administration of SDAC significantly reduced QT prolongation and was shown to reduce the risk of having an abnormal QT by approximately 35% for escitalopram doses above 200 mg. CONCLUSIONS There was a dose-related lengthening of the QT interval that lagged the increase in drug concentration. SDAC resulted in a moderate reduction in fraction of escitalopram absorbed and reduced the risk of the QT interval being abnormal. PMID:21883384

Thyroid remnant ablation with 1110MBq of 131I in outpatients: measurement of effective dose to household members and establishment of safety precautions.

PubMed

Yoshimura, M; Tsutsui, H; Ikeda, N; Koizumi, K

2013-03-01

The aim of this study was to establish and confirm the safety of administering 1110MBq of 131I to outpatients. Total radiation exposure from patients to household members was hypothesized from the measured dose rate at 1 m when the patient is released. Actually we also measured the effective dose to household members who assisted outpatients during the first 7 days after the administration of 131I by personal dosimeter. A list of radiation safety precautions is given to the patient and household members. Behavioral reports about the distances and times of close contact throughout the 7 days are requested of each household member. The effective dose measured using the personal dosimeter to all household members employing several safety precautions was confirmed to be lower than the hypothesized dose calculated using our formula. And the mean whole-body effective dose rate over the 7 days in household members was 0.05±0.08 (range, 0.05 to 0.43) mSv, which specify that radiation exposure to household members of the outpatients who have just received ablative radiation therapy must be below 5.0 mSv/event. Remnant thyroid ablation with 1110MBq for outpatients showed that the radiation doses to household members were within the recommended constraint dose according to several safety precautions. The method of returning home after remnant thyroid ablation is thought to be the most important factor that determines the effective dose to household members of outpatients.

Lower thresholds for lifetime health effects in mammals from high-LET radiation - Comparison with chronic low-LET radiation.

PubMed

Sazykina, Tatiana G; Kryshev, Alexander I

2016-12-01

Lower threshold dose rates and confidence limits are quantified for lifetime radiation effects in mammalian animals from internally deposited alpha-emitting radionuclides. Extensive datasets on effects from internal alpha-emitters are compiled from the International Radiobiological Archives. In total, the compiled database includes 257 records, which are analyzed by means of non-parametric order statistics. The generic lower threshold for alpha-emitters in mammalian animals (combined datasets) is 6.6·10 -5  Gy day -1 . Thresholds for individual alpha-emitting elements differ considerably: plutonium and americium - 2.0·10 -5  Gy day -1 ; radium - 2.1·10 -4  Gy day -1 . Threshold for chronic low-LET radiation is previously estimated at 1·10 -3  Gy day -1 . For low exposures, the following values of alpha radiation weighting factor w R for internally deposited alpha-emitters in mammals are quantified: w R (α) = 15 as a generic value for the whole group of alpha-emitters; w R (Pu) = 50 for plutonium; w R (Am) = 50 for americium; w R (Ra) = 5 for radium. These values are proposed to serve as radiation weighting factors in calculations of equivalent doses to non-human biota. The lower threshold dose rate for long-lived mammals (dogs) is significantly lower than comparing with the threshold for short-lived mammals (mice): 2.7·10 -5  Gy day -1 , and 2.0·10 -4  Gy day -1 , respectively. The difference in thresholds is exactly reflecting the relationship between the natural longevity of these two species. Graded scale of severity in lifetime radiation effects in mammals is developed, based on compiled datasets. Being placed on the severity scale, the effects of internal alpha-emitters are situated in the zones of considerably lower dose rates than effects of the same severity caused by low-LET radiation. RBE values, calculated for effects of equal severity, are found to depend on the intensity of chronic exposure: different RBE values are characteristic for low, moderate, and high lifetime exposures (30, 70, and 13, respectively). The results of the study provide a basis for selecting correct values of radiation weighting factors in dose assessment to non-human biota. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Effects of virus dose and extrinsic incubation temperature on vector competence of Culex nigripalpus (Diptera: Culicidae) for St. Louis encephalitis virus.

PubMed

Richards, Stephanie L; Anderson, Sheri L; Lord, Cynthia C; Tabachnick, Walter J

2012-11-01

Culex nigripalpus Theobald is a primary vector of St. Louis encephalitis virus in the southeastern United States. Cx. nigripalpus females were fed blood containing a low (4.0 +/- 0.01 log10 plaque-forming unit equivalents (PFUeq) /ml) or high (4.7 +/- 0.1 log10 PFUeq/ml) St. Louis encephalitis virus dose and maintained at extrinsic incubation temperatures (EIT) of 25 or 28 degrees C for 12 d. Vector competence was measured via quantitative real-time reverse transcriptase polymerase chain reaction to estimate PFUeq using rates of infection, dissemination, and transmission. There were no differences in infection rates between the two EITs at either dose. The low dose had higher infection rates at both EITs. Dissemination rates were significantly higher at 28 degrees C compared with 25 degrees C at both doses. Virus transmission was observed (<7%) only at 28 degrees C for both doses. The virus titer in body tissues was greater at 28 degrees C compared with 25 degrees C at both doses. The difference between the EITs was greater at the low dose, resulting in a higher titer for the low dose than the high dose at 28 degrees C. Virus titers in leg tissues were greater in mosquitoes fed the high versus low dose, but were not influenced by EIT. Further investigations using a variety of environmental and biological factors would be useful in exploring the complexity of vector competence.

Effects of Virus Dose and Extrinsic Incubation Temperature on Vector Competence of Culex nigripalpus (Diptera: Culicidae) for St. Louis Encephalitis Virus

PubMed Central

RICHARDS, STEPHANIE L.; ANDERSON, SHERI L.; LORD, CYNTHIA C.; TABACHNICK, WALTER J.

2013-01-01

Culex nigripalpus Theobald is a primary vector of St. Louis encephalitis virus in the southeastern United States. Cx. nigripalpus females were fed blood containing a low (4.0 ± 0.01 log10 plaque-forming unit equivalents (PFUeq)/ml) or high (4.7 ± 0.1 log10 PFUeq/ml) St. Louis encephalitis virus dose and maintained at extrinsic incubation temperatures (EIT) of 25 or 28°C for 12 d. Vector competence was measured via quantitative real-time reverse transcriptase polymerase chain reaction to estimate PFUeq using rates of infection, dissemination, and transmission. There were no differences in infection rates between the two EITs at either dose. The low dose had higher infection rates at both EITs. Dissemination rates were significantly higher at 28°C compared with 25°C at both doses. Virus transmission was observed (<7%) only at 28°C for both doses. The virus titer in body tissues was greater at 28°C compared with 25°C at both doses. The difference between the EITs was greater at the low dose, resulting in a higher titer for the low dose than the high dose at 28°C. Virus titers in leg tissues were greater in mosquitoes fed the high versus low dose, but were not influenced by EIT. Further investigations using a variety of environmental and biological factors would be useful in exploring the complexity of vector competence. PMID:23270182

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;

Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates

NASA Astrophysics Data System (ADS)

Fournier, P.; Crosbie, J. C.; Cornelius, I.; Berkvens, P.; Donzelli, M.; Clavel, A. H.; Rosenfeld, A. B.; Petasecca, M.; Lerch, M. L. F.; Bräuer-Krisch, E.

2016-07-01

Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency’s TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, k s , is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called ‘current ramping’ method, to determine k s for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials.

Influence of 12C6+ ion irradiation on mutant avermitilis

NASA Astrophysics Data System (ADS)

Wang, Shu-Yang; Chen, Ji-Hong; Li, Wen-Jian; Liang, Jian-Ping; Bo, Yong-Heng; Ma, Xiao-Qi; Liu, Jing

2012-11-01

The effects of 12C+6 ion irradiation on colony morphology and mycelia morphology, as well as on mutation rate have been studied in the B1a high-product strains (ZJAV-Y1-203) mutated by heavy ion irradiation and compared with that in the original strain (ZJAV-A-1). After irradiating the rate of a straw hat colony type having a high ability of producing B1a in ZJAV-Y1-203 strains was higher than that found in ZJAV-A-1 strains. When strains were cultured in a liquid medium for 24 hours, the mycelium becoming thinner could be observed in all of the irradiated ZJAV- Y1-203 groups, but only in the ZJAV-A-1 groups irradiated at the dose of 50 Gy or more. The early growth of mycelium was inhibited in the ZJAV- Y1-203 group irradiated with a high dose. The highest positive mutation rate (23.5%) of ZJAV - Y1 - 203 was reached at the lower dose of 30 Gy while the highest positive mutation rate of 34.2% in ZJAV-A-1 appeared at 50 Gy. These results indicate that the effects of heavy ion irradiation still exist even in the mutated Streptomyces avermitilis, and only the dose is lower and the effects not so strong compared with the one that is first irradiated with optimized heavy ion doses. This is evidence of the one directional mutation being controlled by many more factors in a organism.

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;

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

Factors impacting the efficacy of venlafaxine extended release 75–225 mg/day in patients with major depressive disorder: exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study in Japan

PubMed Central

Watanabe, Yoshinori; Asami, Yuko; Hirano, Yoko; Kuribayashi, Kazuhiko; Itamura, Rio; Imaeda, Takayuki

2018-01-01

Purpose To explore the potential factors impacting the efficacy of venlafaxine extended release (ER) and treatment differences between 75 mg/day and 75–225 mg/day dose in patients with major depressive disorder (MDD). Methods We performed exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study conducted in Japan. A total of 538 outpatients aged 20 years or older with a primary diagnosis of MDD who experienced single or recurrent episodes were randomized into three groups: fixed-dose, flexible-dose, or placebo. Venlafaxine ER was initiated at 37.5 mg/day and titrated to 75 mg/day for both fixed-dose and flexible-dose group, and to 225 mg/day for flexible-dose group (if well tolerated). Efficacy endpoints were changes from baseline at Week 8 using the Hamilton Rating Scale for Depression–17 items (HAM-D17) total score, Hamilton Rating Scale for Depression–6 items score, and Montgomery–Asberg Depression Rating Scale total score. The following factors were considered in the subgroup analyses: sex, age, HAM-D17 total score at baseline, duration of MDD, duration of current depressive episode, history of previous depressive episodes, history of previous medications for MDD, and CYP2D6 phenotype. For each subgroup, an analysis of covariance model was fitted and the adjusted mean of the treatment effect and corresponding 95% CI were computed. Due to the exploratory nature of the investigation, no statistical hypothesis testing was used. Results Venlafaxine ER improved symptoms of MDD compared with placebo in most subgroups. The subgroup with a long duration of MDD (>22 months) consistently showed greater treatment benefits in the flexible-dose group than in the fixed-dose group. Conclusion These results suggest that a greater treatment response to venlafaxine ER (up to 225 mg/day) can be seen in patients with a longer duration of MDD. Further investigations are needed to identify additional factors impacting the efficacy of venlafaxine ER. PMID:29844674

Factors impacting the efficacy of venlafaxine extended release 75-225 mg/day in patients with major depressive disorder: exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study in Japan.

PubMed

Watanabe, Yoshinori; Asami, Yuko; Hirano, Yoko; Kuribayashi, Kazuhiko; Itamura, Rio; Imaeda, Takayuki

2018-01-01

To explore the potential factors impacting the efficacy of venlafaxine extended release (ER) and treatment differences between 75 mg/day and 75-225 mg/day dose in patients with major depressive disorder (MDD). We performed exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study conducted in Japan. A total of 538 outpatients aged 20 years or older with a primary diagnosis of MDD who experienced single or recurrent episodes were randomized into three groups: fixed-dose, flexible-dose, or placebo. Venlafaxine ER was initiated at 37.5 mg/day and titrated to 75 mg/day for both fixed-dose and flexible-dose group, and to 225 mg/day for flexible-dose group (if well tolerated). Efficacy endpoints were changes from baseline at Week 8 using the Hamilton Rating Scale for Depression-17 items (HAM-D 17 ) total score, Hamilton Rating Scale for Depression-6 items score, and Montgomery-Asberg Depression Rating Scale total score. The following factors were considered in the subgroup analyses: sex, age, HAM-D 17 total score at baseline, duration of MDD, duration of current depressive episode, history of previous depressive episodes, history of previous medications for MDD, and CYP2D6 phenotype. For each subgroup, an analysis of covariance model was fitted and the adjusted mean of the treatment effect and corresponding 95% CI were computed. Due to the exploratory nature of the investigation, no statistical hypothesis testing was used. Venlafaxine ER improved symptoms of MDD compared with placebo in most subgroups. The subgroup with a long duration of MDD (>22 months) consistently showed greater treatment benefits in the flexible-dose group than in the fixed-dose group. These results suggest that a greater treatment response to venlafaxine ER (up to 225 mg/day) can be seen in patients with a longer duration of MDD. Further investigations are needed to identify additional factors impacting the efficacy of venlafaxine ER.

Room model based Monte Carlo simulation study of the relationship between the airborne dose rate and the surface-deposited radon progeny.

PubMed

Sun, Kainan; Field, R William; Steck, Daniel J

2010-01-01

The quantitative relationships between radon gas concentration, the surface-deposited activities of various radon progeny, the airborne radon progeny dose rate, and various residential environmental factors were investigated through a Monte Carlo simulation study based on the extended Jacobi room model. Airborne dose rates were calculated from the unattached and attached potential alpha-energy concentrations (PAECs) using two dosimetric models. Surface-deposited (218)Po and (214)Po were significantly correlated with radon concentration, PAECs, and airborne dose rate (p-values <0.0001) in both non-smoking and smoking environments. However, in non-smoking environments, the deposited radon progeny were not highly correlated to the attached PAEC. In multiple linear regression analysis, natural logarithm transformation was performed for airborne dose rate as a dependent variable, as well as for radon and deposited (218)Po and (214)Po as predictors. In non-smoking environments, after adjusting for the effect of radon, deposited (214)Po was a significant positive predictor for one dose model (RR 1.46, 95% CI 1.27-1.67), while deposited (218)Po was a negative predictor for the other dose model (RR 0.90, 95% CI 0.83-0.98). In smoking environments, after adjusting for radon and room size, deposited (218)Po was a significant positive predictor for one dose model (RR 1.10, 95% CI 1.02-1.19), while a significant negative predictor for the other model (RR 0.90, 95% CI 0.85-0.95). After adjusting for radon and deposited (218)Po, significant increases of 1.14 (95% CI 1.03-1.27) and 1.13 (95% CI 1.05-1.22) in the mean dose rates were found for large room sizes relative to small room sizes in the different dose models.

High-Risk Prescribing to Medicaid Enrollees Receiving Opioid Analgesics: Individual- and County-Level Factors.

PubMed

Heins, Sara E; Sorbero, Mark J; Jones, Christopher M; Dick, Andrew W; Stein, Bradley D

2018-01-05

Prescription opioid overdoses have increased dramatically in recent years, with the highest rates among Medicaid enrollees. High-risk prescribing includes practices associated with overdoses and a range of additional opioid-related problems. To identify individual- and county-level factors associated with high-risk prescribing among Medicaid enrollees receiving opioids. In a four-states, cross-sectional claims data study, Medicaid enrollees 18-64 years old with a new opioid analgesic treatment episode 2007-2009 were identified. Multivariate regression analyses were conducted to identify factors associated with high-risk prescribing, defined as high-dose opioid prescribing (morphine equivalent daily dose ≥100 mg for >6 days), opioid overlap, opioid-benzodiazepine overlap. High-risk prescribing occurred in 39.4% of episodes. Older age, rural county of residence, white race, and major depression diagnosis were associated with higher rates of all types of high-risk prescribing. Individuals with prior opioid, alcohol, and hypnotic/sedative use disorder diagnoses had lower odds of high-dose opioid prescribing but higher odds of opioid overlap and opioid-benzodiazepine overlap than individuals without such disorders. High-dose opioid prescribing in Massachusetts was less common than in California, Illinois, and New York, whereas the rate of benzodiazepine overlap in Massachusetts was more common than in other states. Conclusions/Importance: High-risk prescribing was common and associated with several important demographic, clinical, and community factors. Findings can be used to inform targeted interventions designed to reduce such prescribing, and given state variation observed, further research is needed to better understand the effects of state policies on high-risk prescribing.

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.

Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart.

PubMed

Seawright, John W; Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A; Hauer-Jensen, Martin; Boerma, Marjan

2017-01-01

Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and cardiac remodeling in response to HU with simultaneous exposure to low-dose rate γ-radiation. Results from the late observation time points suggest that the hearts had mostly recovered from these two experimental conditions. However, further research is needed with larger numbers of animals for a more robust statistical power to fully characterize the early and late effects of simulated microgravity combined with exposure to low-dose rate ionizing radiation on the heart.

Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart

PubMed Central

Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A.; Hauer-Jensen, Martin; Boerma, Marjan

2017-01-01

Purpose Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Methods Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. Results The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. Conclusions This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and cardiac remodeling in response to HU with simultaneous exposure to low-dose rate γ-radiation. Results from the late observation time points suggest that the hearts had mostly recovered from these two experimental conditions. However, further research is needed with larger numbers of animals for a more robust statistical power to fully characterize the early and late effects of simulated microgravity combined with exposure to low-dose rate ionizing radiation on the heart. PMID:28678877

Dosimetry in differentiated thyroid carcinoma (12-1402R)

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

Minguez, Pablo; Genolla, Jose; Celeiro, Jose Javier

2013-01-15

Purpose: The aim of this study has been to perform a dosimetric study in the treatments of differentiated thyroid cancer (DTC) performed in our center in order to find a dose-effect correlation. Methods: Thirty patients treated for DTC with 3700 MBq of {sup 131}I have been included in this study. For reasons of radiological protection all of them spent two nights as inpatients. Dose rate at 1 m from all patients was measured approximately 20 and 44 h after the administration of the radioiodine and a whole body scan in the gamma camera was performed approximately 1 week later. Withmore » those measurements and by using a model of two compartments the activities in thyroid bed remnants and in the whole body were calculated as a function of time. The integration of both activities yields the corresponding cumulated activities. Absorbed doses to thyroid bed remnants and to the whole body can be calculated following the MIRDOSE method-that is, by multiplying the corresponding cumulated activities by the corresponding S factors. Results: The absorbed doses to thyroid bed remnants calculated in this study fall into a very wide range (13-1161 Gy) and showed the highest correlation factors with the following parameters: the absorbed dose rate to thyroid bed remnants, the cumulated activity in thyroid bed remnants, and the maximum radioiodine uptake in thyroid bed remnants. The absorbed doses to the whole body range from 0.12 to 0.23 Gy. The ablation was successful in all patients, and in spite of the wide range of absorbed doses to thyroid bed remnants obtained, no dose-effect correlation could be obtained. Conclusions: Facing DTC treatments from a dosimetric viewpoint in which a predosimetry to calculate the activity of {sup 131}I to be administered is performed is a subject difficult to handle. This statement is based on the fact that although a very wide range of absorbed doses to thyroid bed remnants was obtained (including several absorbed doses well below some dose thresholds previously published to achieve ablation of thyroid bed remnants), ablation of thyroid bed remnants was successful for all patients and therefore no dose-effect correlation could be determined.« less

Fractional dosing of yellow fever vaccine to extend supply: a modelling study.

PubMed

Wu, Joseph T; Peak, Corey M; Leung, Gabriel M; Lipsitch, Marc

2016-12-10

The ongoing yellow fever epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa, Democratic Republic of the Congo, in July-August, 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidation of the conditions under which dose fractionation would reduce transmission. We estimate the effective reproductive number for yellow fever in Angola using disease natural history and case report data. With simple mathematical models of yellow fever transmission, we calculate the infection attack rate (the proportion of population infected over the course of an epidemic) with various levels of transmissibility and 5-fold fractional-dose vaccine efficacy for two vaccination scenarios, ie, random vaccination in a hypothetical population that is completely susceptible, and the Kinshasa vaccination campaign in July-August, 2016, with different age cutoff for fractional-dose vaccines. We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (ie, a proportion of vaccine recipients receive complete protection [VE] and the remainder receive no protection), n-fold fractionation can greatly reduce infection attack rate as long as VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (ie, the susceptibility of each vaccine recipient is reduced by a factor that is equal to the vaccine efficacy). The age cutoff for fractional-dose vaccines chosen by WHO for the Kinshasa vaccination campaign (2 years) provides the largest reduction in infection attack rate if the efficacy of 5-fold fractional-dose vaccines exceeds 20%. Dose fractionation is an effective strategy for reduction of the infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected. NIH-MIDAS, HMRF-Hong Kong. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effets pathogènes d'un faible débit de dose : la relation « dose effet »

NASA Astrophysics Data System (ADS)

Masse, Roland

2002-10-01

There is no evidence of pathogenic effects in human groups exposed to less than 100 mSv at low dose-rate. The attributed effects are therefore the result of extrapolations from higher doses. The validity of such extrapolations is discussed from the point of view of epidemiology as well as cellular and molecular biology. The Chernobyl accident resulted in large excess of thyroid cancers in children; it also raised the point that some actual sanitary effects among distressed populations might be a direct consequence of low doses. Studies under the control of UN have not confirmed this point identifying no dose-effect relationship and " severe socio-economic and psychological pressures… poverty, poor diet and living conditions, and lifestyle factors" as the main cause for depressed health. Some hypothesis are considered for explaining the dose-dependence and high prevalence of non-cancer causes of death among human groups exposed to more than 300 mSv. To cite this article: R. Masse, C. R. Physique 3 (2002) 1049-1058.

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.

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

Commentary 2 to Cox and Little: radiation-induced oncogenic transformation: the interplay between dose, dose protraction, and radiation quality

NASA Technical Reports Server (NTRS)

Brenner, D. J.; Hall, E. J.

1992-01-01

There is now a substantial body of evidence for end points such as oncogenic transformation in vitro, and carcinogenesis and life shortening in vivo, suggesting that dose protraction leads to an increase in effectiveness relative to a single, acute exposure--at least for radiations of medium linear energy transfer (LET) such as neutrons. Table I contains a summary of the pertinent data from studies in which the effect is seen. [table: see text] This phenomenon has come to be known as the "inverse dose rate effect," because it is in marked contrast to the situation at low LET, where protraction in delivery of a dose of radiation, either by fractionation or low dose rate, results in a decreased biological effect; additionally, at medium and high LET, for radiobiological end points such as clonogenic survival, the biological effectiveness is independent of protraction. The quantity and quality of the published reports on the "inverse dose rate effect" leaves little doubt that the effect is real, but the available evidence indicates that the magnitude of the effect is due to a complex interplay between dose, dose rate, and radiation quality. Here, we first summarize the available data on the inverse dose rate effect and suggest that it follows a consistent pattern in regard to dose, dose rate, and radiation quality; second, we describe a model that predicts these features; and, finally, we describe the significance of the effect for radiation protection.

Long-term results and prognostic factors of fractionated strontium-90 eye applicator for pterygium.

PubMed

Viani, Gustavo Arruda; Stefano, Eduardo Jose; De Fendi, Ligia Issa; Fonseca, Ellen Carrara

2008-11-15

To evaluate the long-term safety, effectiveness, and prognostic factors of fractionated postoperative beta-irradiation. Between 1993 and 2005, 623 patients with 737 pterygium lesions were treated with a strontium-90 eye applicator after surgical excision. The median follow-up period was 60 months (range, 6.7-139.5). Of the 737 lesions, 644 were primary and 93 were recurrences after surgical removal alone. Fractionated radiotherapy (RT) to a total dose of 35 Gy in five to seven fractions was used. A total of 73 local pterygium recurrences (9.9%) were noted. Of the recurrent cases, 80% were noted within 3 years after treatment. The 5- and 10-year probability of local control was 90% and 88%, respectively. The multivariate analysis for all cases demonstrated that gender, age, total radiation dose, recurrent pterygia, and interval between surgery and RT affected the overall local control rate. Late toxicities that might have been associated with strontium-90 RT included scleromalacia (scleral thinning) in nine eyes, adhesion of the eyelids in eight, cataracts in six, and scleral ulcer in five eyes. Fractionated strontium-90 RT to a total dose of approximately 35 Gy in five to seven fractions results in a similar local control rate as higher doses in other series, with an acceptable complication rate.

Modeling gamma radiation dose in dwellings due to building materials.

PubMed

de Jong, Peter; van Dijk, Willem

2008-01-01

A model is presented that calculates the absorbed dose rate in air of gamma radiation emitted by building materials in a rectangular body construction. The basis for these calculations is formed by a fixed set of specific absorbed dose rates (the dose rate per Bq kg(-1) 238U, 232Th, and 40K), as determined for a standard geometry with the dimensions 4 x 5 x 2.8 m3. Using the computer codes Marmer and MicroShield, correction factors are assessed that quantify the influence of several room and material related parameters on the specific absorbed dose rates. The investigated parameters are the position in the construction; the thickness, density, and dimensions of the construction parts; the contribution from the outer leave; the presence of doors and windows; the attenuation by internal partition walls; the contribution from building materials present in adjacent rooms; and the effect of non-equilibrium due to 222Rn exhalation. To verify the precision, the proposed method is applied to three Dutch reference dwellings, i.e., a row house, a coupled house, and a gallery apartment. The averaged difference with MCNP calculations is found to be 4%.

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.

Factoring vs linear modeling in rate estimation: a simulation study of relative accuracy.

PubMed

Maldonado, G; Greenland, S

1998-07-01

A common strategy for modeling dose-response in epidemiology is to transform ordered exposures and covariates into sets of dichotomous indicator variables (that is, to factor the variables). Factoring tends to increase estimation variance, but it also tends to decrease bias and thus may increase or decrease total accuracy. We conducted a simulation study to examine the impact of factoring on the accuracy of rate estimation. Factored and unfactored Poisson regression models were fit to follow-up study datasets that were randomly generated from 37,500 population model forms that ranged from subadditive to supramultiplicative. In the situations we examined, factoring sometimes substantially improved accuracy relative to fitting the corresponding unfactored model, sometimes substantially decreased accuracy, and sometimes made little difference. The difference in accuracy between factored and unfactored models depended in a complicated fashion on the difference between the true and fitted model forms, the strength of exposure and covariate effects in the population, and the study size. It may be difficult in practice to predict when factoring is increasing or decreasing accuracy. We recommend, therefore, that the strategy of factoring variables be supplemented with other strategies for modeling dose-response.

Effect of detomidine on visceral and somatic nociception and duodenal motility in conscious adult horses.

PubMed

Elfenbein, Johanna R; Sanchez, L Chris; Robertson, Sheilah A; Cole, Cynthia A; Sams, Richard

2009-03-01

To evaluate the effects of detomidine on visceral and somatic nociception, heart and respiratory rates, sedation, and duodenal motility and to correlate these effects with serum detomidine concentrations. Nonrandomized, experimental trial. Five adult horses, each with a permanent gastric cannula weighing 534 +/- 46 kg. Visceral nociception was evaluated by colorectal (CRD) and duodenal distension (DD). The duodenal balloon was used to assess motility. Somatic nociception was assessed via thermal threshold (TT). Nose-to-ground (NTG) height was used as a measure of sedation. Serum was collected for pharmacokinetic analysis. Detomidine (10 or 20 microg kg(-1)) was administered intravenously. Data were analyzed by means of a three-factor anova with fixed factors of treatment and time and random factor of horse. When a significant time x treatment interaction was detected, differences were compared with a simple t-test or Bonferroni t-test. Significance was set at p < 0.05. Detomidine produced a significant, dose-dependent decrease in NTG height, heart rate, and skin temperature and a significant, nondose-dependent decrease in respiratory rate. Colorectal distension threshold was significantly increased with 10 microg kg(-1) for 15 minutes and for at least 165 minutes with 20 microg kg(-1). Duodenal distension threshold was significantly increased at 15 minutes for the 20 microg kg(-1) dose. A significant change in TT was not observed at either dose. A marked, immediate decrease in amplitude of duodenal contractions followed detomidine administration at both doses for 50 minutes. Detomidine caused a longer period of visceral anti-nociception as determined by CRD but a shorter period of anti-nociception as determined by DD than has been previously reported. The lack of somatic anti-nociception as determined by TT testing may be related to the marked decrease in skin temperature, likely caused by peripheral vasoconstriction and the low temperature cut-off of the testing device.

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.

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

Comparative dosimetric characterization for different types of detectors in high-energy electron beams

NASA Astrophysics Data System (ADS)

Lee, Chang Yeol; Kim, Woo Chul; Kim, Hun Jeong; Huh, Hyun Do; Park, Seungwoo; Choi, Sang Hyoun; Kim, Kum Bae; Min, Chul Kee; Kim, Seong Hoon; Shin, Dong Oh

2017-02-01

The purpose of this study is to perform a comparison and on analysis of measured dose factor values by using various commercially available high-energy electron beam detectors to measure dose profiles and energy property data. By analyzing the high-energy electron beam data from each detector, we determined the optimal detector for measuring electron beams in clinical applications. The dose linearity, dose-rate dependence, percentage depth dose, and dose profile of each detector were measured to evaluate the dosimetry characteristics of high-energy electron beams. The dose profile and the energy characteristics of high-energy electron beams were found to be different when measured by different detectors. Through comparison with other detectors based on the analyzed data, the microdiamond detector was found to have outstanding dose linearity, a low dose-rate dependency, and a small effective volume. Thus, this detector has outstanding spatial resolution and is the optimal detector for measuring electron beams. Radiation therapy results can be improved and related medical accidents can be prevented by using the procedure developed in this research in clinical practice for all beam detectors when measuring the electron beam dose.

Space Shuttle drops down the SAA doses on ISS

NASA Astrophysics Data System (ADS)

Dachev, T. P.; Semkova, J.; Tomov, B.; Matviichuk, Yu.; Dimitrov, Pl.; Koleva, R.; Malchev, St.; Reitz, G.; Horneck, G.; De Angelis, G.; Häder, D.-P.; Petrov, V.; Shurshakov, V.; Benghin, V.; Chernykh, I.; Drobyshev, S.; Bankov, N. G.

2011-06-01

Long-term analysis of data from two radiation detection instruments on the International Space Station (ISS) shows that the docking of the Space Shuttle drops down the measured dose rates in the region of the South Atlantic Anomaly (SAA) by a factor of 1.5-3. Measurements either by the R3DE detector, which is outside the ISS at the EuTEF facility on the Columbus module behind a shielding of less than 0.45 g cm -2, and by the three detectors of the Liulin-5 particle telescope, which is inside the Russian PEARS module in the spherical tissue equivalent phantom behind much heavier shielding demonstrate that effect. Simultaneously the estimated averaged incident energies of the incoming protons rise up from about 30 to 45 MeV. The effect is explained by the additional shielding against the SAA 30-150 MeV protons, provided by the 78 tons Shuttle to the instruments inside and outside of the ISS. An additional reason is the ISS attitude change (performed for the Shuttle docking) leading to decreasing of dose rates in two of Liulin-5 detectors because of the East-West proton fluxes asymmetry in SAA. The Galactic Cosmic Rays dose rates are practically not affected.

The impact of variation in scaling factors on the estimation of ...

EPA Pesticide Factsheets

Many physiologically based pharmacokinetic (PBPK) models include values for metabolic rate parameters extrapolated from in vitro metabolism studies using scaling factors such as mg of microsomal protein per gram of liver (MPPGL) and liver mass (FVL). Variation in scaling factor values impacts metabolic rate parameter estimates (Vmax) and hence estimates of internal dose used in dose response analysis. The impacts of adult human variation in MPPGL and FVL on estimates of internal dose were assessed using a human PBPK model for BDCM for several internal dose metrics for two exposure scenarios (single 0.25 liter drink of water or 10 minute shower) under plausible (5 micrograms/L) and high level (20 micrograms/L) water concentrations. For both concentrations, all internal dose metrics were changed less than 5% for the showering scenario (combined inhalation and dermal exposure). In contrast, a 27-fold variation in area under the curve for BDCM in venous blood was observed at both oral exposure concentrations, whereas total amount of BDCM metabolized in liver was relatively unchanged. This analysis demonstrates that variability in the scaling factors used for in vitro to in vivo extrapolation (IVIVE) for metabolic rate parameters can have a significant route-dependent impact on estimates of internal dose under environmentally relevant exposure scenarios. This indicates the need to evaluate both uncertainty and variability for scaling factors used for IVIVE. Sca

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

PubMed

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

2016-05-01

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

Retrospective analysis of factors that affect the success of single-dose methotrexate treatment in ectopic pregnancy

PubMed Central

Var, Altan; Özyurt, Ramazan; Şık, Bulat Aytek; Kumbasar, Serkan; Sever, Erman; Deveci, Mustafa; Çöt, Özgür; Salman, Süleyman; Güzel, Yılmaz

2015-01-01

Objective: Detection of factors that affect the success of single-dose methotrexate treatment in ectopic pregnancy. Materials and Methods: We investigated 99 patients who had been treated with single-dose methotrexate for ectopic pregnancy in our clinic between January 2009 and June 2014. Demographic, clinical, and laboratory results of possible factors that affect treatment success were retrospectively analyzed. Successfully and unsuccessfully treated patients were compared based on their pre-treatment results. Results: The success rate of single-dose methotrexate treatment was found to be 70.7%. No significant difference was found between succesfully and unsuccessfully treated patients before treatment in terms of factors such as gestational weeks, mass size, presence of yolk sac, and presence of free fluid (p=0.224, p=0.201, p=0.200, p=0.200). Serum β-hCG values in patients whose treatment was unsuccessful was found to be higher compared with the successfully treated group (mean β-hCG value of unsuccessful group: 4412±3501 mIU/mL; mean β-hCG value of successful group: 1079±942 mIU/mL; p<0.001). Conclusion: Single-dose methotrexate treatment is an effective and reliable method in the treatment of ectopic pregnancy. Elevation of serum β-hCG value stands as the main prognostic factor that affects the success of single-dose methotrexate treatment. PMID:28913072

Pharmacokinetics, hemodynamic and metabolic effects of epinephrine to prevent post-operative low cardiac output syndrome in children

PubMed Central

2014-01-01

Introduction The response to exogenous epinephrine (Ep) is difficult to predict given the multitude of factors involved such as broad pharmacokinetic and pharmacodynamic between-subject variabilities, which may be more pronounced in children. We investigated the pharmacokinetics and pharmacodynamics of Ep, co-administered with milrinone, in children who underwent open heart surgical repair for congenital defects following cardiopulmonary bypass, including associated variability factors. Methods Thirty-nine children with a high risk of low cardiac output syndrome were prospectively enrolled. Ep pharmacokinetics, hemodynamic and metabolic effects were analyzed using the non-linear mixed effects modeling software MONOLIX. According to the final model, an Ep dosing simulation was suggested. Results Ep dosing infusions ranged from 0.01 to 0.23 μg.kg-1.min-1 in children whose weight ranged from 2.5 to 58 kg. A one-compartment open model with linear elimination adequately described the Ep concentration-time courses. Bodyweight (BW) was the main covariate influencing clearance (CL) and endogenous Ep production rate (q0) via an allometric relationship: CL(BWi) = θCL x (BWi)3/4 and q0(BWi) = θq0 x (BWi )3/4. The increase in heart rate (HR) and mean arterial pressure (MAP) as a function of Ep concentration were well described using an Emax model. The effect of age was significant on HR and MAP basal level parameters. Assuming that Ep stimulated the production rate of plasma glucose, the increases in plasma glucose and lactate levels were well described by turnover models without any significant effect of age, BW or exogenous glucose supply. Conclusions According to this population analysis, the developmental effects of BW and age explained a part of the pharmacokinetic and pharmacodynamics between-subject variabilities of Ep administration in critically ill children. This approach ultimately leads to a valuable Ep dosing simulation which should help clinicians to determine an appropriate a priori dosing regimen. PMID:24456639

Evaluation of Enhanced Low Dose Rate Sensitivity in Discrete Bipolar Junction Transistors

NASA Technical Reports Server (NTRS)

Chen, Dakai; Ladbury Raymond; LaBel, Kenneth; Topper, Alyson; Ladbury, Raymond; Triggs, Brian; Kazmakites, Tony

2012-01-01

We evaluate the low dose rate sensitivity in several families of discrete bipolar transistors across device parameter, quality assurance level, and irradiation bias configuration. The 2N2222 showed the most significant low dose rate sensitivity, with low dose rate enhancement factor of 3.91 after 100 krad(Si). The 2N2907 also showed critical degradation levels. The devices irradiated at 10 mrad(Si)/s exceeded specifications after 40 and 50 krad(Si) for the 2N2222 and 2N2907 devices, respectively.

Electrocardiogram‐gated coronary CT angiography dose estimates using ImPACT

PubMed Central

Asada, Yasuki; Matsubara, Kosuke; Suzuki, Shouichi; Koshida, Kichiro; Matsunaga, Yuta; Haba, Tomonobu; Kawaguchi, Ai; Toyama, Hiroshi; Kato, Ryoichi

2016-01-01

The primary study objective was to assess radiation doses using a modified form of the Imaging Performance Assessment of Computed Tomography (CT) scanner (ImPACT) patient dosimetry for cardiac applications on an Aquilion ONE ViSION Edition scanner, including the Ca score, target computed tomography angiography (CTA), prospective CTA, continuous CTA/cardiac function analysis (CFA), and CTA/CFA modulation. Accordingly, we clarified the CT dose index (CTDI) to determine the relationship between heart rate (HR) and X‐ray exposure. As a secondary objective, we compared radiation doses using modified ImPACT, a whole‐body dosimetry phantom study, and the k‐factor method to verify the validity of the dose results obtained with modified ImPACT. The effective dose determined for the reference person (4.66 mSv at 60 beats per minute (bpm) and 33.43 mSv at 90 bpm) were approximately 10% less than those determined for the phantom study (5.28 mSv and 36.68 mSv). The effective doses according to the k‐factor (0.014 mSv·mGy−1·cm−1; 2.57 mSv and 17.10 mSv) were significantly lower than those obtained with the other two methods. In the present study, we have shown that ImPACT, when modified for cardiac applications, can assess both absorbed and effective doses. The results of our dose comparison indicate that modified ImPACT dose assessment is a promising and practical method for evaluating coronary CTA. PACS number(s): 87.57.Q‐, 87.59.Dj, 87.57.uq PMID:27455500

Risk of solid cancer in low dose-rate radiation epidemiological studies and the dose-rate effectiveness factor.

PubMed

Shore, Roy; Walsh, Linda; Azizova, Tamara; Rühm, Werner

2017-10-01

Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy -1 ) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta-analyses that included only cohorts in which the mean dose was <100 mGy yielded a risk ratio of 1.06 (95% CI 0.30, 1.83) for solid cancer mortality and 0.58 (95% CI 0.10, 1.06) for mortality + incidence data. The interpretation of a best estimate for a value of the DREF depends on the appropriateness of including the Mayak study. This study indicates a range of uncertainty in the value of DREF between 1 and about 2 after protracted radiation exposure. The LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the LSS risk estimates used for radiation protection purposes.

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

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

Software Development for Estimating the Conversion Factor (K-Factor) at Suitable Scan Areas, Relating the Dose Length Product to the Effective Dose.

PubMed

Kobayashi, Masanao; Asada, Yasuki; Matsubara, Kosuke; Suzuki, Syouichi; Koshida, Kichiro; Matsunaga, Yuta; Kawaguchi, Ai; Haba, Tomonobu; Toyama, Hiroshi; Kato, Ryouichi

2017-05-01

We developed a k-factor-creator software (kFC) that provides the k-factor for CT examination in an arbitrary scan area. It provides the k-factor from the effective dose and dose-length product by Imaging Performance Assessment of CT scanners and CT-EXPO. To assess the reliability, we compared the kFC-evaluated k-factors with those of the International Commission on Radiological Protection (ICRP) publication 102. To confirm the utility, the effective dose determined by coronary computed tomographic angiography (CCTA) was evaluated by a phantom study and k-factor studies. In the CCTA, the effective doses were 5.28 mSv in the phantom study, 2.57 mSv (51%) in the k-factor of ICRP, and 5.26 mSv (1%) in the k-factor of the kFC. Effective doses can be determined from the kFC-evaluated k-factors in suitable scan areas. Therefore, we speculate that the flexible k-factor is useful in clinical practice, because CT examinations are performed in various scan regions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Absorbed dose thresholds and absorbed dose rate limitations for studies of electron radiation effects on polyetherimides

NASA Technical Reports Server (NTRS)

Long, Edward R., Jr.; Long, Sheila Ann T.; Gray, Stephanie L.; Collins, William D.

1989-01-01

The threshold values of total absorbed dose for causing changes in tensile properties of a polyetherimide film and the limitations of the absorbed dose rate for accelerated-exposure evaluation of the effects of electron radiation in geosynchronous orbit were studied. Total absorbed doses from 1 kGy to 100 MGy and absorbed dose rates from 0.01 MGy/hr to 100 MGy/hr were investigated, where 1 Gy equals 100 rads. Total doses less than 2.5 MGy did not significantly change the tensile properties of the film whereas doses higher than 2.5 MGy significantly reduced elongation-to-failure. There was no measurable effect of the dose rate on the tensile properties for accelerated electron exposures.

Development of an abiraterone acetate formulation with improved oral bioavailability guided by absorption modeling based on in vitro dissolution and permeability measurements.

PubMed

Solymosi, Tamás; Ötvös, Zsolt; Angi, Réka; Ordasi, Betti; Jordán, Tamás; Semsey, Sándor; Molnár, László; Ránky, Soma; Filipcsei, Genovéva; Heltovics, Gábor; Glavinas, Hristos

2017-10-30

Particle size reduction of drug crystals in the presence of surfactants (often called "top-down" production methods) is a standard approach used in the pharmaceutical industry to improve bioavailability of poorly soluble drugs. Based on the mathematical model used to predict the fraction dose absorbed this formulation approach is successful when dissolution rate is the main rate limiting factor of oral absorption. In case compound solubility is also a major factor this approach might not result in an adequate improvement in bioavailability. Abiraterone acetate is poorly water soluble which is believed to be responsible for its very low bioavailability in the fasted state and its significant positive food effect. In this work, we have successfully used in vitro dissolution, solubility and permeability measurements in biorelevant media to describe the dissolution characteristics of different abiraterone acetate formulations. Mathematical modeling of fraction dose absorbed indicated that reducing the particle size of the drug cannot be expected to result in significant improvement in bioavailability in the fasted state. In the fed state, the same formulation approach can result in a nearly complete absorption of the dose; thereby, further increasing the food effect. Using a "bottom-up" formulation method we improved both the dissolution rate and the apparent solubility of the compound. In beagle dog studies, this resulted in a ≫>10-fold increase in bioavailability in the fasted state when compared to the marketed drug and the elimination of the food effect. Calculated values of fraction dose absorbed were in agreement with the observed relative bioavailability values in beagle dogs. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiation environment on the Mir orbital station during solar minimum.

PubMed

Badhwar, G D; Atwell, W; Cash, B; Petrov, V M; Akatov YuA; Tchernykh, I V; Shurshakov, V A; Arkhangelsky, V A

1998-01-01

The Mir station has been in a 51.65 degrees inclination orbit since March 1986. In March 1995, the first US astronaut flew on the Mir-18 mission and returned on the Space Shuttle in July 1995. Since then three additional US astronauts have stayed on orbit for up to 6 months. Since the return of the first US astronaut, both the Spektr and Priroda modules have docked with Mir station, altering the mass shielding distribution. Radiation measurements, including the direct comparison of US and Russian absorbed dose rates in the Base Block of the Mir station, were made during the Mir-18 and -19 missions. There is a significant variation of dose rates across the core module; the six locations sampled showed a variation of a factor of nearly two. A tissue equivalent proportional counter (TEPC) measured a total absorbed dose rate of 300 microGy/day, roughly equally divided between the rate due to trapped protons from the South Atlantic Anomaly (SAA) and galactic cosmic radiation (GCR). This dose rate is about a factor of two lower than the rate measured by the thinly shielded (0.5 g cm-2 of Al) operational ion chamber (R-16), and about 3/2 of the rate of the more heavily shielded (3.5 g cm-2 of Al) ion chamber. This is due to the differences in the mass shielding properties at the location of these detectors. A comparison of integral linear energy transfer (LET) spectra measured by TEPC and plastic nuclear track detectors (PNTDs) deployed side by side are in remarkable agreement in the LET region of 15-1000 keV/micrometer, where the PNTDs are fully efficient. The average quality factor, using the ICRP-26 definition, was 2.6, which is higher than normally used. There is excellent agreement between the measured GCR dose rate and model calculations, but this is not true for trapped protons. The measured Mir-18 crew skin dose equivalent rate was 1133 microSv/day. Using the skin dose rate and anatomical models, we have estimated the blood-forming organ (BFO) dose rate and the maximum stay time in orbit for International Space Station crew members.

Advances in the management of heart failure: the role of ivabradine

PubMed Central

Müller-Werdan, Ursula; Stöckl, Georg; Werdan, Karl

2016-01-01

A high resting heart rate (≥70–75 b.p.m.) is a risk factor for patients with heart failure (HF) with reduced ejection fraction (EF), probably in the sense of accelerated atherosclerosis, with an increased morbidity and mortality. Beta-blockers not only reduce heart rate but also have negative inotropic and blood pressure-lowering effects, and therefore, in many patients, they cannot be given in the recommended dose. Ivabradine specifically inhibits the pacemaker current (funny current, If) of the sinoatrial node cells, resulting in therapeutic heart rate lowering without any negative inotropic and blood pressure-lowering effect. According to the European Society of Cardiology guidelines, ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients with a reduced left ventricular EF ≤35% and sinus rhythm ≥70 b.p.m. despite treatment with an evidence-based dose of beta-blocker or a dose below the recommended dose (recommendation class “IIa” = weight of evidence/opinion is in favor of usefulness/efficacy: “should be considered”; level of evidence “B” = data derived from a single randomized clinical trial or large nonrandomized studies). Using a heart rate cutoff of ≥ 75 b.p.m., as licensed by the European Medicines Agency, treatment with ivabradine 5–7.5 mg b.i.d. reduces cardiovascular mortality by 17%, HF mortality by 39% and HF hospitalization rate by 30%. A high resting heart rate is not only a risk factor in HF with reduced EF but also at least a risk marker in HF with preserved EF, in acute HF and also in special forms of HF. In this review, we discuss the proven role of ivabradine in the validated indication “HF with reduced EF” together with interesting preliminary findings, and the potential role of ivabradine in further, specific forms of HF. PMID:27895488

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.

Validating the Effectiveness of Switching the Vancomycin TDM Analysis Software Based on the Predictive Accuracy.

PubMed

Imai, Shungo; Yamada, Takehiro; Ishiguro, Nobuhisa; Miyamoto, Takenori; Kagami, Keisuke; Tomiyama, Naoki; Niinuma, Yusuke; Nagasaki, Daisuke; Suzuki, Koji; Yamagami, Akira; Kasashi, Kumiko; Kobayashi, Masaki; Iseki, Ken

2017-01-01

Based on the predictive performance in our previous study, we switched the therapeutic drug monitoring (TDM) analysis software for dose setting of vancomycin (VCM) from "Vancomycin MEEK TDM analysis software Ver2.0" (MEEK) to "SHIONOGI-VCM-TDM ver.2009" (VCM-TDM) in January 2015. In the present study, our aim was to validate the effectiveness of the changing VCM TDM analysis software in initial dose setting of VCM. The enrolled patients were divided into two groups, each having 162 patients in total, who received VCM with the initial dose set using MEEK (MEEK group) or VCM-TDM (VCM-TDM group). We compared the rates of attaining the therapeutic range (trough value; 10-20 μg/mL) of serum VCM concentration between the groups. Multivariate logistic regression analysis was performed to confirm that changing the VCM TDM analysis software was an independent factor related to attaining the therapeutic range. Switching the VCM TDM analysis software from MEEK to VCM-TDM improved the rate of attaining the therapeutic range by 21.6% (MEEK group: 42.6% vs. VCM-TDM group: 64.2%, p<0.01). Patient age ≥65 years, concomitant medication (furosemide) and the TDM analysis software used VCM-TDM were considered to be independent factors for attaining the therapeutic range. These results demonstrated the effectiveness of switching the VCM TDM analysis software from MEEK to VCM-TDM for initial dose setting of VCM.

Radiological Source Terms for Tank Farms Safety Analysis

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

COWLEY, W.L.

2000-06-27

This document provides Unit Liter Dose factors, atmospheric dispersion coefficients, breathing rates and instructions for using and customizing these factors for use in calculating radiological doses for accident analyses in the Hanford Tank Farms.

Development and implementation of a remote audit tool for high dose rate (HDR) Ir-192 brachytherapy using optically stimulated luminescence dosimetry

PubMed Central

Casey, Kevin E.; Alvarez, Paola; Kry, Stephen F.; Howell, Rebecca M.; Lawyer, Ann; Followill, David

2013-01-01

Purpose: The aim of this work was to create a mailable phantom with measurement accuracy suitable for Radiological Physics Center (RPC) audits of high dose-rate (HDR) brachytherapy sources at institutions participating in National Cancer Institute-funded cooperative clinical trials. Optically stimulated luminescence dosimeters (OSLDs) were chosen as the dosimeter to be used with the phantom. Methods: The authors designed and built an 8 × 8 × 10 cm3 prototype phantom that had two slots capable of holding Al2O3:C OSLDs (nanoDots; Landauer, Glenwood, IL) and a single channel capable of accepting all 192Ir HDR brachytherapy sources in current clinical use in the United States. The authors irradiated the phantom with Nucletron and Varian 192Ir HDR sources in order to determine correction factors for linearity with dose and the combined effects of irradiation energy and phantom characteristics. The phantom was then sent to eight institutions which volunteered to perform trial remote audits. Results: The linearity correction factor was kL = (−9.43 × 10−5 × dose) + 1.009, where dose is in cGy, which differed from that determined by the RPC for the same batch of dosimeters using 60Co irradiation. Separate block correction factors were determined for current versions of both Nucletron and Varian 192Ir HDR sources and these vendor-specific correction factors differed by almost 2.6%. For the Nucletron source, the correction factor was 1.026 [95% confidence interval (CI) = 1.023–1.028], and for the Varian source, it was 1.000 (95% CI = 0.995–1.005). Variations in lateral source positioning up to 0.8 mm and distal/proximal source positioning up to 10 mm had minimal effect on dose measurement accuracy. The overall dose measurement uncertainty of the system was estimated to be 2.4% and 2.5% for the Nucletron and Varian sources, respectively (95% CI). This uncertainty was sufficient to establish a ±5% acceptance criterion for source strength audits under a formal RPC audit program. Trial audits of four Nucletron sources and four Varian sources revealed an average RPC-to-institution dose ratio of 1.000 (standard deviation = 0.011). Conclusions: The authors have created an OSLD-based 192Ir HDR brachytherapy source remote audit tool which offers sufficient dose measurement accuracy to allow the RPC to establish a remote audit program with a ±5% acceptance criterion. The feasibility of the system has been demonstrated with eight trial audits to date. PMID:24320455

Brachytherapy devices and methods employing americium-241

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

Gray, L. A.

1985-04-16

Sources and methods for radiation therapy, particularly brachytherapy, employing americium-241 (60 keV gamma emission and 433 year half-life) provide major advantages for radiotherapy, including simplified radiation protection, dose reduction to healthy tissue, increased dose to tumor, and improved dose distributions. A number of apparent drawbacks and unfavorable considerations including low gamma factor, high self-absorption, increased activity required and alpha-particle generation leading to helium gas pressure buildup and potential neutron contamination in the generated radiation are all effectively dealt with and overcome through recognition of subtle favorable factors unique to americium-241 among brachytherapy sources and through suitable constructional techniques. Due tomore » an additional amount of radiation, in the order of 50%, provided primarily to nearby regions as a result of Compton scatter in tissue and water, higher dose rates occur than would be predicted by conventional calculations.« less

A report from the 2013 international symposium: the evaluation of the effects of low-dose radiation exposure in the life span study of atomic bomb survivors and other similar studies.

PubMed

Grant, E J; Ozasa, K; Ban, N; de González, A Berrington; Cologne, J; Cullings, H M; Doi, K; Furukawa, K; Imaoka, T; Kodama, K; Nakamura, N; Niwa, O; Preston, D L; Rajaraman, P; Sadakane, A; Saigusa, S; Sakata, R; Sobue, T; Sugiyama, H; Ullrich, R; Wakeford, R; Yasumura, S; Milder, C M; Shore, R E

2015-05-01

The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation.

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

Predictors of High-grade Esophagitis After Definitive Three-dimensional Conformal Therapy, Intensity-modulated Radiation Therapy, or Proton Beam Therapy for Non-small cell Lung Cancer

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

Gomez, Daniel R., E-mail: dgomez@mdanderson.org; Tucker, Susan L.; Martel, Mary K.

2012-11-15

Introduction: We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT). Methods and Materials: Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade {>=}3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors. Results:more » Overall, 652 patients were included: 405 patients were treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade {>=}3 RE were 8%, 28%, and 6%, respectively, with a median time to onset of 42 days (range, 11-93 days). A fit of the fractional DVH LKB model demonstrated that the fractional effective dose was significantly different (P=.046) than 1 (fractional mean dose) indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (P=.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (P=.105). Conclusions: Fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE, estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT.« less

Predictors of high-grade esophagitis after definitive three-dimensional conformal therapy, intensity-modulated radiation therapy, or proton beam therapy for non-small cell lung cancer.

PubMed

Gomez, Daniel R; Tucker, Susan L; Martel, Mary K; Mohan, Radhe; Balter, Peter A; Lopez Guerra, Jose Luis; Liu, Hongmei; Komaki, Ritsuko; Cox, James D; Liao, Zhongxing

2012-11-15

We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT). Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade≥3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors. Overall, 652 patients were included: 405 patients were treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade≥3 RE were 8%, 28%, and 6%, respectively, with a median time to onset of 42 days (range, 11-93 days). A fit of the fractional DVH LKB model demonstrated that the fractional effective dose was significantly different (P=.046) than 1 (fractional mean dose) indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (P=.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (P=.105). Fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE, estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT. Copyright © 2012 Elsevier Inc. All rights reserved.

[Continued Use of Rotigotine Transdermal Patches for Parkinson Disease].

PubMed

Yasutaka, Yuki; Fujioka, Shinsuke; Shibaguchi, Hirotomo; Imakyure, Osamu; Washiyama, Atsushi; Tsuboi, Yoshio; Futagami, Koujiro

2016-06-01

Transdermal patches containing rotigotine, a dopamine agonist (DA) for treatment of Parkinson disease, continuously exert stable effects when applied once daily. Therefore, they are expected to reduce the patient burdens due to complications such as wearing-off and dysphagia. However, dosing is occasionally reduced or discontinued after application because of several reasons such as skin reactions or unsatisfactory efficacy. To identify the risk factors involved in the reduced or discontinued use of rotigotine patches, a retrospective study was conducted with reference to the medical records of patients with Parkinson disease who received rotigotine patches in our hospital. 85 patients were involved in this study. Dosing of rotigotine was reduced or discontinued in 53 patients during the study period. The factors associated with charges in treatment included combination therapy with clonazepam and oral administration of another DA before the application of rotigotine. The reduction or discontinuation rate of rotigotine patches in patients who reduced the equivalent dose of DA on the introduction of rotigotine patches was 94.7%, showing a significantly higher rate compared with 61.3% in the increased dose group. To improve adherence to rotigotine patch therapy, physicians need to carefully consider concomitant drugs and total dose of DAs. (Received December 7, 2015; Accepted February 22, 2016; Published June 1, 2016).

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

Suitability of point kernel dose calculation techniques in brachytherapy treatment planning

PubMed Central

Lakshminarayanan, Thilagam; Subbaiah, K. V.; Thayalan, K.; Kannan, S. E.

2010-01-01

Brachytherapy treatment planning system (TPS) is necessary to estimate the dose to target volume and organ at risk (OAR). TPS is always recommended to account for the effect of tissue, applicator and shielding material heterogeneities exist in applicators. However, most brachytherapy TPS software packages estimate the absorbed dose at a point, taking care of only the contributions of individual sources and the source distribution, neglecting the dose perturbations arising from the applicator design and construction. There are some degrees of uncertainties in dose rate estimations under realistic clinical conditions. In this regard, an attempt is made to explore the suitability of point kernels for brachytherapy dose rate calculations and develop new interactive brachytherapy package, named as BrachyTPS, to suit the clinical conditions. BrachyTPS is an interactive point kernel code package developed to perform independent dose rate calculations by taking into account the effect of these heterogeneities, using two regions build up factors, proposed by Kalos. The primary aim of this study is to validate the developed point kernel code package integrated with treatment planning computational systems against the Monte Carlo (MC) results. In the present work, three brachytherapy applicators commonly used in the treatment of uterine cervical carcinoma, namely (i) Board of Radiation Isotope and Technology (BRIT) low dose rate (LDR) applicator and (ii) Fletcher Green type LDR applicator (iii) Fletcher Williamson high dose rate (HDR) applicator, are studied to test the accuracy of the software. Dose rates computed using the developed code are compared with the relevant results of the MC simulations. Further, attempts are also made to study the dose rate distribution around the commercially available shielded vaginal applicator set (Nucletron). The percentage deviations of BrachyTPS computed dose rate values from the MC results are observed to be within plus/minus 5.5% for BRIT LDR applicator, found to vary from 2.6 to 5.1% for Fletcher green type LDR applicator and are up to −4.7% for Fletcher-Williamson HDR applicator. The isodose distribution plots also show good agreements with the results of previous literatures. The isodose distributions around the shielded vaginal cylinder computed using BrachyTPS code show better agreement (less than two per cent deviation) with MC results in the unshielded region compared to shielded region, where the deviations are observed up to five per cent. The present study implies that the accurate and fast validation of complicated treatment planning calculations is possible with the point kernel code package. PMID:20589118

Factors influencing botulinum toxin dose instability in spasmodic dysphonia patients.

PubMed

Rosow, David E; Pechman, Amanda; Saint-Victor, Sandra; Lo, Kaming; Lundy, Donna S; Casiano, Roy R

2015-05-01

Many patients with spasmodic dysphonia (SD) see consistent effects from botulinum toxin (BTX) injections of the same dose, whereas others require dosage changes over time. We sought to determine whether demographics (age and gender) or environmental factors (smoking) affect the long-term stability of BTX dosing in these patients. Retrospective review. Charts of all patients undergoing BTX injection for adductor SD were reviewed. Dosage change, defined as whether there was any difference in total dosage used between two beneficial injections, was used as a measure of dosing stability. Beneficial injections were indicated by a voice rating score of at least three of four and any non-zero duration of improved voice. Logistic regression analysis was performed to determine whether age, gender, smoking status, or duration of treatment correlated with odds of having a dosage change. A total of 211 patients were ultimately included. Age, gender, and smoking status were all found to have no correlative effect on dosing stability. The only factor that was predictive of dose stability was the number of previous beneficial injections, as every additional injection led to decreased odds of a change in dosage for the next injection (odds ratio=0.964; 95% confidence interval=0.947-0.981). Dosage of BTX injections for long-term treatment of SD has a significant propensity to remain stable over time. Factors such as age, gender, and smoking status do not appear to influence the dosage stability. These findings should allow for better patient counseling regarding expectations for their long-term treatment. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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.

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.

Study Of Dose Distribution In A Human Body In Space Flight With The Spherical Tissue-Equivalent Phantom

NASA Astrophysics Data System (ADS)

Shurshakov, Vyacheslav; Akatov, Yu; Petrov, V.; Kartsev, I.; Polenov, Boris; Petrov, V.; Lyagushin, V.

In the space experiment MATROSHKA-R, the spherical tissue equivalent phantom (30 kg mass, 35 cm diameter and 10 cm central spherical cave) made in Russia has been installed in the star board crew cabin of the ISS Service Module. Due to the specially chosen phantom shape and size, the chord length distributions of the detector locations are attributed to self-shielding properties of the critical organs in a real human body. If compared with the anthropomorphic phantom Rando used inside and outside the ISS, the spherical phantom has lower mass, smaller size, and requires less crew time for the detector retrieval; its tissue-equivalent properties are closer to the standard human body tissue than the Rando-phantom material. In the first phase of the experiment the dose measurements were realized with only passive detectors (thermoluminescent and solid state track detectors). There were two experimental sessions with the spherical phantom in the crew cabin, (1) from Jan. 29, 2004 to Apr. 30, 2004 and (2) from Aug. 11, 2004 to Oct. 10, 2005. The detectors are placed inside the phantom along the axes of 20 containers and on the phantom outer surface in 32 pockets of the phantom jacket. The results obtained with the passive detectors returned to the ground after each session show the dose difference on the phantom surface as much as a factor of 2, the highest dose being observed close to the outer wall of the crew cabin, and the lowest dose being in the opposite location along the phantom diameter. Maximum dose rate measured in the phantom (0.31 mGy/day) is obviously due to the galactic cosmic ray (GCR) and Earth' radiation belt contribution on the ISS trajectory. Minimum dose rate (0.15 mGy/day) is caused mainly by the strongly penetrating GCR particles and is observed behind more than 5 g/cm2 tissue shielding. Critical organ doses, mean-tissue and effective doses of a crew member in the crew cabin are also estimated with the spherical phantom. The estimated effective dose rate (about 0.49 mSv/day at radiation quality factor of 2.6) is from 12 to 15 per cent lower than the averaged dose on the phantom surface as dependent on the body attitude.

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.

Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I Study Group.

PubMed

Lai, E C; Felice, K J; Festoff, B W; Gawel, M J; Gelinas, D F; Kratz, R; Murphy, M F; Natter, H M; Norris, F H; Rudnicki, S A

1997-12-01

The objective of this study was to investigate the safety and efficacy of recombinant human insulinlike growth factor-I (rhIGF-I) in the treatment of sporadic ALS. A double-blind, placebo-controlled, randomized study of 266 patients was conducted at eight centers in North America. Placebo or rhIGF-I (0.05 mg/kg/day or 0.10 mg/kg/day) was administered for 9 months. The primary outcome measure was disease symptom progression, assessed by the rate of change (per patient slope) in the Appel ALS rating scale total score. The Sickness Impact Profile (SIP), a patient-perceived, health-related quality of life assessment, was a secondary outcome variable. Progression of functional impairment in patients receiving high-dose (0.10 mg/kg/day) rhIGF-I was 26% slower than in patients receiving placebo (p = 0.01). The high-dose treatment group was less likely to terminate the study due to protocol-defined markers of disease symptom progression, and members in this group exhibited a slower decline in quality of life, as assessed by the SIP. Patients receiving 0.05 mg/kg/day of rhIGF-I exhibited trends similar to those associated with high-dose treatment, suggesting a dose-dependent response. The incidence of clinically significant adverse experiences was comparable among the three treatment groups. Recombinant human insulin-like growth factor-I slowed the progression of functional impairment and the decline in health-related quality of life in patients with ALS with no medically important adverse effects.

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.

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

Properties of a commercial PTW-60019 synthetic diamond detector for the dosimetry of small radiotherapy beams.

PubMed

Lárraga-Gutiérrez, José Manuel; Ballesteros-Zebadúa, Paola; Rodríguez-Ponce, Miguel; García-Garduño, Olivia Amanda; de la Cruz, Olga Olinca Galván

2015-01-21

A CVD based radiation detector has recently become commercially available from the manufacturer PTW-Freiburg (Germany). This detector has a sensitive volume of 0.004 mm(3), a nominal sensitivity of 1 nC Gy(-1) and operates at 0 V. Unlike natural diamond based detectors, the CVD diamond detector reports a low dose rate dependence. The dosimetric properties investigated in this work were dose rate, angular dependence and detector sensitivity and linearity. Also, percentage depth dose, off-axis dose profiles and total scatter ratios were measured and compared against equivalent measurements performed with a stereotactic diode. A Monte Carlo simulation was carried out to estimate the CVD small beam correction factors for a 6 MV photon beam. The small beam correction factors were compared with those obtained from stereotactic diode and ionization chambers in the same irradiation conditions The experimental measurements were performed in 6 and 15 MV photon beams with the following square field sizes: 10 × 10, 5 × 5, 4 × 4, 3 × 3, 2 × 2, 1.5 × 1.5, 1 × 1 and 0.5 × 0.5 cm. The CVD detector showed an excellent signal stability (<0.2%) and linearity, negligible dose rate dependence (<0.2%) and lower response angular dependence. The percentage depth dose and off-axis dose profiles measurements were comparable (within 1%) to the measurements performed with ionization chamber and diode in both conventional and small radiotherapy beams. For the 0.5 × 0.5 cm, the measurements performed with the CVD detector showed a partial volume effect for all the dosimetric quantities measured. The Monte Carlo simulation showed that the small beam correction factors were close to unity (within 1.0%) for field sizes ≥1 cm. The synthetic diamond detector had high linearity, low angular and negligible dose rate dependence, and its response was energy independent within 1% for field sizes from 1.0 to 5.0 cm. This work provides new data showing the performance of the CVD detector compared against a high spatial resolution diode. It also presents a comparison of the CVD small beam correction factors with those of diode and ionization chamber for a 6 MV photon beam.

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

Human biokinetics of strontium. Part I: intestinal absorption rate and its impact on the dose coefficient of 90Sr after ingestion.

PubMed

Li, Wei Bo; Höllriegl, Vera; Roth, Paul; Oeh, Uwe

2006-07-01

Intestinal absorption of strontium (Sr) in thirteen healthy adult German volunteers has been investigated by simultaneous oral and intravenous administration of two stable tracer isotopes, i.e. (84)Sr and (86)Sr. The measured Sr tracer concentration in plasma was analyzed using the convolution integral technique to obtain the intestinal absorption rate. The results showed that the Sr labeled in different foodstuffs was absorbed into the body fluids in a large range of difference. The maximum Sr absorption rates were observed within 60-120 min after administration. The rate of absorption is used to evaluate the intestinal absorption fraction, i.e. the f (1) value for various foodstuffs. The equivalent and effective dose coefficients for ingestion of (90)Sr were calculated using these f (1) values, and they were compared with those recommended by the International Commission on Radiological Protection (ICRP). The geometric and arithmetic means of the f (1) values are 0.38 and 0.45 associated with a geometric standard deviation and a standard deviation of 1.88 and 0.22, respectively. The 90% confidence interval of the f (1) values obtained in the present study ranges from 0.13 to 0.98. Expressed as the ratio of the 95 and 50% percentiles of the estimated probability, the uncertainty for the f (1) value corresponds to a factor of 2.58. The effective dose coefficients of (90)Sr after ingestion are 6.1 x 10(-9) Sv Bq(-1) for an f(1) value of 0.05, 1.0 x 10(-8) Sv Bq(-1) for 0.1, 1.9 x 10(-8) Sv Bq(-1) for 0.2, 2.8 x 10(-8) Sv Bq(-1) for 0.3, 3.6 x 10(-8) Sv Bq(-1) for 0.4, 5.3 x 10(-8) Sv Bq(-1) for 0.6, 7.1 x 10(-8) Sv Bq(-1) for 0.8, and 7.9 x 10(-8) Sv Bq(-1) for 0.9, respectively. Taking the effective dose coefficient of 2.8 x 10(-8) Sv Bq(-1) for an f (1) value of 0.3, which is recommended by the ICRP, as a reference, the effective dose coefficient of (90)Sr after ingestion varies by a factor of 2.8 when the f (1) value changes by a factor of 3, i.e. it decreases from 0.3 to 0.1 or increases from 0.3 to 0.9, respectively.

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.

A novel approach to neutron dosimetry.

PubMed

Balmer, Matthew J I; Gamage, Kelum A A; Taylor, Graeme C

2016-11-01

Having been overlooked for many years, research is now starting to take into account the directional distribution of neutron workplace fields. Existing neutron dosimetry instrumentation does not account for this directional distribution, resulting in conservative estimates of dose in neutron workplace fields (by around a factor of 2, although this is heavily dependent on the type of field). This conservatism could influence epidemiological studies on the health effects of radiation exposure. This paper reports on the development of an instrument which can estimate the effective dose of a neutron field, accounting for both the direction and the energy distribution. A 6 Li-loaded scintillator was used to perform neutron assays at a number of locations in a 20 × 20 × 17.5 cm 3 water phantom. The variation in thermal and fast neutron response to different energies and field directions was exploited. The modeled response of the instrument to various neutron fields was used to train an artificial neural network (ANN) to learn the effective dose and ambient dose equivalent of these fields. All experimental data published in this work were measured at the National Physical Laboratory (UK). Experimental results were obtained for a number of radionuclide source based neutron fields to test the performance of the system. The results of experimental neutron assays at 25 locations in a water phantom were fed into the trained ANN. A correlation between neutron counting rates in the phantom and neutron fluence rates was experimentally found to provide dose rate estimates. A radionuclide source behind shadow cone was used to create a more complex field in terms of energy and direction. For all fields, the resulting estimates of effective dose rate were within 45% or better of their calculated values, regardless of energy distribution or direction for measurement times greater than 25 min. This work presents a novel, real-time, approach to workplace neutron dosimetry. It is believed that in the research presented in this paper, for the first time, a single instrument has been able to estimate effective dose.

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.

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

NASA Astrophysics Data System (ADS)

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

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

Gamma radiation effects on polydimethylsiloxane rubber foams under different radiation conditions

NASA Astrophysics Data System (ADS)

Sui, H. L.; Liu, X. Y.; Zhong, F. C.; Li, X. Y.; Wang, L.; Ju, X.

2013-07-01

Polydimethylsiloxane rubber foams were irradiated by gamma ray under different radiation conditions designed by orthogonal design method. Compression set measurement, infrared attenuated total reflectance spectroscopy (ATR) and X-ray induced photoelectron spectroscopy (XPS) were used. Three aging factors' influence effects on the mechanical property and chemical structure were studied. It was found that among the three factors and the chosen levels, both properties were affected most by radiation dose, while radiation dose rate had no obvious influence on both properties. The stiffening of the rubber foams was caused by cross-linking reactions in the Si-CH3. At the same radiation dose, the rigidity of the foams irradiated in air was lower than that in nitrogen. When polydimethylsiloxane was irradiated at a high dose in sealed nitrogen atmosphere, carbon element distribution would be changed. Hydrocarbons produced by gamma ray in the sealed tube would make the carbon content in the skin-deep higher than that in the middle, which indicated that polydimethylsiloxane rubber foams storing in a sealed atmosphere filled with enough hydrocarbons should be helpful to extend the service life.

SU-F-T-673: Effects of Cardiac Induced Brain Pulsations On Proton Minibeams

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

Eagle, J; Marsh, S; Lee, E

Purpose: To quantify the dosimetric impact of internal motion within the brain on spatially modulated proton minibeam radiation therapy (pMRT) for small animal research. Methods: The peak-to-valley dose ratio (PVDR) is an essential dosimetric factor for pMRT. Motion of an animal brain caused by cardiac-induced pulsations (CIP) can impact dose deposition. For synchrotron generated high dose rate X-ray microbeams this effect is evaded due to the quasi-instantaneous delivery. By comparison, pMRT potentially suffers increased spread due to lower dose rates. However, for a given dose rate it is less susceptible to beam spread than microbeams, due to the spatial modulationmore » being an order of magnitude larger. Monte Carlo simulations in TOPAS were used to model the beam spread for a 50.5MeV pMRT beam. Motion effects were simulated for a 50mm thick brass collimator with 0.3mm slit width and 1.0mm center-to-center spacing in a water phantom. The maximum motion in a rat brain due to CIP has been reported to be 0.06mm. Motion was simulated with a peak amplitude in the range 0–0.2mm. Results: The impact of 0.06mm peak motion was minimal and reduced the PVDR by about 1% at a depth of 10mm. For 0.2mm peak motion the PVDR was reduced by 16% at a depth of 10mm. Conclusion: For the pMRT beam the magnitude of cardiac-induced brain motion has minimal impact on the PVDR for the investigated collimator geometry. For more narrow beams the effect is likely to be larger. This indicates that delivery of pMRT to small animal brains should not be affected considerably by beamlines with linac compatible dose rates.« less

Evaluation of Millstone-2 steam generator chemical decontamination

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

Snyder, D.T.; Blok, J.

The steam generator channel heads at Millstone-2 were decontaminated prior to carrying out extensive maintenance work in 1983. Isotopic gamma ray measurements were made of the inner channel head surfaces before and after the decontamination to evaluate the effectiveness of the process. The Combustion Engineering/Kraftwerk Union chemical decontamination, by itself, provided a decontamination factor ranging from 2.7 to 6.6 for the various steam generator surfaces. The corresponding average dose rate reduction factor, based on gross-gamma radiation surveys, was approximately 1.5 to 2.5. Following the chemical treatment, high pressure water flushing reduced the radiation levels still further, to an average overallmore » dose reduction factor of 5.3 to 7.2.« less

Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale.

PubMed

Strassman, R J; Qualls, C R; Uhlenhuth, E H; Kellner, R

1994-02-01

Validation of animal models of hallucinogenic drugs' subjective effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs' dysphoric properties. We describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. We also present preliminary data from a new rating scale for these effects. Twelve highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind," before entering a double-blind, saline placebo-controlled, randomized study using four doses of IV DMT. Subjects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions of DMT's effects. They also were administered a new instrument, the Hallucinogen Rating Scale (HRS). The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users, and modified during early stages of the study. Psychological effects of IV DMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. This time course paralleled DMT blood levels previously described. Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completely replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects. Clustering of HRS items, using either a clinical, mental status method or principal components factor analysis provided better resolution of dose effects than did the biological variables described previously. These clinical and preliminary quantitative data provide bases for further psychopharmacologic characterization of DMT's properties in humans. They also may be used to compare the effects of other agents affecting relevant brain receptors in volunteer and psychiatric populations.

SU-G-TeP3-02: Determination of Geometry-Specific Backscatter Factors for Radiobiology Studies

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

Viscariello, N; Culberson, W; Lawless, M

2016-06-15

Purpose: Radiation biology research relies on an accurate radiation dose delivered to the biological target. Large field irradiations in a cabinet irradiator may use the AAPM TG-61 protocol. This relies on an air-kerma measurement and conversion to absorbed dose to water (Dw) on the surface of a water phantom using provided backscatter factors. Cell or small animal studies differ significantly from this reference geometry. This study aims to determine the impact of the lack of full scatter conditions in four representative geometries that may be used in radiobiology studies. Methods: MCNP6 was used to model the Dw on the surfacemore » of a full scatter phantom in a validated orthovoltage x-ray reference beam. Dw in a cylindrical mouse, 100 mm Petri dish, 6-well and 96-well cell culture dishes was simulated and compared to this full scatter geometry. A reference dose rate was measured using the TG-61 protocol in a cabinet irradiator. This nominal dose rate was used to irradiate TLDs in each phantom to a given dose. Doses were obtained based on TLDs calibrated in a NIST-traceable beam. Results: Compared to the full scattering conditions, the simulated dose to water in the representative geometries were found to be underestimated by 12-26%. The discrepancy was smallest with the cylindrical mouse geometry, which most closely approximates adequate lateral- and backscatter. TLDs irradiated in the mouse and petri dish phantoms using the TG-61 determined dose rate showed similarly lower values of Dw. When corrected for this discrepancy, they agreed with the predicted Dw within 5%. Conclusion: Using the TG-61 in-air protocol and given backscatter factors to determine a reference dose rate in a biological irradiator may not be appropriate given the difference in scattering conditions between irradiation and calibration. Without accounting for this, the dose rate is overestimated and is dependent on irradiation geometry.« less

Long-Term Results and Prognostic Factors of Fractionated Strontium-90 Eye Applicator for Pterygium

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

Arruda Viani, Gustavo; Stefano, Eduardo Jose; Fendi, Ligia Issa de

2008-11-15

Purpose: To evaluate the long-term safety, effectiveness, and prognostic factors of fractionated postoperative {beta}-irradiation. Methods and Materials: Between 1993 and 2005, 623 patients with 737 pterygium lesions were treated with a strontium-90 eye applicator after surgical excision. The median follow-up period was 60 months (range, 6.7-139.5). Of the 737 lesions, 644 were primary and 93 were recurrences after surgical removal alone. Fractionated radiotherapy (RT) to a total dose of 35 Gy in five to seven fractions was used. Results: A total of 73 local pterygium recurrences (9.9%) were noted. Of the recurrent cases, 80% were noted within 3 years aftermore » treatment. The 5- and 10-year probability of local control was 90% and 88%, respectively. The multivariate analysis for all cases demonstrated that gender, age, total radiation dose, recurrent pterygia, and interval between surgery and RT affected the overall local control rate. Late toxicities that might have been associated with strontium-90 RT included scleromalacia (scleral thinning) in nine eyes, adhesion of the eyelids in eight, cataracts in six, and scleral ulcer in five eyes. Conclusion: Fractionated strontium-90 RT to a total dose of approximately 35 Gy in five to seven fractions results in a similar local control rate as higher doses in other series, with an acceptable complication rate.« less

Inhalation and Ingestion Intakes with Associated Dose Estimates for Level II and Level III Personnel Using Capstone Study Data

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

Szrom, Fran; Falo, Gerald A.; Lodde, Gordon M.

2009-03-01

Depleted uranium (DU) intake rates and subsequent dose rates were estimated for personnel entering armored combat vehicles perforated with DU penetrators (level II and level III personnel) using data generated during the Capstone Depleted Uranium (DU) Aerosol Study. Inhalation intake rates and associated dose rates were estimated from cascade impactors worn by sample recovery personnel and from cascade impactors that served as area monitors. Ingestion intake rates and associated dose rates were estimated from cotton gloves worn by sample recovery personnel and from wipe test samples from the interior of vehicles perforated with large caliber DU munitions. The mean DUmore » inhalation intake rate for level II personnel ranged from 0.447 mg h-1 based on breathing zone monitor data (in and around a perforated vehicle) to 14.5 mg h-1 based on area monitor data (in a perforated vehicle). The mean DU ingestion intake rate for level II ranged from 4.8 mg h-1 to 38.9 mg h-1 based on the wipe test data including surface to glove transfer factors derived from the Capstone data. Based on glove contamination data, the mean DU ingestion intake rates for level II and level III personnel were 10.6 mg h-1 was and 1.78 mg h-1, respectively. Effective dose rates and peak kidney uranium concentration rates were calculated based on the intake rates. The peak kidney uranium concentration rate cannot be multiplied by the total exposure duration when multiple intakes occur because uranium will clear from the kidney between the exposures.« less

Effectiveness of cow manure and mycorrhiza on the growth of soybean

NASA Astrophysics Data System (ADS)

Muktiyanta, M. N. A.; Samanhudi; Yunus, A.; Pujiasmanto, B.; Minardi, S.

2018-03-01

Soybean is one of the major food crop commodities in Indonesia. The needs of soybean each year is always increasing, but the the production rate is low. The research aimed to know the influence of treatment doses of cow manure and mycorrhiza towards growth and yield of soybeans. This research was conducted using Randomized Complete Block Design with two factors. The first factor is the dose of cow manure: S0 (0 g/plot), S1 (781.25 g/plot), S2 (1562.5 g/plot), and S3 (2343.75 g/plot). The second factor is the dose of mycorrhiza: M0 (0 g/plot), M1 (100 g/plot), and M2 (200 g/plot). The observed parameters is plant height, the number of productive branches, weight of 100 seeds, root length, fresh weight of biomass, dry weight of biomass, conversion calculation results of soybeans per hectacre and the percentage of roots infected with mycorrhiza. Data were analyzed with ANOVA at 5% significance level, continued with Duncan test at 5% confidence level. The results showed that no interaction between the two treatments. Doses of cow manure provides significant influence to plant height and the length of the root. Whereas, the doses of mycorrhiza provides significant effect to the number of productive branch, weight of 100 seeds, dry weight of biomass, and the conversion of soybean yield per hectare.

Radiation protection for manned space activities

NASA Technical Reports Server (NTRS)

Jordan, T. M.

1983-01-01

The Earth's natural radiation environment poses a hazard to manned space activities directly through biological effects and indirectly through effects on materials and electronics. The following standard practices are indicated that address: (1) environment models for all radiation species including uncertainties and temporal variations; (2) upper bound and nominal quality factors for biological radiation effects that include dose, dose rate, critical organ, and linear energy transfer variations; (3) particle transport and shielding methodology including system and man modeling and uncertainty analysis; (4) mission planning that includes active dosimetry, minimizes exposure during extravehicular activities, subjects every mission to a radiation review, and specifies operational procedures for forecasting, recognizing, and dealing with large solar flaes.

Biological Response to SPE Exposures

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Cucinotta, F. A.; Kim, M.; Shinn, J. L.; Jones, T. D.; Chang, C. K.

2004-01-01

It has long been recognized that a single solar particle event (SPE) can produce, over a short period of time, exposures on the order of LD50 for humans under normal physiological conditions. It is further recognized that recovery from injury over the period of exposure would greatly increase the chances of survival (dose rate effects) although such effects were left unquantified. In the present report we use the bioresponse model derived from a broad range of animal and human exposure data for evaluation of troop readiness in tactical nuclear warfare to evaluate the biological risk posed by the solar event of 4 August 1972. The astronaut blood forming organ (BFO) exposure in deep space would have been 2.2 Sv (1.6 Gy) in a space suit, 1.8 Sv (1.3 Gy) in an aluminum pressure vessel, and 0.7 Sv (0.5 Gy) in an equipment room compared to an X-ray mortality threshold of 1.5 Gy (assuming high dose rate). We find BFO dose rate effectiveness factors for this SPE on the order of 3 to 4, greatly reducing the mortality risks for this event. There is an approximate 3 percent chance that an even larger event may occur for which exposures could be 2-4 times higher. Assured survival of the astronaut requires added shelter shielding and a warning system for this event. The required mass of the shelter shield can be greatly reduced by using hydrogenous materials such as polymers, water, food, and other biological materials in its construction. Limitations of the current bioresponse model arise from the exposures taking place in the microgravity environment wherein the immune system is already challenged and the effective mortality threshold may be reduced by a factor of two. Such microgravity effects could greatly affect astronaut risks.

Beneficial effect of soy isoflavones on bone mineral content was modified by years since menopause, body weight, and calcium intake: a double-blind, randomized, controlled trial.

PubMed

Chen, Yu-Ming; Ho, Suzanne C; Lam, Silvia S H; Ho, Susan S S; Woo, Jean L F

2004-01-01

Many studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss, but no data reported whether such an effect could be influenced by other important factors affecting bone loss. This study examines whether the associations between isoflavone supplementation and rates of change in bone mineral content (BMC) could be modified by years since menopause (YSM), body weight (BW), and dietary calcium intake in postmenopausal Chinese women aged 48 to 62 years. A group of 203 eligible women were randomly assigned to three treatment groups: placebo (daily dose of 0 mg isoflavones + 500 mg calcium, n = 67), mid-dose (40 mg isoflavones + 500 mg calcium, n = 68); and high-dose (80 mg isoflavones + 500 mg calcium, n = 68). Bone mineral density (BMD) and BMC at the whole body, spine, and hip were measured by dual-energy x-ray absorptiometry at baseline and posttreatment after 1 year. YSM, BW, and dietary calcium intake stratified analyses were performed to evaluate whether the associations between isoflavones supplementation and BMC change rates were varied with these factors. Both univariate and multivariate analyses observed significant favorable effect of isoflavone supplementation on rates of change in BMC at the total hip and trochanter among later postmenopausal women (> 4 y), in women with lower BW (< or =median, 55.5 kg), or among women with lower level of calcium intake (< or =median, 1095 mg/d). The independent effect of soy on the maintenance of hip BMC is more marked in women in later menopause or those with lower BW or calcium intake.

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.

Radiation Dose-Response Relationship for Risk of Coronary Heart Disease in Survivors of Hodgkin Lymphoma.

PubMed

van Nimwegen, Frederika A; Schaapveld, Michael; Cutter, David J; Janus, Cècile P M; Krol, Augustinus D G; Hauptmann, Michael; Kooijman, Karen; Roesink, Judith; van der Maazen, Richard; Darby, Sarah C; Aleman, Berthe M P; van Leeuwen, Flora E

2016-01-20

Cardiovascular diseases are increasingly recognized as late effects of Hodgkin lymphoma (HL) treatment. The purpose of this study was to identify the risk factors for coronary heart disease (CHD) and to quantify the effects of radiation dose to the heart, chemotherapy, and other cardiovascular risk factors. We conducted a nested case-control study in a cohort of 2,617 5-year HL survivors, treated between 1965 and 1995. Cases were patients diagnosed with CHD as their first cardiovascular event after HL. Detailed treatment information was collected from medical records of 325 cases and 1,204 matched controls. Radiation charts and simulation radiographs were used to estimate in-field heart volume and mean heart dose (MHD). A risk factor questionnaire was sent to patients still alive. The median interval between HL and CHD was 19.0 years. Risk of CHD increased linearly with increasing MHD (excess relative risk [ERR]) per Gray, 7.4%; 95% CI, 3.3% to 14.8%). This results in a 2.5-fold increased risk of CHD for patients receiving a MHD of 20 Gy from mediastinal radiotherapy, compared with patients not treated with mediastinal radiotherapy. ERRs seemed to decrease with each tertile of age at treatment (ERR/Gy(<27.5years), 20.0%; ERR/Gy(27.5-36.4years), 8.8%; ERR/Gy(36.5-50.9years), 4.2%; P(interaction) = .149). Having ≥ 1 classic CHD risk factor (diabetes mellitus, hypertension, or hypercholesterolemia) independently increased CHD risk (rate ratio, 1.5; 95% CI, 1.1 to 2.1). A high level of physical activity was associated with decreased CHD risk (rate ratio, 0.5; 95% CI, 0.3 to 0.8). The linear radiation dose-response relationship identified can be used to predict CHD risk for future HL patients and survivors. Appropriate early management of CHD risk factors and stimulation of physical activity may reduce CHD risk in HL survivors. © 2015 by American Society of Clinical Oncology.

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.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Cyclosporine A-induced nephrotoxicity is ameliorated by dose reduction and conversion to sirolimus in the rat.

PubMed

Sereno, J; Vala, H; Nunes, S; Rocha-Pereira, P; Carvalho, E; Alves, R; Teixeira, F; Reis, F

2015-04-01

Side-effect minimization strategies to avoid serious side-effects of cyclosporine A (CsA), such as nephrotoxicity, have been mainly based on dose reduction and conversion to other putatively less nephrotoxic drugs, such as sirolimus (SRL), an inhibitor of the mammalian target of rapamycin. This study intended to evaluate the impact of protocols based on CsA dose reduction and further conversion to SRL on kidney function and lesions, based on serum, urine and renal tissue markers. The following 3 groups (n=6) were tested during a 9-week protocol: control (vehicle); CsA (5 mg/kg/day) and Red + Conv (CsA 30 mg/kg/day during 3 weeks + 3 weeks with CsA 5 mg/kg/day + SRL 1 mg/kg/day during the last 3 weeks). The following parameters were analysed: blood pressure, heart rate and biochemical data; serum and urine contents and clearances of creatinine, urea and neutrophil gelatinase-associated lipocalin (NGAL), as well as, glomerular filtration rate; kidney lipid peroxidation and clearance; kidney lesions were evaluated and protein expression was performed by immunohistochemistry. After the first 3 weeks of CsA (30 mg/kg/day) treatment animals showed body weight loss, hypertension, tachycardia, as well as, increased serum levels of non-HDL cholesterol, glucose, triglycerides, creatinine and urea, accompanied by decreased GFR and insulin levels. In addition, a significant increase in the expression of connective tissue growth factor, kidney injury molecule-1 (KIM-1), mammalian target of rapamycin, nuclear factor-κβ1 and transforming growth factor-β was found in the kidney, accompanied by extensive renal damage. The following 3 weeks with CsA dose reduction revealed amelioration of vascular and glomerular lesions, but without significant tubular improvement. The last 3 weeks with the conversion to sirolimus revealed high serum and urine NGAL contents but the CsA-evoked renal damage was substantially ameliorated, by reduced of connective tissue growth factor, mammalian target of rapamycin, nuclear factor-κβ1 protein expression. In conclusion, CsA nephrotoxicity is dose dependent and moderate dysfunction could be ameliorated/prevented by SRL conversion, which could be pivotal for the preservation of kidney function and structure.

Rates of Change in Naturalistic Psychotherapy: Contrasting Dose-Effect and Good-Enough Level Models of Change

ERIC Educational Resources Information Center

Baldwin, Scott A.; Berkeljon, Arjan; Atkins, David C.; Olsen, Joseph A.; Nielsen, Stevan L.

2009-01-01

Most research on the dose-effect model of change has combined data across patients who vary in their total dose of treatment and has implicitly assumed that the rate of change during therapy is constant across doses. In contrast, the good-enough level model predicts that rate of change will be related to total dose of therapy. In this study, the…

Predictive factors and management of rectal bleeding side effects following prostate cancer brachytherapy.

PubMed

Price, Jeremy G; Stone, Nelson N; Stock, Richard G

2013-08-01

To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥ grade 2 proctitis. A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Actuarial risk of ≥ grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

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

Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G., E-mail: Richard.Stock@mountsinai.org

2013-08-01

Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, andmore » treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT.« less

Characterization of a new transmission detector for patient individualized online plan verification and its influence on 6MV X-ray beam characteristics.

PubMed

Thoelking, Johannes; Sekar, Yuvaraj; Fleckenstein, Jens; Lohr, Frank; Wenz, Frederik; Wertz, Hansjoerg

2016-09-01

Online verification and 3D dose reconstruction on daily patient anatomy have the potential to improve treatment delivery, accuracy and safety. One possible implementation is to recalculate dose based on online fluence measurements with a transmission detector (TD) attached to the linac. This study provides a detailed analysis of the influence of a new TD on treatment beam characteristics. The influence of the new TD on surface dose was evaluated by measurements with an Advanced Markus Chamber (Adv-MC) in the build-up region. Based on Monte Carlo simulations, correction factors were determined to scale down the over-response of the Adv-MC close to the surface. To analyze the effects beyond dmax percentage depth dose (PDD), lateral profiles and transmission measurements were performed. All measurements were carried out for various field sizes and different SSDs. Additionally, 5 IMRT-plans (head & neck, prostate, thorax) and 2 manually created test cases (3×3cm(2) fields with different dose levels, sweeping gap) were measured to investigate the influence of the TD on clinical treatment plans. To investigate the performance of the TD, dose linearity as well as dose rate dependency measurements were performed. With the TD inside the beam an increase in surface dose was observed depending on SSD and field size (maximum of +11%, SSD = 80cm, field size = 30×30cm(2)). Beyond dmax the influence of the TD on PDDs was below 1%. The measurements showed that the transmission factor depends slightly on the field size (0.893-0.921 for 5×5cm(2) to 30×30cm(2)). However, the evaluation of clinical IMRT-plans measured with and without the TD showed good agreement after using a single transmission factor (γ(2%/2mm) > 97%, δ±3% >95%). Furthermore, the response of TD was found to be linear and dose rate independent (maximum difference <0.5% compared to reference measurements). When placed in the path of the beam, the TD introduced a slight, clinically acceptable increase of the skin dose even for larger field sizes and smaller SSDs and the influence of the detector on the dose beyond dmax as well as on clinical IMRT-plans was negligible. Since there was no dose rate dependency and the response was linear, the device is therefore suitable for clinical use. Only its absorption has to be compensated during treatment planning, either by the use of a single transmission factor or by including the TD in the incident beam model. Copyright © 2015. Published by Elsevier GmbH.

Computer calculated dose in paediatric prescribing.

PubMed

Kirk, Richard C; Li-Meng Goh, Denise; Packia, Jeya; Min Kam, Huey; Ong, Benjamin K C

2005-01-01

Medication errors are an important cause of hospital-based morbidity and mortality. However, only a few medication error studies have been conducted in children. These have mainly quantified errors in the inpatient setting; there is very little data available on paediatric outpatient and emergency department medication errors and none on discharge medication. This deficiency is of concern because medication errors are more common in children and it has been suggested that the risk of an adverse drug event as a consequence of a medication error is higher in children than in adults. The aims of this study were to assess the rate of medication errors in predominantly ambulatory paediatric patients and the effect of computer calculated doses on medication error rates of two commonly prescribed drugs. This was a prospective cohort study performed in a paediatric unit in a university teaching hospital between March 2003 and August 2003. The hospital's existing computer clinical decision support system was modified so that doctors could choose the traditional prescription method or the enhanced method of computer calculated dose when prescribing paracetamol (acetaminophen) or promethazine. All prescriptions issued to children (<16 years of age) at the outpatient clinic, emergency department and at discharge from the inpatient service were analysed. A medication error was defined as to have occurred if there was an underdose (below the agreed value), an overdose (above the agreed value), no frequency of administration specified, no dose given or excessive total daily dose. The medication error rates and the factors influencing medication error rates were determined using SPSS version 12. From March to August 2003, 4281 prescriptions were issued. Seven prescriptions (0.16%) were excluded, hence 4274 prescriptions were analysed. Most prescriptions were issued by paediatricians (including neonatologists and paediatric surgeons) and/or junior doctors. The error rate in the children's emergency department was 15.7%, for outpatients was 21.5% and for discharge medication was 23.6%. Most errors were the result of an underdose (64%; 536/833). The computer calculated dose error rate was 12.6% compared with the traditional prescription error rate of 28.2%. Logistical regression analysis showed that computer calculated dose was an important and independent variable influencing the error rate (adjusted relative risk = 0.436, 95% CI 0.336, 0.520, p < 0.001). Other important independent variables were seniority and paediatric training of the person prescribing and the type of drug prescribed. Medication error, especially underdose, is common in outpatient, emergency department and discharge prescriptions. Computer calculated doses can significantly reduce errors, but other risk factors have to be concurrently addressed to achieve maximum benefit.

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

PubMed

Lote, H; Sharp, A; Redana, S; Papadimitraki, E; Capelan, M; Ring, A

2016-09-01

Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower rates of febrile neutropenia than in other groups and may indicate relative under-dosing of chemotherapy. This supports international guidelines that state that obese patients should not be dose capped. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Estimated dose rates to members of the public from external exposure to patients with 131I thyroid treatment

DOE PAGES

Dewji, S.; Bellamy, M.; Hertel, N.; ...

2015-03-25

The purpose of this study is to estimate dose rates that may result from exposure to patients who had been administered iodine-131 ( 131I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered 131I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with 131I. Tissue attenuation and iodine biokinetics were considered in the patient in a largermore » comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the 131I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of 131I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after 131I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of 131I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for 131I patients with normal thyroid uptake (peak thyroid uptake of ~27% of administered 131I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ~4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ~3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with 131I therapy, consideration must be given to (patient- and case-specific) administered 131I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. Finally, the method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Estimated dose rates to members of the public from external exposure to patients with 131I thyroid treatment

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

Dewji, S.; Bellamy, M.; Hertel, N.

The purpose of this study is to estimate dose rates that may result from exposure to patients who had been administered iodine-131 ( 131I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered 131I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with 131I. Tissue attenuation and iodine biokinetics were considered in the patient in a largermore » comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the 131I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of 131I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after 131I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of 131I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for 131I patients with normal thyroid uptake (peak thyroid uptake of ~27% of administered 131I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ~4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ~3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with 131I therapy, consideration must be given to (patient- and case-specific) administered 131I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. Finally, the method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Chemopreventive effect of selenium and Chinese medicinal herbs on N-nitrosobis(2-oxopropyl)amine-induced hepatocellular carcinoma in Syrian hamsters.

PubMed

Lee, Chang-Yin; Hsu, Yi-Chao; Wang, Jir-You; Chen, Chien-Chih; Chiu, Jen-Hwey

2008-07-01

Oxidative DNA damage by reactive oxygen species is involved in the process of liver carcinogenesis. To test the hypothesis that a remedy containing Scutellaria baicalensis Georgi (Sb) and Bupleurum scorzonerifolfium Willd (Bs) (Sb/Bs remedy) modulates hepatic neoplastic growth, BOP (N-nitrosobis(2-oxopropyl)amine)-induced liver cancers in hamsters were established. Parameters such as survival rate, tumour area, tumour foci, 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, transforming growth factor (TGF-beta1) and tumour necrosis factor-alpha (TNF-alpha) were measured after Sb/Bs remedy treatment during BOP-induced carcinogenesis. The results showed that the Sb/Bs remedy and its constituents Sb and Bs suppressed the tumour area in BOP-induced liver tumours. Because selenium (Sel) is toxic at a high dose (10 mg/kg), with a low survival rate (0%), the combination of Sb/Bs remedy and low-dose Sel (1 mg/kg) was found to decrease the tumour area and the number of tumour foci while increasing serum TNF-alpha and TGF-beta1, but not IL-6 levels. Besides, the Sb/Bs remedy, when combined with low-dose Sel, not only decreased the expression of 8-OHdG and increased caspase-3 expression within the glutathione S-transferase placental form-positive tumour foci but also increased tumour apoptosis in BOP-induced hamsters. We conclude that low-dose Sel has a chemoprevention effect on BOP-induced liver tumours and such an effect was more enhanced when combined with Sb/Bs treatment.

Dose-rate effect was observed in T98G glioma cells following BNCT.

PubMed

Kinashi, Yuko; Okumura, Kakuji; Kubota, Yoshihisa; Kitajima, Erika; Okayasu, Ryuichi; Ono, Koji; Takahashi, Sentaro

2014-06-01

It is generally said that low LET radiation produce high dose-rate effect, on the other hand, no significant dose rate effect is observed in high LET radiation. Although high LET radiations are produced in BNCT, little is known about dose-rate effect of BNCT. T98G cells, which were tumor cells, were irradiated by neutron mixed beam with BPA. As normal tissue derived cells, Chinese hamster ovary (CHO-K1) cells and DNA double strand breaks (DNA-DSBs) repair deficient cells, xrs5 cells were irradiated by the neutrons (not including BPA). To DNA-DSBs analysis, T98G cells were stained immunochemically with 53BP1 antibody. The number of DNA-DSBs was determined by counting 53BP1 foci. There was no dose-rate effect in xrs5 cells. D0 difference between 4cGy/min and 20cGy/min irradiation were 0.5 and 5.9 at the neutron and gamma-ray irradiation for CHO-K1, and 0.3 at the neutron for T98G cells. D0 difference between 20cGy/min and 80cGy/min irradiation for T98G cells were 1.2 and 0.6 at neutron irradiation plus BPA and gamma-ray. The differences between neutron irradiations at the dose rate in T98G cells were supported by not only the cell viability but also 53BP1 foci assay at 24h following irradiation to monitor DNA-DSBs. Dose-rate effect of BNCT when T98G cells include 20ppm BPA was greater than that of gamma-ray irradiation. Moreover, Dose-rate effect of the neutron beam when CHO-K1 cells did not include BPA was less than that of gamma-ray irradiation These present results may suggest the importance of dose-rate effect for more efficient BNCT and the side effect reduction. © 2013 Published by Elsevier Ltd.

Harderian Gland Tumorigenesis: Low-Dose and LET Response.

PubMed

Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

2016-05-01

Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the results from single 0.13 or 0.26 Gy acute titanium exposures. Theoretical modeling of the data show that a nontargeted effect model provides a better fit than the targeted effect model, providing important information at space-relevant doses of heavy ions.

Harderian Gland Tumorigenesis: Low-Dose and LET Response

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

Chang, Polly Y.; Cucinotta, Francis A.; Bjornstad, Kathleen A.

Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSvmore » are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the results from single 0.13 or 0.26 Gy acute titanium exposures. Theoretical modeling of the data show that a nontargeted effect model provides a better fit than the targeted effect model, providing important information at space-relevant doses of heavy ions.« less

Treatment of periorbital edema with human corticotropin-releasing factor after blepharoplasty.

PubMed

Schendel, S A; Stephanides, M

1996-03-01

This prospective study of 32 patients was undertaken to ev evaluate the formation of postoperative periorbital edema after administration of human corticotropin-releasing factor (hCRF). Human corticotropin-releasing factor has strong antiedematous properties as a result of direct action on blood vessels independent of endocrine function and has been shown to have a positive effect on vascular permeability in animal studies independent of corticosteroid effects. Human corticotropin-releasing factor was administered intravenously preoperatively to patients undergoing blepharoplasty in doses of 2, 4, and 8 mu g/kg body weight as a randomized, double-blind, placebo-controlled study. The periorbital edema was measured by the use of a three-dimensional laser scanner to determine facial and eyelid volume changes as specified times postoperatively. Human corticotropin-releasing factor was well tolerated when administered intravenously over a ten-minute period to healthy patients undergoing blepharoplasty. Mild transitory flushing and hypotension were the most common adverse events. Transient decreases in systolic and diastolic blood pressure and increases in heart rate occurred at hCRF doses greater than 2 mu g/kg and were most prominent at 8 mu g/kg. The 8 mu g/kg hCRF dose also showed a trend toward less postoperative edema but this was not statistically significant at the p<0.05 level. Human corticotropin-releasing factor appears to be safe for intravenous use in patients undergoing blepharoplasty; however, its efficacy in reducing postoperative edema as a single preoperative administration was not conclusively demonstrated in this study. Further research with a larger study population and other dosing regimens is indicated.

A composite microdose Adaptive Response (AR) and Bystander Effect (BE) model-application to low LET and high LET AR and BE data.

PubMed

Leonard, Bobby E

2008-08-01

It has been suggested that Adaptive Response (AR) may reduce risk of adverse health effects due to ionizing radiation. But very low dose Bystander Effects (BE) may impose dominant deleterious human risks. These conflicting behaviors have stimulated controversy regarding the Linear No-Threshold human risk model. A dose and dose rate-dependent microdose model, to examine AR behavior, was developed in prior work. In the prior work a number of in vitro and in vivo dose response data were examined with the model. Recent new data show AR behavior with some evidence of very low dose BE. The purpose of this work is to supplement the microdose model to encompass the Brenner and colleagues BaD (Bystander and Direct Damage) model and apply this composite model to obtain new knowledge regarding AR and BE and illustrate the use of the model to plan radio-biology experiments. The biophysical composite AR and BE Microdose Model quantifies the accumulation of hits (Poisson distributed, microdose specific energy depositions) to cell nucleus volumes. This new composite AR and BE model provides predictions of dose response at very low dose BE levels, higher dose AR levels and even higher dose Direct (linear-quadratic) Damage radiation levels. We find good fits of the model to both BE data from the Columbia University microbeam facility and combined AR and BE data for low Linear Energy Transfer (LET) and high LET data. A Bystander Factor of about 27,000 and an AR protection factor of 0.61 are obtained for the low LET in vivo mouse spleen exposures. A Bystander Factor of 317 and an AR protection factor of 0.53 are obtained for high LET radon alpha particles in human lymphocytes. In both cases the AR is activated at most by one or two radiation induced charged particle traversals through the cell nucleus. The results of the model analysis is consistent with a premise that both Bystander damage and Adaptive Response radioprotection can occur in the same cell type, derived from the same cell species. The model provides an analytical tool to biophysically study the combined effects of BE and AR.

Shielding synchrotron light sources: Advantages of circular shield walls tunnels

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

Kramer, S. L.; Ghosh, V. J.; Breitfeller, M.

Third generation high brightness light sources are designed to have low emittance and high current beams, which contribute to higher beam loss rates that will be compensated by Top-Off injection. Shielding for these higher loss rates will be critical to protect the projected higher occupancy factors for the users. Top-Off injection requires a full energy injector, which will demand greater consideration of the potential abnormal beam miss-steering and localized losses that could occur. The high energy electron injection beam produce significantly higher neutron component dose to the experimental floor than lower energy injection and ramped operations. High energy neutrons producedmore » in the forward direction from thin target beam losses are a major component of the dose rate outside the shield walls of the tunnel. The convention has been to provide thicker 90° ratchet walls to reduce this dose to the beam line users. We present an alternate circular shield wall design, which naturally and cost effectively increases the path length for this forward radiation in the shield wall and thereby substantially decreasing the dose rate for these beam losses. Here, this shield wall design will greatly reduce the dose rate to the users working near the front end optical components but will challenge the beam line designers to effectively utilize the longer length of beam line penetration in the shield wall. Additional advantages of the circular shield wall tunnel are that it's simpler to construct, allows greater access to the insertion devices and the upstream in tunnel beam line components, as well as reducing the volume of concrete and therefore the cost of the shield wall.« less

Shielding synchrotron light sources: Advantages of circular shield walls tunnels

DOE PAGES

Kramer, S. L.; Ghosh, V. J.; Breitfeller, M.

2016-04-26

Third generation high brightness light sources are designed to have low emittance and high current beams, which contribute to higher beam loss rates that will be compensated by Top-Off injection. Shielding for these higher loss rates will be critical to protect the projected higher occupancy factors for the users. Top-Off injection requires a full energy injector, which will demand greater consideration of the potential abnormal beam miss-steering and localized losses that could occur. The high energy electron injection beam produce significantly higher neutron component dose to the experimental floor than lower energy injection and ramped operations. High energy neutrons producedmore » in the forward direction from thin target beam losses are a major component of the dose rate outside the shield walls of the tunnel. The convention has been to provide thicker 90° ratchet walls to reduce this dose to the beam line users. We present an alternate circular shield wall design, which naturally and cost effectively increases the path length for this forward radiation in the shield wall and thereby substantially decreasing the dose rate for these beam losses. Here, this shield wall design will greatly reduce the dose rate to the users working near the front end optical components but will challenge the beam line designers to effectively utilize the longer length of beam line penetration in the shield wall. Additional advantages of the circular shield wall tunnel are that it's simpler to construct, allows greater access to the insertion devices and the upstream in tunnel beam line components, as well as reducing the volume of concrete and therefore the cost of the shield wall.« less

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.

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.

Prediction of obliteration after gamma knife surgery for cerebral arteriovenous malformations.

PubMed

Karlsson, B; Lindquist, C; Steiner, L

1997-03-01

To define the factors of importance for the obliteration of cerebral arteriovenous malformations (AVMs), thus making a prediction of the probability for obliteration possible. In 945 AVMs of a series of 1319 patients treated with the gamma knife during 1970 to 1990, the relationship between patient, AVMs, and treatment parameters on the one hand and the obliteration of the nidus on the other was analyzed. The obliteration rate increased both with increased minimum (lowest periphery) and average dose and decreased with increased AVM volume. The minimum dose to the AVMs was the decisive dose factor for the treatment result. The higher the minimum dose, the higher the chance for total obliteration. The curve illustrating this relation increased logarithmically to a value of 87%. A higher average dose shortened the latency to AVM obliteration. For the obliterated cases, the larger the malformation, the lower the minimum dose used. This prompted us to relate the obliteration rate to the product minimum dose (AVM volume)1/3 (K index). The obliteration rate increased linearly with the K index up to a value of approximately 27, and for higher K values, the obliteration rate had a constant value of approximately 80%. For the group of 273 cases treated with a minimum dose of at least 25 Gy, the obliteration rate at the study end point (defined as 2-yr latency) was 80% (95% confidence interval = 75-85%). If obliterations that occurred beyond the end point are included, the obliteration rate increased to 85% (81-89%). The probability of obliteration of AVMs after gamma knife surgery is related both to the lowest dose to the AVMs and the AVM volume, and it can be predicted using the K index.

SU-E-T-467: Implementation of Monte Carlo Dose Calculation for a Multileaf Collimator Equipped Robotic Radiotherapy System

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

Li, JS; Fan, J; Ma, C-M

Purpose: To improve the treatment efficiency and capabilities for full-body treatment, a robotic radiosurgery system has equipped with a multileaf collimator (MLC) to extend its accuracy and precision to radiation therapy. To model the MLC and include it in the Monte Carlo patient dose calculation is the goal of this work. Methods: The radiation source and the MLC were carefully modeled to consider the effects of the source size, collimator scattering, leaf transmission and leaf end shape. A source model was built based on the output factors, percentage depth dose curves and lateral dose profiles measured in a water phantom.more » MLC leaf shape, leaf end design and leaf tilt for minimizing the interleaf leakage and their effects on beam fluence and energy spectrum were all considered in the calculation. Transmission/leakage was added to the fluence based on the transmission factors of the leaf and the leaf end. The transmitted photon energy was tuned to consider the beam hardening effects. The calculated results with the Monte Carlo implementation was compared with measurements in homogeneous water phantom and inhomogeneous phantoms with slab lung or bone material for 4 square fields and 9 irregularly shaped fields. Results: The calculated output factors are compared with the measured ones and the difference is within 1% for different field sizes. The calculated dose distributions in the phantoms show good agreement with measurements using diode detector and films. The dose difference is within 2% inside the field and the distance to agreement is within 2mm in the penumbra region. The gamma passing rate is more than 95% with 2%/2mm criteria for all the test cases. Conclusion: Implementation of Monte Carlo dose calculation for a MLC equipped robotic radiosurgery system is completed successfully. The accuracy of Monte Carlo dose calculation with MLC is clinically acceptable. This work was supported by Accuray Inc.« less

Prescription order risk factors for pediatric dosing alerts.

PubMed

Stultz, J S; Porter, K; Nahata, M C

2015-02-01

To determine dosing alert rates based on prescription order characteristics and identify prescription order risk factors for the occurrence of dosing alerts. A retrospective analysis of inpatient medication orders and dosing alerts occurring during October 2011 and January, April, and July 2012 at a pediatric institution. Prescription orders and alerts were categorized by: medication class, patient age, route of administration, and month of the year. There were 228,259 orders during the studied period, with 11,072 alerted orders (4.9%). The most frequently alerted medication class was the non-analgesic central nervous system agent class (14% of alerts). Age, route, medication class, and month all independently affected dosing alert rates. The alert rate was highest for immunosuppressive agents (54%), neonates (6.7%), and orders for rectal administration (9.5%). The alert rate was higher in adult patients receiving their care at a pediatric institution (5.7%) compared to children (4.7%), but after multivariate analysis, pediatric orders had higher odds for an alert (OR 1.1, 95% CI 1.05-1.16). Mercaptopurine had the highest alert rate when categorized by active ingredient (73.9%). Albuterol 2.5mg/mL continuous aerosol and heparin 1000 units in 0.9% sodium chloride injection solution were the unique medications with the highest alert rates (100.0% and 97.7%, respectively). Certain types of prescription orders have a higher risk for causing dosing alerts than others. Patient age, medication class, route of administration, and the month of year can affect dosing alert rates. Design and customization efforts should focus on these medications and prescription order characteristics that increase the risk for dosing alerts. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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.

Remanent dose rates around the collimators of the LHC beam cleaning insertions.

PubMed

Brugger, M; Roesler, S

2005-01-01

The LHC will require an extremely powerful and unprecedented collimation system. As approximately 30% of the LHC beam is lost in the cleaning insertions, these will become some of the most radioactive locations around the entire LHC ring. Thus, remanent dose rates to be expected during later repair or maintenance interventions must be considered in the design phase itself. As a consequence, the beam cleaning insertions form a unique test bed for a recently developed approach to calculate remanent dose rates. A set of simulations, different in complexity, is used in order to evaluate methods for the estimation of remanent dose rates. The scope, as well as the restrictions, of the omega-factor method are shown and compared with the explicit simulation approach. The latter is then used to calculate remanent dose rates in the beam cleaning insertions. Furthermore, a detailed example for maintenance dose planning is given.

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

Effect of platelet activating factor on endothelial permeability to plasma macromolecules

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

Handley, D.A.; Arbeeny, C.M.; Lee, M.L.

The effect of intrajugular administration of platelet activating factor (PAF-C16) on vascular permeability was examined in the guinea pig. To examine the loss of selective endothelial permeability, the extravasative effect of PAF was assessed by monitoring hemoconcentration and the plasma loss of /sup 125/I-albumin (6.7 nm), /sup 125/I-low density lipoproteins (22.0 nm) or /sup 125/I-very low density lipoproteins (62.1 nm). Extravasation was dose-dependent and began 1 min after PAF administration, continuing for 5-7 min. During extravasation, there was no evidence for selective plasma retention of any of the labeled plasma tracers, as measured by plasma radioactivity. These results suggest thatmore » PAF-induced extravasation is dose-dependent, with increases in vascular permeability sufficient to permit similar plasma efflux rates of albumin, low density lipoproteins and very low density lipoproteins.« less

Higher dose rate Gamma Knife radiosurgery may provide earlier and longer-lasting pain relief for patients with trigeminal neuralgia.

PubMed

Lee, John Y K; Sandhu, Sukhmeet; Miller, Denise; Solberg, Timothy; Dorsey, Jay F; Alonso-Basanta, Michelle

2015-10-01

Gamma Knife radiosurgery (GKRS) utilizes cobalt-60 as its radiation source, and thus dose rate varies as the fixed source decays over its half-life of approximately 5.26 years. This natural decay results in increasing treatment times when delivering the same cumulative dose. It is also possible, however, that the biological effective dose may change based on this dose rate even if the total dose is kept constant. Because patients are generally treated in a uniform manner, radiosurgery for trigeminal neuralgia (TN) represents a clinical model whereby biological efficacy can be tested. The authors hypothesized that higher dose rates would result in earlier and more complete pain relief but only if measured with a sensitive pain assessment tool. One hundred thirty-three patients were treated with the Gamma Knife Model 4C unit at a single center by a single neurosurgeon during a single cobalt life cycle from January 2006 to May 2012. All patients were treated with 80 Gy with a single 4-mm isocenter without blocking. Using an output factor of 0.87, dose rates ranged from 1.28 to 2.95 Gy/min. The Brief Pain Inventory (BPI)-Facial was administered before the procedure and at the first follow-up office visit 1 month from the procedure (mean 1.3 months). Phone calls were made to evaluate patients after their procedures as part of a retrospective study. Univariate and multivariate linear regression was performed on several independent variables, including sex, age in deciles, diagnosis, follow-up duration, prior surgery, and dose rate. In the short-term analysis (mean 1.3 months), patients' self-reported pain intensity at its worst was significantly correlated with dose rate on multivariate analysis (p = 0.028). Similarly, patients' self-reported interference with activities of daily living was closely correlated with dose rate on multivariate analysis (p = 0.067). A 1 Gy/min decrease in dose rate resulted in a 17% decrease in pain intensity at its worst and a 22% decrease in pain interference with activities of daily living. In longer-term follow-up (mean 1.9 years), GKRS with higher dose rates (> 2.0 Gy/min; p = 0.007) and older age in deciles (p = 0.012) were associated with a lower likelihood of recurrence of pain. Prior studies investigating the role of dose rate in Gamma Knife radiosurgical ablation for TN have not used validated outcome tools to measure pain preoperatively. Consequently, differences in pain outcomes have been difficult to measure. By administering pain scales both preoperatively as well as postoperatively, the authors have identified statistically significant differences in pain intensity and pain interference with activities of daily living when comparing higher versus lower dose rates. Radiosurgery with a higher dose rate results in more pain relief at the early follow-up evaluation, and it may result in a lower recurrence rate at later follow-up.

High-dose-rate Intracavitary Radiotherapy in the Management of Cervical Intraepithelial Neoplasia 3 and Carcinoma In Situ Presenting With Poor Histologic Factors After Undergoing Excisional Procedures

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

Kim, Yong Bae, E-mail: ybkim3@yuhs.ac; Kim, Young Tae; Cho, Nam Hoon

2012-09-01

Purpose: To assess the effectiveness of high-dose-rate intracavitary radiotherapy (HDR-ICR) in patients with cervical intraepithelial neoplasia 3 (CIN 3) and carcinoma in situ (CIS) presenting with poor histologic factors for predicting residual disease after undergoing diagnostic excisional procedures. Methods and Materials: This study was a retrospective analysis of 166 patients with CIN 3 (n=15) and CIS (n=151) between October 1986 and December 2005. They were diagnosed by conization (n=158) and punch biopsy (n=8). Pathologic analysis showed 135 cases of endocervical gland involvement (81.4%), 74 cases of positive resection margins (44.5%), and 52 cases of malignant cells on endocervical curettage (31.3%).more » All patients were treated with HDR-ICR using Co{sup 60} or Ir{sup 192} at a cancer center. The dose was prescribed at point A located 2 cm superior to the external os and 2 cm lateral to the axis of the tandem for intact uterus. Results: Median age was 61 years (range, 29-77). The median total dose of HDR-ICR was 30 Gy/6 fractions (range, 30-52). At follow-up (median, 152 months), 2 patients developed recurrent diseases: 1 CIN 2 and 1 invasive carcinoma. One hundred and forty patients survived and 26 patients died, owing to nonmalignant intercurrent disease. Rectal bleeding occurred in one patient; however, this symptom subsided with conservative management. Conclusions: Our data showed HDR-ICR is an effective modality for CIN 3 and CIS patients presenting with poor histologic factors after excisional procedures. HDR-ICR should be considered as a definitive treatment in CIN 3 and CIS patients with possible residual disease after undergoing excisional procedures.« less

Gastrointestinal Bleeding With Edoxaban Versus Warfarin: Results From the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction).

PubMed

Aisenberg, James; Chatterjee-Murphy, Prapti; Friedman Flack, Kathryn; Weitz, Jeffrey I; Ruff, Christian T; Nordio, Francesco; Mercuri, Michele F; Choi, Youngsook; Antman, Elliott M; Braunwald, Eugene; Giugliano, Robert P

2018-05-01

The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction) compared higher-dose edoxaban regimen (HD-ER) and lower-dose edoxaban regimen with well-managed warfarin in 21 105 patients with atrial fibrillation. The risk factors and clinical impact of gastrointestinal bleeding (GIB) in this trial have not been described in detail. This analysis was undertaken to identify risk factors for major GIB (MGIB) and compare the severity and outcomes of GIB with edoxaban and warfarin. During 2.8 years mean follow-up, there were 579 MGIB (1.22% per year), of which 63 were life-threatening or fatal (0.13% per year). Male sex, increased age, prior GIB, concomitant aspirin, lower baseline hemoglobin, renal dysfunction, and higher HAS-BLED and CHADS 2 scores were independently associated with the risk of MGIB. Whereas the annual rate of MGIB was higher with HD-ER than with warfarin (1.53% and 1.25%, respectively; hazard ratio, 1.23; 95% confidence interval, 1.02-1.48; P =0.033), the annual rates of life-threatening or fatal GIB were similar (0.15% and 0.18%, respectively). Several indicators of more severe GIB, including hemodynamic instability, hospitalization, ≥ 4 U transfusion, and hemoglobin loss ≥5 g/dL, were similar with HD-ER and warfarin, whereas surgery required to manage bleeding was less frequent with HD-ER. Lower-dose edoxaban regimen, which achieved 50% lower trough edoxaban levels, was associated with significantly less MGIB than warfarin. MGIB occurred more frequently with HD-ER than warfarin. The rates of life-threatening or fatal GIB were low and similar with both HD-ER and warfarin. Clinical outcomes were generally favorable. The correlation between dose, trough edoxaban level, and the risk of GIB risk suggests GIB is exposure-related. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00781391. © 2018 American Heart Association, Inc.

Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer.

PubMed

Eisbruch, A; Kim, H M; Terrell, J E; Marsh, L H; Dawson, L A; Ship, J A

2001-07-01

To assess long-term xerostomia in patients receiving parotid-sparing radiation therapy (RT) for head-and-neck cancer, and to find the patient and therapy-related factors that affect its severity. From March 1994 through January 2000, 84 patients received comprehensive bilateral neck RT using conformal and multisegmental intensity-modulated RT (IMRT) aiming to spare the major salivary glands. Before RT and periodically through 2 years after the completion of RT, salivary flow rates from each of the major salivary glands were selectively measured. At the same time intervals, each patient completed an 8-item self-reported xerostomia-specific questionnaire (XQ). To gain a relative measure of the effect of RT on the minor salivary glands, whose output could not be measured, the surfaces of the oral cavity (extending to include the surface of the base of tongue) were outlined in the planning CT scans. The mean doses to the new organ ("oral cavity") were recorded. Forty-eight patients receiving unilateral neck RT were similarly studied and served as a benchmark for comparison. Factors predicting the XQ scores were analyzed using a random-effects model. The XQ was found to be reliable and valid in measuring patient-reported xerostomia. The spared salivary glands which had received moderate doses in the bilateral RT group recovered to their baseline salivary flow rates during the second year after RT, and the spared glands in the unilateral RT group, which had received very low doses, demonstrated increased salivary production beyond their pre-RT levels. The increase in the salivary flow rates during the second year after RT paralleled an improvement in xerostomia in both patient groups. The improvement in xerostomia was faster in the unilateral compared with the bilateral RT group, but the difference narrowed at 2 years. The major salivary gland flow rates had only a weak correlation with the xerostomia scores. Factors found to be independently associated with the xerostomia scores were the pre-RT baseline scores, the time since RT, and the mean doses to the major salivary glands (notably to the submandibular glands) and to the oral cavity. An improvement over time in xerostomia, occurring in tandem with rising salivary production from the spared major salivary glands, suggests a long-term clinical benefit from their sparing. The oral cavity mean dose, representing RT effect on the minor salivary glands, was found to be a significant, independent predictor of xerostomia. Thus, in addition to the major salivary glands, sparing the uninvolved oral cavity should be considered as a planning objective to further reduce xerostomia.

Development and implementation of a remote audit tool for high dose rate (HDR) Ir-192 brachytherapy using optically stimulated luminescence dosimetry

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

Casey, Kevin E.; Kry, Stephen F.; Howell, Rebecca M.

Purpose: The aim of this work was to create a mailable phantom with measurement accuracy suitable for Radiological Physics Center (RPC) audits of high dose-rate (HDR) brachytherapy sources at institutions participating in National Cancer Institute-funded cooperative clinical trials. Optically stimulated luminescence dosimeters (OSLDs) were chosen as the dosimeter to be used with the phantom.Methods: The authors designed and built an 8 × 8 × 10 cm{sup 3} prototype phantom that had two slots capable of holding Al{sub 2}O{sub 3}:C OSLDs (nanoDots; Landauer, Glenwood, IL) and a single channel capable of accepting all {sup 192}Ir HDR brachytherapy sources in current clinicalmore » use in the United States. The authors irradiated the phantom with Nucletron and Varian {sup 192}Ir HDR sources in order to determine correction factors for linearity with dose and the combined effects of irradiation energy and phantom characteristics. The phantom was then sent to eight institutions which volunteered to perform trial remote audits.Results: The linearity correction factor was k{sub L}= (−9.43 × 10{sup −5}× dose) + 1.009, where dose is in cGy, which differed from that determined by the RPC for the same batch of dosimeters using {sup 60}Co irradiation. Separate block correction factors were determined for current versions of both Nucletron and Varian {sup 192}Ir HDR sources and these vendor-specific correction factors differed by almost 2.6%. For the Nucletron source, the correction factor was 1.026 [95% confidence interval (CI) = 1.023–1.028], and for the Varian source, it was 1.000 (95% CI = 0.995–1.005). Variations in lateral source positioning up to 0.8 mm and distal/proximal source positioning up to 10 mm had minimal effect on dose measurement accuracy. The overall dose measurement uncertainty of the system was estimated to be 2.4% and 2.5% for the Nucletron and Varian sources, respectively (95% CI). This uncertainty was sufficient to establish a ±5% acceptance criterion for source strength audits under a formal RPC audit program. Trial audits of four Nucletron sources and four Varian sources revealed an average RPC-to-institution dose ratio of 1.000 (standard deviation = 0.011).Conclusions: The authors have created an OSLD-based {sup 192}Ir HDR brachytherapy source remote audit tool which offers sufficient dose measurement accuracy to allow the RPC to establish a remote audit program with a ±5% acceptance criterion. The feasibility of the system has been demonstrated with eight trial audits to date.« less

Do stress responses promote leukemia progression? An animal study suggesting a role for epinephrine and prostaglandin-E2 through reduced NK activity.

PubMed

Inbar, Shelly; Neeman, Elad; Avraham, Roi; Benish, Marganit; Rosenne, Ella; Ben-Eliyahu, Shamgar

2011-04-29

In leukemia patients, stress and anxiety were suggested to predict poorer prognosis. Oncological patients experience ample physiological and psychological stress, potentially leading to increased secretion of stress factors, including epinephrine, corticosteroids, and prostaglandins. Here we tested whether environmental stress and these stress factors impact survival of leukemia-challenged rats, and studied mediating mechanisms. F344 rats were administered with a miniscule dose of 60 CRNK-16 leukemia cells, and were subjected to intermittent forced swim stress or to administration of physiologically relevant doses of epinephrine, prostaglandin-E(2) or corticosterone. Stress and each stress factor, and/or their combinations, doubled mortality rates when acutely applied simultaneously with, or two or six days after tumor challenge. Acute administration of the β-adrenergic blocker nadolol diminished the effects of environmental stress, without affecting baseline survival rates. Prolonged β-adrenergic blockade or COX inhibition (using etodolac) also increased baseline survival rates, possibly by blocking tumor-related or normal levels of catecholamines and prostaglandins. Searching for mediating mechanisms, we found that each of the stress factors transiently suppressed NK activity against CRNK-16 and YAC-1 lines on a per NK basis. In contrast, the direct effects of stress factors on CRNK-16 proliferation, vitality, and VEGF secretion could not explain or even contradicted the in vivo survival findings. Overall, it seems that environmental stress, epinephrine, and prostaglandins promote leukemia progression in rats, potentially through suppressing cell mediated immunity. Thus, patients with hematological malignancies, which often exhibit diminished NK activity, may benefit from extended β-blockade and COX inhibition.

Elective neck irradiation for nasopharyngeal carcinoma.

PubMed

Wang, C J; Chen, H C; Huang, E Y; Lee, S P

2000-07-01

This study was conducted to evaluate the effectiveness of elective neck irradiation (ENI) for nasopharyngeal carcinoma (NPC), and to analyze factors associated with ENI failure. A radiation port covering the side of a neck without gross nodal metastasis was qualified for evaluation of the effectiveness of ENI. From 1988 through 1992, a total of 261 patients with N0 (130 cases), N1 (91 cases), and N3 (40 cases) NPCs were studied. All patients were irradiated with 60Co teletherapy or 10 MV x-ray to a total dose of 46.8 Gy/26 fractions, followed by a boost treatment to the primary site to a total dose of 64.8 to 75.6 Gy/36-42 fractions. All ENI ports received irradiation to a dose of 46.8 to 60.8 Gy. The duration of follow-up was 6 to 10 years, with a median of 8.1 years. Factors associated with to the risk of ENI failure were analyzed. (1) The overall 5-year actuarial local control rate and actuarial survival rate were 74% and 63%, respectively. (2) Among the 261 cases in which ENI treatment was used, the treatment failed in 12 cases, accounting for a crude ENI failure rate of 5%. The overall 5- and 10-year cumulative risk of ENI failure was 5% and 7%, respectively. (3) Time from the start of treatment to ENI failure ranged from 9 to 66 months, with a median of 17 months. (4) Of the 12 patients for whom EMI failed, 11 (92%) had recurrence in the upper neck, and one in the lower neck. (5) Existence of prior failure at the primary site was the only factor significantly correlated with the risk of ENI failure (p < 0.001). The 5-year cumulative risk of ENI failure for patients with local failure vs. those without was 16% vs. 1% (p < 0.0001). Moderate-dose ENI was highly effective in the control of subclinical disease in the neck for NPC. ENI failure was closely associated with prior failure at the primary site, implying that local primary tumor failure may lead to an increased potential for metastasis to the neck.

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.

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.

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

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

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.

Measurements of the radiation quality factor Q at aviation altitudes during solar minimum (2006-2008)

NASA Astrophysics Data System (ADS)

Meier, Matthias M.; Hubiak, Melina

2010-05-01

In radiation protection, the Q-factor has been defined to describe the biological effectiveness of the energy deposition or absorbed dose to humans in the mixed radiation fields at aviation altitudes. This particular radiation field is generated by the interactions of primary cosmic particles with the atoms of the constituents of the Earth’s atmosphere. Thus the intensity, characterized by the ambient dose equivalent rate H∗(10), depends on the flight altitude and the energy spectra of the particles, mainly protons and alpha particles, impinging on the atmosphere. These charged cosmic projectiles are deflected both by the interplanetary and the Earth’s magnetic field such that the corresponding energy spectra are modulated by these fields. The solar minimum is a time period of particular interest since the interplanetary magnetic field is weakest within the 11-year solar cycle and the dose rates at aviation altitudes reach their maximum due to the reduced shielding of galactic cosmic radiation. For this reason, the German Aerospace Center (DLR) performed repeated dosimetric on-board measurements in cooperation with several German airlines during the past solar minimum from March 2006 to August 2008. The Q-factors measured with a TEPC range from 1.98 at the equator to 2.60 in the polar region.

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

Determination of in vitro lung solubility and intake-to-dose conversion factor for tritiated lanthanum nickel aluminum alloy.

PubMed

Farfán, Eduardo B; Labone, Thomas R; Staack, Gregory C; Cheng, Yung-Sung; Zhou, Yue; Varallo, Thomas P

2012-09-01

A sample of tritiated lanthanum nickel aluminum alloy (LaNi4.25Al0.75 or LANA.75) similar to that used at the Savannah River Site Tritium Facilities was analyzed to estimate the particle size distribution of this metal tritide powder and the rate at which this material dissolves in the human respiratory tract after it is inhaled. This information is used to calculate the committed effective dose received by a worker after inhaling the material. These doses, which were calculated using the same methodology given in the U.S. Department of Energy Tritium Handbook, are presented as inhalation intake-to-dose conversion factors (DCF). The DCF for this metal tritide was determined to be 9.4 × 10 Sv Bq, which is less than the DCF for tritiated water. Therefore, the radiation worker bioassay programs designed for tritiated water are adequate to monitor for intakes of this material.

Dose-rate effect of ultrashort electron beam radiation on DNA damage and repair in vitro.

PubMed

Babayan, Nelly; Hovhannisyan, Galina; Grigoryan, Bagrat; Grigoryan, Ruzanna; Sarkisyan, Natalia; Tsakanova, Gohar; Haroutiunian, Samvel; Aroutiounian, Rouben

2017-11-01

Laser-generated electron beams are distinguished from conventional accelerated particles by ultrashort beam pulses in the femtoseconds to picoseconds duration range, and their application may elucidate primary radiobiological effects. The aim of the present study was to determine the dose-rate effect of laser-generated ultrashort pulses of 4 MeV electron beam radiation on DNA damage and repair in human cells. The dose rate was increased via changing the pulse repetition frequency, without increasing the electron energy. The human chronic myeloid leukemia K-562 cell line was used to estimate the DNA damage and repair after irradiation, via the comet assay. A distribution analysis of the DNA damage was performed. The same mean level of initial DNA damages was observed at low (3.6 Gy/min) and high (36 Gy/min) dose-rate irradiation. In the case of low-dose-rate irradiation, the detected DNA damages were completely repairable, whereas the high-dose-rate irradiation demonstrated a lower level of reparability. The distribution analysis of initial DNA damages after high-dose-rate irradiation revealed a shift towards higher amounts of damage and a broadening in distribution. Thus, increasing the dose rate via changing the pulse frequency of ultrafast electrons leads to an increase in the complexity of DNA damages, with a consequent decrease in their reparability. Since the application of an ultrashort pulsed electron beam permits us to describe the primary radiobiological effects, it can be assumed that the observed dose-rate effect on DNA damage/repair is mainly caused by primary lesions appearing at the moment of irradiation. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Effect of Brain Stem and Dorsal Vagus Complex Dosimetry on Nausea and Vomiting in Head and Neck Intensity-Modulated Radiation Therapy

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

Ciura, Katherine; McBurney, Michelle; Nguyen, Baongoc

Intensity-modulated radiation therapy (IMRT) is becoming the treatment of choice for many head and neck cancer patients. IMRT reduces some toxicities by reducing radiation dose to uninvolved normal tissue near tumor targets; however, other tissues not irradiated using previous 3D techniques may receive clinically significant doses, causing undesirable side effects including nausea and vomiting (NV). Irradiation of the brainstem, and more specifically, the area postrema and dorsal vagal complex (DVC), has been linked to NV. We previously reported preliminary hypothesis-generating dose effects associated with NV in IMRT patients. The goal of this study is to relate brainstem dose to NVmore » symptoms. We retrospectively studied 100 consecutive patients that were treated for oropharyngeal cancer with IMRT. We contoured the brainstem, area postrema, and DVC with the assistance of an expert diagnostic neuroradiologist. We correlated dosimetry for the 3 areas contoured with weekly NV rates during IMRT. NV rates were significantly higher for patients who received concurrent chemotherapy. Post hoc analysis demonstrated that chemoradiation cases exhibited a trend towards the same dose-response relationship with both brainstem mean dose (p = 0.0025) and area postrema mean dose (p = 0.004); however, both failed to meet statistical significance at the p {<=} 0.002 level. Duration of toxicity was also greater for chemoradiation patients, who averaged 3.3 weeks with reported Common Terminology Criteria for Adverse Events (CTC-AE), compared with an average of 2 weeks for definitive RT patients (p = 0.002). For definitive RT cases, no dose-response trend could be ascertained. The mean brainstem dose emerged as a key parameter of interest; however, no one dose parameter (mean/median/EUD) best correlated with NV. This study does not address extraneous factors that would affect NV incidence, including the use of antiemetics, nor chemotherapy dose schedule specifics before and during RT. A prospective study will be required to depict exactly how IMRT dose affects NV.« less

Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study

PubMed Central

Peak, Corey M.; Leung, Gabriel M.

2016-01-01

Background The ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July–August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission. Methods We estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July–August 2016 with different age cutoff for fractional-dose vaccines. Findings We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%. Interpretation Dose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected. PMID:27837923

A new model for biological effects of radiation and the driven force of molecular evolution

NASA Astrophysics Data System (ADS)

Wada, Takahiro; Manabe, Yuichiro; Nakajima, Hiroo; Tsunoyama, Yuichi; Bando, Masako

We proposed a new mathematical model to estimate biological effects of radiation, which we call Whack-A-Mole (WAM) model. A special feature of WAM model is that it involves the dose rate of radiation as a key ingredient. We succeeded to reproduce the experimental data of various species concerning the radiation induced mutation frequencies. From the analysis of the mega-mouse experiments, we obtained the mutation rate per base-pair per year for mice which is consistent with the so-called molecular clock in evolution genetics, 10-9 mutation/base-pair/year. Another important quantity is the equivalent dose rate for the whole spontaneous mutation, deff. The value of deff for mice is 1.1*10-3 Gy/hour which is much larger than the dose rate of natural radiation (10- (6 - 7) Gy/hour) by several orders of magnitude. We also analyzed Drosophila data and obtained essentially the same numbers. This clearly indicates that the natural radiation is not the dominant driving force of the molecular evolution, but we should look for other factors, such as miscopy of DNA in duplication process. We believe this is the first quantitative proof of the small contribution of the natural radiation in the molecular evolution.

Measurements of the neutron spectrum on the Martian surface with MSL/RAD

NASA Astrophysics Data System (ADS)

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

2014-03-01

The Radiation Assessment Detector (RAD), onboard the Mars Science Laboratory (MSL) rover Curiosity, measures the energetic charged and neutral particles and the radiation dose rate on the surface of Mars. An important factor for determining the biological impact of the Martian surface radiation is the specific contribution of neutrons, with their deeper penetration depth and ensuing high biological effectiveness. This is very difficult to measure quantitatively, resulting in considerable uncertainties in the total radiation dose. In contrast to charged particles, neutral particles (neutrons and gamma rays) are generally only measured indirectly. Measured spectra are a complex convolution of the incident particle spectrum with the detector response function and must be unfolded. We apply an inversion method (based on a maximum likelihood estimation) to calculate the neutron and gamma spectra from the RAD neutral particle measurements. Here we show the first spectra on the surface of Mars and compare them to theoretical predictions. The measured neutron spectrum (ranging from 8 to 740 MeV) translates into a radiation dose rate of 14±4μGy/d and a dose equivalent rate of 61±15μSv/d. This corresponds to 7% of the measured total surface dose rate and 10% of the biologically relevant surface dose equivalent rate on Mars. Measuring the Martian neutron and gamma spectra is an essential step for determining the mutagenic influences to past or present life at or beneath the Martian surface as well as the radiation hazard for future human exploration, including the shielding design of a potential habitat.

Factors modifying the response of large animals to low-intensity radiation exposure

NASA Technical Reports Server (NTRS)

Page, N. P.; Still, E. T.

1972-01-01

In assessing the biological response to space radiation, two of the most important modifying factors are dose protraction and dose distribution to the body. Studies are reported in which sheep and swine were used to compare the hematology and lethality response resulting from radiation exposure encountered in a variety of forms, including acute (high dose-rate), chronic (low dose-rate), combinations of acute and chronic, and whether received as a continuous or as fractionated exposure. While sheep and swine are basically similar in response to acute radiation, their sensitivity to chronic irradiation is markedly different. Sheep remain relatively sensitive as the radiation exposure is protracted while swine are more resistant and capable of surviving extremely large doses of chronic irradiation. This response to chronic irradiation correlated well with changes in radiosensitivity and recovery following an acute, sublethal exposure.

Dosimetric evaluation of a MOSFET detector for clinical application in photon therapy.

PubMed

Kohno, Ryosuke; Hirano, Eriko; Nishio, Teiji; Miyagishi, Tomoko; Goka, Tomonori; Kawashima, Mitsuhiko; Ogino, Takashi

2008-01-01

Dosimetric characteristics of a metal oxide-silicon semiconductor field effect transistor (MOSFET) detector are studied with megavoltage photon beams for patient dose verification. The major advantages of this detector are its size, which makes it a point dosimeter, and its ease of use. In order to use the MOSFET detector for dose verification of intensity-modulated radiation therapy (IMRT) and in-vivo dosimetry for radiation therapy, we need to evaluate the dosimetric properties of the MOSFET detector. Therefore, we investigated the reproducibility, dose-rate effect, accumulated-dose effect, angular dependence, and accuracy in tissue-maximum ratio measurements. Then, as it takes about 20 min in actual IMRT for the patient, we evaluated fading effect of MOSFET response. When the MOSFETs were read-out 20 min after irradiation, we observed a fading effect of 0.9% with 0.9% standard error of the mean. Further, we applied the MOSFET to the measurement of small field total scatter factor. The MOSFET for dose measurements of small field sizes was better than the reference pinpoint chamber with vertical direction. In conclusion, we assessed the accuracy, reliability, and usefulness of the MOSFET detector in clinical applications such as pinpoint absolute dosimetry for small fields.

WE-DE-201-05: Evaluation of a Windowless Extrapolation Chamber Design and Monte Carlo Based Corrections for the Calibration of Ophthalmic Applicators

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

Hansen, J; Culberson, W; DeWerd, L

Purpose: To test the validity of a windowless extrapolation chamber used to measure surface dose rate from planar ophthalmic applicators and to compare different Monte Carlo based codes for deriving correction factors. Methods: Dose rate measurements were performed using a windowless, planar extrapolation chamber with a {sup 90}Sr/{sup 90}Y Tracerlab RA-1 ophthalmic applicator previously calibrated at the National Institute of Standards and Technology (NIST). Capacitance measurements were performed to estimate the initial air gap width between the source face and collecting electrode. Current was measured as a function of air gap, and Bragg-Gray cavity theory was used to calculate themore » absorbed dose rate to water. To determine correction factors for backscatter, divergence, and attenuation from the Mylar entrance window found in the NIST extrapolation chamber, both EGSnrc Monte Carlo user code and Monte Carlo N-Particle Transport Code (MCNP) were utilized. Simulation results were compared with experimental current readings from the windowless extrapolation chamber as a function of air gap. Additionally, measured dose rate values were compared with the expected result from the NIST source calibration to test the validity of the windowless chamber design. Results: Better agreement was seen between EGSnrc simulated dose results and experimental current readings at very small air gaps (<100 µm) for the windowless extrapolation chamber, while MCNP results demonstrated divergence at these small gap widths. Three separate dose rate measurements were performed with the RA-1 applicator. The average observed difference from the expected result based on the NIST calibration was −1.88% with a statistical standard deviation of 0.39% (k=1). Conclusion: EGSnrc user code will be used during future work to derive correction factors for extrapolation chamber measurements. Additionally, experiment results suggest that an entrance window is not needed in order for an extrapolation chamber to provide accurate dose rate measurements for a planar ophthalmic applicator.« less

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.

Uptake and effects of americium-241 on a brackishwater amphipod

NASA Astrophysics Data System (ADS)

Hoppenheit, M.; Murray, C. N.; Woodhead, D. S.

1980-03-01

The present paper reports the results of experimental work undertaken using the brackish-water amphipod Gammarus duebeni duebeni and the transuranium nuclide americium-241. Data on the accumulation of this actinide showed that the larger fraction of the total body burden is associated with the exoskeleton. It was found that the body burden remained constant in the range pH 8.0 6.5 even though the water concentrations changed markedly. It would thus appear that the concept of a concentration factor should be re-examined and it is proposed that a factor should be defined in terms of environmental and chemical parameters which represent the bioavailable fraction of the actinide. The effect of americium on survival and moulting was studied at two activity concentrations; the dose rates and absorbed doses under the experimental conditions employed have been estimated. The differences in survival rates between the control and irradiated groups were statistically analyzed and the significant difference at the higher concentration is believed to be due to a synergism between physiological stress and radiotoxicity of americium rather than the chemical toxicity of the element.

The damage equivalence of electrons, protons, alphas and gamma rays in rad-hard MOS devices

NASA Technical Reports Server (NTRS)

Stassinopoulos, E. G.; Van Gunten, O.; Brucker, G. J.; Knudson, A. R.; Jordan, T. M.

1983-01-01

This paper reports on a study of damage equivalence in rad-hard MOS devices with 100,000 rads (SiO2) capability. Damage sensitivities for electrons of 1, 2, 3, 5, and 7 MeV, protons of 1, 3, 7, 22, and 40 MeV, 3.4-MeV alphas, and Co-60 gammas were measured and compared. Results indicated that qualitatively the same charge recombination effects occurred in hard oxide devices for doses of 100,000 rads (SiO2) as in soft oxide parts for doses of 1 to 4 krads (SiO2). Consequently, damage equivalency or non-equivalency depended on radiation type and energy. However, recovery effects, both during and after irradiation, controlled relative damage sensitivity and its dependency on total dose, dose rate, supply bias, gate bias, radiation type, and energy. Correction factors can be derived from these data or from similar tests of other hard oxide type, so as to properly evaluate the combined effects of the total space environment.

Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

PubMed

Bianchi, C; Botta, F; Conte, L; Vanoli, P; Cerizza, L

2008-10-01

This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

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

The rate of decay of fresh fission products from a nuclear reactor

NASA Astrophysics Data System (ADS)

Dolan, David J.

Determining the rate of decay of fresh fission products from a nuclear reactor is complex because of the number of isotopes involved, different types of decay, half-lives of the isotopes, and some isotopes decay into other radioactive isotopes. Traditionally, a simplified rule of 7s and 10s is used to determine the dose rate from nuclear weapons and can be to estimate the dose rate from fresh fission products of a nuclear reactor. An experiment was designed to determine the dose rate with respect to time from fresh fission products of a nuclear reactor. The experiment exposed 0.5 grams of unenriched Uranium to a fast and thermal neutron flux from a TRIGA Research Reactor (Lakewood, CO) for ten minutes. The dose rate from the fission products was measured by four Mirion DMC 2000XB electronic personal dosimeters over a period of six days. The resulting dose rate following a rule of 10s: the dose rate of fresh fission products from a nuclear reactor decreases by a factor of 10 for every 10 units of time.

Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

PubMed Central

He, Chao; Zhang, Wei; Li, Suobei; Ruan, Wei; Xu, Junmei

2018-01-01

Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP) with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp.) before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg), after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction. PMID:29765498

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

Characterization of the radiation environment at the UNLV accelerator facility during operation of the Varian M6 linac

NASA Astrophysics Data System (ADS)

Hodges, M.; Barzilov, A.; Chen, Y.; Lowe, D.

2016-10-01

The bremsstrahlung photon flux from the UNLV particle accelerator (Varian M6 model) was determined using MCNP5 code for 3 MeV and 6 MeV incident electrons. Human biological equivalent dose rates due to accelerator operation were evaluated using the photon flux with the flux-to-dose conversion factors. Dose rates were computed for the accelerator facility for M6 linac use under different operating conditions. The results showed that the use of collimators and linac internal shielding significantly reduced the dose rates throughout the facility. It was shown that the walls of the facility, in addition to the earthen berm enveloping the building, provide equivalent shielding to reduce dose rates outside to below the 2 mrem/h limit.

Passive dosimetry aboard the Mir Orbital Station: external measurements.

PubMed

Benton, E R; Benton, E V; Frank, A L

2002-10-01

This paper reports results from the first measurements made on the exterior of a LEO spacecraft of mean dose equivalent rate and average quality factor as functions of shielding depth for shielding less than 1 g/cm2 Al equivalent. Two sets of measurements were made on the outside of the Mir Orbital Station; one near solar maximum in June 1991 and one near solar minimum in 1997. Absorbed dose was measured using stacks of TLDs. LET spectrum from charged particles of LET infinity H2O > o r= 5keV/micrometers was measured using stacks of CR-39 PNTDs. Results from the TLD and PNTD measurements at a given shielding depth were combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Measurements made near solar maximum tend to be greater than those made during solar minimum. Both mean dose rate and mean dose equivalent rate decrease by nearly four orders of magnitude within the first g/cm2 shielding illustrating the attenuation of both trapped electrons and low-energy trapped protons. In order to overcome problems with detector saturation after standard chemical processing, measurement of LET spectrum in the least shielded CR-39 PNTD layer (0.005 g/cm2 Al) was carried out using an atomic force microscope. c2002 Elsevier Science Ltd. All rights reserved.

Passive dosimetry aboard the Mir Orbital Station: external measurements

NASA Technical Reports Server (NTRS)

Benton, E. R.; Benton, E. V.; Frank, A. L.

2002-01-01

This paper reports results from the first measurements made on the exterior of a LEO spacecraft of mean dose equivalent rate and average quality factor as functions of shielding depth for shielding less than 1 g/cm2 Al equivalent. Two sets of measurements were made on the outside of the Mir Orbital Station; one near solar maximum in June 1991 and one near solar minimum in 1997. Absorbed dose was measured using stacks of TLDs. LET spectrum from charged particles of LET infinity H2O > o r= 5keV/micrometers was measured using stacks of CR-39 PNTDs. Results from the TLD and PNTD measurements at a given shielding depth were combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Measurements made near solar maximum tend to be greater than those made during solar minimum. Both mean dose rate and mean dose equivalent rate decrease by nearly four orders of magnitude within the first g/cm2 shielding illustrating the attenuation of both trapped electrons and low-energy trapped protons. In order to overcome problems with detector saturation after standard chemical processing, measurement of LET spectrum in the least shielded CR-39 PNTD layer (0.005 g/cm2 Al) was carried out using an atomic force microscope. c2002 Elsevier Science Ltd. All rights reserved.

Immune tolerance: a synopsis of the international experience.

PubMed

Di Michele, D M

1998-07-01

Because of the increased morbidity and cost of care associated with inhibitor development, immune tolerance therapy (ITT) is of crucial value in the care of haemophilia. The 24-year experience with this modality, primarily in the treatment of factor VIII inhibitors, has included the use of both high and low doses of clotting factor, with and without immune modulation. Overall success rates for ITT in haemophilia A have been similar (63-83%), while median time to IT has been variable (1.2-24 months). The role of type and purity of clotting factor used remains unclear. Three immune tolerance registries have suggested the potential importance of treatment parameters such as pre-induction inhibitor titer and daily factor dose in the prediction of successful outcome. Ultimately, prospective randomized studies of ITT are required to definitively compare therapeutic regimens with respect to efficacy, safety, and cost effectiveness.

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

NASA Astrophysics Data System (ADS)

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

2003-08-01

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

Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

PubMed

Camarata, Andrew S; Switchenko, Jeffrey M; Demidenko, Eugene; Flood, Ann B; Swartz, Harold M; Ali, Arif N

2016-04-01

Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures.

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

Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

PubMed

Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

2012-11-01

Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

Correlation of radiation dose and heart rate in dual-source computed tomography coronary angiography.

PubMed

Laspas, Fotios; Tsantioti, Dimitra; Roussakis, Arkadios; Kritikos, Nikolaos; Efthimiadou, Roxani; Kehagias, Dimitrios; Andreou, John

2011-04-01

Computed tomography coronary angiography (CTCA) has been widely used since the introduction of 64-slice scanners and dual-source CT technology, but the relatively high radiation dose remains a major concern. To evaluate the relationship between radiation exposure and heart rate (HR), in dual-source CTCA. Data from 218 CTCA examinations, performed with a dual-source 64-slices scanner, were statistically evaluated. Effective radiation dose, expressed in mSv, was calculated as the product of the dose-length product (DLP) times a conversion coefficient for the chest (mSv = DLPx0.017). Heart rate range and mean heart rate, expressed in beats per minute (bpm) of each individual during CTCA, were also provided by the system. Statistical analysis of effective dose and heart rate data was performed by using Pearson correlation coefficient and two-sample t-test. Mean HR and effective dose were found to have a borderline positive relationship. Individuals with a mean HR >65 bpm observed to receive a statistically significant higher effective dose as compared to those with a mean HR ≤65 bpm. Moreover, a strong correlation between effective dose and variability of HR of more than 20 bpm was observed. Dual-source CT scanners are considered to have the capability to provide diagnostic examinations even with high HR and arrhythmias. However, it is desirable to keep the mean heart rate below 65 bpm and heart rate fluctuation less than 20 bpm in order to reduce the radiation exposure.

Low-energy electron effects on tensile modulus and infrared transmission properties of a polypyromellitimide film

NASA Technical Reports Server (NTRS)

Ferl, J. E.; Long, E. R., Jr.

1981-01-01

Infrared (IR) spectroscopy and tensile modulus testing were used to evaluate the importance of experimental procedure on changes in properties of pyromellitic dianhydride-p,p prime-oxydianiline film exposed to electron radiation. The radiation exposures were accelerated, approximate equivalents to the total dose expected for a 30 year mission in geosynchronous Earth orbit. The change in the tensile modulus depends more on the dose rate and the time interval between exposure and testing than on total dose. The IR data vary with both total dose and dose rate. A threshold dose rate exists below which reversible radiation effects on the IR spectra occur. Above the threshold dose rate, irreversible effects occur with the appearance of a new band. Post-irradiation and in situ IR absorption bands are significantly different. It is suggested that the electron radiation induced metastable, excites molecular states.

Measurements of the neutron spectrum in transit to Mars on the Mars Science Laboratory.

PubMed

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

2015-04-01

The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011. Although designed for measuring the radiation on the surface of Mars, the Radiation Assessment Detector (RAD) measured the radiation environment inside the spacecraft during most of the 253-day, 560-million-kilometer cruise to Mars. An important factor for determining the biological impact of the radiation environment inside the spacecraft is the specific contribution of neutrons with their high biological effectiveness. We apply an inversion method (based on a maximum-likelihood estimation) to calculate the neutron and gamma spectra from the RAD neutral particle measurements. The measured neutron spectrum (12-436 MeV) translates into a radiation dose rate of 3.8±1.2 μGy/day and a dose equivalent of 19±5 μSv/day. Extrapolating the measured spectrum (0.1-1000 MeV), we find that the total neutron-induced dose rate is 6±2 μGy/day and the dose equivalent rate is 30±10 μSv/day. For a 360 day round-trip from Earth to Mars with comparable shielding, this translates into a neutron induced dose equivalent of about 11±4 mSv. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

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.

Application of computational models to estimate organ radiation dose in rainbow trout from uptake of molybdenum-99 with comparison to iodine-131.

PubMed

Martinez, N E; Johnson, T E; Pinder, J E

2016-01-01

This study compares three anatomical phantoms for rainbow trout (Oncorhynchus mykiss) for the purpose of estimating organ radiation dose and dose rates from molybdenum-99 ((99)Mo) uptake in the liver and GI tract. Model comparison and refinement is important to the process of determining accurate doses and dose rates to the whole body and the various organs. Accurate and consistent dosimetry is crucial to the determination of appropriate dose-effect relationships for use in environmental risk assessment. The computational phantoms considered are (1) a geometrically defined model employing anatomically relevant organ size and location, (2) voxel reconstruction of internal anatomy obtained from CT imaging, and (3) a new model utilizing NURBS surfaces to refine the model in (2). Dose Conversion Factors (DCFs) for whole body as well as selected organs of O. mykiss were computed using Monte Carlo modeling and combined with empirical models for predicting activity concentration to estimate dose rates and ultimately determine cumulative radiation dose (μGy) to selected organs after several half-lives of (99)Mo. The computational models provided similar results, especially for organs that were both the source and target of radiation (less than 30% difference between all models). Values in the empirical model as well as the 14 day cumulative organ doses determined from (99)Mo uptake are compared to similar models developed previously for (131)I. Finally, consideration is given to treating the GI tract as a solid organ compared to partitioning it into gut contents and GI wall, which resulted in an order of magnitude difference in estimated dose for most organs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Failed heart rate control with oral metoprolol prior to coronary CT angiography: effect of additional intravenous metoprolol on heart rate, image quality and radiation dose.

PubMed

Jiménez-Juan, Laura; Nguyen, Elsie T; Wintersperger, Bernd J; Moshonov, Hadas; Crean, Andrew M; Deva, Djeven P; Paul, Narinder S; Torres, Felipe S

2013-01-01

The purpose of this study was to evaluate the effect of intravenous (i.v.) metoprolol after a suboptimal heart rate (HR) response to oral metoprolol (75-150 mg) on HR control, image quality (IQ) and radiation dose during coronary CTA using 320-MDCT. Fifty-three consecutive patients who failed to achieve a target HR of < 60 bpm after an oral dose of metoprolol and required supplementary i.v. metoprolol (5-20 mg) prior to coronary CTA were evaluated. Patients with HR < 60 bpm during image acquisition were defined as responders (R) and those with HR ≥ 60 bpm as non-responders (NR). Two observers assessed IQ using a 3-point scale (1-2, diagnostic and 3, non-diagnostic). Effective dose (ED) was estimated using dose-length product and a 0.014 mSV/mGy.cm conversion factor. Baseline characteristics and HR on arrival were similar in the two groups. 58% of patients didn't achieve the target HR after receiving i.v. metoprolol (NR). R had a significantly higher HR reduction after oral (mean HR 63.9 ± 4.5 bpm vs. 69.6 ± 5.6 bpm) (p < 0.005) and i.v. (mean HR 55.4 ± 3.9 bpm vs. 67.4 ± 5.3 bpm) (p < 0.005) doses of metoprolol. Studies from NR showed a significantly higher ED in comparison to R (8.0 ± 2.9 vs. 6.1 ± 2.2 mSv) (p = 0.016) and a significantly higher proportion of non-diagnostic coronary segments (9.2 vs. 2.5%) (p < 0.001). 58% of patients who do not achieve a HR of <60 bpm prior to coronary CTA with oral fail to respond to additional i.v. metoprolol and have studies with higher radiation dose and worse image quality.

High Resolution Mesoscale Weather Data Improvement to Spatial Effects for Dose-Rate Contour Plot Predictions

DTIC Science & Technology

2007-03-01

time. This is a very powerful tool in determining fine spatial resolution , as boundary conditions are not only updated at every timestep, but the ...HIGH RESOLUTION MESOSCALE WEATHER DATA IMPROVEMENT TO SPATIAL EFFECTS FOR DOSE-RATE CONTOUR PLOT PREDICTIONS THESIS Christopher P...11 1 HIGH RESOLUTION MESOSCALE WEATHER DATA IMPROVEMENT TO SPATIAL EFFECTS FOR DOSE-RATE CONTOUR PLOT

Clinical Outcomes and Prognostic Factors of High-Dose Proton Beam Therapy for Peripheral Stage I Non-Small-Cell Lung Cancer.

PubMed

Hatayama, Yoshiomi; Nakamura, Tatsuya; Suzuki, Motohisa; Azami, Yusuke; Ono, Takashi; Yabuuchi, Tomonori; Hayashi, Yuichiro; Kimura, Kanako; Hirose, Katsumi; Wada, Hitoshi; Hareyama, Masato; Kikuchi, Yasuhiro; Takai, Yoshihiro

2016-09-01

The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Ethylenediamine grafted to graphene oxide@Fe3O4 for chromium(VI) decontamination: Performance, modelling, and fractional factorial design

PubMed Central

Xu, Jiawen; Wu, Cuiyu; Deng, Jianbin; Liao, Wenwei; Ling, Yuxiang; Yang, Yuanxiu; Zhao, Yina; Zhao, Yunlin; Hu, Xi; Wang, Hui; Liu, Yunguo

2017-01-01

A method for grafting ethylenediamine to a magnetic graphene oxide composite (EDA-GO@Fe3O4) was developed for Cr(VI) decontamination. The physicochemical properties of EDA-GO@Fe3O4 were characterized using HRTEM, EDS, FT-IR, TG-DSC, and XPS. The effects of pH, sorbent dose, foreign anions, time, Cr(VI) concentration, and temperature on decontamination process were studied. The solution pH can largely affect the decontamination process. The pseudo-second-order model is suitable for being applied to fit the adsorption processes of Cr(VI) with GO@Fe3O4 and EDA-GO@Fe3O4. The intra-particle diffusion is not the rate-controlling step. Isotherm experimental data can be described using the Freundlich model. The effects of multiple factors on the Cr(VI) decontamination was investigated by a 25−1 fractional factorial design (FFD). The adsorption process can significantly be affected by the main effects of A (pH), B (Cr(VI) concentration), and E (Adsorbent dose). The combined factors of AB (pH × Cr(VI) concentration), AE (pH × Adsorbent dose), and BC (Cr(VI) concentration × Temperature) had larger effects than other factors on Cr(VI) removal. These results indicated that EDA-GO@Fe3O4 is a potential and suitable candidate for treatment of heavy metal wastewater. PMID:29084287

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

PubMed Central

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

2011-01-01

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

Investigation of natural effective gamma dose rates case study: Ardebil Province in Iran

PubMed Central

2012-01-01

Gamma rays pose enough energy to induce chemical changes that may be biologically important for the normal functioning of body cells. The external exposure of human beings to natural environmental gamma radiation normally exceeds that from all man-made sources combined. In this research natural background gamma dose rates and corresponding annual effective doses were determined for selected cities of Ardebil province. Outdoor gamma dose rates were measured using an Ion Chamber Survey Meter in 105 locations in selected districts. Average absorbed doses for Ardebil, Sar-Ein, Germy, Neer, Shourabil Recreational Lake, and Kosar were determined as 265, 219, 344, 233, 352, and 358 nSv/h, respectively. Although dose rates recorded for Germi and Kosar are comparable with some areas with high natural radiation background, however, the dose rates in other districts are well below the levels reported for such locations. Average annual effective dose due to indoor and outdoor gamma radiation for Ardebil province was estimated as 1.73 (1.35–2.39) mSv, which is on average 2 times higher than the world population weighted average. PMID:23369115

Effects of breast-air and breast-lung interfaces on the dose rate at the planning target volume of a MammoSite catheter for Yb-169 and Ir-192 HDR sources

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

Cazeca, Mario J.; Medich, David C.; Munro, John J. III

2010-08-15

Purpose: To study the effects of the breast-air and breast-lung interfaces on the absorbed dose within the planning target volume (PTV) of a MammoSite balloon dose delivery system as well as the effect of contrast material on the dose rate in the PTV. Methods: The Monte Carlo MCNP5 code was used to simulate dose rate in the PTV of a 2 cm radius MammoSite balloon dose delivery system. The simulations were carried out using an average female chest phantom (AFCP) and a semi-infinite water phantom for both Yb-169 and Ir-192 high dose rate sources for brachytherapy application. Gastrografin was introducedmore » at varying concentrations to study the effect of contrast material on the dose rate in the PTV. Results: The effect of the density of the materials surrounding the MammoSite balloon containing 0% contrast material on the calculated dose rate at different radial distances in the PTV was demonstrated. Within the PTV, the ratio of the calculated dose rate for the AFCP and the semi-infinite water phantom for the point closest to the breast-air interface (90 deg.) is less than that for the point closest to the breast-lung interface (270 deg.) by 11.4% and 4% for the HDR sources of Yb-169 and Ir-192, respectively. When contrast material was introduced into the 2 cm radius MammoSite balloon at varying concentrations, (5%, 10%, 15%, and 20%), the dose rate in the AFCP at 3.0 cm radial distance at 90 deg. was decreased by as much as 14.8% and 6.2% for Yb-169 and Ir-192, respectively, when compared to that of the semi-infinite water phantom with contrast concentrations of 5%, 10%, 15%, and 20%, respectively. Conclusions: Commercially available software used to calculate dose rate in the PTV of a MammoSite balloon needs to account for patient anatomy and density of surrounding materials in the dosimetry analyses in order to avoid patient underdose.« less

Comparison of the effective dose rate to aircrew members using hybrid computational phantoms in standing and sitting postures.

PubMed

Alves, M C; Galeano, D C; Santos, W S; Lee, Choonsik; Bolch, Wesley E; Hunt, John G; da Silva, A X; Carvalho, A B

2016-12-01

Aircraft crew members are occupationally exposed to considerable levels of cosmic radiation at flight altitudes. Since aircrew (pilots and passengers) are in the sitting posture for most of the time during flight, and up to now there has been no data on the effective dose rate calculated for aircrew dosimetry in flight altitude using a sitting phantom, we therefore calculated the effective dose rate using a phantom in the sitting and standing postures in order to compare the influence of the posture on the radiation protection of aircrew members. We found that although the better description of the posture in which the aircrews are exposed, the results of the effective dose rate calculated with the phantom in the sitting posture were very similar to the results of the phantom in the standing posture. In fact we observed only a 1% difference. These findings indicate the adequacy of the use of dose conversion coefficients for the phantom in the standing posture in aircrew dosimetry. We also validated our results comparing the effective dose rate obtained using the standing phantom with values reported in the literature. It was observed that the results presented in this study are in good agreement with other authors (the differences are below 30%) who have measured and calculated effective dose rates using different phantoms.

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.

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.

Radiation-induced hemopoietic death in mice as a function of photon energy and dose rate

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

Gengozian, N.; Taylor, T.; Jameson, H.

1986-03-01

Radiation-induced hemopoietic death was measured in mice exposed to photons of four different energies: 250-kVp X rays, /sup 60/Co gamma rays (1.25 MeV), and 6- and 25-MV photons from a linear accelerator. For each radiation source, the lethal dose which killed 50% of the population in 30 days (LD50/30) associated with the hemopoietic syndrome was determined in groups of mice exposed to graded doses from 600 to 1150 cGy at dose rates of 20, 40, and 80 cGy/min. The calculated LD50/30 values for 25 and 6 MV were significantly different from each other at all exposure rates while no differencemore » was observed between 6 MV and /sup 60/Co. Using /sup 60/Co gamma rays as the standard, the relative biologic effectiveness was as follows: 250 kVp greater than 25 MV greater than 6 MV = /sup 60/Co. The data suggest that there may be a greater damage to tissue within the marrow cavities following exposure to very high megavoltage radiation, a factor which must be considered with the increasing utilization of linear accelerators in the clinic and laboratory.« less

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

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

Spriggs, G D

In a previous paper, the composite exposure rate conversion factor (ECF) for nuclear fallout was calculated using a simple theoretical photon-transport model. The theoretical model was used to fill in the gaps in the FGR-12 table generated by ORNL. The FGR-12 table contains the individual conversion factors for approximate 1000 radionuclides. However, in order to calculate the exposure rate during the first 30 minutes following a nuclear detonation, the conversion factors for approximately 2000 radionuclides are needed. From a human-effects standpoint, it is also necessary to have the dose rate conversion factors (DCFs) for all 2000 radionuclides. The DCFs aremore » used to predict the whole-body dose rates that would occur if a human were standing in a radiation field of known exposure rate. As calculated by ORNL, the whole-body dose rate (rem/hr) is approximately 70% of the exposure rate (R/hr) at one meter above the surface. Hence, the individual DCFs could be estimated by multiplying the individual ECFs by 0.7. Although this is a handy rule-of-thumb, a more consistent (and perhaps, more accurate) method of estimating the individual DCFs for the missing radionuclides in the FGR-12 table is to use the linear relationship between DCF and total gamma energy released per decay. This relationship is shown in Figure 1. The DCFs for individual organs in the body can also be estimated from the estimated whole-body DCF. Using the DCFs given FGR-12, the ratio of the organ-specific DCFs to the whole-body DCF were plotted as a function of the whole-body DCF. From these plots, the asymptotic ratios were obtained (see Table 1). Using these asymptotic ratios, the organ-specific DCFs can be estimated using the estimated whole-body DCF for each of the missing radionuclides in the FGR-12 table. Although this procedure for estimating the organ-specific DCFs may over-estimate the value for some low gamma-energy emitters, having a finite value for the organ-specific DCFs in the table is probably better than having no value at all. A summary of the complete ECF and DCF values are given in Table 2.« less

Clinical radiobiology of stage T2-T3 bladder cancer.

PubMed

Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

2004-09-01

To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which included the treatment-related parameters and other clinical factors, revealed that the hemoglobin level and bladder capacity before RT and T-stage were statistically significant factors determining local control and overall survival. The total radiation dose was of borderline statistical significance for overall survival (p = 0.087), and OTT did not reach statistical significance. The results of our study showed that the treatment outcome after RT for bladder cancer depends mainly on clinical factors: hemoglobin level and bladder capacity before RT, and clinical T stage. An increase in the total radiation dose seemed to be associated with a better treatment outcome. The effect of the OTT was difficult to define, because it was influenced by other prognostic factors.

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.

Effects of Charged Particles on Human Tumor Cells

PubMed Central

Held, Kathryn D.; Kawamura, Hidemasa; Kaminuma, Takuya; Paz, Athena Evalour S.; Yoshida, Yukari; Liu, Qi; Willers, Henning; Takahashi, Akihisa

2016-01-01

The use of charged particle therapy in cancer treatment is growing rapidly, in large part because the exquisite dose localization of charged particles allows for higher radiation doses to be given to tumor tissue while normal tissues are exposed to lower doses and decreased volumes of normal tissues are irradiated. In addition, charged particles heavier than protons have substantial potential clinical advantages because of their additional biological effects, including greater cell killing effectiveness, decreased radiation resistance of hypoxic cells in tumors, and reduced cell cycle dependence of radiation response. These biological advantages depend on many factors, such as endpoint, cell or tissue type, dose, dose rate or fractionation, charged particle type and energy, and oxygen concentration. This review summarizes the unique biological advantages of charged particle therapy and highlights recent research and areas of particular research needs, such as quantification of relative biological effectiveness (RBE) for various tumor types and radiation qualities, role of genetic background of tumor cells in determining response to charged particles, sensitivity of cancer stem-like cells to charged particles, role of charged particles in tumors with hypoxic fractions, and importance of fractionation, including use of hypofractionation, with charged particles. PMID:26904502

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source.

PubMed

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

2010-09-21

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V(100) reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V(100) to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

NASA Astrophysics Data System (ADS)

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

2010-09-01

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent™ x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V100 to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

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.

Clinical effectiveness of hymenoptera venom immunotherapy: a prospective observational multicenter study of the European academy of allergology and clinical immunology interest group on insect venom hypersensitivity.

PubMed

Ruëff, Franziska; Przybilla, Bernhard; Biló, Maria Beatrice; Müller, Ulrich; Scheipl, Fabian; Seitz, Michael J; Aberer, Werner; Bodzenta-Lukaszyk, Anna; Bonifazi, Floriano; Campi, Paolo; Darsow, Ulf; Haeberli, Gabrielle; Hawranek, Thomas; Küchenhoff, Helmut; Lang, Roland; Quercia, Oliviero; Reider, Norbert; Schmid-Grendelmeier, Peter; Severino, Maurizio; Sturm, Gunter Johannes; Treudler, Regina; Wüthrich, Brunello

2013-01-01

Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.

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

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

Dunning, D.E.

1982-01-01

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

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

PubMed

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

2016-12-01

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

Comparison of fluence-to-dose conversion coefficients for deuterons, tritons and helions.

PubMed

Copeland, Kyle; Friedberg, Wallace; Sato, Tatsuhiko; Niita, Koji

2012-02-01

Secondary radiation in aircraft and spacecraft includes deuterons, tritons and helions. Two sets of fluence-to-effective dose conversion coefficients for isotropic exposure to these particles were compared: one used the particle and heavy ion transport code system (PHITS) radiation transport code coupled with the International Commission on Radiological Protection (ICRP) reference phantoms (PHITS-ICRP) and the other the Monte Carlo N-Particle eXtended (MCNPX) radiation transport code coupled with modified BodyBuilder™ phantoms (MCNPX-BB). Also, two sets of fluence-to-effective dose equivalent conversion coefficients calculated using the PHITS-ICRP combination were compared: one used quality factors based on linear energy transfer; the other used quality factors based on lineal energy (y). Finally, PHITS-ICRP effective dose coefficients were compared with PHITS-ICRP effective dose equivalent coefficients. The PHITS-ICRP and MCNPX-BB effective dose coefficients were similar, except at high energies, where MCNPX-BB coefficients were higher. For helions, at most energies effective dose coefficients were much greater than effective dose equivalent coefficients. For deuterons and tritons, coefficients were similar when their radiation weighting factor was set to 2.

Treatment modifications in tumour necrosis factor-α (TNF)-based isolated limb perfusion in patients with advanced extremity soft tissue sarcomas.

PubMed

Deroose, Jan P; Grünhagen, Dirk J; de Wilt, Johannes H W; Eggermont, Alexander M M; Verhoef, Cornelis

2015-02-01

Tumour necrosis factor-α (TNF) and melphalan based isolated limb perfusion (TM-ILP) is an attractive treatment option for advanced extremity soft tissue sarcomas (STS). This study reports on a 20-year single centre experience and discusses the evolution and changes in methodology since the introduction of TNF in ILP. We performed 306 TM-ILPs in 275 patients with extremity STS. All patients were candidates for amputation or mutilating surgery in order to achieve local control. Clinical response evaluation consisted of clinical examination and magnetic resonance imaging. To evaluate the importance of TNF-dose, treatment results of two periods (1991-2003 high dose (3-4 mg) TNF; 2003-2012 reduced dose (1-2mg) TNF) were compared. During the study period, more femoral perfusions were done instead of iliac perfusions. Reduction of TNF dose and reduction of total ILP time did not lead to different clinical response rates (70% and 69% for periods 1 and 2 respectively) or different local recurrence rates, but was associated with less local toxicity (23% and 14% for periods 1 and 2 respectively). Hospital stay was significantly reduced during the study period. There was an improved pathological response in the high dose TNF group without consequences for clinical outcome. TM-ILP remains a very effective treatment modality for limb threatening extremity STS. Moreover, reduction of dose and the growing experience in ILP led to less local toxicity and shorter hospital stay. Copyright © 2014 Elsevier Ltd. All rights reserved.

Physiologic variability at the verge of systemic inflammation: multiscale entropy of heart rate variability is affected by very low doses of endotoxin.

PubMed

Herlitz, Georg N; Arlow, Renee L; Cheung, Nora H; Coyle, Susette M; Griffel, Benjamin; Macor, Marie A; Lowry, Stephen F; Calvano, Steve E; Gale, Stephen C

2015-02-01

Human injury or infection induces systemic inflammation with characteristic neuroendocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and investigate the size of data sets required for meaningful use of multiscale entropy (MSE) analysis of HRV. Healthy human volunteers (n = 25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 min for 6 h and then at 9, 12, and 24 h after LPS. Blood samples were drawn at specific time points for cytokine measurements. Heart rate variability analysis was performed using electrocardiogram epochs of 5 min. Multiscale entropy for HRV was calculated for all dose groups to scale factor 40. The lowest significant threshold dose was noted in core temperature at 0.25 ng/kg. Endogenous tumor necrosis factor α and interleukin 6 were significantly responsive at the next dosage level (0.5 ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures analysis of variance across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 h after exposure to LPS. Although not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes. By using repeated-measures analysis of variance across scale factors, MSE can detect autonomic change after LPS challenge in a group of 25 subjects using electrocardiogram epochs of only 5 min and entropy analysis to scale factor of only 40, potentially facilitating MSE's wider use as a research tool or bedside monitor. Traditional markers of inflammation generally exhibit threshold dose behavior. In contrast, MSE's apparent continuous dose-response pattern, although not statistically verifiable in this study, suggests a potential subclinical harbinger of infectious or other insult. The possible derangement of autonomic complexity prior to or independent of the cytokine surge cannot be ruled out. Future investigation should focus on confirmation of overt inflammation following observed decreases in MSE in a clinical setting.

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

PubMed

Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-06-01

To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

DOSE COEFFICIENTS FOR LIVER CHEMOEMBOLISATION PROCEDURES USING MONTE CARLO CODE.

PubMed

Karavasilis, E; Dimitriadis, A; Gonis, H; Pappas, P; Georgiou, E; Yakoumakis, E

2016-12-01

The aim of the present study is the estimation of radiation burden during liver chemoembolisation procedures. Organ dose and effective dose conversion factors, normalised to dose-area product (DAP), were estimated for chemoembolisation procedures using a Monte Carlo transport code in conjunction with an adult mathematical phantom. Exposure data from 32 patients were used to determine the exposure projections for the simulations. Equivalent organ (H T ) and effective (E) doses were estimated using individual DAP values. The organs receiving the highest amount of doses during these exams were lumbar spine, liver and kidneys. The mean effective dose conversion factor was 1.4 Sv Gy -1 m -2 Dose conversion factors can be useful for patient-specific radiation burden during chemoembolisation procedures. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation.

PubMed

Barrett, A; Depledge, M H; Powles, R L

1983-07-01

Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to less than 0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

Luminescence isochron dating: a new approach using different grain sizes.

PubMed

Zhao, H; Li, S H

2002-01-01

A new approach to isochron dating is described using different sizes of quartz and K-feldspar grains. The technique can be applied to sites with time-dependent external dose rates. It is assumed that any underestimation of the equivalent dose (De) using K-feldspar is by a factor F, which is independent of grain size (90-350 microm) for a given sample. Calibration of the beta source for different grain sizes is discussed, and then the sample ages are calculated using the differences between quartz and K-feldspar De from grains of similar size. Two aeolian sediment samples from north-eastern China are used to illustrate the application of the new method. It is confirmed that the observed values of De derived using K-feldspar underestimate the expected doses (based on the quartz De) but, nevertheless, these K-feldspar De values correlate linearly with the calculated internal dose rate contribution, supporting the assumption that the underestimation factor F is independent of grain size. The isochron ages are also compared with the results obtained using quartz De and the measured external dose rates.

Effects of epidermal growth factor on bone formation and resorption in vivo

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

Marie, P.J.; Hott, M.; Perheentupa, J.

1990-02-01

The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double (3H)proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in themore » periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at physiological doses induces distinct effects on endosteal and periosteal bone formation and that the effects are dependent on EGF dosage and duration of treatment. This study indicates that EGF at physiological dosage stimulates periosteal bone formation and increases endosteal bone resorption in the growing mouse.« less

Modelling of aircrew radiation exposure from galactic cosmic rays and solar particle events.

PubMed

Takada, M; Lewis, B J; Boudreau, M; Al Anid, H; Bennett, L G I

2007-01-01

Correlations have been developed for implementation into the semi-empirical Predictive Code for Aircrew Radiation Exposure (PCAIRE) to account for effects of extremum conditions of solar modulation and low altitude based on transport code calculations. An improved solar modulation model, as proposed by NASA, has been further adopted to interpolate between the bounding correlations for solar modulation. The conversion ratio of effective dose to ambient dose equivalent, as applied to the PCAIRE calculation (based on measurements) for the legal regulation of aircrew exposure, was re-evaluated in this work to take into consideration new ICRP-92 radiation-weighting factors and different possible irradiation geometries of the source cosmic-radiation field. A computational analysis with Monte Carlo N-Particle eXtended Code was further used to estimate additional aircrew exposure that may result from sporadic solar energetic particle events considering real-time monitoring by the Geosynchronous Operational Environmental Satellite. These predictions were compared with the ambient dose equivalent rates measured on-board an aircraft and to count rate data observed at various ground-level neutron monitors.

SU-F-T-322: A Comparison of Two Si Detectors for in Vivo Dosimetry

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

Talarico, O; Krylova, T; Lebedenko, I

Purpose: To compare two types of semiconductor detectors for in vivo dosimetry by their dependence from various parameters in different conditions. Methods: QED yellow (Sun Nuclear) and EDP (Scanditronix) Si detectors were radiated by a Varian Clinac 2300 ix with 6 and 18 MV energies. 10 cm thickness water equivalent phantom consisted of 30×30 cm{sup 2} squared plates was used for experiments. Dose dependencies for different beam angles (0 – 180°), field size (3–40 cm), dose (50 – 300 MU), and dose rates (50 – 300 MU/min) were obtained and calibrated with Standard Farmer chamber (PTW). Results: Reproducibility, linearity, dosemore » rate, angular dependence, and field size dependence were obtained for QED and EDP. They show no dose-rate dependence in available clinical dose rate range (100–600 MU/min). Both diodes have linear dependence with increasing the dose. Therefore even in case of high radiation therapy (including total body irradiation) it is not necessary to apply an additional correction during in vivo dosimetry. The diodes have different behavior for angular and field size dependencies. QED diode showed that dose value is stable for beam angles from 0 to 60°, for 60–180° correction factor has to be applied for each beam angle during in vivo measurements. For EDP diode dose value is sensitive to beam angle in whole range of angles. Conclusion: The study shows that QED diode is more suitable for in vivo dosimetry due to dose value independence from incident beam angle in the range 0–60°. There is no need in correction factors for increasing of dose and dose rate for both diodes. The next step will be to carry out measurements in non-standard conditions of total body irradiation. After this modeling of these experiments with Monte Carlo simulation for comparison calculated and obtained data is planned.« less

Synergistic Effects of Incubation in Rotating Bioreactors and Cumulative Low Dose 60Co γ-ray Irradiation on Human Immortal Lymphoblastoid Cells

NASA Astrophysics Data System (ADS)

Wei, Lijun; Han, Fang; Yue, Lei; Zheng, Hongxia; Yu, Dan; Ma, Xiaohuan; Cheng, Huifang; Li, Yu

2012-11-01

The complex space environments can influence cell structure and function. The research results on space biology have shown that the major mutagenic factors in space are microgravity and ionizing radiation. In addition, possible synergistic effects of radiation and microgravity on human cells are not well understood. In this study, human immortal lymphoblastoid cells were established from human peripheral blood lymphocytes and the cells were treated with low dose (0.1, 0.15 and 0.2 Gy) cumulative 60Co γ-irradiation and simulated weightlessness [obtained by culturing cells in the Rotating Cell Culture System (RCCS)]. The commonly used indexes of cell damage such as micronucleus rate, cell cycle and mitotic index were studied. Previous work has proved that Gadd45 (growth arrest and DNA-damage-inducible protein 45) gene increases with a dose-effect relationship, and will possibly be a new biological dosimeter to show irradiation damage. So Gadd45 expression is also detected in this study. The micronucleus rate and the expression of Gadd45α gene increased with irradiation dose and were much higher after incubation in the rotating bioreactor than that in the static irradiation group, while the cell proliferation after incubation in the rotating bioreactor decreased at the same time. These results indicate synergetic effects of simulated weightlessness and low dose irradiation in human cells. The cell damage inflicted by γ-irradiation increased under simulated weightlessness. Our results suggest that during medium- and long-term flight, the human body can be damaged by cumulative low dose radiation, and the damage will even be increased by microgravity in space.

NASA space cancer risk model-2014: Uncertainties due to qualitative differences in biological effects of HZE particles

NASA Astrophysics Data System (ADS)

Cucinotta, Francis

Uncertainties in estimating health risks from exposures to galactic cosmic rays (GCR) — comprised of protons and high-energy and charge (HZE) nuclei are an important limitation to long duration space travel. HZE nuclei produce both qualitative and quantitative differences in biological effects compared to terrestrial radiation leading to large uncertainties in predicting risks to humans. Our NASA Space Cancer Risk Model-2012 (NSCR-2012) for estimating lifetime cancer risks from space radiation included several new features compared to earlier models from the National Council on Radiation Protection and Measurements (NCRP) used at NASA. New features of NSCR-2012 included the introduction of NASA defined radiation quality factors based on track structure concepts, a Bayesian analysis of the dose and dose-rate reduction effectiveness factor (DDREF) and its uncertainty, and the use of a never-smoker population to represent astronauts. However, NSCR-2012 did not include estimates of the role of qualitative differences between HZE particles and low LET radiation. In this report we discuss evidence for non-targeted effects increasing cancer risks at space relevant HZE particle absorbed doses in tissue (<0.2 Gy), and for increased tumor lethality due to the propensity for higher rates of metastatic tumors from high LET radiation suggested by animal experiments. The NSCR-2014 model considers how these qualitative differences modify the overall probability distribution functions (PDF) for cancer mortality risk estimates from space radiation. Predictions of NSCR-2014 for International Space Station missions and Mars exploration will be described, and compared to those of our earlier NSCR-2012 model.

High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

PubMed Central

Carter, Lawrence P.; Johnson, Matthew W.; Mintzer, Miriam Z.; Klinedinst, Margaret A.; Griffiths, Roland R.

2013-01-01

Rationale Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours. Results Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin. PMID:22526529

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kirby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce; Little, Bradley;

Problems and solutions in the estimation of genetic risks from radiation and chemicals

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

Russell, W. L.

1980-01-01

Extensive investigations with mice on the effects of various physical and biological factors, such as dose rate, sex and cell stage, on radiation-induced mutation have provided an evaluation of the genetics hazards of radiation in man. The mutational results obtained in both sexes with progressive lowering of the radiation dose rate have permitted estimation of the mutation frequency expected under the low-level radiation conditions of most human exposure. Supplementing the studies on mutation frequency are investigations on the phenotypic effects of mutations in mice, particularly anatomical disorders of the skeleton, which allow an estimation of the degree of human handicapmore » associated with the occurrence of parallel defects in man. Estimation of the genetic risk from chemical mutagens is much more difficult, and the research is much less advanced. Results on transmitted mutations in mice indicate a poor correlation with mutation induction in non-mammalian organisms.« less

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

PubMed

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

2014-10-01

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

Effect of gamma irradiation on antinutritional factors in broad bean

NASA Astrophysics Data System (ADS)

Al-Kaisey, Mahdi T.; Alwan, Abdul-Kader H.; Mohammad, Manal H.; Saeed, Amjed H.

2003-06-01

The effect of gamma irradiation on the level of antinutritional factors (trypsin inhibitor (TI), phytic acid and oligosaccharides) of broad bean was investigated. The seeds were subjected to gamma irradiation at 0, 2.5, 5, 7.5 and 10 kGy, respectively using cobalt-60 gamma radiation with a dose rate 2.37 kGy/h. TI activity was reduced by 4.5%, 6.7%, 8.5% and 9.2% at 2.5, 5, 7.5 and 10 kGy, respectively. Meanwhile, irradiation at 10.2, 12.3, 15.4 and 18.2 kGy reduced the phytic acid content. The flatulence causing oligosaccharides were decreased as the radiation dose increased. The chemical composition (protein, oil, ash and total carbohydrates) of the tested seeds was determined. Gamma radiation seems to be a good procedure to improve the quality of broad bean from the nutritional point of view.

Restless legs syndrome augmentation among Japanese patients receiving pramipexole therapy: Rate and risk factors in a retrospective study

PubMed Central

Takahashi, Masayoshi; Nishida, Shingo; Nakamura, Masaki; Kobayashi, Mina; Matsui, Kentaro; Ito, Eiki; Usui, Akira; Inoue, Yuichi

2017-01-01

To investigate the rate of and risk factors for restless legs syndrome (RLS) augmentation in Japanese patients receiving pramipexole (PPX) treatment. Records of 231 consecutive patients with idiopathic RLS who received PPX therapy for more than one month in a single sleep disorder center were analyzed retrospectively. Augmentation was diagnosed based on the Max Planck Institute criteria; associated factors were identified by logistic regression analysis. Mean age at PPX initiation was 60.6 ± 14.9 years and mean treatment duration was 48.5 ± 26.4 months. Augmentation was diagnosed in 21 patients (9.1%). Daily PPX dose and treatment duration were significantly associated with augmentation. By analyzing the receiver operating characteristic curve, a PPX dose of 0.375 mg/day was found to be the optimal cut-off value for predicting augmentation. After stratifying patients according to PPX treatment duration, at median treatment duration of 46 months, optimal cut-off values for daily doses were 0.375 and 0.500 mg/day for <46 months and ≥46 months of treatment, respectively. The RLS augmentation with PPX treatment in Japanese patients was occurred at rate of 9.1%, being quite compatible with previously reported rates in Caucasian patients. The symptom could appear within a relatively short period after starting the treatment in possibly vulnerable cases even with a smaller drug dose. Our results support the importance of keeping doses of PPX low throughout the RLS treatment course to prevent augmentation. PMID:28264052

Measurements of the Martian Gamma/Neutron Spectra with MSL/RAD

NASA Astrophysics Data System (ADS)

Kohler, J.; Zeitlin, C. J.; Ehresmann, B.; Wimmer-Schweingruber, R. F.; Hassler, D.; Reitz, G.; Brinza, D.; Weigle, E.; Boettcher, S.; Burmeister, S.; Guo, J.; Martin-Garcia, C.; Boehm, E.; Posner, A.; Rafkin, S. C.; Kortmann, O.

2013-12-01

The Radiation Assessment Detector (RAD) onboard Mars Science Laboratory's rover curiosity measures the energetic charged and neutral particle spectra and the radiation dose rate on the Martian surface. An important factor for determining the biological impact of the Martian surface radiation is the specific contribution of neutrons, which possess a high biological effectiveness. In contrast to charged particles, neutrons and gamma rays are generally only measured indirectly. Their measurement is the result of a complex convolution of the incident particle spectrum with the measurement process. We apply an inversion method to calculate the gamma/neutron spectra from the RAD neutral particle measurements. Here we show first measurements of the Martian gamma/neutron spectra and compare them to theoretical predictions. We find that the shape of the gamma spectrum is very similar to the predicted one, but with a ~50% higher intensity. The measured neutron spectrum agrees well with prediction up to ~100 MeV, but shows a considerably increased intensity for higher energies. The measured neutron spectrum translates into a radiation dose rate of 25 μGy/day and a dose equivalent rate of 106 μSv/day. This corresponds to 10% of the total surface dose rate, and 15% of the biological relevant surface dose equivalent rate on Mars. Measuring the Martian neutron spectra is an essential step for determining the mutagenic influences to past or present life at or beneath the Martian surface as well as the radiation hazard for future human exploration, including the shielding design of a potential habitat. The contribution of neutrons to the dose equivalent increases considerably with shielding thickness, so our measurements provide an important figure to mitigate cancer risk.

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.

Image processing techniques revealing the relationship between the field-measured ambient gamma dose equivalent rate and geological conditions at a granitic area, Velence Mountains, Hungary

NASA Astrophysics Data System (ADS)

Beltran Torres, Silvana; Petrik, Attila; Zsuzsanna Szabó, Katalin; Jordan, Gyozo; Szabó, Csaba

2017-04-01

In order to estimate the annual dose that the public receive from natural radioactivity, the identification of the potential risk areas is required which, in turn, necessitates understanding the relationship between the spatial distribution of natural radioactivity and the geogenic risk factors (e.g., rock types, dykes, faults, soil conditions, etc.). A detailed spatial analysis of ambient gamma dose equivalent rate was performed in the western side of Velence Mountains, the largest outcropped granitic area in Hungary. In order to assess the role of local geology in the spatial distribution of ambient gamma dose rates, field measurements were carried out at ground level at 300 sites along a 250 m x 250 m regular grid in a total surface of 14.7 km2. Digital image processing methods were applied to identify anomalies, heterogeneities and spatial patterns in the measured gamma dose rates, including local maxima and minima determination, digital cross sections, gradient magnitude and gradient direction, second derivative profile curvature, local variability, lineament density, 2D autocorrelation and directional variogram analyses. Statistical inference showed that different gamma dose rate levels are associated with the rock types (i.e., Carboniferous granite, Pleistocene colluvial, proluvial, deluvial sediments and talus, and Pannonian sand and pebble), with the highest level on the Carboniferous granite including outlying values. Moreover, digital image processing revealed that linear gamma dose rate spatial features are parallel to the SW-NE dyke system and possibly to the NW-SE main fractures. The results of this study underline the importance of understanding the role of geogenic risk factors influencing the ambient gamma dose rate received by public. The study also demonstrates the power of the image processing techniques for the identification of spatial pattern in field-measured geogenic radiation.

The space radiation environment

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

Robbins, D E

There are three primary sources of space radiation: galactic cosmic rays (GCR), trapped belt radiation, and solar particle events (SPE). All are composed of ions, the nuclei of atoms. Their energies range from a few MeV u{sup -1} to over a GeV u{sup -1}. These ions can fragment when they interact with spacecraft materials and produce energetic neutrons and ions of lower atomic mass. Absorbed dose rates inside a typical spacecraft (like the Space Shuttle) in a low inclination (28.5 degrees) orbit range between 0.05 and 2 mGy d{sup -1} depending on the altitude and flight inclination (angle of orbitmore » with the equator). The quality factor of radiation in orbit depends on the relative contributions of trapped belt radiation and GCR, and the dose rate varies both with orbital altitude and inclination. The corresponding equivalent dose rate ranges between 0.1 and 4 mSv d{sup -1}. In high inclination orbits, like that of the Mir Space Station and as is planned for the International Space Station, blood-forming organ (BFO) equivalent dose rates as high as 1.5 mSv d{sup -1}. Thus, on a 1 y mission, a crew member could obtain a total dose of 0.55 Sv. Maximum equivalent dose rates measured in high altitude passes through the South Atlantic Anomaly (SAA) were 10 mSv h{sup -1}. For an interplanetary space mission (e.g., to Mars) annual doses from GCR alone range between 150 mSv y{sup -1} at solar maximum and 580 mSv y{sup -1} at solar minimum. Large SPE, like the October 1989 series, are more apt to occur in the years around solar maximum. In free space, such an event could contribute another 300 mSv, assuming that a warning system and safe haven can be effectively used with operational procedures to minimize crew exposures. Thus, the total dose for a 3 y mission to Mars could exceed 2 Sv.« less

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

PubMed Central

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

2008-01-01

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

Effective dose rate coefficients for exposure to contaminated soil

DOE PAGES

Veinot, Kenneth G.; Eckerman, Keith F.; Bellamy, Michael B.; ...

2017-05-10

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose ratemore » calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. As a result, the coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.« less

Effective dose rate coefficients for exposure to contaminated soil

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

Veinot, Kenneth G.; Eckerman, Keith F.; Bellamy, Michael B.

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose ratemore » calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. As a result, the coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.« less

Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma.

PubMed

Kim, Joong Sun; Son, Yeonghoon; Bae, Min Ji; Lee, Seung Sook; Park, Sun Hoo; Lee, Hae June; Lee, Soong In; Lee, Chang Geun; Kim, Sung Dae; Jo, Wol Soon; Kim, Sung Ho; Shin, In Sik

2015-01-01

Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to low-dose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation.

Use of radiation protraction to escalate biologically effective dose to the treatment target

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

Kuperman, V. Y.; Spradlin, G. S.; Department of Mathematics, Embry-Riddle University, Daytona Beach, Florida 32114

2011-12-15

Purpose: The aim of this study is to evaluate how simultaneously increasing fraction time and dose per fraction affect biologically effective dose for the target (BED{sub tar}) while biologically effective dose for the normal tissue (BED{sub nt}) is fixed. Methods: In this investigation, BED{sub tar} and BED{sub nt} were studied by assuming mono-exponential repair of sublethal damage with tissue dependent repair half-time. Results: Our results demonstrate that under certain conditions simultaneously increasing fraction time and dose per fraction result in increased BED{sub tar} while BED{sub nt} is fixed. The dependence of biologically effective dose on fraction time is influenced bymore » the dose rate. In this investigation we analytically determined time-varying dose rate R-tilde which minimizes BED. Changes in BED with fraction time were compared for constant dose rate and for R-tilde. Conclusions: A number of recent experimental and theoretical studies have demonstrated that slow delivery of radiation (known as radiation protraction) leads to reduced therapeutic effect because of increased repair of sublethal damage. In contrast, our analysis shows that under certain conditions simultaneously increasing fraction time and dose per fraction are radiobiologically advantageous.« less

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.

The effects of perphenazine on self-administration behavior.

PubMed

Johanson, C E; Kandel, D A; Bonese, K

1976-04-01

In Experiment 1.6 rhesus monkeys prepared with intravenous catheters responded on a fixed-ratio 10 schedule for either an injection of 0.2 mg/kg of cocaine or 0.5 mg/kg of pentobarbital during a daily 3 hr session. The substitution of saline or various doses of perphenazine resulted in very low rates of responding. These results indicate that perphenazine is not a positive reinforcer. Pretreating animals maintained on 0.1 mg/kg or 0.2 mg/kg of cocaine with perphenazine resulted in increases in rate of self-administration at some doses and a decrease in rate at higher doses. The dose of perphenazine which resulted in the maximal increase in cocaine self-administration was directly related to the dose of cocaine maintaining responding. Pretreating animals maintained on 0.5 mg/kg of pentobarbital with perphenazine had no effect at doses which increased cocaine self-administration but decreased rate of pentobarbital self-administration at higher doses. These results indicate that perphenazine is capable of antagonizing some of the effects of cocaine.

Final report for project "Effects of Low-Dose Irradiation on NFkB Signaling Networks and Mitochondria"

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

Woloschak, Gayle E; Grdina, David; Li, Jian-Jian

Low dose ionizing radiation effects are difficult to study in human population because of the numerous confounding factors such as genetic and lifestyle differences. Research in mammalian model systems and in vitro is generally used in order to overcome this difficulty. In this program project three projects have joined together to investigate effects of low doses of ionizing radiation. These are doses at and below 10 cGy of low linear energy transfer ionizing radiation such as X-ray and gamma rays. This project was focused on cellular signaling associated with nuclear factor kappa B (NFkB) and mitochondria - subcellular organelles criticalmore » for cell aging and aging-like changes induced by ionizing radiation. In addition to cells in culture this project utilized animal tissues accumulated in a radiation biology tissue archive housed at Northwestern University (http://janus.northwestern.edu/janus2/index.php). Major trust of Project 1 was to gather all of the DoE sponsored irradiated animal (mouse, rat and dog) data and tissues under one roof and investigate mitochondrial DNA changes and micro RNA changes in these samples. Through comparison of different samples we were trying to delineate mitochondrial DNA quantity alterations and micro RNA expression differences associated with different doses and dose rates of radiation. Historic animal irradiation experiments sponsored by DoE were done in several national laboratories and universities between 1950’s and 1990’s; while these experiments were closed data and tissues were released to Project 1. Project 2 used cells in culture to investigate effects that low doses or radiation have on NFκB and its target genes manganese superoxide dismutase (MnSOD) and genes involved in cell cycle: Cyclins (B1 and D1) and cyclin dependent kinases (CDKs). Project 3 used cells in culture such as “normal” human cells (breast epithelial cell line MCF10A cells and skin keratinocyte cells HK18) and mouse embryo fibroblast (mef) cells to focus on role of NFkB protein and several other proteins such as survivin (BIRC5) in radiation dependent regulation of tumor necrosis factor alpha (TNFα) and its downstream signaling.« less

Capstone Depleted Uranium Aerosol Biokinetics, Concentrations, and Doses

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

Guilmette, Raymond A.; Miller, Guthrie; Parkhurst, MaryAnn

2009-02-26

One of the principal goals of the Capstone Depleted Uranium (DU) Aerosol Study was to quantify and characterize DU aerosols generated inside armored vehicles by perforation with a DU penetrator. This study consequently produced a database in which the DU aerosol source terms were specified both physically and chemically for a variety of penetrator-impact geometries and conditions. These source terms were used to calculate radiation doses and uranium concentrations for various scenarios as part of the Capstone DU Human Health Risk Assessment (HHRA). This paper describes the scenario-related biokinetics of uranium, and summarizes intakes, chemical concentrations to the organs, andmore » E(50) and HT(50) for organs and tissues based on exposure scenarios for personnel in vehicles at the time of perforation as well as for first responders. For a given exposure scenario (duration time and breathing rates), the range of DU intakes among the target vehicles and shots was not large, about a factor of 10, with the lowest being from a ventilated operational Abrams tank and the highest being for an unventilated Abrams with DU penetrator perforating DU armor. The ranges of committed effective doses were more scenario-dependent than were intakes. For example, the largest range, a factor of 20, was shown for scenario A, a 1-min exposure, whereas, the range was only a factor of two for the first-responder scenario (E). In general, the committed effective doses were found to be in the tens of mSv. The risks ascribed to these doses are discussed separately.« less

Modeling the acute health effects of astronauts from exposure to large solar particle events.

PubMed

Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

2009-04-01

Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed.

The estimation of absorbed dose rates for non-human biota : an extended inter-comparison.

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

Batlle, J. V. I.; Beaugelin-Seiller, K.; Beresford, N. A.

An exercise to compare 10 approaches for the calculation of unweighted whole-body absorbed dose rates was conducted for 74 radionuclides and five of the ICRP's Reference Animals and Plants, or RAPs (duck, frog, flatfish egg, rat and elongated earthworm), selected for this exercise to cover a range of body sizes, dimensions and exposure scenarios. Results were analysed using a non-parametric method requiring no specific hypotheses about the statistical distribution of data. The obtained unweighted absorbed dose rates for internal exposure compare well between the different approaches, with 70% of the results falling within a range of variation of {+-}20%. Themore » variation is greater for external exposure, although 90% of the estimates are within an order of magnitude of one another. There are some discernible patterns where specific models over- or under-predicted. These are explained based on the methodological differences including number of daughter products included in the calculation of dose rate for a parent nuclide; source-target geometry; databases for discrete energy and yield of radionuclides; rounding errors in integration algorithms; and intrinsic differences in calculation methods. For certain radionuclides, these factors combine to generate systematic variations between approaches. Overall, the technique chosen to interpret the data enabled methodological differences in dosimetry calculations to be quantified and compared, allowing the identification of common issues between different approaches and providing greater assurance on the fundamental dose conversion coefficient approaches used in available models for assessing radiological effects to biota.« less

Dosimetric characterization of a synthetic single crystal diamond detector in a clinical 62 MeV ocular therapy proton beam

NASA Astrophysics Data System (ADS)

Marinelli, Marco; Pompili, F.; Prestopino, G.; Verona, C.; Verona-Rinati, G.; Cirrone, G. A. P.; Cuttone, G.; La Rosa, R. M.; Raffaele, L.; Romano, F.; Tuvè, C.

2014-12-01

A synthetic single crystal diamond based Schottky photodiode was tested at INFN-LNS on the proton beam line (62 MeV) dedicated to the radiation treatment of ocular disease. The diamond detector response was studied in terms of pre-irradiation dose, linearity with dose and dose rate, and angular dependence. Depth dose curves were measured for the 62 MeV pristine proton beam and for three unmodulated range-shifted proton beams; furthermore, the spread-out Bragg peak was measured for a modulated therapeutic proton beam. Beam parameters, recommended by the ICRU report 78, were evaluated to analyze depth-dose curves from diamond detector. Measured dose distributions were compared with the corresponding dose distributions acquired with reference plane-parallel ionization chambers. Field size dependence of the output factor (dose per monitor unit) in a therapeutic modulated proton beam was measured with the diamond detector over the range of ocular proton therapy collimator diameters (5-30 mm). Output factors measured with the diamond detector were compared to the ones by a Markus ionization chamber, a Scanditronix Hi-p Si stereotactic diode and a radiochromic EBT2 film. Signal stability within 0.5% was demonstrated for the diamond detector with no need of any pre-irradiation dose. Dose and dose rate dependence of the diamond response was measured: deviations from linearity resulted to be within ±0.5% over the investigated ranges of 0.5-40.0 Gy and 0.3-30.0 Gy/min respectively. Output factors from diamond detector measured with the smallest collimator (5 mm in diameter) showed a maximum deviation of about 3% with respect to the high resolution radiochromic EBT2 film. Depth-dose curves measured by diamond for unmodulated and modulated beams were in good agreement with those from the reference plane-parallel Markus chamber, with relative differences lower than ±1% in peak-to-plateau ratios, well within experimental uncertainties. A 2.5% variation in diamond detector response was observed in angular dependence measurements carried-out by varying the proton beam incidence angle in the polar direction. The dosimetric characterization of the tested synthetic single crystal diamond detector clearly indicates its suitability for relative dosimetry in ocular therapy proton beams, with no need of any correction factors accounting for dose rate and linear energy transfer dependence.

Estimated dose rates to members of the public from external exposure to patients with {sup 131}I thyroid treatment

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

Dewji, S., E-mail: dewjisa@ornl.gov; Bellamy, M.; Leggett, R.

Purpose: Estimated dose rates that may result from exposure to patients who had been administered iodine-131 ({sup 131}I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered {sup 131}I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with {sup 131}I. Tissue attenuation and iodine biokinetics were considered in the patient in a larger comprehensive effort to improvemore » external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the {sup 131}I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of {sup 131}I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after {sup 131}I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of {sup 131}I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for {sup 131}I patients with normal thyroid uptake (peak thyroid uptake of ∼27% of administered {sup 131}I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ∼4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ∼3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with {sup 131}I therapy, consideration must be given to (patient- and case-specific) administered {sup 131}I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. The method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Rationale for combination therapy in hypertension management: focus on angiotensin receptor blockers and thiazide diuretics.

PubMed

Nash, David T

2007-04-01

Despite recognition that hypertension is a major risk factor for cardiovascular events and mortality, blood pressure control rates remain low in the US population. Reflecting clinical trial results, hypertension management guidelines assert the clinical benefit of achieving current blood pressure goals and indicate that most patients will require 2 or more drugs to reach goal. Well-designed drug combinations counter hypertension via complementary mechanisms that increase antihypertensive efficacy, potentially with lower rates of adverse events than higher dose monotherapy regimens. Lower adverse event rates, in turn, may contribute to greater adherence with treatment. The combination of a low-dose diuretic with agents that block the effects of the renin-angiotensin system (RAS), such as angiotensin receptor blockers, has been found in numerous clinical trials to be highly effective for lowering blood pressure in patients with uncomplicated as well as high-risk hypertension, with a comparable favorable side effect profile compared with monotherapy. Moreover, agents that block the RAS are associated with a lower risk of new-onset diabetes mellitus than other antihypertensive classes. Complementary combinations of antihypertensive agents provide an efficient and effective approach to hypertension management.

Dose and dose rate effects of whole-body proton irradiation on leukocyte populations and lymphoid organs: part I

NASA Technical Reports Server (NTRS)

Gridley, Daila S.; Pecaut, Michael J.; Dutta-Roy, Radha; Nelson, Gregory A.

2002-01-01

The goal of part I of this study was to evaluate the effects of whole-body proton irradiation on lymphoid organs and specific leukocyte populations. C57BL/6 mice were exposed to the entry region of the proton Bragg curve to total doses of 0.5 gray (Gy), 1.5 Gy, and 3.0 Gy, each delivered at a low dose rate (LDR) of 1 cGy/min and high dose rate (HDR) of 80 cGy/min. Non-irradiated and 3 Gy HDR gamma-irradiated groups were included as controls. At 4 days post-irradiation, highly significant radiation dose-dependent reductions were observed in the mass of both lymphoid organs and the numbers of leukocytes and T (CD3(+)), T helper (CD3(+)/CD4(+)), T cytotoxic (CD3(+)/CD8(+)), and B (CD19(+)) cells in both blood and spleen. A less pronounced dose effect was noted for natural killer (NK1.1(+) NK) cells in spleen. Monocyte, but not granulocyte, counts in blood were highly dose-dependent. The numbers for each population generally tended to be lower with HDR than with LDR radiation; a significant dose rate effect was found in the percentages of T and B cells, monocytes, and granulocytes and in CD4(+):CD8(+) ratios. These data indicate that mononuclear cell response to the entry region of the proton Bragg curve is highly dependent upon the total dose and that dose rate effects are evident with some cell types. Results from gamma- and proton-irradiated groups (both at 3 Gy HDR) were similar, although proton-irradiation gave consistently lower values in some measurements.

Dosimetry for Small Fields in Stereotactic Radiosurgery Using Gafchromic MD-V2-55 Film, TLD-100 and Alanine Dosimeters

PubMed Central

Massillon-JL, Guerda; Cueva-Prócel, Diego; Díaz-Aguirre, Porfirio; Rodríguez-Ponce, Miguel; Herrera-Martínez, Flor

2013-01-01

This work investigated the suitability of passive dosimeters for reference dosimetry in small fields with acceptable accuracy. Absorbed dose to water rate was determined in nine small radiation fields with diameters between 4 and 35 mm in a Leksell Gamma Knife (LGK) and a modified linear accelerator (linac) for stereotactic radiosurgery treatments. Measurements were made using Gafchromic film (MD-V2-55), alanine and thermoluminescent (TLD-100) dosimeters and compared with conventional dosimetry systems. Detectors were calibrated in terms of absorbed dose to water in 60Co gamma-ray and 6 MV x-ray reference (10×10 cm2) fields using an ionization chamber calibrated at a standards laboratory. Absorbed dose to water rate computed with MD-V2-55 was higher than that obtained with the others dosimeters, possibly due to a smaller volume averaging effect. Ratio between the dose-rates determined with each dosimeter and those obtained with the film was evaluated for both treatment modalities. For the LGK, the ratio decreased as the dosimeter size increased and remained constant for collimator diameters larger than 8 mm. The same behaviour was observed for the linac and the ratio increased with field size, independent of the dosimeter used. These behaviours could be explained as an averaging volume effect due to dose gradient and lack of electronic equilibrium. Evaluation of the output factors for the LGK collimators indicated that, even when agreement was observed between Monte Carlo simulation and measurements with different dosimeters, this does not warrant that the absorbed dose to water rate in the field was properly known and thus, investigation of the reference dosimetry should be an important issue. These results indicated that alanine dosimeter provides a high degree of accuracy but cannot be used in fields smaller than 20 mm diameter. Gafchromic film can be considered as a suitable methodology for reference dosimetry. TLD dosimeters are not appropriate in fields smaller than 10 mm diameters. PMID:23671677

Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

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

Healy, W.L.; Lo, T.C.; Covall, D.J.

1990-12-01

Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700more » centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy.« less

Propylene glycol accumulation in critically ill patients receiving continuous intravenous lorazepam infusions.

PubMed

Horinek, Erica L; Kiser, Tyree H; Fish, Douglas N; MacLaren, Robert

2009-12-01

Lorazepam is recommended by the Society of Critical Care Medicine as the preferred agent for sedation of critically ill patients. Intravenous lorazepam contains propylene glycol, which has been associated with toxicity when high doses of lorazepam are administered. To evaluate the accumulation of propylene glycol in critically ill patients receiving lorazepam by continuous infusion and determine factors associated with propylene glycol concentration. A 6-month, retrospective, safety assessment was conducted of adults admitted to the medical intensive care unit who were receiving lorazepam by continuous infusion for 12 hours or more. Propylene glycol serum concentrations were obtained 24-48 hours after continuous-infusion lorazepam was initiated and every 3-5 days thereafter. Propylene glycol accumulation was defined as concentrations of 25 mg/dL or more. Groups with and without propylene glycol accumulation were compared and factors associated with propylene glycol concentration were determined using multivariate correlation regression analyses. Forty-eight propylene glycol serum samples were obtained from 33 patients. Fourteen (42%) patients had propylene glycol accumulation, representing 23 (48%) serum samples. Univariate analyses showed the following factors were related to propylene glycol accumulation: baseline renal dysfunction, presence of alcohol withdrawal, sex, age, Acute Physiology and Chronic Health Evaluation (APACHE II) score, rate of lorazepam continuous infusion, and 24-hour lorazepam dose. Multivariate linear regression modeling demonstrated that propylene glycol concentration was strongly associated with the continuous infusion rate and 24-hour dose (adjusted r(2) > or = 0.77; p < 0.001). Independent correlation analyses showed that these 2 variables were so strongly associated with propylene glycol concentration (r(2) > or = 0.71; p < 0.001) that they alone predicted propylene glycol concentration. Seven (21%) patients developed renal dysfunction after continuous-infusion lorazepam was initiated, but associated causes were indeterminable. Other possible propylene glycol-associated adverse effects were not observed. The continuous infusion rate and cumulative 24-hour lorazepam dose are strongly associated with and independently predict propylene glycol concentrations. Despite the absence of confirmed propylene glycol-associated adverse effects, clinicians should be aware that propylene glycol accumulation may occur with continuous-infusion lorazepam.

Bioincompatibility of dialyzer membranes may have a negative impact on outcome of acute renal failure, independent of the dose of dialysis delivered: a retrospective multicenter analysis.

PubMed

Schiffl, H; Lang, S M; Haider, M

1998-01-01

The mortality rate of critically ill patients with acute renal failure (ARF) has remained high. The impact of vigorous intermittent hemodialysis (IHD) on the outcome of ARF has not been validated. In this retrospective multicenter analysis, 154 patients with ARF were treated daily (intensive) or on alternate days (conventional) using complement and cell activating cuprophane (bioincompatible) or high-flux polysulfone dialyzer membranes with insignificant effects on circulating complement or cells (biocompatible). At initiation of IHD, all four groups were similar in patient characteristics and ARF factors. The use of synthetic membranes resulted in a reduced mortality rate (18% vs 45%; p < 0.001) and shorter duration of ARF (8 vs 15 sessions; p < 0.001). Daily IHD with cellulose based membranes tended to increase mortality rates compared with conventional cuprophane dialysis (37% vs 53%). Intensive IHD with polysulfone membranes resulted in a further decrease in overall mortality rates (15% vs 22%). This retrospective analysis shows that bioincompatibility of dialyzer membranes may be more important for the outcome of patients with ARF than the dose of dialysis. Its impact on outcome occurs independently of the dose of dialysis delivered.

Prospective Measurement of Patient Exposure to Radiation During Pediatric Ureteroscopy

PubMed Central

Kokorowski, Paul J.; Chow, Jeanne S.; Strauss, Keith; Pennison, Melanie; Routh, Jonathan C.; Nelson, Caleb P.

2013-01-01

Objective Little data have been reported regarding radiation exposure during pediatric endourologic procedures, including ureteroscopy (URS). We sought to measure radiation exposure during pediatric URS and identify opportunities for exposure reduction. Methods We prospectively observed URS procedures as part of a quality improvement initiative. Pre-operative patient characteristics, operative factors, fluoroscopy settings and radiation exposure were recorded. Our outcomes were entrance skin dose (ESD, in mGy) and midline dose (MLD, in mGy). Specific modifiable factors were identified as targets for potential quality improvement. Results Direct observation was performed on 56 consecutive URS procedures. Mean patient age was 14.8 ± 3.8 years (range 7.4 to 19.2); 9 children were under age 12 years. Mean ESD was 46.4 ± 48 mGy. Mean MLD was 6.2 ± 5.0 mGy. The most important major determinant of radiation dose was total fluoroscopy time (mean 2.68 ± 1.8 min) followed by dose rate setting, child anterior-posterior (AP) diameter, and source to skin distance (all p<0.01). The analysis of factors affecting exposure levels found that the use of ureteral access sheaths (p=0.01) and retrograde pyelography (p=0.04) were significantly associated with fluoroscopy time. We also found that dose rate settings were higher than recommended in up to 43% of cases and ideal C-arm positioning could have reduced exposure 14% (up to 49% in some cases). Conclusions Children receive biologically significant radiation doses during URS procedures. Several modifiable factors contribute to dose and could be targeted in efforts to implement dose reduction strategies. PMID:22341275

Medical management of early pregnancy failure (EPF): a retrospective analysis of a combined protocol of mifepristone and misoprostol used in clinical practice.

PubMed

Colleselli, Valeria; Schreiber, Courtney A; D'Costa, Elisabeth; Mangesius, Stephanie; Wildt, Ludwig; Seeber, Beata E

2014-06-01

To evaluate the efficacy of a combined protocol of mifepristone and misoprostol in the management of early pregnancy failure (EPF) and the average time to expulsion of tissue and rate of side effects. Retrospective chart review of all consecutive women treated with primary medical management for EPF at our institution from 2006 to 2012. 168 patients were included in the present study. The overall success rate, defined as the absence of the need for surgical intervention, was 61 % and did not differ by calendar year. There was no difference in success rate grouped by diagnosis [intrauterine embryonic/fetal demise (IUED/IUFD) vs. anembryonic gestation; p = 0.30] or gestational age (<9 or ≥9 weeks; p = 0.48). The success rate varied significantly according to the required dose of misoprostol, ≤800 or >800 μg (68 vs. 50 %, p = 0.029). Of the possible predictive factors of success, only the dose of misoprostol required was a significant independent negative predictor. Mean and median time to tissue expulsion after the first dose of misoprostol were 8.4 and 5.5 h, respectively. The incidence of side effects was low with no blood transfusions required. The success rate in this study is markedly below published data. This can possibly be attributed to retrospective study design, allowing for physician subjectivity and patients' wishes in the absence of strict study requirements. The protocol was well tolerated with a paucity of side effects. We make suggestions for enhancing success rates in the clinical setting by optimizing medication protocols, establishing precise treatment guidelines and training physicians in the accurate interpretation of treatment outcomes.

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.

A New Approach for the Determination of Dose Rate and Radioactivity for Detected Gamma Nuclides Using an Environmental Radiation Monitor Based on an NaI(Tl) Detector.

PubMed

Ji, Young-Yong; Kim, Chang-Jong; Lim, Kyo-Sun; Lee, Wanno; Chang, Hyon-Sock; Chung, Kun Ho

2017-10-01

To expand the application of dose rate spectroscopy to the environment, the method using an environmental radiation monitor (ERM) based on a 3' × 3' NaI(Tl) detector was used to perform real-time monitoring of the dose rate and radioactivity for detected gamma nuclides in the ground around an ERM. Full-energy absorption peaks in the energy spectrum for dose rate were first identified to calculate the individual dose rates of Bi, Ac, Tl, and K distributed in the ground through interference correction because of the finite energy resolution of the NaI(Tl) detector used in an ERM. The radioactivity of the four natural radionuclides was then calculated from the in situ calibration factor-that is, the dose rate per unit curie-of the used ERM for the geometry of the ground in infinite half-space, which was theoretically estimated by Monte Carlo simulation. By an intercomparison using a portable HPGe and samples taken from the ground around an ERM, this method to calculate the dose rate and radioactivity of four nuclides using an ERM was experimentally verified and finally applied to remotely monitor them in real-time in the area in which the ERM had been installed.

An investigation of the operating characteristics of two PTW diamond detectors in photon and electron beams.

PubMed

De Angelis, C; Onori, S; Pacilio, M; Cirrone, G A P; Cuttone, G; Raffaele, L; Bucciolini, M; Mazzocchi, S

2002-02-01

The dosimetric properties of two PTW Riga diamond detectors type 60003 were studied in high-energy photon and electron therapy beam. Properties under study were current-voltage characteristic, polarization effect, time stability of response, dose response, dose-rate dependence, temperature stability, and beam quality dependence of the sensitivity factor. Differences were shown between the two detectors for most of the previous properties. Also, the observed behavior was, to some extent, different from what was reported in the PTW technical specifications. The necessity to characterize each diamond detector individually was addressed.

Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico

PubMed Central

Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

2015-01-01

Determining ionizing radiation in a geographic area serves to assess its effects on a population’s health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h−1. At the same sites, 48 soil samples were taken to obtain the activity concentrations of 226Ra, 232Th and 40K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h−1. Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg−1, for 226Ra, 232Th and 40K, respectively. From the analysis, the spatial distribution of 232Th, 226Ra and 40K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize. PMID:26437425

Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico.

PubMed

Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

2015-09-30

Determining ionizing radiation in a geographic area serves to assess its effects on a population's health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h(-1). At the same sites, 48 soil samples were taken to obtain the activity concentrations of (226)Ra, (232)Th and (40)K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h(-1). Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg(-1), for (226)Ra, (232)Th and (40)K, respectively. From the analysis, the spatial distribution of (232)Th, (226)Ra and (40)K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize.

Evaluation of optimal parameters for using low-dose computed tomography to diagnose urolithiasis

NASA Astrophysics Data System (ADS)

Chen, Hui-Hsien; Yu, Cheng-Ching; Hsu, Fang-Yuh

2017-11-01

Urolithiasis is a common disease; patients suspected of suffering from urolithiasis will be examined by abdomen x-ray, Sono, Intraudio Videonous Urography (IVU) and Computed Tomography (CT). The detection rates for calculus in above examinations are respectively: 50-70% (x-ray), 50-60% (Sono), 70-90% (IVU) and 97% (CT). In addition, the effective doses are respectively: 0.63 mSv (x-ray), no radiation dose (Sono), 2.6 mSv (IVU) and 8-16 mSv (CT). Although CT has the highest detection rate for calculus, it also has the highest radiation dose. This research sought to lower the radiation dose by using CT scans with different dose conditions of standard dose (SD), 50% SD, 25% SD, and 15% SD to diagnose patients who suffer from urolithiasis and thus explore the feasibility of examining urolithiasis via CT with lower dose conditions. This research simulated the examination of patients with RANDO phantom, collocating PMMA slice phantom and pig's kidney. Fake calculuses made of five different materials of different sizes were put into the phantom and scanned individually. The results of the scanned images were given to two physicians who had many years of diagnostic experience to interpret the urolithiasis images. This study explored the different image qualities of CT with different dose conditions. In addition, this research used thermoluminescent dosimeters (TLD) to measure the radiation doses and compared the results with the dose values shown on the screen of the CT scanner to estimate the dose conversion factor (k). The research results showed that a low-dose CT was able to provide good image quality and thus have a lower radiation dose. Therefore, a low-dose CT is suggested the main examination method to diagnose patients with urolithiasis.

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

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

NASA Astrophysics Data System (ADS)

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

2010-08-01

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

New image-processing and noise-reduction software reduces radiation dose during complex endovascular procedures.

PubMed

Kirkwood, Melissa L; Guild, Jeffrey B; Arbique, Gary M; Tsai, Shirling; Modrall, J Gregory; Anderson, Jon A; Rectenwald, John; Timaran, Carlos

2016-11-01

A new proprietary image-processing system known as AlluraClarity, developed by Philips Healthcare (Best, The Netherlands) for radiation-based interventional procedures, claims to lower radiation dose while preserving image quality using noise-reduction algorithms. This study determined whether the surgeon and patient radiation dose during complex endovascular procedures (CEPs) is decreased after the implementation of this new operating system. Radiation dose to operators, procedure type, reference air kerma, kerma area product, and patient body mass index were recorded during CEPs on two Philips Allura FD 20 fluoroscopy systems with and without Clarity. Operator dose during CEPs was measured using optically stimulable, luminescent nanoDot (Landauer Inc, Glenwood, Ill) detectors placed outside the lead apron at the left upper chest position. nanoDots were read using a microStar ii (Landauer Inc) medical dosimetry system. For the CEPs in the Clarity group, the radiation dose to surgeons was also measured by the DoseAware (Philips Healthcare) personal dosimetry system. Side-by-side measurements of DoseAware and nanoDots allowed for cross-calibration between systems. Operator effective dose was determined using a modified Niklason algorithm. To control for patient size and case complexity, the average fluoroscopy dose rate and the dose per radiographic frame were adjusted for body mass index differences and then compared between the groups with and without Clarity by procedure. Additional factors, for example, physician practice patterns, that may have affected operator dose were inferred by comparing the ratio of the operator dose to procedural kerma area product with and without Clarity. A one-sided Wilcoxon rank sum test was used to compare groups for radiation doses, reference air kermas, and operating practices for each procedure type. The analysis included 234 CEPs; 95 performed without Clarity and 139 with Clarity. Practice patterns of operators during procedures with and without Clarity were not significantly different. For all cases, procedure radiation dose to the patient and the primary and assistant operators were significantly decreased in the Clarity group by 60% compared with the non-Clarity group. By procedure type, fluorography dose rates decreased from 44% for fenestrated endovascular repair and up to 70% with lower extremity interventions. Fluoroscopy dose rates also significantly decreased, from about 37% to 47%, depending on procedure type. The AlluraClarity system reduces the patient and primary operator's radiation dose by more than half during CEPs. This feature appears to be an effective tool in lowering the radiation dose while maintaining image quality. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy.

PubMed

Mena, Guillermo; García-Basteiro, Alberto L; Llupià, Anna; Díez, Consolación; Costa, Josep; Gatell, Josep-María; García, Felipe; Bayas, José-María

2013-08-12

HIV seropositivity is considered a risk factor for complications in hepatitis A virus (HAV) infection. HAV vaccination schedules are widely implemented in HIV-infected patients, but the immune response remains impaired. We analysed the response to vaccination (antiHAV titres ≥20IU/l) in 282 HIV-infected patients included in a standard (1440 Elisa Units (EU) at 0, 6 months) or rapidly accelerated schedule (720 EU at 0, 7, 21 days and 6 months) between 1997 and 2009. Factors associated with the response to vaccination were analysed using logistic regression. The overall response rate was 73.4%. Male sex (OR: 0.16, 95% CI 0.05-0.51) and hepatitis C virus co-infection (OR: 0.30, 95% CI 0.14-0.74) were associated with a lower probability of response. Protective antibody response was associated with a higher CD4/CD8 ratio (OR: 3.69, 95% CI 1.3-10.5) and having received two doses of standard schedule (compared with patients receiving only one dose of the same schedule) (OR: 2.51, 95% CI 1.22-5.15). Three doses of the rapidly accelerated schedule were not more effective than a single dose of 1440 EU (OR: 1.32, 95% CI 0.48-3.63). The low responses observed in patients receiving a single dose suggest the need to emphasize adhesion to vaccination protocols to avoid failure. The CD4/CD8 ratio may be considered as an immune status marker which could help to better choose the moment of vaccination. Our findings underscore the importance of identifying strategies that optimize the timing and effectiveness of hepatitis A vaccination in HIV-infected patients and of the need for further studies on individual factors such as sex and hepatitis C co-infection that may affect the response to vaccination. Likewise, the sub-optimal effectiveness of three doses of 720 EU in the rapidly accelerated schedule, if confirmed in future studies, might lead to a revision of the current schedule recommended for HIV-infected travellers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Towards evaluating post-irradiation tissue alterations

NASA Astrophysics Data System (ADS)

Daar, Eman; Bradley, D. A.; Alkhorayef, M.; Al-Mugren, K. S.; Abdallat, R. G.; Al-Dousari, H.

2017-08-01

There is apaucity of data concerning irradiation effects on the extracellular matrix and on organised tissues. Examples of such research are cited as are some of the limiting factors towards obtaining meaningful results. This would engender a range of research towards further improving the quality of life, most pointedly of those receiving radiotherapy. As cancer survivor rates increase, survivors are more likely to experience side effects of radiotherapy. This study examines the effects of radiotherapy doses on the extracellular matrix as hyaluronic acid (HA) and pericardium.

The correlation between elongation at break and thermal decomposition of aged EPDM cable polymer

NASA Astrophysics Data System (ADS)

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

2017-03-01

The effect of simultaneous thermal and gamma irradiation ageing on the mechanical and physicochemical properties of industrial EPDM was investigated. Accelerated ageing, covering a wide range of dose rates, doses and temperatures, was preformed in stagnant air on EPDM polymer samples extracted from the cables in use in the Belgian nuclear power plants. The mechanical properties, ultimate tensile stress and elongation at break, are found to exhibit the strong dependence on the dose, ageing temperature and dose rate. The thermal decomposition of aged polymer is observed to be the dose dependent when thermogravimetry test is performed under air atmosphere. No dose dependence is observed when thermal decomposition is performed under nitrogen atmosphere. The thermal decomposition rates are found to fully mimic the reduction of elongation at break for all dose rates and ageing temperatures. This effect is argued to be the result of thermal and radiation mediated oxidation degradation process.

Space radiation absorbed dose distribution in a human phantom

NASA Technical Reports Server (NTRS)

Badhwar, G. D.; Atwell, W.; Badavi, F. F.; Yang, T. C.; Cleghorn, T. F.

2002-01-01

The radiation risk to astronauts has always been based on measurements using passive thermoluminescent dosimeters (TLDs). The skin dose is converted to dose equivalent using an average radiation quality factor based on model calculations. The radiological risk estimates, however, are based on organ and tissue doses. This paper describes results from the first space flight (STS-91, 51.65 degrees inclination and approximately 380 km altitude) of a fully instrumented Alderson Rando phantom torso (with head) to relate the skin dose to organ doses. Spatial distributions of absorbed dose in 34 1-inch-thick sections measured using TLDs are described. There is about a 30% change in dose as one moves from the front to the back of the phantom body. Small active dosimeters were developed specifically to provide time-resolved measurements of absorbed dose rates and quality factors at five organ locations (brain, thyroid, heart/lung, stomach and colon) inside the phantom. Using these dosimeters, it was possible to separate the trapped-proton and the galactic cosmic radiation components of the doses. A tissue-equivalent proportional counter (TEPC) and a charged-particle directional spectrometer (CPDS) were flown next to the phantom torso to provide data on the incident internal radiation environment. Accurate models of the shielding distributions at the site of the TEPC, the CPDS and a scalable Computerized Anatomical Male (CAM) model of the phantom torso were developed. These measurements provided a comprehensive data set to map the dose distribution inside a human phantom, and to assess the accuracy and validity of radiation transport models throughout the human body. The results show that for the conditions in the International Space Station (ISS) orbit during periods near the solar minimum, the ratio of the blood-forming organ dose rate to the skin absorbed dose rate is about 80%, and the ratio of the dose equivalents is almost one. The results show that the GCR model dose-rate predictions are 20% lower than the observations. Assuming that the trapped-belt models lead to a correct orbit-averaged energy spectrum, the measurements of dose rates inside the phantom cannot be fully understood. Passive measurements using 6Li- and 7Li-based detectors on the astronauts and inside the brain and thyroid of the phantom show the presence of a significant contribution due to thermal neutrons, an area requiring additional study.

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.

A Multicountry Ecological Study of Cancer Incidence Rates in 2008 with Respect to Various Risk-Modifying Factors

PubMed Central

Grant, William B.

2013-01-01

Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15–25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer. PMID:24379012

A multicountry ecological study of cancer incidence rates in 2008 with respect to various risk-modifying factors.

PubMed

Grant, William B

2013-12-27

Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15-25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer.

Health Impacts from Acute Radiation Exposure

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

Strom, Daniel J.

2003-09-30

Absorbed doses above1-2 Gy (100-200 rads) received over a period of a day or less lead to one or another of the acute radiation syndromes. These are the hematopoietic syndrome, the gastrointestinal (GI) syndrome, the cerebrovascular (CV) syndrome, the pulmonary syndrome, or the cutaneous syndrome. The dose that will kill about 50% of the exposed people within 60 days with minimal medical care, LD50-60, is around 4.5 Gy (450 rads) of low-LET radiation measured free in air. The GI syndrome may not be fatal with supportive medical care and growth factors below about 10 Gy (1000 rads), but above thismore » is likely to be fatal. Pulmonary and cutaneous syndromes may or may not be fatal, depending on many factors. The CV syndrome is invariably fatal. Lower acute doses, or protracted doses delivered over days or weeks, may lead to many other health outcomes than death. These include loss of pregnancy, cataract, impaired fertility or temporary or permanent sterility, hair loss, skin ulceration, local tissue necrosis, developmental abnormalities including mental and growth retardation in persons irradiated as children or fetuses, radiation dermatitis, and other symptoms listed in Table 2 on page 12. Children of parents irradiated prior to conception may experience heritable ill-health, that is, genetic changes from their parents. These effects are less strongly expressed than previously thought. Populations irradiated to high doses at high dose rates have increased risk of cancer incidence and mortality, taken as about 10-20% incidence and perhaps 5-10% mortality per sievert of effective dose of any radiation or per gray of whole-body absorbed dose low-LET radiation. Cancer risks for non-uniform irradiation will be less.« less

Age-specific radiation dose commitment factors for a one-year chronic intake

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

Hoenes, G.R.; Soldat, J.K.

1977-11-01

During the licensing process for nuclear facilities, radiation doses and dose commitments must be calculated for people in the environs of a nuclear facility. These radiation doses are determined by examining characteristics of population groups, pathways to people, and radionuclides found in those pathways. The pertinent characteristics, which are important in the sense of contributing a significant portion of the total dose, must then be analyzed in depth. Dose factors are generally available for adults, see Reference 1 for example, however numerous improvements in data on decay schemes and half-lives have been made in recent years. In addition, it ismore » advisable to define parameters for calculation of the radiation dose for ages other than adults since the population surrounding nuclear facilities will be composed of various age groups. Further, since infants, children, and teens may have higher rates of intake per unit body mass, it is conceivable that the maximally exposed individual may not be an adult. Thus, it was necessary to develop new radiation-dose commitment factors for various age groups. Dose commitment factors presented in this report have been calculated for a 50-year time period for four age groups.« less

Dose-rate effects of Co60 irradiation on performance and physiology in monkeys. Topical report

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

Bruner, A.; Bogo, V.; Henderson, E.A.

1975-07-30

One thousand rad /sup 60/Co was administered to 12 monkeys at 75 rad/min and to 8 monkeys at 50 rad/min while they performed a delayed match-to-sample, shock avoidance task. Only four at 75 rad/min and two at 50 rad/min showed early performance decrement and/or early transient incapacitation (PD-ETI), in contrast to 13 of 16 previously studied monkeys who showed PD-ETI with an average dose rate of 180 rad/min. A dose-rate effect was concluded. When these three groups were compared with an untrained group exposed to a 4000-rad gamma-neutron pulse, all showed similar degrees of hypotension postirradiation. But the onset ofmore » hypotension was delayed and its rate of fall prolonged as dose rate decreased. Tentative interpretation was that radiation thresholds for the induction of PD-ETI exist for cumulative dose (+ or - 300 rad, midbody) and dose rate (+ or - 30 rad/min). (GRA)« less

Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

PubMed

Alam, Nausheen; Najam, Rahila

2015-01-01

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

Local tumour control and eye preservation after gamma-knife radiosurgery of choroidal melanomas.

PubMed

Wackernagel, Werner; Holl, Etienne; Tarmann, Lisa; Mayer, Christoph; Avian, Alexander; Schneider, Mona; Kapp, Karin S; Langmann, Gerald

2014-02-01

To report on local tumour control and eye preservation after gamma knife radiosurgery (GK-RS) to treat choroidal melanomas. A total of 189 patients with choroidal melanoma were treated with GK-RS, with treatment doses between 25 and 80 Grays. The main outcome measures of our retrospective analysis were local tumour control, time to recurrence, eye retention rate and the reason for and time to secondary enucleation. Patient-associated, tumour-associated and treatment-associated parameters were evaluated as potential risk factors. Local tumour control was achieved in 94.4% of patients. The estimated tumour control rates were 97.6% at 1 year, 94.2% at 5 years and 92.4% at 10 years after treatment. Recurrence was observed between 3.1 months and 60.7 months post-treatment (median: 13.5 months). Advanced tumour stage (Tumour, Node, Metastasis (TNM) 3-4) was the most important risk factor for recurrence (Fine-Gray model; subhazard ratio, SHR: 3.3; p=0.079). The treatment dose was not related to tumour recurrence. The eye preservation rate was 81.6% at 5 years after treatment, remaining stable thereafter. Twenty-five eyes (14.1%) had to be enucleated at between 17 days and 68.0 months (median: 13.9 months) after GK-RS, and advanced tumour stage (Cox model; p=0.005), treatment dose (p=0.048), pretreatment visual acuity (p=0.016), and retinal detachment (p=0.027) were risk factors for requiring enucleation. GK-RS achieved a high tumour control rate, comparable to linear accelerator-based radiotherapy. Advanced TNM stage was a predictive risk factor for tumour recurrence and for secondary enucleation after GK-RS. Lower treatment doses were unrelated to tumour recurrence, although they were associated with an improved eye retention rate.

Analysis and evaluation for consumer goods containing NORM in Korea.

PubMed

Jang, Mee; Chung, Kun Ho; Lim, Jong Myoung; Ji, Young Yong; Kim, Chang Jong; Kang, Mun Ja

2017-08-01

We analyzed the consumer goods containing NORM by ICP-MS and evaluated the external dose. To evaluate the external dose, we assumed the small room model as irradiation scenario and calculated the specific effective dose rate using MCNPX code. The external doses for twenty goods are less than 1 mSv considering the specific effective dose rates and usage quantities. However, some of them have relatively high dose and the activity concentration limits are necessary as a screening tool. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding.

PubMed

George, K; Willingham, V; Wu, H; Gridley, D; Nelson, G; Cucinotta, F A

2002-01-01

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding

NASA Technical Reports Server (NTRS)

George, K.; Willingham, V.; Wu, H.; Gridley, D.; Nelson, G.; Cucinotta, F. A.

2002-01-01

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

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

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

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

1957-11-22

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

Effects of dietary methylmercury on juvenile Sacramento blackfish bioenergetics.

PubMed

Houck, Ann; Cech, Joseph J

2004-08-10

Although much is known about the biogeochemical cycling of mercury in the environment, relatively little is known about methylmercury (MeHg) bioaccumulation in fishes and how chronic sub-lethal exposures affect their functioning. Several species of fish in Clear Lake, California have high MeHg tissue levels, including Sacramento blackfish, Orthodon microlepidotus, a large native cyprinid that is fished commercially. We fed juvenile blackfish one of four diets containing MeHg (0.21 mg/kg control; 0.52 mg/kg low; 22.2 mg/kg medium; and 55.5 mg/kg high treatments) for 70 days. There were no statistical differences (P > 0.05) in food consumption among the treatment groups. By 35 days the high treatment group had a significantly depressed growth rate when compared to the control group (P < 0.05) and by 70 days both the medium and the high groups had significantly lower growth rates (P < 0.05). The high-dose group had a significantly (P < 0.05) lower specific growth rate (SGR) compared all other treatment groups at 35 days, although by 70 days these differences were not significant. The wet/dry muscle mass and muscle mass/total mass ratios, condition factor, and resting routine metabolic rates at both 35 and 70 days were statistically indistinguishable (P > 0.05) between treatment groups. All treatment groups assimilated the dietary MeHg into muscle tissue in a dose-dependent fashion. Percent assimilation was significantly lower (P < 0.05) in the high-dose group compared to the low-dose group at 35 days, (control 53%, low-dose 61%, medium-dose 50%, and high-dose 40%) but at 70 days assimilation was lower (35, 43, 42, and 32%, respectively) and statistically indistinguishable (P > 0.05) among the treatment groups. Dietary MeHg concentrations and bioaccumulation rates were correlated (r2 = 0.98 at 35 days, 0.99 at 70 days). These results may contribute to construction of ecosystem mercury models and more informed natural resources management at Clear Lake.

Dosimetry around metallic ports in tissue expanders in patients receiving postmastectomy radiation therapy: an ex vivo evaluation.

PubMed

Moni, Janaki; Graves-Ditman, Maria; Cederna, Paul; Griffith, Kent; Krueger, Editha A; Fraass, Benedick A; Pierce, Lori J

2004-01-01

Postmastectomy breast reconstruction can be accomplished utilizing tissue expanders and implants. However, in patients who require postoperative radiotherapy, the complication rate with tissue expander/implant reconstruction can exceed 50%. One potential cause of this high complication rate may be the metallic port in the tissue expander producing altered dosimetry in the region of the metallic device. The purpose of this study was to quantify the radiation dose distribution in the vicinity of the metallic port and determine its potential contribution to this extremely high complication rate. The absolute dosimetric effect of the tissue expander's metallic port was quantified using film and thermoluminescent dosimetry (TLD) studies with a single beam incident on a metallic port extracted from an expander. TLD measurements were performed at 11 reproducible positions on an intact expander irradiated with tangential fields. A computed tomography (CT)-based treatment plan without inhomogeneity corrections was used to derive expected doses for all TLD positions. Multiple irradiation experiments were performed for all TLD data. Confidence intervals for the dose at TLD sites with the metallic port in place were compared to the expected dose at the site without the metallic port. Film studies did not reveal a significant component of scatter around the metallic port. TLD studies of the extracted metallic port revealed highest doses within the casing of the metallic port and no consistent increased dose at the surface of the expander. No excess dose due to the metallic port in the expander was noted with the phantom TLD data. Based upon these results, it does not appear that the metallic port in tissue expanders significantly contributes to the high complication rate experienced in patients undergoing tissue expander breast reconstruction and receiving radiation therapy. Strategies designed to reduce the breast reconstruction complication rate in this clinical setting will need to focus on factors other than adjusting the dosimetry around the tissue expander metallic port.

Dosimetric characteristics of a MOSFET dosimeter for clinical electron beams.

PubMed

Manigandan, D; Bharanidharan, G; Aruna, P; Devan, K; Elangovan, D; Patil, Vikram; Tamilarasan, R; Vasanthan, S; Ganesan, S

2009-09-01

The fundamental dosimetric characteristics of commercially available metal oxide semiconductor field effect transistor (MOSFET) detectors were studied for clinical electron beam irradiations. MOSFET showed excellent linearity against doses measured using an ion chamber in the dose range of 20-630cGy. MOSFET reproducibility is better at high doses compared to low doses. The output factors measured with the MOSFET were within +/-3% when compared with those measured with a parallel plate chamber. From 4 to 12MeV, MOSFETs showed a large angular dependence in the tilt directions and less in the axial directions. MOSFETs do not show any dose-rate dependence between 100 and 600MU/min. However, MOSFETs have shown under-response when the dose per pulse of the beam is decreased. No measurable effect in MOSFET response was observed in the temperature range of 23-40 degrees C. The energy dependence of a MOSFET dosimeter was within +/-3.0% for 6-18MeV electron beams and 5.5% for 4MeV ones. This study shows that MOSFET detectors are suitable for dosimetry of electron beams in the energy range of 4-18MeV.

Clinical review: Treatment of neurohypophyseal diabetes insipidus.

PubMed

Oiso, Yutaka; Robertson, Gary L; Nørgaard, Jens Peter; Juul, Kristian Vinter

2013-10-01

In recent years, there have been several improvements in the treatment of neurohypophyseal diabetes insipidus (DI). They include new formulations of the vasopressin analog, desmopressin; a better understanding of the effect of fluid intake on dosing; and more information about treatments of infants, children, and pregnant women who present special challenges. This review aims to summarize past and current information relative to the safety and efficacy of treatments for the types of DI caused by a primary deficiency of vasopressin. The review is based on publications identified primarily by a PubMed search of the international literature without limitations of date. In acute settings where fluid intake is determined by factors other than thirst, desmopressin should be given iv in doses that have a short duration of action and can be adjusted quickly in accordance with changes in hydration as indicated by plasma sodium. In ambulatory patients, the oral formulations (tablet or melt) are preferred for their convenience. If fluid intake is regulated normally by the thirst mechanism, the tablets or melt can be taken safely 1 to 3 times a day in doses sufficient to completely eliminate the polyuria. However, if fluid intake consistently exceeds replacement needs as evidenced by the development of hyponatremia, the dose should be reduced to allow higher than normal rates of urine output or intermittent breakthrough diuresis. This regimen is often indicated in infants or children because their rate of fluid intake tends to be greater than in adults. In all cases, the appropriate dose should be determined by titration, owing to considerable interindividual differences in bioavailability and antidiuretic effect. Desmopressin can provide effective and safe therapy for all patients with neurohypophyseal or gestational DI if given in doses and by a route that takes into account the determinants of fluid intake.

Measurements of environmental terrestrial gamma radiation dose rate in three mountainous locations in the western region of Saudi Arabia

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

Al-Ghorabie, Fayez H.H.

2005-06-01

This paper describes measurements of external gamma radiation dose rate from terrestrial gamma-rays 1 m above the ground in three different mountainous locations in the western region of the Kingdom of Saudi Arabia. These locations are At-Taif city, Al-Hada village, and Ash-Shafa village. CaSO{sub 4}:Dy (TLD-900) thermoluminescent dosimeters were used for the detection of terrestrial gamma radiation at 40 different places in the three locations. The values of terrestrial gamma radiation dose rate measured ranged between 14 and 279 nGy h{sup -1} for the time interval from June 2001 to June 2002. The measured dose rate varied with the seasonmore » of the year. The average gamma radiation dose rates were 468, 541, and 781 {mu}Gy y{sup -1} for At-Taif city, Al-Hada village, and Ash-Shafa village, respectively. The corresponding average absorbed doses to the population of the three locations were 328, 379, and 547 {mu}Sv y{sup -1}, respectively. The quality factor of 0.7 Sv Gy{sup -1} was applied in the calculations of the absorbed dose to humans.« less

Drug liking and wanting, not impulsive action or reflection is increased by 4-fluoroamphetamine.

PubMed

Kuypers, K P C; de Sousa Fernandes Perna, E B; Dolder, P C; Toennes, S W; Theunissen, E L; Mason, N L; Hutten, N R P W; Ramaekers, J G

2018-05-31

New psychoactive substances (NPS) are chemical analogues designed to mimic the effects of various classic recreational drugs of abuse including MDMA, LSD, and cannabis. NPS use is associated with concern about the acute and longer-term effects particular substances might have, with abuse and addiction as potential consequences. Impulsivity and sensitivity to the rewarding effects of drugs have been considered as risk factors for drug abuse. In light of the popularity of 4-fluoroamphetamine (4-FA), it is important to assess whether 4-FA can lead to subjective drug liking and wanting, and impulsive behavior, all factors contributing to the abuse likelihood of a substance. A placebo-controlled 2-way crossover study in 12 healthy poly-drug using participants was conducted to test subjective and behavioral effects of 4-FA (100 mg). 4-FA concentrations were determined in serum up to 12 h after administration and two impulsivity tasks and two drug experience questionnaires assessing drug liking and wanting, and good and bad drug effect, were administered between 1 and 11 h post-administration. Findings showed that 4-FA did not affect impulsive behavior. Self-ratings of drug liking and wanting and good drug effect were increased 1 h after administration; this effect was absent 11 h after drug intake. To conclude, 4-FA (single dose) increased self-rated liking and wanting, which is known to contribute to the abuse likelihood of a substance; however, it left another factor impulsive behavior unaffected. It has to be noted that the current picture is limited and might change with increased sample size, and/or different 4-FA doses. Trial acronym: 4-FA. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6164 . Registration number: NTR6164 (Dutch clinical trial registry number).

Outcome of stroke patients receiving different doses of recombinant tissue plasminogen activator.

PubMed

Ong, Cheung-Ter; Wong, Yi-Sin; Wu, Chi-Shun; Su, Yu-Hsiang

2017-01-01

Intravenous recombinant tissue plasminogen activator (tPA) at a dose of 0.9 mg/kg body weight is associated with a high hemorrhagic transformation (HT) rate. Low-dose tPA (0.6 mg/kg) may have a lower hemorrhage rate but the mortality and disability rates at 90 days cannot be confirmed as non-inferior to standard-dose tPA. Whether the doses 0.7 and 0.8 mg/kg have better efficacy and safety needs further investigation. Therefore, this study is to compare the efficacy and safety of each dose of tPA (0.6, 0.7, 0.8, and 0.9 mg/kg body weight) and to investigate the factors affecting early neurological improvement (ENI) and early neurological deterioration (END). For this observational study, data were obtained from 274 patients who received tPA thrombolytic therapy in Chia-Yi Christian Hospital stroke unit. The tPA dose was given at the discretion of each physician. The definition of ENI was a >8 point improvement (compared with baseline) at 24 h following thrombolytic therapy or an improvement in the National Institutes of Health Stroke Score (NIHSS) to 0 or 1 toward the end of tPA infusion. The definition of END was a >4 point increase in NIHSS (compared with baseline) within 24 h of tPA infusion. The primary objective was to investigate whether 0.7 and 0.8 mg/kg of tPA have higher ENI rate, lower END rate, and better outcome at 6 months. Poor outcome was defined as having a modified Rankin Scale of 3 to 6 (range, 0 [no symptoms] to 6 [death]). The secondary objective was to investigate whether low-dose tPA has a lower risk of intracerebral HT than that with standard-dose tPA. We also investigated the factors affecting ENI, END, HT, and 6-month outcome. A total of 274 patients were included during the study period, of whom 260 were followed up for >6 months. There was a trend for the HT rate to increase as the dose increased ( P =0.02). The symptomatic HT rate was not significantly different among the low-dose and standard-dose groups. The ENI and END ( P =0.52) were not significantly different among the four dosage groups. The clinical functional outcome at 6 months after stroke onset was poorer in the standard-dose group ( P =0.02). Stroke severity ( P <0.01), stroke type ( P =0.03), and diabetes mellitus ( P =0.04) affected the functional outcome at 6 months. Among the 274 patients receiving tPA thrombolytic therapy, the HT rate increased as dose increased. The symptomatic HT, ENI and END rates were not significantly different among the low-dose (0.6, 0.7, and 0.8 mg/kg) and standard-dose groups. Stroke severity (NIHSS >12), stroke type (cardioembolism and large artery atherosclerosis) and diabetes mellitus were associated with poor outcome at 6 months.

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.

Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

DOE PAGES

Stark, Karolina; Scott, David E.; Tsyusko, Olga; ...

2015-04-30

Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad ( Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments didmore » not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.« less

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

Optimal mapping of terrestrial gamma dose rates using geological parent material and aerogeophysical survey data.

PubMed

Rawlins, B G; Scheib, C; Tyler, A N; Beamish, D

2012-12-01

Regulatory authorities need ways to estimate natural terrestrial gamma radiation dose rates (nGy h⁻¹) across the landscape accurately, to assess its potential deleterious health effects. The primary method for estimating outdoor dose rate is to use an in situ detector supported 1 m above the ground, but such measurements are costly and cannot capture the landscape-scale variation in dose rates which are associated with changes in soil and parent material mineralogy. We investigate the potential for improving estimates of terrestrial gamma dose rates across Northern Ireland (13,542 km²) using measurements from 168 sites and two sources of ancillary data: (i) a map based on a simplified classification of soil parent material, and (ii) dose estimates from a national-scale, airborne radiometric survey. We used the linear mixed modelling framework in which the two ancillary variables were included in separate models as fixed effects, plus a correlation structure which captures the spatially correlated variance component. We used a cross-validation procedure to determine the magnitude of the prediction errors for the different models. We removed a random subset of 10 terrestrial measurements and formed the model from the remainder (n = 158), and then used the model to predict values at the other 10 sites. We repeated this procedure 50 times. The measurements of terrestrial dose vary between 1 and 103 (nGy h⁻¹). The median absolute model prediction errors (nGy h⁻¹) for the three models declined in the following order: no ancillary data (10.8) > simple geological classification (8.3) > airborne radiometric dose (5.4) as a single fixed effect. Estimates of airborne radiometric gamma dose rate can significantly improve the spatial prediction of terrestrial dose rate.

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

NASA Astrophysics Data System (ADS)

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

2012-03-01

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

Evaluation of radiation dose to anthropomorphic paediatric models from positron-emitting labelled tracers

NASA Astrophysics Data System (ADS)

Xie, Tianwu; Zaidi, Habib

2014-03-01

PET uses specific molecules labelled with positron-emitting radionuclides to provide valuable biochemical and physiological information. However, the administration of radiotracers to patients exposes them to low-dose ionizing radiation, which is a concern in the paediatric population since children are at a higher cancer risk from radiation exposure than adults. Therefore, radiation dosimety calculations for commonly used positron-emitting radiotracers in the paediatric population are highly desired. We evaluate the absorbed dose and effective dose for 19 positron-emitting labelled radiotracers in anthropomorphic paediatric models including the newborn, 1-, 5-, 10- and 15-year-old male and female. This is achieved using pre-calculated S-values of positron-emitting radionuclides of UF-NCI paediatric phantoms and published biokinetic data for various radiotracers. The influence of the type of anthropomorphic model, tissue weight factors and direct human- versus mouse-derived biokinetic data on the effective dose for paediatric phantoms was also evaluated. In the case of 18F-FDG, dosimetry calculations of reference paediatric patients from various dose regimens were also calculated. Among the considered radiotracers, 18F-FBPA and 15O-water resulted in the highest and lowest effective dose in the paediatric phantoms, respectively. The ICRP 103 updated tissue-weighting factors decrease the effective dose in most cases. Substantial differences of radiation dose were observed between direct human- versus mouse-derived biokinetic data. Moreover, the effect of using voxel- versus MIRD-type models on the calculation of the effective dose was also studied. The generated database of absorbed organ dose and effective dose for various positron-emitting labelled radiotracers using new generation computational models and the new ICRP tissue-weighting factors can be used for the assessment of radiation risks to paediatric patients in clinical practice. This work also contributes to a better understanding of the factors influencing patient-specific radiation dose calculation.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Characterization of responses and comparison of calibration factor for commercial MOSFET detectors.

PubMed

Bharanidharan, Ganesan; Manigandan, Durai; Devan, Krishnamurthy; Subramani, Vellaiyan; Gopishankar, Natanasabapathi; Ganesh, Tharmar; Joshi, Rakeshchander; Rath, Gourakishore; Velmurugan, Jagadeesan; Aruna, Prakasarao; Ganesan, Singaravelu

2005-01-01

A commercial metal oxide silicon field effect transistor (MOSFET) dosimeter of model TN502-RD has been characterized for its linearity, reproducibility, field size dependency, dose rate dependency, and angular dependency for Cobalt-60 (60Co), 6-MV, and 15-MV beam energies. The performance of the MOSFET clearly shows that it is highly reproducible, independent of field size and dose rate. Furthermore, MOSFET has a very high degree of linearity, with r-value>0.9 for all 3 energies. The calibration factor for 2 similar MOSFET detectors of model TN502-RD were also estimated and compared for all 3 energies. The calibration factor between the 2 similar MOSFET detectors shows a variation of about 1.8% for 60Co and 15 MV, and for 6 MV it shows variation of about 2.5%, indicating that calibration should be done whenever a new MOSFET is used. However, the detector shows considerable angular dependency of about 8.8% variation. This may be due to the variation in radiation sensitivity between flat and bubble sides of the MOSFET, and indicates that positional care must be taken while using MOSFET for stereotactic radiosurgery and stereotactic radiotherapy dosimetric applications.

A Radiobiological Analysis of Multicenter Data for Postoperative Keloid Radiotherapy

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

Flickinger, John C., E-mail: flickingerjc@upmc.ed

2011-03-15

Purpose: To identify factors significantly affecting recurrence rates after postoperative external beam radiotherapy (XRT) of keloids, and to delineate any radiation dose response and effects of radiation dose per fraction. Methods and Materials: A comprehensive literature review was performed to compile a database of 2,515 resected keloids (36.9% earlobe). Postoperative XRT was 45- to 100-kV X-rays in 27.0% or 120- to 250-kV X-rays in 11.1%, Co-60 in 1.9%, Sr-90 in 4.7%, 1.5- to 9-MeV electrons in 26.5%, and no XRT in 28.8%. In the 1,791 irradiated patients, the median radiation parameters were as follows: total dose, 15 Gy (range, 6-30more » Gy); dose per fraction, 5.0 Gy (range, 2-15 Gy); fractions, 3 (range, 1-10); and time, 7 days (range, 0-33 days). Results: Multivariate stepwise logistic regression correlated decreased keloid recurrence with earlobe location (p = 1.98E-10; odds ratio, 0.34), biologically effective dose (p = 1.01E-27), and treatment with electron beam or Co-60 vs. other techniques (p = 0.0014; odds ratio, 0.72). Different radiobiological models calculated values of {alpha}/{beta} = 1.12 to 2.86 (mean, 2.08) and time (repopulation) correction factors for biologically effective dose from 0.98 to 2.13 Gy per day (mean, 1.34) starting 10 days after surgery. Different models (with {alpha}/{beta} = 2.08) predicted that doses needed for 90% and 95% control with 3 fractions of postoperative electron beam were 16.0 to 16.2 Gy and 18.3 to 19.2 Gy, respectively, in less than 10 days for earlobe keloids and 21.5 to 22.2 Gy and 23.4 to 24.8 Gy, respectively, in less than 10 days for other sites. Conclusions: Postoperative keloid radiotherapy requires moderately high doses and optimal technique to be effective. The relatively low {alpha}/{beta} ratio indicates that radiotherapy with a limited number of fractions and high doses per fraction is the best strategy.« less

A double-blind, placebo-controlled, multicenter study with alprazolam and extended-release alprazolam in the treatment of panic disorder.

PubMed

Pecknold, J; Luthe, L; Munjack, D; Alexander, P

1994-10-01

This is a double-blind, placebo-controlled, flexible-dose, multicenter, 6-week study comparing regular alprazolam (compressed tablet, CT), given four times per day, and extended release alprazolam (XR), given once in the morning. The aim of the XR preparation is to offer less frequent dosing and to reduce interdose anxiety. Of the intent-to-treat group of 209 patients, 184 completed 3 weeks of medication and were evaluated according to protocol. There was a completer rate for the 6 weeks of 94% (CT), 97% (XR), and 87% (placebo). On global measures, Hamilton Rating Scale for Anxiety, phobia rating, and work disability measures, both active treatment groups were equally effective and significantly more efficacious than the placebo cell on endpoint MANOVA analysis. On analysis of the panic factor with endpoint data, both active treatment groups were equally effective throughout the 6-week trial and significantly more efficacious than the placebo group. Drowsiness occurred more frequently with CT alprazolam (86% of patients) than with the XR preparation (79%) or placebo (49%).

Calibration factors for the SNOOPY NP-100 neutron dosimeter

NASA Astrophysics Data System (ADS)

Moscu, D. F.; McNeill, F. E.; Chase, J.

2007-10-01

Within CANDU nuclear power facilities, only a small fraction of workers are exposed to neutron radiation. For these individuals, roughly 4.5% of the total radiation equivalent dose is the result of exposure to neutrons. When this figure is considered across all workers receiving external exposure of any kind, only 0.25% of the total radiation equivalent dose is the result of exposure to neutrons. At many facilities, the NP-100 neutron dosimeter, manufactured by Canberra Industries Incorporated, is employed in both direct and indirect dosimetry methods. Also known as "SNOOPY", these detectors undergo calibration, which results in a calibration factor relating the neutron count rate to the ambient dose equivalent rate, using a standard Am-Be neutron source. Using measurements presented in a technical note, readings from the dosimeter for six different neutron fields in six source-detector orientations were used, to determine a calibration factor for each of these sources. The calibration factor depends on the neutron energy spectrum and the radiation weighting factor to link neutron fluence to equivalent dose. Although the neutron energy spectra measured in the CANDU workplace are quite different than that of the Am-Be calibration source, the calibration factor remains constant - within acceptable limits - regardless of the neutron source used in the calibration; for the specified calibration orientation and current radiation weighting factors. However, changing the value of the radiation weighting factors would result in changes to the calibration factor. In the event of changes to the radiation weighting factors, it will be necessary to assess whether a change to the calibration process or resulting calibration factor is warranted.

Comparison of organ doses for patients undergoing balloon brachytherapy of the breast with HDR 192Ir or electronic sources using Monte Carlo simulations in a heterogeneous human phantom1

PubMed Central

Mille, Matthew M.; Xu, X. George; Rivard, Mark J.

2010-01-01

Purpose: Accelerated partial breast irradiation via interstitial balloon brachytherapy is a fast and effective treatment method for certain early stage breast cancers. The radiation can be delivered using a conventional high-dose rate (HDR) 192Ir gamma-emitting source or a novel electronic brachytherapy (eBx) source which uses lower energy x rays that do not penetrate as far within the patient. A previous study [A. Dickler, M. C. Kirk, N. Seif, K. Griem, K. Dowlatshahi, D. Francescatti, and R. A. Abrams, “A dosimetric comparison of MammoSite high-dose-rate brachytherapy and Xoft Axxent electronic brachytherapy,” Brachytherapy 6, 164–168 (2007)] showed that the target dose is similar for HDR 192Ir and eBx. This study compares these sources based on the dose received by healthy organs and tissues away from the treatment site. Methods: A virtual patient with left breast cancer was represented by a whole-body, tissue-heterogeneous female voxel phantom. Monte Carlo methods were used to calculate the dose to healthy organs in a virtual patient undergoing balloon brachytherapy of the left breast with HDR 192Ir or eBx sources. The dose-volume histograms for a few organs which received large doses were also calculated. Additional simulations were performed with all tissues in the phantom defined as water to study the effect of tissue inhomogeneities. Results: For both HDR 192Ir and eBx, the largest mean organ doses were received by the ribs, thymus gland, left lung, heart, and sternum which were close to the brachytherapy source in the left breast. eBx yielded mean healthy organ doses that were more than a factor of ∼1.4 smaller than for HDR 192Ir for all organs considered, except for the three closest ribs. Excluding these ribs, the average and median dose-reduction factors were ∼28 and ∼11, respectively. The volume distribution of doses in nearby soft tissue organs that were outside the PTV were also improved with eBx. However, the maximum dose to the closest rib with the eBx source was 5.4 times greater than that of the HDR 192Ir source. The ratio of tissue-to-water maximum rib dose for the eBx source was ∼5. Conclusions: The results of this study indicate that eBx may offer lower toxicity to most healthy tissues, except nearby bone. TG-43 methods have a tendency to underestimate dose to bone, especially the ribs. Clinical studies evaluating the negative health effects caused by irradiating healthy organs are needed so that physicians can better understand when HDR 192Ir or eBx might best benefit a patient. PMID:20229875

Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice

NASA Astrophysics Data System (ADS)

Yu, Kanglun; Doherty, Alison H.; Genik, Paula C.; Gookin, Sara E.; Roteliuk, Danielle M.; Wojda, Samantha J.; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E.; Weil, Michael M.; Donahue, Seth W.

2017-11-01

During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation.

Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study.

PubMed

Feuvret, Loïc; Bracci, Stefano; Calugaru, Valentin; Bolle, Stéphanie; Mammar, Hamid; De Marzi, Ludovic; Bresson, Damien; Habrand, Jean-Louis; Mazeron, Jean-Jacques; Dendale, Rémi; Noël, Georges

2016-05-01

Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study

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

Feuvret, Loïc, E-mail: loic.feuvret@psl.aphp.fr; Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d'Orsay; Bracci, Stefano

Purpose: Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). Methods and Materials: From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE];more » range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. Results: With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. Conclusions: Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended.« less

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

Simulation of internal contamination screening with dose rate meters

NASA Astrophysics Data System (ADS)

Fonseca, T. C. F.; Mendes, B. M.; Hunt, J. G.

2017-11-01

Assessing the intake of radionuclides after an accident in a nuclear power plant or after the intentional release of radionuclides in public places allows dose calculations and triage actions to be carried out for members of the public and for emergency response teams. Gamma emitters in the lung, thyroid or the whole body may be detected and quantified by making dose rate measurements at the surface of the internally contaminated person. In an accident scenario, quick measurements made with readily available portable equipment are a key factor for success. In this paper, the Monte Carlo program Visual Monte Carlo (VMC) and MCNPx code are used in conjunction with voxel phantoms to calculate the dose rate at the surface of a contaminated person due to internally deposited radionuclides. A whole body contamination with 137Cs and a thyroid contamination with 131I were simulated and the calibration factors in kBq per μSv/h were calculated. The calculated calibration factors were compared with real data obtained from the Goiania accident in the case of 137Cs and the Chernobyl accident in terms of the 131I. The close comparison of the calculated and real measurements indicates that the method may be applied to other radionuclides. Minimum detectable activities are discussed.

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

PubMed

Garibaldi, Elisabetta; Gabriele, Domenico; Maggio, Angelo; Delmastro, Elena; Garibaldi, Monica; Russo, Filippo; Bresciani, Sara; Stasi, Michele; Gabriele, Pietro

2017-09-01

The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.

Proton flux and radiation dose from galactic cosmic rays in the lunar regolith and implications for organic synthesis at the poles of the Moon and Mercury

NASA Astrophysics Data System (ADS)

Crites, S. T.; Lucey, P. G.; Lawrence, D. J.

2013-11-01

Galactic cosmic rays are a potential energy source to stimulate organic synthesis from simple ices. The recent detection of organic molecules at the polar regions of the Moon by LCROSS (Colaprete, A. et al. [2010]. Science 330, 463-468, http://dx.doi.org/10.1126/science.1186986), and possibly at the poles of Mercury (Paige, D.A. et al. [2013]. Science 339, 300-303, http://dx.doi.org/10.1126/science.1231106), introduces the question of whether the organics were delivered by impact or formed in situ. Laboratory experiments show that high energy particles can cause organic production from simple ices. We use a Monte Carlo particle scattering code (MCNPX) to model and report the flux of GCR protons at the surface of the Moon and report radiation dose rates and absorbed doses at the Moon’s surface and with depth as a result of GCR protons and secondary particles, and apply scaling factors to account for contributions to dose from heavier ions. We compare our results with dose rate measurements by the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) experiment on Lunar Reconnaissance Orbiter (Schwadron, N.A. et al. [2012]. J. Geophys. Res. 117, E00H13, http://dx.doi.org/10.1029/2011JE003978) and find them in good agreement, indicating that MCNPX can be confidently applied to studies of radiation dose at and within the surface of the Moon. We use our dose rate calculations to conclude that organic synthesis is plausible well within the age of the lunar polar cold traps, and that organics detected at the poles of the Moon may have been produced in situ. Our dose rate calculations also indicate that galactic cosmic rays can induce organic synthesis within the estimated age of the dark deposits at the pole of Mercury that may contain organics.

Protection of Salivary Function by Concomitant Pilocarpine During Radiotherapy: A Double-Blind, Randomized, Placebo-Controlled Study

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

Burlage, Fred R.; Roesink, Judith M.; Kampinga, Harm H.

2008-01-01

Purpose: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. Methods and Materials: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dosemore » distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Results: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Conclusions: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.« less

Fate and effects of nitrogen and phosphorus in shallow vegetated aquatic ecosystems

USGS Publications Warehouse

Fairchild, James F.; Vradenburg, Leigh Ann

2006-01-01

Nitrate concentrations have greatly increased in streams and rivers draining agricultural regions of the Midwestern United States, increasing nitrate transport to the Gulf of Mexico has been implicated in the hypoxic conditions that threaten the productivity of marine fisheries. Increases in nitrate concentrations have been attributed to a combination of factors including agricultural expansion, increased nitrogen application rates, increased tile drainage, and loss of riparian Wetlands, These landscape-level changes have resulted in a decreased natural capacity for nitrogen uptake, removal, and cycling back to the atmosphere. Land managers are increasingly interested in using wetland construction and rehabilitation as a management practice to reduce loss of nitrate from the terrestrial systems. Yet, relatively little is known about the limnological factors involved in nitrate removal by Wetland systems.We conducted a series of studies from 1999-2000 to investigate the functional capacity of shallow, macrophyte-dominated pond wetland systems for uptake, assimilation, and retention of nitrogen (N) and phosphorus (P). We evaluated four factors that were hypothesized to influence nutrient uptake and assimilation: 1) nitrate loading rates; 2) nitrogen to phosphorus (N.P) ratios; 3) frequency of dosing/application; and 4) timing of dose initiation.Nutrient assimilation was rapid; store than 90% of added nutrients were removed from the water column in all treatments. Neither variation in N:P ratios (evaluated range, <13:1 to -114.1), frequency of application (weekly or bi-weekly), nor liming of dose initiation relative to macrophyte development (0%, 15-25%, or 75-90% maximum biomass) had significant effects on nutrient assimilation of wetland community dynamics. Maximum loading of nitrate (60 g N/m2 2.4 g P/m2) applied as six weekly doses stimulated algal communities, but inhibited macrophyte communities.Predicted shifts from a stable state of macrophyte- to phytoplankton-dominance did not occur due to nutrient additions. Macrophytes, phytoplankton, and the sediment surface were all significant factors in the removal of nitrate from the Water column. Overall, these shallow macrophyte-dominated systems provided an efficient means of removing nutrients from the water column. Construction or rehabilitation of shallow, vegetated wetlands may offer promise as land management practices for nutrient removal in agricultural watersheds.

Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A meta-analysis of contemporary randomized controlled trials.

PubMed

Wang, Kang-Ling; Giugliano, Robert P; Goto, Shinya; Chiu, Chun-Chih; Lin, Chun-Yi; Lai, En-Yu; Chiang, Chern-En

2016-12-01

Although randomized controlled trials (RCTs) indicated that standard dose non-vitamin K antagonist oral anticoagulants (NOACs) were more compelling, low dose NOACs are commonly used in clinical practice in Asia. The purpose of this study was to assess the relative therapeutic benefit and risk of standard dose vs low dose NOACs in Asian patients enrolled in contemporary RCTs. We performed a prespecified meta-analysis of 3155 Asian patients with NOACs in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trials. Efficacy and safety with standard dose vs low dose NOACs were compared by risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model. An evidence network incorporating additional Asian patients from ROCKET AF, J- ROCKET AF, and ARISTOTLE was constructed with the Bayesian method. Risks of stroke or systemic embolism and ischemic stroke were significantly reduced with standard dose vs low dose NOACs (RR 0.62, 95% CI 0.45-0.85; and RR 0.55, 95% CI 0.38-0.79, respectively). Rates of major, intracranial, and life-threatening bleeding with 2 dosing regimens were broadly similar (RR 1.31, 95% CI 0.74-2.33; RR 1.54, 95% CI 0.72-3.30; and RR 1.49, 95% CI 0.87-2.55, respectively). Absolute rates of all-cause mortality and the net clinical outcome with standard dose NOACs were lower but not statistically significant (absolute reduction 0.4% per year and 1.1% per year, respectively). Network meta-analyses demonstrated that standard dose NOACs had the most favorable risk-benefit profile among oral anticoagulants. In Asian patients, standard dose NOACs represent a more appealing therapeutic option than low dose NOACs, with a significant reduction in ischemic stroke without an excess of major bleeding. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Measles vaccination in the presence or absence of maternal measles antibody: impact on child survival.

PubMed

Aaby, Peter; Martins, Cesário L; Garly, May-Lill; Andersen, Andreas; Fisker, Ane B; Claesson, Mogens H; Ravn, Henrik; Rodrigues, Amabelia; Whittle, Hilton C; Benn, Christine S

2014-08-15

Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present. To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data from 2 previously published randomized trials of a 2-dose schedule with MV given at 4-6 months and at 9 months of age. In both trials antibody levels had been measured before early measles vaccination. In trial I (1993-1995), the mortality rate was 0.0 per 1000 person-years among children vaccinated with MV in the presence of maternal antibody and 32.3 per 1000 person-years without maternal antibody (mortality rate ratio [MRR], 0.0; 95% confidence interval [CI], 0-.52). In trial II (2003-2007), the mortality rate was 4.2 per 1000 person-years among children vaccinated in presence of maternal measles antibody and 14.5 per 1000 person-years without measles antibody (MRR, 0.29; 95% CI, .09-.91). Possible confounding factors did not explain the difference. In a combined analysis, children who had measles antibody detected when they received their first dose of MV at 4-6 months of age had lower mortality than children with no maternal antibody, the MRR being 0.22 (95% CI, .07-.64) between 4-6 months and 5 years. Child mortality in low-income countries may be reduced by vaccinating against measles in the presence of maternal antibody, using a 2-dose schedule with the first dose at 4-6 months (earlier than currently recommended) and a booster dose at 9-12 months of age. NCT00168558. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Health-Related Quality of Life After Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Prostate Cancer

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

Morton, Gerard C., E-mail: gerard.morton@sunnybrook.ca; Loblaw, D. Andrew; Chung, Hans

Purpose: To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change. Methods and Materials: Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received high-dose-rate brachytherapy as a single 15-Gy implant, followed by external beam radiotherapy to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]). The proportion of patients developing a clinically significant difference in the EPIC domainmore » score (minimally important difference of >0.5 standard deviation) was determined and correlated with the baseline clinical and dosimetric factors. The study accrued 125 patients, with a median follow-up of 24 months. Results: By 24 months, 23% had Grade 2 urinary toxicity and only 5% had Grade 2 bowel toxicity, with no Grade 3 toxicity. The proportion of patients reporting a significant decrease in EPIC urinary, bowel, sexual, and hormonal domain scores was 53%, 51%, 45%, and 40% at 12 months and 57%, 65%, 51%, and 30% at 24 months, respectively. The proportion with a >1 standard deviation decrease in the EPIC urinary, bowel, sexual, and hormonal domain scores was 38%, 36%, 24%, and 20% at 12 months and 46%, 48%, 19%, and 8% at 24 months, respectively. On multivariate analysis, the dose to 10% of the urethra was associated with a decreasing EPIC urinary domain score (p = .0089) and, less strongly (p = .0312) with a decreasing hormonal domain score. No association was found between the prostate volume, bladder dose, or high-dose volume and urinary health-related quality of life. A high baseline International Index of Erectile Function score was associated (p = .0019) with a decreasing sexual domain score. The optimal maximal dose to 10% of the urethra cutpoint for urinary health-related quality of life was 120% of the prescription dose. Conclusion: EPIC was a more sensitive tool for detecting the effects on function and bother than were the generic toxicity scales. The urethral dose had the strongest association with a deteriorating urinary quality of life.« less

Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer.

PubMed

Matsuo, Koji; Cahoon, Sigita S; Yoshihara, Kosuke; Shida, Masako; Kakuda, Mamoru; Adachi, Sosuke; Moeini, Aida; Machida, Hiroko; Garcia-Sayre, Jocelyn; Ueda, Yutaka; Enomoto, Takayuki; Mikami, Mikio; Roman, Lynda D; Sood, Anil K

2016-07-01

To examine the survival outcomes in women with endometrial cancer who were taking low-dose aspirin (81-100 mg/d). A multicenter retrospective study was conducted examining patients with stage I-IV endometrial cancer who underwent hysterectomy-based surgical staging between January 2000 and December 2013 (N=1,687). Patient demographics, medical comorbidities, medication types, tumor characteristics, and treatment patterns were correlated to survival outcomes. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio for disease-free and disease-specific overall survival. One hundred fifty-eight patients (9.4%, 95% confidence interval [CI] 8.8-11.9) were taking low-dose aspirin. Median follow-up time for the study cohort was 31.5 months. One hundred twenty-seven patients (7.5%) died of endometrial cancer. Low-dose aspirin use was significantly correlated with concurrent obesity, hypertension, diabetes mellitus, and hypercholesterolemia (all P<.001). Low-dose aspirin users were more likely to take other antihypertensive, antiglycemic, and anticholesterol agents (all P<.05). Low-dose aspirin use was not associated with histologic subtype, tumor grade, nodal metastasis, or cancer stage (all P>.05). On multivariable analysis, low-dose aspirin use remained an independent prognostic factor associated with an improved 5-year disease-free survival rate (90.6% compared with 80.9%, adjusted hazard ratio 0.46, 95% CI 0.25-0.86, P=.014) and disease-specific overall survival rate (96.4% compared with 87.3%, adjusted hazard ratio 0.23, 95% CI 0.08-0.64, P=.005). The increased survival effect noted with low-dose aspirin use was greatest in patients whose age was younger than 60 years (5-year disease-free survival rates, 93.9% compared with 84.0%, P=.013), body mass index was 30 or greater (92.2% compared with 81.4%, P=.027), who had type I cancer (96.5% compared with 88.6%, P=.029), and who received postoperative whole pelvic radiotherapy (88.2% compared with 61.5%, P=.014). These four factors remained significant for disease-specific overall survival (all P<.05). Our results suggest that low-dose aspirin use is associated with improved survival outcomes in women with endometrial cancer, especially in those who are young, obese, with low-grade disease, and who receive postoperative radiotherapy.

The direct biologic effects of radioactive 125I seeds on pancreatic cancer cells PANC-1, at continuous low-dose rates.

PubMed

Wang, Jidong; Wang, Junjie; Liao, Anyan; Zhuang, Hongqing; Zhao, Yong

2009-08-01

The relative biologic effectiveness of model 6711 125I seeds (Ningbo Junan Pharmaceutical Technology Company,Ningbo, China) and their effects on growth, cell cycle, and apoptosis in human pancreatic cancer cell line PANC-1 were examined in the present study. PANC-1 cells were exposed to the absorbed doses of 1, 2, 4, 6, 8, and 10 Gyeither with 125I seeds (initial dose rate, 2.59 cGy=h) or with 60Co g-ray irradiation (dose rate, 221 cGy=min),respectively. Significantly greater numbers of apoptotic PANC-1 cells were detected following the continuouslow-dose-rate (CLDR) irradiation of 125I seeds, compared with cells irradiated with identical doses of 60Co g-ray. The D(0) for 60Co g-ray and 125I seed irradiation were 2.30 and 1.66, respectively. The survival fraction after 125Iseed irradiation was significantly lower than that of 60Co g-ray, with a relative biologic effectiveness of 1.39.PANC-1 cells were dose dependently arrested in the S-phase by 60Co g-rays and in the G2=M phase by 125I seeds,24 hour after irradiation. CLDR irradiation by 125I seeds was more effective in inducing cell apoptosis in PANC-1cells than acute high-dose-rate 60Co g irradiation. Interestingly, CLDR irradiation by 125I seeds can cause PANC-1cell-cycle arrest at the G2=M phase and induce apoptosis, which may be an important mechanism underlying 125Iseed-induced PANC-1 cell inhibition.

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

Liu, H; Lin, H; Darafsheh, A

Purpose: To characterize basic performance of plastic scintillator detectors (PSD) designed for dosimetry of radiation therapy. Methods: The Exradin W1 Scintillator is a plastic scintillating fiber-based detector designed for highly accurate measurement of small radiotherapy fields used in patient plan verification and machine commissioning and QA procedures. The Cerenkov emissions were corrected using spectral separation. The optical signal was converted to electronic signal with a photodiode. We measured its dosimetry performance, including percentage depth dose, output factor, dose and dose rate linear response. We compared the dosimetry results with reference ion chamber measurements. Results: The dosimetry results of PSD agreemore » well with reference ion chamber measurements. For percentage depth dose, the differences between PSD and ion chamber results are on average 1.7±1.1% and 0.8±0.8% with a maximum of 3.5% and 2.7% for 6MV and 15MV beams, respectively. For the output factors, PSD measurements are within 2% from ion chamber results. The dose linear response is within 1% when dose is larger than 20 MU for both 6 MV and 15 MV. The dose rate linear response is within 1% for the entire dose rate used (100 MU/min to 600MU/min). Conclusions: The current design of PSD is feasible for the dosimtry measurement in radiation therapy. This combination of PSD and photodiode system could be extended to multichannel array detection of dose distribution. It might as well be used as range verification in proton therapy. The work is partially supported by: DOD (W81XWH-09-2-0174) and American Cancer Society (IRG-78-002-28)« less

Protracted exposure to fallout: the Rongelap and Utirik experience.

PubMed

Lessard, E T; Miltenberger, R P; Cohn, S H; Musolino, S V; Conard, R A

1984-03-01

From June 1946 to August 1958, the U.S. Department of Defense and the U.S. Atomic Energy Commission (AEC) conducted nuclear weapons tests in the Northern Marshall Islands. On 1 March 1954, BRAVO, an above-ground test in the Castle series, produced high levels of radioactive material, some of which subsequently fell on Rongelap and Utirik Atolls due to an unexpected wind shift. On 3 March 1954, the inhabitants of these atolls were moved out of the affected area. They later returned to Utirik in June 1954 and to Rongelap in June 1957. Comprehensive environmental and personnel radiological monitoring programs were initiated in the mid 1950s by Brookhaven National Laboratory to ensure that body burdens of the exposed Marshallese subjects remained within AEC guidelines. Their body-burden histories and calculated activity ingestion rate patterns post-return are presented along with estimates of internal committed effective dose equivalents. External exposure data are also included. In addition, relationships between body burden or urine-activity concentration and declining continuous intake were developed. The implications of these studies are: (1) the dietary intake of 137Cs was a major component contributing to the committed effective dose equivalent for the years after the initial contamination of the atolls; (2) for persons whose diet included fish, 65Zn was a major component of committed effective dose equivalent during the first years post-return; (3) a decline in the daily activity ingestion rate greater than that resulting from radioactive decay of the source was estimated for 137Cs, 65Zn, 90Sr and 60Co; (4) the relative impact of each nuclide on the estimate of committed effective dose equivalent was dependent upon the time interval between initial contamination and rehabilitation; and (5) the internal committed effective dose equivalent exceeded the external dose equivalent by a factor of 1.1 at Utirik and 1.5 at Rongelap during the rehabitation period. Few reliable 239Pu measurements on human excreta were made. An analysis of the tentative data leads to the conclusion that a reliable estimate of committed effective dose equivalent requires further research.

Biology Based Lung Cancer Model for Chronic Low Radon Exposures

NASA Astrophysics Data System (ADS)

TruÅ£ǎ-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

2008-08-01

Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival. To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates.

TU-H-CAMPUS-IeP1-03: Comparison of Monte Carlo Simulation and Conversion Factor Based Method On Estimation of Effective Dose in Pediatric Patients Undergoing Interventional Cardiac Procedures

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

Leung, K; Wong, M; Ng, Y

Purpose: Interventional cardiac procedures utilize frequent fluoroscopy and cineangiography, which impose considerable radiation risk to patients, especially pediatric patients. Accurate calculation of effective dose is important in order to estimate cancer risk over the rest of their lifetime. This study evaluates the difference in effective dose calculated by Monte Carlo simulation with those estimated by locally-derived conversion factors (CF-local) and by commonly quoted conversion factors from Karambatsakidou et al (CF-K). Methods: Effective dose (E),of 12 pediatric patients, age between 2.5–19 years old, who had undergone interventional cardiac procedures, were calculated using PCXMC-2.0 software. Tube spectrum, irradiation geometry, exposure parameters andmore » dose-area product (DAP) of each projection were included in the software calculation. Effective doses for each patient were also estimated by two Methods: 1) CF-local: conversion factor derived locally by generalizing results of 12 patients, multiplied by DAP of each patient gives E-local. 2) CF-K: selected factor from above-mentioned literature, multiplied by DAP of each patient gives E-K. Results: Mean of E, E-local and E-K were 16.01 mSv, 16.80 mSv and 22.25 mSv respectively. A deviation of −29.35% to +34.85% between E and E-local, while a greater deviation of −28.96% to +60.86% between E and EK were observed. E-K overestimated the effective dose for patients at age 7.5–19. Conclusion: Effective dose obtained by conversion factors is simple and quick to estimate radiation risk of pediatric patients. This study showed that estimation by CF-local may bear an error of 35% when compared with Monte Carlo calculation. If using conversion factors derived by other studies may result in an even greater error, of up to 60%, due to factors that are not catered for in the estimation, including patient size, projection angles, exposure parameters, tube filtration, etc. Users must be aware of these potential inaccuracies when simple conversion method is employed.« less

Environmental radioactivity in the UK: the airborne geophysical view of dose rate estimates.

PubMed

Beamish, David

2014-12-01

This study considers UK airborne gamma-ray data obtained through a series of high spatial resolution, low altitude surveys over the past decade. The ground concentrations of the naturally occurring radionuclides Potassium, Thorium and Uranium are converted to air absorbed dose rates and these are used to assess terrestrial exposure levels from both natural and technologically enhanced sources. The high resolution airborne information is also assessed alongside existing knowledge from soil sampling and ground-based measurements of exposure levels. The surveys have sampled an extensive number of the UK lithological bedrock formations and the statistical information provides examples of low dose rate lithologies (the formations that characterise much of southern England) to the highest sustained values associated with granitic terrains. The maximum dose rates (e.g. >300 nGy h(-1)) encountered across the sampled granitic terrains are found to vary by a factor of 2. Excluding granitic terrains, the most spatially extensive dose rates (>50 nGy h(-1)) are found in association with the Mercia Mudstone Group (Triassic argillaceous mudstones) of eastern England. Geological associations between high dose rate and high radon values are also noted. Recent studies of the datasets have revealed the extent of source rock (i.e. bedrock) flux attenuation by soil moisture in conjunction with the density and porosity of the temperate latitude soils found in the UK. The presence or absence of soil cover (and associated presence or absence of attenuation) appears to account for a range of localised variations in the exposure levels encountered. The hypothesis is supported by a study of an extensive combined data set of dose rates obtained from soil sampling and by airborne geophysical survey. With no attenuation factors applied, except those intrinsic to the airborne estimates, a bias to high values of between 10 and 15 nGy h(-1) is observed in the soil data. A wide range of technologically enhanced, localised contributions to dose rate values are also apparent in the data sets. Two detailed examples are provided that reveal the detectability of site-scale environmental impacts due to former industrial activities and the high dose values (>500 nGy h(-1)) that are associated with former, small-scale Uranium mining operations. Copyright © 2014. Published by Elsevier Ltd.

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

PubMed

Fisher, Darrell R; Fahey, Frederic H

2017-08-01

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

Calibration of strontium-90 eye applicator using a strontium external beam standard.

PubMed

Siddle, D; Langmack, K

1999-07-01

Four techniques for measuring the dose rate from Sr-90 concave eye plaques are presented. The techniques involve calibrating a concave eye plaque against a Sr-90 teletherapy unit using X-Omat film, radiochromic film, black LiF TLD discs and LiF chips. The mean dose rate predicted by these dosimeters is 7.5 cGy s(-1). The dose rate quoted by the manufacturer is 33% lower than this value, which is consistent with discrepancies reported by other authors. Calibration against a 6 MV linear accelerator was also carried out using each of the above dosimetric devices, and appropriate sensitivity correction factors have been presented.

Calibration of strontium-90 eye applicator using a strontium external beam standard

NASA Astrophysics Data System (ADS)

Siddle, D.; Langmack, K.

1999-07-01

Four techniques for measuring the dose rate from Sr-90 concave eye plaques are presented. The techniques involve calibrating a concave eye plaque against a Sr-90 teletherapy unit using X-Omat film, radiochromic film, black LiF TLD discs and LiF chips. The mean dose rate predicted by these dosimeters is 7.5 cGy s-1. The dose rate quoted by the manufacturer is 33% lower than this value, which is consistent with discrepancies reported by other authors. Calibration against a 6 MV linear accelerator was also carried out using each of the above dosimetric devices, and appropriate sensitivity correction factors have been presented.

Are radiosensitivity data derived from natural field conditions consistent with data from controlled exposures? A case study of Chernobyl wildlife chronically exposed to low dose rates.

PubMed

Garnier-Laplace, J; Geras'kin, S; Della-Vedova, C; Beaugelin-Seiller, K; Hinton, T G; Real, A; Oudalova, A

2013-07-01

The discrepancy between laboratory or controlled conditions ecotoxicity tests and field data on wildlife chronically exposed to ionising radiation is presented for the first time. We reviewed the available chronic radiotoxicity data acquired in contaminated fields and used a statistical methodology to support the comparison with knowledge on inter-species variation of sensitivity to controlled external γ irradiation. We focus on the Chernobyl Exclusion Zone and effects data on terrestrial wildlife reported in the literature corresponding to chronic dose rate exposure situations (from background ~100 nGy/h up to ~10 mGy/h). When needed, we reconstructed the dose rate to organisms and obtained consistent unbiased data sets necessary to establish the dose rate-effect relationship for a number of different species and endpoints. Then, we compared the range of variation of radiosensitivity of species from the Chernobyl-Exclusion Zone with the statistical distribution established for terrestrial species chronically exposed to purely gamma external irradiation (or chronic Species radioSensitivity Distribution - SSD). We found that the best estimate of the median value (HDR50) of the distribution established for field conditions at Chernobyl (about 100 μGy/h) was eight times lower than the one from controlled experiments (about 850 μGy/h), suggesting that organisms in their natural environmental were more sensitive to radiation. This first comparison highlights the lack of mechanistic understanding and the potential confusion coming from sampling strategies in the field. To confirm the apparent higher sensitive of wildlife in the Chernobyl Exclusion Zone, we call for more a robust strategy in field, with adequate design to deal with confounding factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin

PubMed Central

Media, Joseph; Chen, Ben; Valeriote, Fredrick

2013-01-01

Purpose UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. Materials and Methods BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg respectively on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and bodyweights were monitored. Results UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150% of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200% of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight-loss induced by cisplatin indicating that bodyweight may not be a sensitive enough measure for chemoprotection of UTL-5g against cisplatin. Conclusions In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted. PMID:23881213

The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin.

PubMed

Shaw, Jiajiu; Media, Joseph; Chen, Ben; Valeriote, Fredrick

2013-09-01

UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg, respectively, on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and body weights were monitored. UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150 % of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200 % of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight loss induced by cisplatin, indicating that body weight may not be a sensitive-enough measure for chemoprotection of UTL-5g against cisplatin. In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin, indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted.

Risk of ischemic heart disease in women after radiotherapy for breast cancer.

PubMed

Darby, Sarah C; Ewertz, Marianne; McGale, Paul; Bennet, Anna M; Blom-Goldman, Ulla; Brønnum, Dorthe; Correa, Candace; Cutter, David; Gagliardi, Giovanna; Gigante, Bruna; Jensen, Maj-Britt; Nisbet, Andrew; Peto, Richard; Rahimi, Kazem; Taylor, Carolyn; Hall, Per

2013-03-14

Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain. We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart. The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy. Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.).

Spatial distribution and vertical migration of (137)Cs in soils of Belgrade (Serbia) 25 years after the Chernobyl accident.

PubMed

Petrović, Jelena; Ćujić, Mirjana; Đorđević, Milan; Dragović, Ranko; Gajić, Boško; Miljanić, Šćepan; Dragović, Snežana

2013-06-01

In this study, the specific activity of (137)Cs was determined by gamma-ray spectrometry in 72 surface soil samples and 11 soil profiles collected from the territory of Belgrade 25 years after the Chernobyl accident. Based on the data obtained the external effective gamma dose rates due to (137)Cs were assessed and geographically mapped. The influence of pedogenic factors (pH, specific electrical conductivity, cation exchange capacity, organic matter content, soil particle size and carbonate content) on the spatial and vertical distribution of (137)Cs in soil was estimated through Pearson correlations. The specific activity of (137)Cs in surface soil samples ranged from 1.00 to 180 Bq kg(-1), with a mean value of 29.9 Bq kg(-1), while in soil profiles they ranged from 0.90 to 58.0 Bq kg(-1), with a mean value of 15.3 Bq kg(-1). The mean external effective gamma dose at 1 m above the ground due to (137)Cs in the soil was calculated to be 1.96 nSv h(-1). Geographic mapping of the external effective gamma dose rates originating from (137)Cs revealed much higher dose rates in southern parts of Belgrade city and around the confluence of the Sava and Danube. Negative Pearson correlation coefficients were found between pH, cation exchange capacity and (137)Cs specific activity in surface soil. There were positive correlations between organic matter and (137)Cs specific activity in surface soil; and between specific electrical conductivity, organic matter, silt content and (137)Cs specific activity in soil profiles.

Dose-volume effects in pathologic lymph nodes in locally advanced cervical cancer.

PubMed

Bacorro, Warren; Dumas, Isabelle; Escande, Alexandre; Gouy, Sebastien; Bentivegna, Enrica; Morice, Philippe; Haie-Meder, Christine; Chargari, Cyrus

2018-03-01

In cervical cancer patients, dose-volume relationships have been demonstrated for tumor and organs-at-risk, but not for pathologic nodes. The nodal control probability (NCP) according to dose/volume parameters was investigated. Patients with node-positive cervical cancer treated curatively with external beam radiotherapy (EBRT) and image-guided brachytherapy (IGABT) were identified. Nodal doses during EBRT, IGABT and boost were converted to 2-Gy equivalent (α/β = 10 Gy) and summed. Pathologic nodes were followed individually from diagnosis to relapse. Statistical analyses comprised log-rank tests (univariate analyses), Cox proportional model (factors with p ≤ 0.1 in univariate) and Probit analyses. A total of 108 patients with 254 unresected pathological nodes were identified. The mean nodal volume at diagnosis was 3.4 ± 5.8 cm 3 . The mean total nodal EQD2 doses were 55.3 ± 5.6 Gy. Concurrent chemotherapy was given in 96%. With a median follow-up of 33.5 months, 20 patients (18.5%) experienced relapse in nodes considered pathologic at diagnosis. Overall nodal recurrence rate was 9.1% (23/254). On univariate analyses, nodal volume (threshold: 3 cm 3 , p < .0001) and lymph node dose (≥57.5 Gy α/β10 , p = .039) were significant for nodal control. The use of simultaneous boost was borderline for significance (p = .07). On multivariate analysis, volume (HR = 8.2, 4.0-16.6, p < .0001) and dose (HR = 2, 1.05-3.9, p = .034) remained independent factors. Probit analysis combining dose and volume showed significant relationships with NCP, with increasing gap between the curves with higher nodal volumes. A nodal dose-volume effect on NCP is demonstrated for the first time, with increasing NCP benefit of additional doses to higher-volume nodes. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of two oral doses of 17beta-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled study.

PubMed

Rousseau, Alexandra; Robert, Annie; Gerotziafas, Grigoris; Torchin, Dahlia; Zannad, Faiez; Lacut, Karine; Libersa, Christian; Dasque, Eric; Démolis, Jean-Louis; Elalamy, Ismail; Simon, Tabassome

2010-04-01

Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17beta-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17beta-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 +/- 50.23 nm, E2: 31.08 +/- 85.86 nm vs. 10.52 +/- 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 +/- 0.69 min vs. E1: -0.26 +/- 0.80 min, E2: -0.55 +/- 0.79 min, P <10(-3) for both comparisons) and mean rate index of the propagation phase of TG was significantly increased. Among the studied clotting factors, only the levels of FVII were significantly increased after treatment administration. The two doses of 17beta-estradiol induced in a similar degree an acceleration of the initiation and propagation phase of tissue factor triggered thrombin generation and a significant increase of FVII coagulant activity.

SU-E-I-78: Establishing a Protocol for Quick Estimation of Thyroid Internal Contamination with 131I in Normal and Emergency Situations

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

Naderi, S Mehdizadeh; Karimipourfard, M; Lotfalizadeh, F

2015-06-15

Purpose: I-131 is one of the most frequent radionuclides used in nuclear medicine departments. The radiation workers, who manipulate the unsealed radio-toxic iodine, should be monitored for internal contamination. In this study a protocol was established for estimating I-131 activity absorbed in the thyroid glands of the nuclear medicine staff in normal working condition and also in accidents. Methods: I-131 with the activity of 10 μCi was injected inside the thyroid gland of a home-made anthropomorphic neck phantom. The phantom is made up of PMMA as soft tissue, and Aluminium as bone. The dose rate at different distances from themore » surface of the neck phantom was measured using a scintillator detector for duration of two months. Then, calibration factors were obtained, for converting the dose rate at each distance to the iodine activity inside the thyroid. Results: According to the results of this study, the calibration factors for converting the dose rates (nSv/h) at distances of 0cm, 1cm, 6cm, 11cm, and 16cm to the activity (kBq) inside the thyroid were found to be 0.03, 0.04, 0.14, 0.29, and 0.49 . Conclusion: This method can be effectively used for quick estimation of the I-131 concentration inside the thyroid of the staff for daily checks in normal working conditions and also in accidents.« less

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.

Cardiovascular Responses to Caffeine by Gender and Pubertal Stage

PubMed Central

Ziegler, Amanda M.; Graczyk, Adam; Bendlin, Ashley; Sion, Teresa; Vattana, Karina

2014-01-01

BACKGROUND: Caffeine use is on the rise among children and adolescents. Previous studies from our laboratory reported gender differences in the effects of caffeine in adolescents. The purpose of this study was to test the hypotheses that gender differences in cardiovascular responses to caffeine emerge after puberty and that cardiovascular responses to caffeine differ across the phases of the menstrual cycle. METHODS: To test these hypotheses, we examined heart rate and blood pressure before and after administration of placebo and 2 doses of caffeine (1 and 2 mg/kg) in prepubertal (8- to 9-year-olds; n = 52) and postpubertal (15- to 17-year-olds; n = 49) boys (n = 54) and girls (n = 47) by using a double-blind, placebo-controlled, dose-response design. RESULTS: There was an interaction between gender and caffeine dose, with boys having a greater response to caffeine than girls. In addition, we found interactions between pubertal phase, gender, and caffeine dose, with gender differences present in postpubertal, but not in prepubertal, participants. Finally, we found differences in responses to caffeine across the menstrual cycle in post-pubertal girls, with decreases in heart rate greater in the midluteal phase and blood pressure increases greater in the midfollicular phase of the menstrual cycle. CONCLUSIONS: These data suggest that gender differences in response to caffeine emerge after puberty. Future research will determine the extent to which these gender differences are mediated by physiological factors, such as steroid hormones, or psychosocial factors, such as more autonomy and control over beverage purchases. PMID:24935999

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.

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.

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.

Reinforcing effects of sigma-receptor agonists in rats trained to self-administer cocaine.

PubMed

Hiranita, Takato; Soto, Paul L; Tanda, Gianluigi; Katz, Jonathan L

2010-02-01

sigma-Receptor (sigmaR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of sigmaR ligands in rats trained to self-administer cocaine (0.032-1.0 mg/kg/inj i.v.) under fixed-ratio 5-response schedules of reinforcement. Maximal rates of responding were maintained by 0.32 mg/kg/inj cocaine, or by the sigmaR agonists, 1,3-di-(2-tolyl)guanidine (DTG; 1.0 mg/kg/inj) or 2-(4-morpholinethyl) 1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084; 0.32 mg/kg/inj), when substituted for cocaine. Lower response rates were maintained at higher and lower doses of the compounds. No dose of the sigmaR antagonists [N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD 1047), N-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine (BD 1063)] maintained responding appreciably above levels obtained when responding had no consequences. Presession treatment with sigmaR agonists dose-dependently shifted the cocaine self-administration dose-effect curve leftward. The dopamine-uptake inhibitor, (-)-2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (WIN 35,428), dose-dependently shifted the DTG and PRE-084 self-administration dose-effect curves leftward. Treatment with the sigmaR antagonists dose-dependently decreased response rates maintained by DTG or PRE-084, but did not affect cocaine self-administration. Response rates maintained by maximally effective DTG or PRE-084 doses were decreased by sigmaR antagonists at lower doses than those that decreased response rates maintained by food reinforcement. Although sigmaR antagonists block some cocaine-induced effects, the lack of effect on cocaine self-administration suggests that the primary reinforcing effects of cocaine do not involve direct effects at sigmaRs. However, the self-administration of sigmaR agonists in cocaine-trained subjects, facilitation of cocaine self-administration by sigmaR-agonist pretreatment, and the facilitation of sigmaR-agonist self-administration by WIN 35,428, together suggest enhanced abuse-related effects resulting from concomitant dopaminergically mediated actions and sigmaR-mediated actions of the drugs.

Reinforcing Effects of σ-Receptor Agonists in Rats Trained to Self-Administer Cocaine

PubMed Central

Hiranita, Takato; Soto, Paul L.; Tanda, Gianluigi

2010-01-01

σ-Receptor (σR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of σR ligands in rats trained to self-administer cocaine (0.032–1.0 mg/kg/inj i.v.) under fixed-ratio 5-response schedules of reinforcement. Maximal rates of responding were maintained by 0.32 mg/kg/inj cocaine, or by the σR agonists, 1,3-di-(2-tolyl)guanidine (DTG; 1.0 mg/kg/inj) or 2-(4-morpholinethyl) 1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084; 0.32 mg/kg/inj), when substituted for cocaine. Lower response rates were maintained at higher and lower doses of the compounds. No dose of the σR antagonists [N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD 1047), N-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine (BD 1063)] maintained responding appreciably above levels obtained when responding had no consequences. Presession treatment with σR agonists dose-dependently shifted the cocaine self-administration dose-effect curve leftward. The dopamine-uptake inhibitor, (−)-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428), dose-dependently shifted the DTG and PRE-084 self-administration dose-effect curves leftward. Treatment with the σR antagonists dose-dependently decreased response rates maintained by DTG or PRE-084, but did not affect cocaine self-administration. Response rates maintained by maximally effective DTG or PRE-084 doses were decreased by σR antagonists at lower doses than those that decreased response rates maintained by food reinforcement. Although σR antagonists block some cocaine-induced effects, the lack of effect on cocaine self-administration suggests that the primary reinforcing effects of cocaine do not involve direct effects at σRs. However, the self-administration of σR agonists in cocaine-trained subjects, facilitation of cocaine self-administration by σR-agonist pretreatment, and the facilitation of σR-agonist self-administration by WIN 35,428, together suggest enhanced abuse-related effects resulting from concomitant dopaminergically mediated actions and σR-mediated actions of the drugs. PMID:19892920

Limitations of silicon diodes for clinical electron dosimetry.

PubMed

Song, Haijun; Ahmad, Munir; Deng, Jun; Chen, Zhe; Yue, Ning J; Nath, Ravinder

2006-01-01

This work investigates the relevance of several factors affecting the response of silicon diode dosemeters in depth-dose scans of electron beams. These factors are electron energy, instantaneous dose rate, dose per pulse, photon/electron dose ratio and electron scattering angle (directional response). Data from the literature and our own experiments indicate that the impact of these factors may be up to +/-15%. Thus, the different factors would have to cancel out perfectly at all depths in order to produce true depth-dose curves. There are reports of good agreement between depth-doses measured with diodes and ionisation chambers. However, our measurements with a Scantronix electron field detector (EFD) diode and with a plane-parallel ionisation chamber show discrepancies both in the build-up and in the low-dose regions, with a ratio up to 1.4. Moreover, the absolute sensitivity of two diodes of the same EFD model was found to differ by a factor of 3, and this ratio was not constant but changed with depth between 5 and 15% in the low-dose regions of some clinical electron beams. Owing to these inhomogeneities among diodes even of the same model, corrections for each factor would have to be diode-specific and beam-specific. All these corrections would have to be determined using parallel plane chambers, as recommended by AAPM TG-25, which would be unrealistic in clinical practice. Our conclusion is that in general diodes are not reliable in the measurement of depth-dose curves of clinical electron beams.

Fixed-dose combination therapy for the prevention of cardiovascular disease

PubMed Central

de Cates, Angharad N; Farr, Matthew RB; Wright, Nicola; Jarvis, Morag C; Rees, Karen; Ebrahim, Shah; Huffman, Mark D

2014-01-01

Background Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, yet CVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure and cholesterol lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of CVD by up to 80% given its potential for better adherence and lower costs. Objectives To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD. We also aimed to determine discontinuation rates, adverse events, health-related quality of life, and costs of fixed-dose combination therapy. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library(2013, Issue 6), MEDLINE Ovid (1946 to week 2 July 2013), EMBASE Ovid (1980 to Week 28 2013), ISI Web of Science (1970 to 19 July 2013), and the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), and Health Economics Evaluations Database (HEED) (2011, Issue 4) in The Cochrane Library. We used no language restrictions. Selection criteria We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure lowering and one lipid lowering component versus usual care, placebo, or a single drug active component for any treatment duration in adults ≥ 18 years old with no restrictions on presence or absence of pre-existing cardiovascular disease. Data collection and analysis Three review authors independently selected studies for inclusion and extracted the data. We evaluated risk of bias using the Cochrane risk of bias assessment tool. We sought to include outcome data on all-cause mortality, fatal and non-fatal CVD events, adverse events, changes in systolic and diastolic blood pressure, total and low density lipoprotein (LDL) cholesterol concentrations, discontinuation rates, quality of life, and costs. We calculated risk ratios (RR) for dichotomous data and weighted mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 > 50%). Main results We found nine randomised controlled trials with a total of 7047 participants. Seven of the nine trials evaluated the effects of fixed-dose combination therapy on primary CVD prevention, and the trial length ranged from six weeks to 15 months. We found a moderate to high risk of bias in the domains of selection, performance, detection, attrition, and other types of bias in five of the nine trials. Compared with the comparator groups, the effects of the fixed-dose combination treatment on mortality (1.2% versus 1.0%, RR 1.26, 95% CI 0.67 to 2.38, N = 3465) and cardiovascular events (4.0% versus 2.9%, RR 1.38, 95% CI 0.91 to 2.10, N = 2479) were uncertain (low quality evidence). The low event rates for these outcomes, limited availability of data as only two out of nine trials reported on these outcomes, and a high risk of bias in at least one domain suggest that these results should not be viewed with confidence. Adverse events were common in both the intervention (30%) and comparator (24%) groups, with participants randomised to fixed-dose combination therapy being 20% (95% CI 9% to 30%) more likely to report an adverse event. Notably, no serious adverse events were reported. Compared with placebo, the rate of discontinuation among participants randomised to fixed-dose combination was higher (14% versus 11%, RR 1.26 95% CI 1.02 to 1.55). The weighted mean differences in systolic and diastolic blood pressure between the intervention and control arms were -7.05 mmHg (95% CI -10.18 to -3.87) and -3.65 mmHg (95% CI -5.44 to -1.85), respectively. The weighted mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.75 mmol/L (95% CI -1.05 to -0.46) and -0.81 mmol/L (95% CI -1.09 to -0.53), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 70% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multi-drug strategy by 33% (26% to 41%) compared with usual care, but this comparison was reported in only one study. The effects of fixed-dose combination therapy on quality of life are uncertain, though these results were reported in only one trial. No trials reported costs. Authors' conclusions Compared with placebo, single drug active component, or usual care, the effects of fixed-dose combination therapy on all-cause mortality or CVD events are uncertain; only few trials report these outcomes and the included trials were primarily designed to observe changes in CVD risk factor levels rather than clinical events. Reductions in blood pressure and lipid parameters are generally lower than those previously projected, though substantial heterogeneity of results exists. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, single drug active component, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing trials of fixed-dose combination therapy will likely inform key outcomes. PMID:24737108

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

Effects of Solar Particle Event Proton Radiation on Parameters Related to Ferret Emesis

PubMed Central

Sanzari, J. K.; Wan, X. S.; Krigsfeld, G. S.; King, G. L.; Miller, A.; Mick, R.; Gridley, D. S.; Wroe, A. J.; Rightnar, S.; Dolney, D.; Kennedy, A. R.

2013-01-01

The effectiveness of simulated solar particle event (SPE) proton radiation to induce retching and vomiting was evaluated in the ferret experimental animal model. The endpoints measured in the study included: (1) the fraction of animals that retched or vomited, (2) the number of retches or vomits observed, (3) the latency period before the first retch or vomit and (4) the duration between the first and last retching or vomiting events. The results demonstrated that γ ray and proton irradiation delivered at a high dose rate of 0.5 Gy/min induced dose-dependent changes in the endpoints related to retching and vomiting. The minimum radiation doses required to induce statistically significant changes in retching- and vomiting-related endpoints were 0.75 and 1.0 Gy, respectively, and the relative biological effectiveness (RBE) of proton radiation at the high dose rate did not significantly differ from 1. Similar but less consistent and smaller changes in the retching- and vomiting-related endpoints were observed for groups irradiated with γ rays and protons delivered at a low dose rate of 0.5 Gy/h. Since this low dose rate is similar to a radiation dose rate expected during a SPE, these results suggest that the risk of SPE radiation-induced vomiting is low and may reach statistical significance only when the radiation dose reaches 1 Gy or higher. PMID:23883319

Development of a high sensitivity pinhole type gamma camera using semiconductors for low dose rate fields

NASA Astrophysics Data System (ADS)

Ueno, Yuichiro; Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi; Fujishima, Yasutake; Yoshida, Akira; Umegaki, Kikuo

2018-06-01

We developed a pinhole type gamma camera, using a compact detector module of a pixelated CdTe semiconductor, which has suitable sensitivity and quantitative accuracy for low dose rate fields. In order to improve the sensitivity of the pinhole type semiconductor gamma camera, we adopted three methods: a signal processing method to set the discriminating level lower, a high sensitivity pinhole collimator and a smoothing image filter that improves the efficiency of the source identification. We tested basic performances of the developed gamma camera and carefully examined effects of the three methods. From the sensitivity test, we found that the effective sensitivity was about 21 times higher than that of the gamma camera for high dose rate fields which we had previously developed. We confirmed that the gamma camera had sufficient sensitivity and high quantitative accuracy; for example, a weak hot spot (0.9 μSv/h) around a tree root could be detected within 45 min in a low dose rate field test, and errors of measured dose rates with point sources were less than 7% in a dose rate accuracy test.

Effective dose estimation for pediatric upper gastrointestinal examinations using an anthropomorphic phantom set and metal oxide semiconductor field-effect transistor (MOSFET) technology.

PubMed

Emigh, Brent; Gordon, Christopher L; Connolly, Bairbre L; Falkiner, Michelle; Thomas, Karen E

2013-09-01

There is a need for updated radiation dose estimates in pediatric fluoroscopy given the routine use of new dose-saving technologies and increased radiation safety awareness in pediatric imaging. To estimate effective doses for standardized pediatric upper gastrointestinal (UGI) examinations at our institute using direct dose measurement, as well as provide dose-area product (DAP) to effective dose conversion factors to be used for the estimation of UGI effective doses for boys and girls up to 10 years of age at other centers. Metal oxide semiconductor field-effect transistor (MOSFET) dosimeters were placed within four anthropomorphic phantoms representing children ≤10 years of age and exposed to mock UGI examinations using exposures much greater than used clinically to minimize measurement error. Measured effective dose was calculated using ICRP 103 weights and scaled to our institution's standardized clinical UGI (3.6-min fluoroscopy, four spot exposures and four examination beam projections) as determined from patient logs. Results were compared to Monte Carlo simulations and related to fluoroscope-displayed DAP. Measured effective doses for standardized pediatric UGI examinations in our institute ranged from 0.35 to 0.79 mSv in girls and were 3-8% lower for boys. Simulation-derived and measured effective doses were in agreement (percentage differences <19%, T > 0.18). DAP-to-effective dose conversion factors ranged from 6.5 ×10(-4) mSv per Gy-cm(2) to 4.3 × 10(-3) mSv per Gy-cm(2) for girls and were similarly lower for boys. Using modern fluoroscopy equipment, the effective dose associated with the UGI examination in children ≤10 years at our institute is < 1 mSv. Estimations of effective dose associated with pediatric UGI examinations can be made for children up to the age of 10 using the DAP-normalized conversion factors provided in this study. These estimates can be further refined to reflect individual hospital examination protocols through the use of direct organ dose measurement using MOSFETs, which were shown to agree with Monte Carlo simulated doses.

Caffeine's Influence on Nicotine's Effects in Nonsmokers

PubMed Central

Blank, Melissa D.; Kleykamp, Bethea A.; Jennings, Janine M.; Eissenberg, Thomas

2011-01-01

Objective To determine if nicotine's effects are influenced by caffeine in nonsmoking, moderate-caffeine consuming individuals (N=20). Methods The first 3 sessions included one of 3 randomly ordered, double-blind caffeine doses (0, 75, or 150 mg, oral [po]) and 2 single-blind nicotine gum doses (2 and 4 mg) in ascending order. The fourth session (single blind) repeated the 0 mg caffeine condition. Results Nicotine increased heart rate and subjective ratings indicative of aversive effects, and decreased reaction times. These effects were independent of caffeine dose and reliable across sessions. Conclusions In nonsmokers, nicotine effects are not influenced by moderate caffeine doses. PMID:17555378

Surface effects on the radiation response of nanoporous Au foams

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

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

2012-11-05

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

Once daily oral mesalamine compared to conventional dosing for induction and maintenance of remission in ulcerative colitis: a systematic review and meta-analysis.

PubMed

Feagan, Brian G; MacDonald, John K

2012-09-01

We systematically reviewed and compared the efficacy and safety of once daily (OD) mesalamine to conventional dosing for induction and maintenance of remission in ulcerative colitis (UC). A literature search to January 2012 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to assess the overall quality of the evidence. Studies were subgrouped by formulation for meta-analysis. Eleven studies that evaluated 4070 patients were identified. The risk of bias was low for most factors, although five studies were single-blind and one was open-label. No difference was observed between the dosing strategies in the proportion of patients with clinical remission (relative risk [RR] 0.95; 95% confidence interval [CI] 0.82-1.10), clinical improvement (RR 0.87 95% CI 0.68-1.10), or relapse at 6 (RR 1.10; 95% CI 0.83-1.46) or 12 months (RR 0.92; 95% CI 0.83-1.03). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of medication adherence or adverse events between OD and conventional dosing. OD mesalamine appears to be as effective and safe as conventional dosing for both the treatment of mild to moderately active UC and for maintenance of remission in quiescent UC. The failure to demonstrate a superior rate of adherence to OD dosing may be due to the high rate of adherence observed in the clinical trials environment. Future research should assess the value of OD dosing in community settings. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

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.

Absorbed doses of lungs from radon retained in airway lumens of mice and rats.

PubMed

Sakoda, Akihiro; Ishimori, Yuu; Yamaoka, Kiyonori; Kataoka, Takahiro; Mitsunobu, Fumihiro

2013-08-01

This paper provides absorbed doses arising from radon gas in air retained in lung airway lumens. Because radon gas exposure experiments often use small animals, the calculation was performed for mice and rats. For reference, the corresponding computations were also done for humans. Assuming that radon concentration in airway lumens is the same as that in the environment, its progeny's production in and clearance from airways were simulated. Absorbed dose rates were obtained for three lung regions and the whole lung, considering that secretory and basal cells are sensitive to radiation. The results showed that absorbed dose rates for all lung regions and whole lung generally increase from mice to rats to humans. For example, the dose rates for the whole lung were 25.4 in mice, 41.7 in rats, and 59.9 pGy (Bq m⁻³)⁻¹ h⁻¹ in humans. Furthermore, these values were also compared with lung dose rates from two other types of exposures, that is, due to inhalation of radon or its progeny, which were already reported. It was confirmed that the direct inhalation of radon progeny in the natural environment, which is known as a cause of lung cancer, results in the highest dose rates for all species. Based on the present calculations, absorbed dose rates of the whole lung from radon gas were lower by a factor of about 550 (mice), 200 (rats), or 70 (humans) than those from radon progeny inhalation. The calculated dose rate values are comparatively small. Nevertheless, the present study is considered to contribute to our understanding of doses from inhalation of radon and its progeny.

Diamond detector in absorbed dose measurements in high-energy linear accelerator photon and electron beams.

PubMed

Ravichandran, Ramamoorthy; Binukumar, John Pichy; Al Amri, Iqbal; Davis, Cheriyathmanjiyil Antony

2016-03-08

Diamond detectors (DD) are preferred in small field dosimetry of radiation beams because of small dose profile penumbras, better spatial resolution, and tissue-equivalent properties. We investigated a commercially available 'microdiamond' detector in realizing absorbed dose from first principles. A microdiamond detector, type TM 60019 with tandem electrometer is used to measure absorbed doses in water, nylon, and PMMA phantoms. With sensitive volume 0.004 mm3, radius 1.1mm, thickness 1 x10(-3) mm, the nominal response is 1 nC/Gy. It is assumed that the diamond detector could collect total electric charge (nC) developed during irradiation at 0 V bias. We found that dose rate effect is less than 0.7% for changing dose rate by 500 MU/min. The reproducibility in obtaining readings with diamond detector is found to be ± 0.17% (1 SD) (n = 11). The measured absorbed doses for 6 MV and 15 MV photons arrived at using mass energy absorption coefficients and stop-ping power ratios compared well with Nd, water calibrated ion chamber measured absorbed doses within 3% in water, PMMA, and nylon media. The calibration factor obtained for diamond detector confirmed response variation is due to sensitivity due to difference in manufacturing process. For electron beams, we had to apply ratio of electron densities of water to carbon. Our results qualify diamond dosimeter as a transfer standard, based on long-term stability and reproducibility. Based on micro-dimensions, we recommend these detectors for pretreatment dose verifications in small field irradiations like stereotactic treatments with image guidance.

Breathing-motion-compensated robotic guided stereotactic body radiation therapy : Patterns of failure analysis.

PubMed

Stera, Susanne; Balermpas, Panagiotis; Chan, Mark K H; Huttenlocher, Stefan; Wurster, Stefan; Keller, Christian; Imhoff, Detlef; Rades, Dirk; Dunst, Jürgen; Rödel, Claus; Hildebrandt, Guido; Blanck, Oliver

2018-02-01

We retrospectively evaluated the patterns of failure for robotic guided real-time breathing-motion-compensated (BMC) stereotactic body radiation therapy (SBRT) in the treatment of tumors in moving organs. Between 2011 and 2016, a total of 198 patients with 280 lung, liver, and abdominal tumors were treated with BMC-SBRT. The median gross tumor volume (GTV) was 12.3 cc (0.1-372.0 cc). Medians of mean GTV BED α/β = 10   Gy (BED = biological effective dose) was 148.5 Gy 10 (31.5-233.3 Gy 10 ) and prescribed planning target volume (PTV) BED α/β = 10   Gy was 89.7 Gy 10 (28.8-151.2 Gy 10 ), respectively. We analyzed overall survival (OS) and local control (LC) based on various factors, including BEDs with α/β ratios of 15 Gy (lung metastases), 21 Gy (primary lung tumors), and 27 Gy (liver metastases). Median follow-up was 10.4 months (2.0-59.0 months). The 2‑year actuarial LC was 100 and 86.4% for primary early and advanced stage lung tumors, respectively, 100% for lung metastases, 82.2% for liver metastases, and 90% for extrapulmonary extrahepatic metastases. The 2‑year OS rate was 47.9% for all patients. In uni- and multivariate analysis, comparatively lower PTV prescription dose (equivalence of 3 × 12-13 Gy) and higher average GTV dose (equivalence of 3 × 18 Gy) to current practice were significantly associated with LC. For OS, Karnofsky performance score (100%), gender (female), and SBRT without simultaneous chemotherapy were significant prognostic factors. Grade 3 side effects were rare (0.5%). Robotic guided BMC-SBRT can be considered a safe and effective treatment for solid tumors in moving organs. To reach sufficient local control rates, high average GTV doses are necessary. Further prospective studies are warranted to evaluate these points.

Effect of γ-dose rate and total dose interrelation on the polymeric hydrogel: A novel injectable male contraceptive

NASA Astrophysics Data System (ADS)

Jha, Pradeep K.; Jha, Rakhi; Gupta, B. L.; Guha, Sujoy K.

2010-05-01

Functional necessity to use a particular range of dose rate and total dose of γ-initiated polymerization to manufacture a novel polymeric hydrogel RISUG ® (reversible inhibition of sperm under guidance) made of styrene maleic anhydride (SMA) dissolved in dimethyl sulphoxide (DMSO), for its broad biomedical application explores new dimension of research. The present work involves 16 irradiated samples. They were tested by fourier transform infrared spectroscopy, matrix assisted laser desorption/ionization-TOF, field emission scanning electron microscopy, high resolution transmission electron microscopy, etc. to see the interrelation effect of gamma dose rates (8.25, 17.29, 20.01 and 25.00 Gy/min) and four sets of doses (1.8, 2.0, 2.2 and 2.4 kGy) on the molecular weight, molecular weight distribution and porosity analysis of the biopolymeric drug RISUG ®. The results of randomized experiment indicated that a range of 18-24 Gy/min γ-dose rate and 2.0-2.4 kGy γ-total doses is suitable for the desirable in vivo performance of the contraceptive copolymer.

Managing Lunar and Mars Mission Radiation Risks. Part 1; Cancer Risks, Uncertainties, and Shielding Effectiveness

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Kim, Myung-Hee Y.; Ren, Lei

2005-01-01

This document addresses calculations of probability distribution functions (PDFs) representing uncertainties in projecting fatal cancer risk from galactic cosmic rays (GCR) and solar particle events (SPEs). PDFs are used to test the effectiveness of potential radiation shielding approaches. Monte-Carlo techniques are used to propagate uncertainties in risk coefficients determined from epidemiology data, dose and dose-rate reduction factors, quality factors, and physics models of radiation environments. Competing mortality risks and functional correlations in radiation quality factor uncertainties are treated in the calculations. The cancer risk uncertainty is about four-fold for lunar and Mars mission risk projections. For short-stay lunar missins (<180 d), SPEs present the most significant risk, but one effectively mitigated by shielding. For long-duration (>180 d) lunar or Mars missions, GCR risks may exceed radiation risk limits. While shielding materials are marginally effective in reducing GCR cancer risks because of the penetrating nature of GCR and secondary radiation produced in tissue by relativisitc particles, polyethylene or carbon composite shielding cannot be shown to significantly reduce risk compared to aluminum shielding. Therefore, improving our knowledge of space radiobiology to narrow uncertainties that lead to wide PDFs is the best approach to ensure radiation protection goals are met for space exploration.

Consideration of the ICRP 2006 revised tissue weighting factors on age-dependent values of the effective dose for external photons

NASA Astrophysics Data System (ADS)

Lee, Choonsik; Lee, Choonik; Han, Eun Young; Bolch, Wesley E.

2007-01-01

The effective dose recommended by the International Commission on Radiological Protection (ICRP) is the sum of organ equivalent doses weighted by corresponding tissue weighting factors, wT. ICRP is in the process of revising its 1990 recommendations on the effective dose where new values of organs and tissue weighting factors have been proposed and published in draft form for consultation by the radiological protection community. In its 5 June 2006 draft recommendations, new organs and tissues have been introduced in the effective dose which do not exist within the 1987 Oak Ridge National Laboratory (ORNL) phantom series (e.g., salivary glands). Recently, the investigators at University of Florida have updated the series of ORNL phantoms by implementing new organ models and adopting organ-specific elemental composition and densities. In this study, the effective dose changes caused by the transition from the current recommendation of ICRP Publication 60 to the 2006 draft recommendations were investigated for external photon irradiation across the range of ICRP reference ages (newborn, 1-year, 5-year, 10-year, 15-year and adult) and for six idealized irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), left-lateral (LLAT), right-lateral (RLAT), rotational (ROT) and isotropic (ISO). Organ-absorbed doses were calculated by implementing the revised ORNL phantoms in the Monte Carlo radiation transport code, MCNPX2.5, after which effective doses were calculated under the 1990 and draft 2006 evaluation schemes of the ICRP. Effective doses calculated under the 2006 draft scheme were slightly higher than estimated under ICRP Publication 60 methods for all irradiation geometries exclusive of the AP geometry where an opposite trend was observed. The effective doses of the adult phantom were more greatly affected by the change in tissue weighting factors than that seen within the paediatric members of the phantom series. Additionally, dose conversion coefficients for newly identified radiosensitive organs—salivary glands, gall bladder, heart and prostate—were reported, as well as the brain, which was originally considered in ICRP Publication 60 as a member of the remainder category of the effective dose.

Modelling the dynamics of ambient dose rates induced by radiocaesium in the Fukushima terrestrial environment

NASA Astrophysics Data System (ADS)

Gonze, Marc-André; Mourlon, Christophe; Calmon, Philippe; Manach, Erwan; Debayle, Christophe; Baccou, Jean

2017-09-01

Since the Fukushima accident, Japanese scientists have been intensively monitoring ambient radiations in the highly contaminated territories situated within 80 km of the nuclear site. The surveys that were conducted through mainly carborne, airborne and in situ gamma-ray measurement devices, enabled to efficiently characterize the spatial distribution and temporal evolution of air dose rates induced by Caesium-134 and Caesium-137 in the terrestrial systems. These measurements revealed that radiation levels decreased at rates greater than expected from physical decay in 2011-2012 (up to a factor of 2), and dependent on the type of environment (i.e. urban, agricultural or forest). Unlike carborne measurements that may have been strongly influenced by the depuration of road surfaces, no obvious reason can be invoked for airborne measurements, especially above forests that are known to efficiently retain and recycle radiocaesium. The purpose of our research project is to develop a comprehensive understanding of the data acquired by Japanese, and identify the environmental mechanisms or factors that may explain such decays. The methodology relies on the use of a process-based and spatially-distributed dynamic model that predicts radiocaesium transfer and associated air dose rates inside/above a terrestrial environment (e.g., forests, croplands, meadows, bare soils and urban areas). Despite the lack of site-specific data, our numerical study predicts decrease rates that are globally consistent with both aerial and in situ observations. The simulation at a flying altitude of 200 m indicated that ambient radiation levels decreased over the first 12 months by about 45% over dense urban areas, 15% above evergreen coniferous forests and between 2 and 12% above agricultural lands, owing to environmental processes that are identified and discussed. In particular, we demonstrate that the decrease over evergreen coniferous regions might be due the combined effects of canopy depuration (through biological and physical mechanisms) and the shielding of gamma rays emitted from the forest floor by vegetation. Our study finally suggests that airborne surveys might have not reflected dose rates at ground level in forest systems, which were predicted to slightly increase by 5 to 10% during the same period of time.

High dose psilocybin is associated with positive subjective effects in healthy volunteers.

PubMed

Nicholas, Christopher R; Henriquez, Kelsey M; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Hetzel, Scott; Brown, Randall T; Cozzi, Nicholas V; Thomas, Chantelle; Hutson, Paul R

2018-06-01

The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects. Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8-36.6 mg; 27.1-54.0 mg; 36.3-59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire. There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience. High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.

Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats.

PubMed

Figueiró-Filho, Ernesto Antonio; Aydos, Ricardo Dutra; Senefonte, Flávio Renato de Almeida; Ferreira, Cristiane Munaretto; Pereira, Erica Freire de Vasconcelos; Oliveira, Vanessa Marcon de; Menezes, Giovanna Pádoa de; Bósio, Marco Antonio Costa

2014-07-01

To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A p<0.05 was considered statistically significant. We did not observe statistically significant differences between groups when comparing the average weight of the foetuses and placentas, rate of female VS males, rates of pre-implantation loss (RPL), rates of efficiency implantation (REI), rates of post-implantation loss (RPIL) and rates of foetal viability (RFV). There was no significant effect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats.

Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice.

PubMed

Yu, Kanglun; Doherty, Alison H; Genik, Paula C; Gookin, Sara E; Roteliuk, Danielle M; Wojda, Samantha J; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E; Weil, Michael M; Donahue, Seth W

2017-11-01

During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

MPC and ALI: their basis and their comparison

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

Kennedy, W.E. Jr.; Watson, E.C.

Radiation protection regulations in the United States have evolved from the recommendations of the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP). In 1959, the ICRP issued Publication 2 which contained specific recommendations on dose rate limits, permissible body burdens, metabolic data for radionuclides, and maximum permissible concentrations (MPC) in air or water. Over the next 20 years, new information became available concerning the effects of radiation, the uptake and retention of radionuclides, and the radioactive decay schemes of parent radionuclides. To include this newer information, the ICRP issued Publication 30 inmore » 1978 to supersede Publication 2. One of the secondary limits defined in Publication 30 is the annual limit of intake (ALI). Radionuclide specific ALI values are intended to replace MPC values in determining whether or not ambient air and water concentrations are sufficiently low to maintain the dose to workers within accepted dose rate limits. In this paper, we discuss the derivation of MPC and ALI values, compare inhalation committed dose equivalent factors derived from ICRP Publications 2 and 30, and discuss the practical implications of using either MPC or ALI in determining compliance with occupational exposure limits. 6 references.« less

Effectiveness of urban shelter-in-place—II: Residential districts

NASA Astrophysics Data System (ADS)

Chan, Wanyu R.; Nazaroff, William W.; Price, Phillip N.; Gadgil, Ashok J.

In the event of a short-term, large-scale toxic chemical release to the atmosphere, shelter-in-place (SIP) may be used as an emergency response to protect public health. We modeled hypothetical releases using realistic, empirical parameters to explore how key factors influence SIP effectiveness for single-family dwellings in a residential district. Four classes of factors were evaluated in this case study: (a) time scales associated with release duration, SIP implementation delay, and SIP termination; (b) building air-exchange rates, including air infiltration and ventilation; (c) the degree of sorption of toxic chemicals to indoor surfaces; and (d) the shape of the dose-response relationship for acute adverse health effects. Houses with lower air leakage are more effective shelters, and thus variability in the air leakage of dwellings is associated with varying degrees of SIP protection in a community. Sorption on indoor surfaces improves SIP effectiveness by lowering the peak indoor concentrations and reducing the amount of contamination in the indoor air. Nonlinear dose-response relationships imply substantial reduction in adverse health effects from lowering the peak exposure concentration. However, if the scenario is unfavorable for indefinite sheltering (e.g. sheltering in leaky houses for protection against a nonsorbing chemical with a linear dose-response), the community must implement SIP without delay and exit from shelter when it first becomes safe to do so. Otherwise, the community can be subjected to even greater risk than if they did not take shelter indoors.

[Mechanism of leukocytapheresis effect in the treatment of ulcerative colitis].

PubMed

Sawada, K; Ohnishi, K; Fukunaga, K; Chikano, S; Egashira, A; Satomi, M; Shimoyama, T

1999-12-01

To solve adverse effects of high dose steroid administration for patients with moderately severe and severe ulcerative colitis (UC), additional use of leukocytapheresis (LCAP) was tried to settle colonic inflammation. We evaluated immunological changes in the treatment of LCAP using leukocyte removal filter for UC patients. We then assessed the clinical effectiveness of LCAP compared with that of high dose of steroid therapy. LCAP removed monocytes, granulocytes, and lymphocytes presenting CD 11 b+, CD 11 c+, and HLADR+, selectively from the patients. Proinflammatory cytokine productions measured such as TNF alpha, IL-1 beta, and IL 8 reduced and IL 10 increased immediately after LCAP compared with before perfusion. Improved rate was about 70% for LCAP group and about 40% for high dose steroid group (Refer J Gastroenterol). Selective removal of granulocyte, monocytes, and activated lymphocytes inhibits proinflammatory cytokine production and increases immune modulating cytokine productions (Refer Therapeutic Apheresis). Then quick inhibition of several inflammatory deteriorated factors simultaneously controls the activity and clinical symptoms of UC with less severe adverse effects. It can be considered one option for treatment of UC.

Protection by GDNF and other trophic factors against the dopamine-depleting effects of neurotoxic doses of methamphetamine.

PubMed

Cass, Wayne A; Peters, Laura E; Harned, Michael E; Seroogy, Kim B

2006-08-01

Repeated methamphetamine (METH) administration to animals can result in long-lasting decreases in striatal dopamine (DA) content. It has previously been shown that glial cell line-derived neurotrophic factor (GDNF) can reduce the DA-depleting effects of neurotoxic doses of METH. However, there are several other trophic factors that are protective against dopaminergic toxins. Thus, the present experiments further investigated the protective effect of GDNF as well as the protective effects of several other trophic factors. Male Fischer-344 rats were given an intracerebral injection of trophic factor (2-10 microg) 1 day before METH (5 mg/kg, s.c., 4 injections at 2-h intervals). Seven days later DA levels in the striatum were measured using high-performance liquid chromatography (HPLC). Initial experiments indicated that only intrastriatal GDNF, and not intranigral GDNF, was protective. Thereafter, all other trophic factors were administered into the striatum. Members of the GDNF family (GDNF, neurturin, and artemin) all provided significant protection against the DA-depleting effects of METH, with GDNF providing the greatest protection. Brain-derived neurotrophic factor, neurotrophin-3, acidic fibroblast growth factor, basic fibroblast growth factor, ciliary neurotrophic factor, transforming growth factor-alpha (TGF-alpha), heregulin beta1 (HRG-beta1), and amphiregulin (AR) provided no significant protection at the doses examined. These results suggest that the GDNF family of trophic factors can provide significant protection against the DA-depleting effects of neurotoxic doses of METH.

Results on Dose Distributions in a Human Body from the Matroshka-R Experiment onboard the ISS Obtained with the Tissue-Equivalent Spherical Phantom

NASA Astrophysics Data System (ADS)

Shurshakov, Vyacheslav; Nikolaev, Igor; Kartsev, Ivan; Tolochek, Raisa; Lyagushin, Vladimir

The tissue-equivalent spherical phantom (32 kg mass, 35 cm diameter and 10 cm central spherical cave) made in Russia has been used on board the ISS in Matroshka-R experiment for more than 10 years. Both passive and active space radiation detectors can be located inside the phantom and on its surface. Due to the specially chosen phantom shape and size, the chord length distributions of the detector locations are attributed to self-shielding properties of the critical organs in a human body. Originally the spherical phantom was installed in the star board crew cabin of the ISS Service Module, then in the Piers-1, MIM-2, and MIM-1 modules of the ISS Russian segment, and finally in JAXA Kibo module. Total duration of the detector exposure is more than 2000 days in 9 sessions of the space experiment. In the first phase of the experiment with the spherical phantom the dose measurements were realized with only passive detectors (thermoluminescent and solid state track detectors). The detectors are placed inside the phantom along the axes of 20 containers and on the phantom outer surface in 32 pockets of the phantom jacket. After each session the passive detectors are returned to the ground. The results obtained show the dose difference on the phantom surface as much as a factor of 2, the highest dose being usually observed close to the outer wall of the compartment, and the lowest dose being in the opposite location along the phantom diameter. However, because of the ISS module shielding properties an inverse dose distribution in a human body can be observed when the dose rate maximum is closer to the geometrical center of the module. Maximum dose rate measured in the phantom is obviously due to the action of two radiation sources, namely, galactic cosmic rays (GCR) and Earth’ radiation belts. Minimum dose rate is produced mainly by the strongly penetrating GCR particles and is mostly observed behind more than 5 g/cm2 tissue shielding. Critical organ doses, mean-tissue and effective doses of a crew member in the ISS compartments are also estimated with the spherical phantom data. The estimated effective dose rate is found to be from 10 % to 15 % lower than the averaged dose on the phantom surface as dependent on the attitude of the critical organs. If compared with the anthropomorphic phantom Rando used inside and outside the ISS earlier, the Matroshka-R space experiment spherical phantom has lower mass, smaller size, and requires less crew time for the detector installation/retrieval; its tissue-equivalent properties are closer to the standard human body tissue than the Rando-phantom material. New sessions with the two tissue-equivalent phantoms are of great interest. Development of modified passive and active detector sets is in progress for the future ISS expeditions. Both the spherical and Rando-type phantoms proved their effectiveness to measure the critical organ doses and effective doses in-flight and if supplied with modernized dosimeters can be recommended for future exploratory manned missions to monitor continuously the crew exposure to space radiation.

Biological effectiveness of nuclear fragments produced by high-energy protons interacting in tissues near the bone- soft tissue interface

NASA Astrophysics Data System (ADS)

Shavers, Mark Randall

1999-12-01

High-energy protons in the galactic cosmic rays (GCR)-or generated by nuclear interactions of GCR heavy-ions with material-are capable of penetrating great thicknesses of shielding to irradiate humans in spacecraft or in lunar or Martian habitats. As protons interact with the nuclei of the elemental constituents of soft tissue and bone, low energy nuclei-target fragments-are emitted into the cells responsible for bone development and maintenance and for hematopoiesis. Leukemogenesis is the principal endpoint of concern because it is the most likely deleterious effect, and it has a short latency period and comparatively low survival rate, although other myelo- proliferative disorders and osteosarcoma also may be induced. A one-dimensional proton-target fragment transport model was used to calculate the energy spectra of fragments produced in bone and soft tissue, and present in marrow cavities at distances from a bone interface. In terms of dose equivalent, the target fragments are as significant as the incident protons. An average radiation quality factor was found to be between 1.8 and 2.6. Biological response to the highly non- uniform energy deposition of the target fragments is such that an alternative approach to conventional predictive risk assessment is needed. Alternative procedures are presented. In vitro cell response and relative biological effectiveness were calculated from the radial dose distribution of each fragment produced by 1-GeV protons using parameters of a modified Ion-Gamma- Kill (IGK) model of radiation action. The modelled endpoints were survival of C3H10t 1/2 and V79 cells, neoplastic transformation of C3H10t1/2 cells, and mutation of the X-linked hypoxanthine phosphoribosyltransferase (HPRT) locus in V79 cells. The dose equivalent and cell responses increased by 10% or less near the interface. Since RBE increases with decreasing dose in the IGK model, comparisons with quality factors were made at dose levels 0.01 <= D [Gy] <= 2. Applying average quality factors derived herein to GCR exposures results in a <= 5% increase of in average quality. Calculated RBEs indicate that accepted quality factors for high-energy protons may be too low due to the relatively high effectiveness of the low-charged target fragments. Derived RBEs for target fragments increase the calculated biological effectiveness of GCR by 20% to 180%.

Identification of heavy-ion radiation-induced microRNAs in rice

NASA Astrophysics Data System (ADS)

Zhang, Meng; Liang, Shujian; Hang, Xiaoming; Xiang, Yingxia; Cheng, Zhenlong; Li, Wenjian; Shi, Jinming; Huang, Lei; Sun, Yeqing

2011-03-01

MicroRNAs (miRNAs) are a family of small non-coding RNAs, which play significant roles in regulating development and stress responses in plant. As an excellent model organism for studying the effects of environmental stress, rice has been used to assess the damage of the space radiation environment for decades. Heavy-ions radiation show higher relative biological effectiveness compared to other cosmic-rays radiation. To identify the specific miRNAs that underlie biological effects of heavy-ion radiation, the germinated seeds of rice were exposed to 1 Gy, 10 Gy and 20 Gy dose of 12C heavy-ion radiation, respectively. Analysis of phenotype indicated that 20 Gy dose of heavy-ion radiation was the semi-lethal dose of rice seedling. The microarray of μparaflo™ chip was employed to monitor the expression profiles of miRNAs in rice (Oryza sativa) under 20 Gy dose of radiation stress. miR164a, miR164c, miR164d and miR156a-j were identified as heavy-ion radiation-induced miRNAs. miR164 and miR156 family were increased in all three exposed samples by using quantitative real-time PCR (qRT-RCP). As targets of miR156 and miR164, SQUAMOSA PROMOTER BINDING-LIKE (SPL) transcription factors and NAM/ATAF/CUC (NAC) transcription factors expression were down-regulated correlating with an up-regulated level of the regulated miRNAs. Since SPL transcription factors and NAC transcription factors regulated growth and development of plant, we used 2-dimension electrophoresis (2-DE) gel to analyze changes of functional proteins in 20 Gy exposed samples. It was evident that both the height and survival rates of seedlings were markedly decreased. The abundance of some developmentally regulated proteins was also changed. To our knowledge, this study is the first to report heavy-ion radiation stress responsive miRNAs in plant. Moreover, our findings are important to understand the molecular mechanism of space biology.

Mumps vaccine effectiveness and risk factors for disease in households during an outbreak in New York City.

PubMed

Livingston, Kara A; Rosen, Jennifer B; Zucker, Jane R; Zimmerman, Christopher M

2014-01-09

Mumps outbreaks have been reported among vaccinated populations, and declining mumps vaccine effectiveness (VE) has been suggested as one possible cause. During a large mumps outbreak in New York City, we assessed: (1) VE of measles-mumps-rubella vaccine (MMR) against mumps and (2) risk factors for acquiring mumps in households. Cases of mumps were investigated using standard methods. Additional information on disease and vaccination status of household contacts was collected. Case households completed follow-up phone interviews 78-198 days after initial investigation to ascertain additional cases. Mumps cases meeting the study case definition were included in the analysis. Risk factors for mumps were assessed, and VE was calculated using secondary household attack rates. Three hundred and eleven households with 2176 residents were included in the analysis. The median age of residents was 13 years (range <1-85), and 462 (21.2%) residents met the study mumps case definition. Among 7-17 year olds, 89.7% received one or more doses of MMR vaccine, with 76.7% receiving two doses. Young adults aged 10-14 years (OR=2.4, CI=1.3-4.7) and 15-19 years (OR=2.5, CI=1.3-5.0) were at highest risk of mumps. The overall 2-dose VE for secondary contacts aged five and older was 86.3% (CI 63.3-94.9). The two-dose effectiveness of MMR vaccine against mumps was 86.3%, consistent with other published mumps VE estimates. Many factors likely contributed to this outbreak. Suboptimal MMR coverage in the affected population combined with VE may not have conferred adequate immunity to prevent transmission and may have contributed to this outbreak. Achieving high MMR coverage remains the best available strategy for prevention of mumps outbreaks. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Influence of dose regimen on gentamycin nephrotoxicity in rats].

PubMed

Oliveira, V C; Tejos, C R; Hosaka, E M; Andrade, S C; Araújo, M; Vattimo, M F

2001-06-01

The acute renal failure (ARF), that still presents a right mortality rate (50%) can be defined as an abrupt decline of the glomerular filtration, resultant of ischemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27%) of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100 mg/kg) in one dose or in two doses (2 x 50 mg/kg), by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracellular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, shows advantages not only related to the nephrotoxicity effect, but also it is relevant to the cost and safety, which can be rationable factors in the administration of this drug.

Monte Carlo calculation of dose rate conversion factors for external exposure to photon emitters in soil

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

Clovas, A.; Zanthos, S.; Antonopoulos-Domis, M.

2000-03-01

The dose rate conversion factors {dot D}{sub CF} (absorbed dose rate in air per unit activity per unit of soil mass, nGy h{sup {minus}1} per Bq kg{sup {minus}1}) are calculated 1 m above ground for photon emitters of natural radionuclides uniformly distributed in the soil. Three Monte Carlo codes are used: (1) The MCNP code of Los Alamos; (2) The GEANT code of CERN; and (3) a Monte Carlo code developed in the Nuclear Technology Laboratory of the Aristotle University of Thessaloniki. The accuracy of the Monte Carlo results is tested by the comparison of the unscattered flux obtained bymore » the three Monte Carlo codes with an independent straightforward calculation. All codes and particularly the MCNP calculate accurately the absorbed dose rate in air due to the unscattered radiation. For the total radiation (unscattered plus scattered) the {dot D}{sub CF} values calculated from the three codes are in very good agreement between them. The comparison between these results and the results deduced previously by other authors indicates a good agreement (less than 15% of difference) for photon energies above 1,500 keV. Antithetically, the agreement is not as good (difference of 20--30%) for the low energy photons.« less

[Correlation study of physical and biologic parameters to acute radiation pneumonitis].

PubMed

Zhao, Yan-hai; Li, Zhi-ping; Chen, Xiao-mei; Liu, Xiao-jing; Wu, Wen-chao; Xu, Yong; Li, Ping; Zhang, Jin-tao; Zeng, Hui

2008-09-01

To study the relationship between the level of plasma transform growth factor-betal (TGF-betal), interleukin-6 (IL-6), thrombomodulin (TM) dose-volume factors and acute radiation pneumonitis (ARP). Three dimensional conformal radiation therapy and chemotherapy were applied to 27 lung cancer patients, 15 esophageal carcinoma, and 1 thymoma patients. 19 patients received adjuvant radiochemotherapy, and 25 patients received concurrent radio-chemotherapy. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the serum IL-6, TGF-betal and TM levels of patients before radiotherapy (B-RT) and at 30 Gy(M-RT). ARP was graded according to NCI common toxicity criteria (CTCAE v 3.0), Grade 2 or more ARP was taken as the main end point. The relationship between the levels of serum TGF-betal, IL-6, TM, parameters of lung function and dose-volume factors, and the incidence rate of ARP were analyzed. Mean lung dose (MLD) and the Vx were considered as the dose-volume factors. Among 44 patients, 15 of them had ARP. 9 got grade 2 ARP and 6 had grade 3. After received a dose of 30 Gy, TGF-betal value in M-RT was (396 +/- 338) and (866 +/- 270) pg/mL in non-ARP and ARP group (P = 0.000). The ARP incidence rate in <60 and > or =60 age group were 46.15% (12/26) and 16.67% (3/18) (P = 0.042), and 45.45% (15/33), 0% (0/11) (P = 0.017) in had smoking history and nonsmoking history group, respectively. 1 out of 13 patients (7.69%) who had increased M-RT TM value suffered of ARP, while 14 out of 31 patients (45.16%) whose M-RT TM value lower than pr-RT suffered of ARP (P = 0.044). The results of multivariate analysis implied that the MLD and the value of TGF-betal in M-RT were associated with severe ARP. TGF-beta1 and MLD are significant indicators of ARP. FEV1 actual value/predicted value% might have predicting effect for the severity of ARP.

Risk Factors and Dose-Effect Relationship for Mandibular Osteoradionecrosis in Oral and Oropharyngeal Cancer Patients

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

Lee, Ik Jae; Koom, Woong Sub; Lee, Chang Geol, E-mail: cglee1023@yuhs.a

2009-11-15

Purpose: To analyze risk factors and the dose-effect relationship for osteoradionecrosis (ORN) of the mandible after radiotherapy of oral and oropharyngeal cancers. Materials and Methods: One-hundred ninety-eight patients with oral (45%) and oropharyngeal cancer (55%) who had received external radiotherapy between 1990 and 2000 were retrospectively reviewed. All patients had a dental evaluation before radiotherapy. The median radiation dose was 60 Gy (range, 16-75 Gy), and the median biologically effective dose for late effects (BED{sub late}) in bone was 114 Gy{sub 2} (range, 30-167 Gy{sub 2}). Results: The frequency of ORN was 13 patients (6.6%). Among patients with mandibular surgery,more » eight had ORN at the surgical site. Among patients without mandibular surgery, five patients had ORN on the molar area of the mandible. The median time to ORN was 22 months (range, 1-69 months). Univariate analysis revealed that mandibular surgery and Co-60 were significant risk factors for ORN (p = 0.01 and 0.04, respectively). In multivariate analysis, mandibular surgery was the most important factor (p = 0.001). High radiation doses over BED 102.6 Gy{sub 2} (conventional dose of 54 Gy at 1.8 Gy/fraction) were also a significant factor for ORN (p = 0.008) and showed a positive dose-effect relationship in logistic regression (p = 0.04) for patients who had undergone mandibular surgery. Conclusions: Mandibular surgery was the most significant risk factor for ORN of mandible in oral and oropharyngeal cancers patients. A BED of 102.6 Gy{sub 2} or higher to the mandible also significantly increases the risk of ORN.« less

Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

PubMed

Skedgel, Chris; Rayson, Daniel; Younis, Tallal

2016-01-01

Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

FIIDOS--A Computer Code for the Computation of Fallout Inhalation and Ingestion Dose to Organs Computer User’s Guide (Revision 4)

DTIC Science & Technology

2007-05-01

35 5 Actinide product radionuclides... actinides , and fission products in fallout. Doses from low-linear energy transfer (LET) radiation (beta particles and gamma rays) are reported separately...assumptions about the critical parameters used in calculating internal doses – resuspension factor, breathing rate, fractionation, and scenario elements – to

Surgical Responses of Medial Rectus Muscle Recession in Thyroid Eye Disease-Related Esotropia

PubMed Central

Lyu, In Jeong; Lee, Ju-Yeun; Kong, Mingui; Park, Kyung-Ah; Oh, Sei Yeul

2016-01-01

We evaluate the surgical outcomes and surgical responses of medial rectus muscle (MR) recession patients with thyroid eye disease (TED)-related esotropia (ET). The surgical dose-response curves 1 week postoperatively and at the final visit were analyzed. Univariable and multivariable linear regression analyses were applied to investigate factors influencing surgical dose-response. A total of 43 patients with TED-related ET that underwent MR recession were included. The final success rate was 86.0% and the rate of undercorrection was 14.0%. The surgical dose-response curves of TED-related ET showed a gentle slope compared with those of standard surgical tables. In the univariable model, simultaneous vertical rectus muscle recession was the only significant factor influencing surgical dose-response of MR recession in TED-related ET (β = -0.397, P = 0.044). In a model adjusted for age, sex, type of surgery, and preoperative horizontal angle of deviation, simultaneous vertical rectus muscle recession showed marginal significance (β = -0.389, P = 0.064). The surgical dose-response curve of TED-related ET was unique. Simultaneous vertical rectus muscle recession was associated with increased surgical dose-response in TED-related ET. PMID:26796354

Risk Factors for Neovascular Glaucoma After Proton Beam Therapy of Uveal Melanoma: A Detailed Analysis of Tumor and Dose–Volume Parameters

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

Mishra, Kavita K., E-mail: kmishra@radonc.ucsf.edu; Daftari, Inder K.; Weinberg, Vivian

2013-10-01

Purpose: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). Methods and Materials: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log–rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose–volumemore » histogram parameters. Results: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose–volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). Conclusions: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height, diameter, and anterior as well as posterior critical structure dose–volume parameters may be used to predict NVG risk.« less

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.

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

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

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

2014-07-15

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

Chromosome translocations in T. scripta: the dose-rate effect and in vivo lymphocyte radiation response.

PubMed

Ulsh, B A; Whicker, F W; Congdon, J D; Bedford, J S; Hinton, T G

2001-01-01

Using a whole-chromosome FISH painting probe we previously developed for chromosome 1 of the yellow-bellied slider turtle (Trachemys scripta), we investigated the dose-rate effect for radiation-induced symmetrical translocations in T. scripta fibroblasts and lymphocytes. The dose rate below which no reduction in effect per unit dose is observed with further dose protraction was approximately 23 cGy h(-1). We estimated the whole-genome spontaneous background level of complete, apparently simple symmetrical translocations in T. scripta lymphocytes to be approximately 1.20 x 10(-3)/cell projected from aberrations occurring in chromosome 1. Similar spontaneous background levels reported for humans are some 6- to 25-fold higher, ranging from about 6 x 10(-3) to 3.4 x 10(-2) per cell. This relatively low background level for turtles would be a significant advantage for resolution of effects at low doses and dose rates. We also chronically irradiated turtles over a range of doses from 0-8 Gy delivered at approximately 5.5 cGy h(-1) and constructed a lymphocyte dose-response curve for complete, apparently simple symmetrical translocations suitable for use with animals chronically exposed to radiation in contaminated environments. The best-fitting calibration curve (not constrained through the zero dose estimate) was of the form Y(as) = c + aD + bD(2), where Y(as) was the number of apparently simple symmetrical translocations per cell, D was the dose (Gy), a = (0.0058 +/- 0.0009), b = (-0.00033 +/- 0.00011), and c = (0.0015 +/- 0.0013). With additional whole-chromosome probes to improve sensitivity, environmental biodosimetry using stable chromosome translocations could provide a practical and genetically relevant measurement end point for ecological risk assessments and biomonitoring programs.

Characteristics of mobile MOSFET dosimetry system for megavoltage photon beams

PubMed Central

Kumar, A. Sathish; Sharma, S. D.; Ravindran, B. Paul

2014-01-01

The characteristics of a mobile metal oxide semiconductor field effect transistor (mobile MOSFET) detector for standard bias were investigated for megavoltage photon beams. This study was performed with a brass alloy build-up cap for three energies namely Co-60, 6 and 15 MV photon beams. The MOSFETs were calibrated and the performance characteristics were analyzed with respect to dose rate dependence, energy dependence, field size dependence, linearity, build-up factor, and angular dependence for all the three energies. A linear dose-response curve was noted for Co-60, 6 MV, and 15 MV photons. The calibration factors were found to be 1.03, 1, and 0.79 cGy/mV for Co-60, 6 MV, and 15 MV photon energies, respectively. The calibration graph has been obtained to the dose up to 600 cGy, and the dose-response curve was found to be linear. The MOSFETs were found to be energy independent both for measurements performed at depth as well as on the surface with build-up. However, field size dependence was also analyzed for variable field sizes and found to be field size independent. Angular dependence was analyzed by keeping the MOSFET dosimeter in parallel and perpendicular orientation to the angle of incidence of the radiation with and without build-up on the surface of the phantom. The maximum variation for the three energies was found to be within ± 2% for the gantry angles 90° and 270°, the deviations without the build-up for the same gantry angles were found to be 6%, 25%, and 60%, respectively. The MOSFET response was found to be independent of dose rate for all three energies. The dosimetric characteristics of the MOSFET detector make it a suitable in vivo dosimeter for megavoltage photon beams. PMID:25190992

Characteristics of mobile MOSFET dosimetry system for megavoltage photon beams.

PubMed

Kumar, A Sathish; Sharma, S D; Ravindran, B Paul

2014-07-01

The characteristics of a mobile metal oxide semiconductor field effect transistor (mobile MOSFET) detector for standard bias were investigated for megavoltage photon beams. This study was performed with a brass alloy build-up cap for three energies namely Co-60, 6 and 15 MV photon beams. The MOSFETs were calibrated and the performance characteristics were analyzed with respect to dose rate dependence, energy dependence, field size dependence, linearity, build-up factor, and angular dependence for all the three energies. A linear dose-response curve was noted for Co-60, 6 MV, and 15 MV photons. The calibration factors were found to be 1.03, 1, and 0.79 cGy/mV for Co-60, 6 MV, and 15 MV photon energies, respectively. The calibration graph has been obtained to the dose up to 600 cGy, and the dose-response curve was found to be linear. The MOSFETs were found to be energy independent both for measurements performed at depth as well as on the surface with build-up. However, field size dependence was also analyzed for variable field sizes and found to be field size independent. Angular dependence was analyzed by keeping the MOSFET dosimeter in parallel and perpendicular orientation to the angle of incidence of the radiation with and without build-up on the surface of the phantom. The maximum variation for the three energies was found to be within ± 2% for the gantry angles 90° and 270°, the deviations without the build-up for the same gantry angles were found to be 6%, 25%, and 60%, respectively. The MOSFET response was found to be independent of dose rate for all three energies. The dosimetric characteristics of the MOSFET detector make it a suitable in vivo dosimeter for megavoltage photon beams.

What we need to know about the effect of lithium on the kidney.

PubMed

Gong, Rujun; Wang, Pei; Dworkin, Lance

2016-12-01

Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic index and concerns for its toxicity in various organ systems. Renal side effects associated with lithium include polyuria, nephrogenic diabetes insipidus, proteinuria, distal renal tubular acidosis, and reduction in glomerular filtration rate. Histologically, chronic lithium nephrotoxicity is characterized by interstitial nephritis with microcyst formation and occasional focal segmental glomerulosclerosis. Nevertheless, this type of toxicity is uncommon, with the strongest risk factors being high serum levels of lithium and longer time on lithium therapy. In contrast, in experimental models of acute kidney injury and glomerular disease, lithium has antiproteinuric, kidney protective, and reparative effects. This paradox may be partially explained by lower lithium doses and short duration of therapy. While long-term exposure to higher psychiatric doses of lithium may be nephrotoxic, short-term low dose of lithium may be beneficial and ameliorate kidney and podocyte injury. Mechanistically, lithium targets glycogen synthase kinase-3β, a ubiquitously expressed serine/threonine protein kinase implicated in the processes of tissue injury, repair, and regeneration in multiple organ systems, including the kidney. Future studies are warranted to discover the exact "kidney-protective dose" of lithium and test the effects of low-dose lithium on acute and chronic kidney disease in humans. Copyright © 2016 the American Physiological Society.

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

An overview of zinc addition for BWR dose rate control

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

Marble, W.J.

1995-03-01

This paper presents an overview of the BWRs employing feedwater zinc addition to reduce primary system dose rates. It identifies which BWRs are using zinc addition and reviews the mechanical injection and passive addition hardware currently being employed. The impact that zinc has on plant chemistry, including the factor of two to four reduction in reactor water Co-60 concentrations, is discussed. Dose rate results, showing the benefits of implementing zinc on either fresh piping surfaces or on pipes with existing films are reviewed. The advantages of using zinc that is isotopically enhanced by the depletion of the Zn-64 precursor tomore » Zn-65 are identified.« less

[Disseminated intravascular coagulation induced by endotoxin in rabbits: effect of treatment with t-PA and urokinase].

PubMed

Paloma, M J; Páramo, J A; Rifón, J; Rocha, E

1992-12-01

To assess the therapeutic efficacy of agents capable of stimulating the fibrinolytic system, such as tissue plasminogen activator (t-PA) and urokinase (UK) on endotoxin-induced disseminated intravascular coagulation (DIC) in the rabbit. DIC was induced by intravenous administration of endotoxin, 20 micrograms/kg/hr during 6 hr. Four different groups were established: a) control group, receiving only saline solution; b) t-PA group receiving 0.2 mg/kg; c) t-PA group receiving 0.7 mg/kg, and d) UK group, which was given 3,000 IU/kg/hr for 6 hr. Blood samples were drawn before and after 2 hr and 6 hr of endotoxin administration. Platelet count, and fibrinogen, factor XII and antithrombin III concentrations, were assessed in each sample. Mean, standard deviation and percentage of increase or decrease with respect to the basal value, this considered 100%, were used to evaluate the findings. For comparison of values, Student's t and Mann Whitney's U were used; the Fisher test was used for mortality studies. No statistical differences appeared for any of the values in the rabbits under basal conditions. The rabbits in the control group developed DIC. No doses of t-PA modified the changes appearing in blood coagulation. UK reduced the fibrinogen and factor XII consumption induced by endotoxin. The mortality rate in the control group reached 70%. High-dose t-PA decreased such figure to 50%, while low-dose t-PA or UK failed to reduce mortality. High-dose t-PA has beneficial effects on endotoxin-induced DIC in rabbits. UK failed to achieve such effect at the doses given in this experimental DIC model.

Blockade of hyperpolarizing currents produces a dose-dependent effect on heart rate.

PubMed

Ziyatdinova, N I; Giniatullin, R A; Svyatova, N V; Zefirov, T L

2001-03-01

Intravenous injection of ZD 7288, a new specific hyperpolarizing current blocker, dose-dependently reduces heart rate in adult rats. The autonomic nervous system modulates changes in heart rate caused by hyperpolarizing currents.

Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England.

PubMed

Long, D R; Lihn, A L; Friedrich, S; Scheffenbichler, F T; Safavi, K C; Burns, S M; Schneider, J C; Grabitz, S D; Houle, T T; Eikermann, M

2018-05-01

The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission. We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors. Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0-2 vs 3-30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors. High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

The effect of radiation on the anaerobic corrosion of steel

NASA Astrophysics Data System (ADS)

Smart, N. R.; Rance, A. P.; Werme, L. O.

2008-09-01

To ensure the safe encapsulation of spent nuclear fuel elements for geological disposal, SKB of Sweden are considering using a canister, which consists of an outer copper canister and a cast iron insert. Previous work has investigated the rate of gas generation due to the anaerobic corrosion of ferrous materials over a range of conditions. This paper examines the effect of radiation on the corrosion of steel in repository environments. Tests were carried out at two temperatures (30 °C and 50 °C), two dose rates (11 Gray h -1 and 300 Gray h -1) and in two different artificial groundwaters, for exposure periods of several months. Radiation was found to enhance the corrosion rate at both dose rates but the greatest enhancement occurred at the higher dose rate. The corrosion products were predominantly magnetite, with some indications of unidentified higher oxidation state corrosion products being formed at the higher dose rates.

SEMICONDUCTOR PHYSICS Dose-rate dependence of optically stimulated luminescence signal

NASA Astrophysics Data System (ADS)

Pingqiang, Wei; Zhaoyang, Chen; Yanwei, Fan; Yurun, Sun; Yun, Zhao

2010-10-01

Optically stimulated luminescence (OSL) is the luminescence emitted from a semiconductor during its exposure to light. The OSL intensity is a function of the total dose absorbed by the sample. The dose-rate dependence of the OSL signal of the semiconductor CaS doped Ce and Sm was studied by numerical simulation and experiments. Based on a one-trap/one-center model, the whole OSL process was represented by a series of differential equations. The dose-rate properties of the materials were acquired theoretically by solving the equations. Good coherence was achieved between numerical simulation and experiments, both of which showed that the OSL signal was independent of dose rate. This result validates that when using OSL as a dosimetry technique, the dose-rate effect can be neglected.

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

PubMed

Miyatake, Hirokazu; Yoshizawa, Nobuaki; Suzuki, Gen

2018-05-11

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

Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Naïve Patients With Type 2 Diabetes.

PubMed

Matfin, Glenn; Van Brunt, Kate; Zimmermann, Alan G; Threlkeld, Rebecca; Ignaut, Debra A

2015-04-21

This 4-week, phase 3b, multicenter, open-label, single-arm, outpatient study demonstrated the safe and effective use of the dulaglutide single-dose pen containing 0.5 mL of placebo for subcutaneous injection in injection-naïve adult patients with type 2 diabetes (T2D), with A1C ≤ 8.5% (69 mmol/mol), BMI ≥ 23 kg/m2 and ≤ 45 kg/m(2). Patients completed a modified self-injecting subscale of the Diabetes Fear of Injecting and Self-Testing Questionnaire (mD-FISQ) and were trained to self-inject with the single-dose pen. Patients completed the initial self-injection at the site, injected at home for 2 subsequent weeks, and returned to the site for the final injection. The initial and final self-injections were evaluated for success; the final (initial) self-injection success rate was the primary (secondary) outcome measure, and the primary (secondary) objective was to demonstrate this success rate as being significantly greater than 80%. Patients recorded their level of pain after each injection. After the final injection, patients completed the mD-FISQ and the Medication Delivery Device Assessment Battery (MDDAB) to assess their perceptions of the single-dose pen, including ease of use and experience with the device. Among 211 patients (mean age: 61 years), the primary objective was met, with a final injection success rate of 99.1% (95% CI: 96.6% to 99.7%). Among 214 patients, the initial injection success rate was 97.2% (95% CI: 94.0% to 98.7%), meeting the key secondary objective. Overall, most patients (>96%) found the device easy to use, were satisfied with the device, and would be willing to continue to use the single-dose pen after the study. There was a significant reduction (P < .001) from baseline to study end in patients' fear of self-injecting, as measured by the mD-FISQ. The dulaglutide single-dose pen was found to be a safe and effective device for use by patients with T2D who were injection-naïve. A positive injection experience is an important factor for patients and providers when initiating injectable therapy. © 2015 Diabetes Technology Society.

Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Naïve Patients With Type 2 Diabetes

PubMed Central

Matfin, Glenn; Van Brunt, Kate; Zimmermann, Alan G.; Threlkeld, Rebecca; Ignaut, Debra A.

2015-01-01

Background: This 4-week, phase 3b, multicenter, open-label, single-arm, outpatient study demonstrated the safe and effective use of the dulaglutide single-dose pen containing 0.5 mL of placebo for subcutaneous injection in injection-naïve adult patients with type 2 diabetes (T2D), with A1C ≤ 8.5% (69 mmol/mol), BMI ≥ 23 kg/m2 and ≤ 45 kg/m2. Method: Patients completed a modified self-injecting subscale of the Diabetes Fear of Injecting and Self-Testing Questionnaire (mD-FISQ) and were trained to self-inject with the single-dose pen. Patients completed the initial self-injection at the site, injected at home for 2 subsequent weeks, and returned to the site for the final injection. The initial and final self-injections were evaluated for success; the final (initial) self-injection success rate was the primary (secondary) outcome measure, and the primary (secondary) objective was to demonstrate this success rate as being significantly greater than 80%. Patients recorded their level of pain after each injection. After the final injection, patients completed the mD-FISQ and the Medication Delivery Device Assessment Battery (MDDAB) to assess their perceptions of the single-dose pen, including ease of use and experience with the device. Results: Among 211 patients (mean age: 61 years), the primary objective was met, with a final injection success rate of 99.1% (95% CI: 96.6% to 99.7%). Among 214 patients, the initial injection success rate was 97.2% (95% CI: 94.0% to 98.7%), meeting the key secondary objective. Overall, most patients (>96%) found the device easy to use, were satisfied with the device, and would be willing to continue to use the single-dose pen after the study. There was a significant reduction (P < .001) from baseline to study end in patients’ fear of self-injecting, as measured by the mD-FISQ. Conclusions: The dulaglutide single-dose pen was found to be a safe and effective device for use by patients with T2D who were injection-naïve. A positive injection experience is an important factor for patients and providers when initiating injectable therapy. PMID:25901022

Dose-Dependent Effect of Statin Pretreatment on Preventing the Periprocedural Complications of Carotid Artery Stenting.

PubMed

Hong, Jeong-Ho; Sohn, Sung-Il; Kwak, Jaehyuk; Yoo, Joonsang; Chang, Hyuk Won; Kwon, O-Ki; Jung, Cheolkyu; Chung, Inyoung; Bae, Hee-Joon; Lee, Ji Sung; Han, Moon-Ku

2017-07-01

We investigated whether statin pretreatment can dose dependently reduce periprocedural complications in patients undergoing carotid artery stenting because of symptomatic carotid artery stenosis. We enrolled a consecutive series of 397 symptomatic carotid artery stenosis (≥50% stenosis on conventional angiography) treated with carotid artery stenting at 2 tertiary university hospitals over a decade. Definition of periprocedural complications included any stroke, myocardial infarction, and death within 1 month after or during the procedure. Statin pretreatment was divided into 3 categories according to the atorvastatin equivalent dose: none (n=158; 39.8%), standard dose (<40 mg of atorvastatin, n=155; 39.0%), and high dose (≥40 mg; n=84; 21.2%). A multivariable logistic regression analysis with the generalized estimating equation method was used to investigate independent factors in periprocedural complications. The patients' mean age was 68.7 years (81.6% men). The periprocedural complication rates across the 3 categories of statin use were 12.0%, 4.5%, and 1.2%. After adjustment, a change in the atorvastatin dose category was associated with reduction in the odds of periprocedural complications for each change in dose category (standard-dose statin: odds ratio, 0.24; 95% confidence interval, 0.07-0.81; high-dose statin: odds ratio, 0.11; 95% confidence interval, 0.01-0.96; P for trend=0.01). Administration of antiplatelet drugs was also an independent factor in periprocedural complications (OR, 0.18; 95% CI, 0.05-0.69). This study shows that statin pretreatment may reduce the incidence of periprocedural complications dose dependently in patients with symptomatic carotid artery stenting. © 2017 American Heart Association, Inc.

Assessment of doses to game animals in Finland.

PubMed

Vetikko, Virve; Kostiainen, Eila

2013-11-01

A study was carried out to assess the dose rates to game animals in Finland affected by the radioactive caesium deposition that occurred after the accident at the Chernobyl nuclear power plant in Ukraine in 1986. The aim of this assessment was to obtain new information on the dose rates to mammals and birds under Finnish conditions. Dose rates were calculated using the ERICA Assessment Tool developed within the EC 6th Framework Programme. The input data consisted of measured activity concentrations of (137)Cs and (134)Cs in soil and lake water samples and in flesh samples of selected animal species obtained for environmental monitoring. The study sites were located in the municipality of Lammi, Southern Finland, where the average (137)Cs deposition was 46.5 kBq m(-2) (1 October 1987). The study sites represented the areas receiving the highest deposition in Finland after the Chernobyl accident. The selected species included moose (Alces alces), arctic hare (Lepus timidus) and several bird species: black grouse (Tetrao tetrix), hazel hen (Bonasia bonasia), mallard (Anas platurhynchos), goldeneye (Bucephala clangula) and teal (Anas crecca). For moose, dose rates were calculated for the years 1986-1990 and for the 2000s. For all other species, maximal measured activity concentrations were used. The results showed that the dose rates to these species did not exceed the default screening level of 10 μGy h(-1) used as a protection criterion. The highest total dose rate (internal and external summed), 3.7 μGy h(-1), was observed for the arctic hare in 1986. Although the dose rate of 3.7 μGy h(-1) cannot be considered negligible given the uncertainties involved in predicting the dose rates, the possible harmful effects related to this dose rate are too small to be assessed based on current knowledge on the biological effects of low doses in mammals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dose estimates for the solid waste performance assessment

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

Rittman, P.D.

1994-08-30

The Solid Waste Performance Assessment calculations by PNL in 1990 were redone to incorporate changes in methods and parameters since then. The ten scenarios found in their report were reduced to three, the Post-Drilling Resident, the Post-Excavation Resident, and an All Pathways Irrigator. In addition, estimates of population dose to people along the Columbia River are also included. The attached report describes the methods and parameters used in the calculations, and derives dose factors for each scenario. In addition, waste concentrations, ground water concentrations, and river water concentrations needed to reach the performance objectives of 100 mrem/yr and 500 person-rem/yrmore » are computed. Internal dose factors from DOE-0071 were applied when computing internal dose. External dose rate factors came from the GENII Version 1.485 software package. Dose calculations were carried out on a spreadsheet. The calculations are described in detail in the report for 63 nuclides, including 5 not presently in the GENII libraries. The spreadsheet calculations were checked by comparison with GENII, as described in Appendix D.« less

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.

Evaluation of organ doses and specific k effective dose of 64-slice CT thorax examination using an adult anthropomorphic phantom

NASA Astrophysics Data System (ADS)

Hashim, S.; Karim, M. K. A.; Bakar, K. A.; Sabarudin, A.; Chin, A. W.; Saripan, M. I.; Bradley, D. A.

2016-09-01

The magnitude of radiation dose in computed tomography (CT) depends on the scan acquisition parameters, investigated herein using an anthropomorphic phantom (RANDO®) and thermoluminescence dosimeters (TLD). Specific interest was in the organ doses resulting from CT thorax examination, the specific k coefficient for effective dose estimation for particular protocols also being determined. For measurement of doses representing five main organs (thyroid, lung, liver, esophagus and skin), TLD-100 (LiF:Mg, Ti) were inserted into selected holes in a phantom slab. Five CT thorax protocols were investigated, one routine (R1) and four that were modified protocols (R2 to R5). Organ doses were ranked from greatest to least, found to lie in the order: thyroid>skin>lung>liver>breast. The greatest dose, for thyroid at 25 mGy, was that in use of R1 while the lowest, at 8.8 mGy, was in breast tissue using R3. Effective dose (E) was estimated using three standard methods: the International Commission on Radiological Protection (ICRP)-103 recommendation (E103), the computational phantom CT-EXPO (E(CTEXPO)) method, and the dose-length product (DLP) based approach. E103 k factors were constant for all protocols, 8% less than that of the universal k factor. Due to inconsistency in tube potential and pitch factor the k factors from CTEXPO were found to vary between 0.015 and 0.010 for protocols R3 and R5. With considerable variation between scan acquisition parameters and organ doses, optimization of practice is necessary in order to reduce patient organ dose.

Methodological variations and their effects on reported medication administration error rates.

PubMed

McLeod, Monsey Chan; Barber, Nick; Franklin, Bryony Dean

2013-04-01

Medication administration errors (MAEs) are a problem, yet methodological variation between studies presents a potential barrier to understanding how best to increase safety. Using the UK as a case-study, we systematically summarised methodological variations in MAE studies, and their effects on reported MAE rates. Nine healthcare databases were searched for quantitative observational MAE studies in UK hospitals. Methodological variations were analysed and meta-analysis of MAE rates performed using studies that used the same definitions. Odds ratios (OR) were calculated to compare MAE rates between intravenous (IV) and non-IV doses, and between paediatric and adult doses. We identified 16 unique studies reporting three MAE definitions, 44 MAE subcategories and four different denominators. Overall adult MAE rates were 5.6% of a total of 21 533 non-IV opportunities for error (OE) (95% CI 4.6% to 6.7%) and 35% of a total of 154 IV OEs (95% CI 2% to 68%). MAEs were five times more likely in IV than non-IV doses (pooled OR 5.1; 95% CI 3.5 to 7.5). Including timing errors of ±30 min increased the MAE rate from 27% to 69% of 320 IV doses in one study. Five studies were unclear as to whether the denominator included dose omissions; omissions accounted for 0%-13% of IV doses and 1.8%-5.1% of non-IV doses. Wide methodological variations exist even within one country, some with significant effects on reported MAE rates. We have made recommendations for future MAE studies; these may be applied both within and outside the UK.

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.

Physiologic variability at the verge of systemic inflammation: multi-scale entropy of heart rate variability is affected by very low doses of endotoxin

PubMed Central

Herlitz, Georg N.; Sanders, Renee L.; Cheung, Nora H.; Coyle, Susette M.; Griffel, Benjamin; Macor, Marie A.; Lowry, Stephen F.; Calvano, Steve E.; Gale, Stephen C.

2014-01-01

Introduction Human injury or infection induces systemic inflammation with characteristic neuro-endocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, we investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and we investigate the size of data sets required for meaningful use of multi-scale entropy (MSE) analysis of HRV. Methods Healthy human volunteers (n=25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 minutes for 6 hours and then at 9, 12, and 24 hours after LPS. Blood samples were drawn at specific time points for cytokine measurements. HRV analysis was performed using EKG epochs of 5 minutes. MSE for HRV was calculated for all dose groups to scale factor 40. Results The lowest significant threshold dose was noted in core temperature at 0.25ng/kg. Endogenous TNF-α and IL-6 were significantly responsive at the next dosage level (0.5ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures ANOVA across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 hours post exposure to LPS. While not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes. Conclusions By usingrANOVA across scale factors, MSE can detect autonomic change after LPS challenge in a group of 25 subjects using EKG epochs of only 5 minutes and entropy analysis to scale factor of only 40, potentially facilitating MSE’s wider use as a research tool or bedside monitor. Traditional markers of inflammation generally exhibit threshold dose behavior. In contrast, MSE’s apparent continuous dose-response pattern, while not statistically verifiable in this study, suggests a potential subclinical harbinger of infectious or other insult. The possible derangement of autonomic complexity prior to or independent of the cytokine surge cannot be ruled out. Future investigation should focus on confirmation of overt inflammation following observed decreases in MSE in a clinical setting. PMID:25526373

Vaccination coverage and its determinants among migrant children in Guangdong, China

PubMed Central

2014-01-01

Background Guangdong province attracted more than 31 million migrants in 2010. But few studies were performed to estimate the complete and age-appropriate immunization coverage and determine risk factors of migrant children. Methods 1610 migrant children aged 12–59 months from 70 villages were interviewed in Guangdong. Demographic characteristics, primary caregiver’s knowledge and attitude toward immunization, and child’s immunization history were obtained. UTD and age-appropriate immunization rates for the following five vaccines and the overall series (1:3:3:3:1 immunization series) were assessed: one dose of BCG, three doses of DTP, OPV and HepB, one dose of MCV. Risk factors for not being UTD for the 1:3:3:3:1 immunization series were explored. Results For each antigen, the UTD immunization rate was above 71%, but the age-appropriate immunization rates for BCG, HepB, OPV, DPT and MCV were only 47.8%, 45.1%, 47.1%, 46.8% and 37.2%, respectively. The 1st dose was most likely to be delayed within them. For the 1:3:3:3:1 immunization series, the UTD immunization rate and age-appropriate immunization rate were 64.9% and 12.4% respectively. Several factors as below were significantly associated with UTD immunization. The primary caregiver’s determinants were their occupation, knowledge and attitude toward immunization. The child’s determinants were sex, Hukou, birth place, residential buildings and family income. Conclusions Alarmingly low immunization coverage of migrant children should be closely monitored by NIISS. Primary caregiver and child’s determinants should be considered when taking measures. Strategies to strengthen active out-reach activities and health education for primary caregivers needed to be developed to improve their immunization coverage. PMID:24568184

Dose factor entry and display tool for BNCT radiotherapy

DOEpatents

Wessol, Daniel E.; Wheeler, Floyd J.; Cook, Jeremy L.

1999-01-01

A system for use in Boron Neutron Capture Therapy (BNCT) radiotherapy planning where a biological distribution is calculated using a combination of conversion factors and a previously calculated physical distribution. Conversion factors are presented in a graphical spreadsheet so that a planner can easily view and modify the conversion factors. For radiotherapy in multi-component modalities, such as Fast-Neutron and BNCT, it is necessary to combine each conversion factor component to form an effective dose which is used in radiotherapy planning and evaluation. The Dose Factor Entry and Display System is designed to facilitate planner entry of appropriate conversion factors in a straightforward manner for each component. The effective isodose is then immediately computed and displayed over the appropriate background (e.g. digitized image).

Choosing the optimal dose in sublingual immunotherapy: Rationale for the 300 index of reactivity dose.

PubMed

Demoly, Pascal; Passalacqua, Gianni; Calderon, Moises A; Yalaoui, Tarik

2015-01-01

Sublingual immunotherapy (SLIT) is an effective and well-tolerated method of treating allergic respiratory diseases associated with seasonal and perennial allergens. In contrast to the subcutaneous route, SLIT requires a much greater amount of antigen to achieve a clinical effect. Many studies have shown that SLIT involves a dose-response relationship, and therefore it is important to use a proven clinically effective dose from the onset of treatment, because low doses are ineffective and very high doses may increase the risk of side effects. A well-defined standardization of allergen content is also crucial to ensure consistent quality, potency and appropriate immunomodulatory action of the SLIT product. Several methods of measuring antigenicity are used by manufacturers of SLIT products, including the index of reactivity (IR), standardized quality tablet unit, and bioequivalent allergy unit. A large body of evidence has established the 300 IR dose of SLIT as offering optimal efficacy and tolerability for allergic rhinitis due to grass and birch pollen and HDM, and HDM-induced moderate, persistent allergic asthma. The 300 IR dose also offers consistency of dosing across a variety of different allergens, and is associated with higher rates of adherence and patient satisfaction. Studies in patients with grass pollen allergies showed that the 300 IR dose has a rapid onset of action, is effective in both adults and children in the short term and, when administered pre-coseasonally in the long term, and maintains the clinical benefit, even after cessation of treatment. In patients with HDM-associated AR and/or asthma, the 300 IR dose also demonstrated significant improvements in symptoms and quality of life, and significantly decreased use of symptomatic medication. The 300 IR dose is well tolerated, with adverse events generally being of mild or moderate severity, declining in frequency and severity over time and in the subsequent courses. We discuss herein the most important factors that affect the selection of the optimal dose of SLIT with natural allergens, and review the rationale and evidence supporting the use of the 300 IR dose.

Risk factors for neovascular glaucoma after carbon ion radiotherapy of choroidal melanoma using dose-volume histogram analysis

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

Hirasawa, Naoki; Tsuji, Hiroshi; Ishikawa, Hitoshi

2007-02-01

Purpose: To determine the risk factors for neovascular glaucoma (NVG) after carbon ion radiotherapy (C-ion RT) of choroidal melanoma. Methods and Materials: A total of 55 patients with choroidal melanoma were treated between 2001 and 2005 with C-ion RT based on computed tomography treatment planning. All patients had a tumor of large size or one located close to the optic disk. Univariate and multivariate analyses were performed to identify the risk factors of NVG for the following parameters; gender, age, dose-volumes of the iris-ciliary body and the wall of eyeball, and irradiation of the optic disk (ODI). Results: Neovascular glaucomamore » occurred in 23 patients and the 3-year cumulative NVG rate was 42.6 {+-} 6.8% (standard error), but enucleation from NVG was performed in only three eyes. Multivariate analysis revealed that the significant risk factors for NVG were V50{sub IC} (volume irradiated {>=}50 GyE to iris-ciliary body) (p = 0.002) and ODI (p = 0.036). The 3-year NVG rate for patients with V50{sub IC} {>=}0.127 mL and those with V50{sub IC} <0.127 mL were 71.4 {+-} 8.5% and 11.5 {+-} 6.3%, respectively. The corresponding rate for the patients with and without ODI were 62.9 {+-} 10.4% and 28.4 {+-} 8.0%, respectively. Conclusion: Dose-volume histogram analysis with computed tomography indicated that V50{sub IC} and ODI were independent risk factors for NVG. An irradiation system that can reduce the dose to both the anterior segment and the optic disk might be worth adopting to investigate whether or not incidence of NVG can be decreased with it.« less

Assessment of dose rate to terrestrial biota in the area around coal fired power plant applying ERICA tool and RESRAD BIOTA code.

PubMed

Ćujić, Mirjana; Dragović, Snežana

2018-08-01

This paper presents the environmental radiation risk assessment based on two software program approaches ERICA Tool (version 1.2) and RESRAD BIOTA (version 1.5) to estimate dose rates to terrestrial biota in the area around the largest coal fired power plant in Serbia. For dose rate assessment software's default reference animals and plants and the best estimated values of activity concentrations of 238 U, 234 U, 234 Th, 232 Th, 230 Th, 226 Ra, 210 Pb, 210 Po, 137 Cs in soil were used. Both approaches revealed the highest contribution to the internal dose rate due to 226 Ra and 210 Po, while 137 Cs contributed the most to the external dose rate. In the investigated area total dose rate to biota derived using ERICA Tool ranged from 0.3 to 14.4 μGy h -1 . The natural radionuclides exhibited significantly higher contribution to the total dose rate than the artificial one. In the investigated area, only dose rate for lichens and bryophytes exceeded ERICA Tool screening value of total dose rate of 10 μGy h -1 suggested as confident that environmental risks are negligible. The assessed total dose rates for reference animals and plants using RESRAD BIOTA were found to be 7 and 3 μGy h -1 , respectively. In RESRAD BIOTA - Level 3, 10 species (Lumbricus terrestris, Rana lessonae, Sciurus vulgaris, Anas platyrhynchos, Lepus europaeus, Vulpes vulpes, Capreolus capreolus, Suss crofa, Quercu srobur, Tilia spp.) representative for the study area were modeled. Among them the highest total dose rate (4.5 μGy h -1 ) was obtained for large mammals. Differences in the predicted dose rates to biota using the two software programs are the consequence of the difference in the values of transfer parameters used to calculate activity concentrations in biota. Doses of ionizing radiation estimated in this study will not exhibit deterministic effects at the population level. Thus, the obtained results indicate no significant radiation impact of coal fired power plant operation on terrestrial biota. This paper confirms the use ERICA Tool and RESRAD BIOTA softwares as flexible and effective means of radiation impact assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Optimizing staff radiation protection in radiology by minimizing the effective dose].

PubMed

von Boetticher, H; Lachmund, J; Hoffmann, W; Luska, G

2006-03-01

In the present study the optimization of radiation protection devices is achieved by minimizing the effective dose of the staff members since the stochastic radiation effects correlate to the effective dose. Radiation exposure dosimetry was performed with TLD measurements using one Alderson Phantom in the patient position and a second phantom in the typical position of the personnel. Various types of protective clothing as well as fixed shields were considered in the calculations. It was shown that the doses of the unshielded organs (thyroid, parts of the active bone marrow) contribute significantly to the effective dose of the staff. Therefore, there is no linear relationship between the shielding factors for protective garments and the effective dose. An additional thyroid protection collar reduces the effective dose by a factor of 1.7 - 3.0. X-ray protective clothing with a 0.35 mm lead equivalent and an additional thyroid protection collar provides better protection against radiation than an apron with a 0.5 mm lead equivalent but no collar. The use of thyroid protection collars is an effective preventive measure against exceeding occupational organ dose limits, and a thyroid shield also considerably reduces the effective dose. Therefore, thyroid protection collars should be a required component of anti-X protection.

Menopausal hormone therapy and breast cancer phenotype: does dose matter?

PubMed

Garwood, Elisabeth R; Kumar, Anjali S; Shim, Veronica

2008-09-01

Duration and type of menopausal hormone therapy (HT) has been associated with increased breast cancer risk and the development of estrogen receptor (ER)-positive tumors. The effect of HT dose on breast cancer tumor characteristics remains undefined. We sought to determine if HT dosing regimens influence breast cancer phenotype. We conducted a retrospective review of incident female breast cancers occurring in the year 2003 listed in the Kaiser Permanente Northern California Cancer Registry. Type of HT, dose, number of tablets dispensed, tumor phenotype, stage, grade, and histology were obtained from electronic records for women aged >/=50 years who had more than 1 year of uninterrupted pharmacy data (n = 1701). A dose index of HT exposure was created and odds ratios were used to determine if tumor phenotype varied between exposure groups. These results were compared with a previously published analysis of HT duration on tumor phenotype conducted with the same dataset. The cumulative effect of estrogen and progesterone hormone therapy as calculated by factoring both dose and duration of HT use prior to breast cancer diagnosis did not reveal any new associations that were not previously identified by analysis of HT duration of exposure alone. Low-dose-index combination-HT users were less likely to have tumors with an ER-positive phenotype. An overall trend developed in which low- and high-dose-index exposed women had the lowest rates of ER- and progesterone receptor (PR) -positive tumors. Duration of use is an adequate surrogate for determining overall exposure to HT when considering the effect of HT on breast cancer phenotype.

Better Efficacy of Synchrotron Spatially Microfractionated Radiation Therapy Than Uniform Radiation Therapy on Glioma.

PubMed

Bouchet, Audrey; Bräuer-Krisch, Elke; Prezado, Yolanda; El Atifi, Michèle; Rogalev, Léonid; Le Clec'h, Céline; Laissue, Jean Albert; Pelletier, Laurent; Le Duc, Géraldine

2016-08-01

Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood. Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control and on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis. MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P<.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT. These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Better Efficacy of Synchrotron Spatially Microfractionated Radiation Therapy Than Uniform Radiation Therapy on Glioma

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

Bouchet, Audrey, E-mail: audrey.m.bouchet@gmail.com; Biomedical Beamline, European Synchrotron Radiation Facility, Grenoble; Bräuer-Krisch, Elke

Purpose: Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood. Methods and Materials: Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control andmore » on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis. Results: MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P<.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT. Conclusions: These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses.« less

Time-resolved in vivo luminescence dosimetry for online error detection in pulsed dose-rate brachytherapy.

PubMed

Andersen, Claus E; Nielsen, Søren Kynde; Lindegaard, Jacob Christian; Tanderup, Kari

2009-11-01

The purpose of this study is to present and evaluate a dose-verification protocol for pulsed dose-rate (PDR) brachytherapy based on in vivo time-resolved (1 s time resolution) fiber-coupled luminescence dosimetry. Five cervix cancer patients undergoing PDR brachytherapy (Varian GammaMed Plus with 192Ir) were monitored. The treatments comprised from 10 to 50 pulses (1 pulse/h) delivered by intracavitary/interstitial applicators (tandem-ring systems and/or needles). For each patient, one or two dosimetry probes were placed directly in or close to the tumor region using stainless steel or titanium needles. Each dosimeter probe consisted of a small aluminum oxide crystal attached to an optical fiber cable (1 mm outer diameter) that could guide radioluminescence (RL) and optically stimulated luminescence (OSL) from the crystal to special readout instrumentation. Positioning uncertainty and hypothetical dose-delivery errors (interchanged guide tubes or applicator movements from +/-5 to +/-15 mm) were simulated in software in order to assess the ability of the system to detect errors. For three of the patients, the authors found no significant differences (P>0.01) for comparisons between in vivo measurements and calculated reference values at the level of dose per dwell position, dose per applicator, or total dose per pulse. The standard deviations of the dose per pulse were less than 3%, indicating a stable dose delivery and a highly stable geometry of applicators and dosimeter probes during the treatments. For the two other patients, the authors noted significant deviations for three individual pulses and for one dosimeter probe. These deviations could have been due to applicator movement during the treatment and one incorrectly positioned dosimeter probe, respectively. Computer simulations showed that the likelihood of detecting a pair of interchanged guide tubes increased by a factor of 10 or more for the considered patients when going from integrating to time-resolved dose verification. The likelihood of detecting a +/-15 mm displacement error increased by a factor of 1.5 or more. In vivo fiber-coupled RL/OSL dosimetry based on detectors placed in standard brachytherapy needles was demonstrated. The time-resolved dose-rate measurements were found to provide a good way to visualize the progression and stability of PDR brachytherapy dose delivery, and time-resolved dose-rate measurements provided an increased sensitivity for detection of dose-delivery errors compared with time-integrated dosimetry.

Prediction of error rates in dose-imprinted memories on board CRRES by two different methods. [Combined Release and Radiation Effects Satellite

NASA Technical Reports Server (NTRS)

Brucker, G. J.; Stassinopoulos, E. G.

1991-01-01

An analysis of the expected space radiation effects on the single event upset (SEU) properties of CMOS/bulk memories onboard the Combined Release and Radiation Effects Satellite (CRRES) is presented. Dose-imprint data from ground test irradiations of identical devices are applied to the predictions of cosmic-ray-induced space upset rates in the memories onboard the spacecraft. The calculations take into account the effect of total dose on the SEU sensitivity of the devices as the dose accumulates in orbit. Estimates of error rates, which involved an arbitrary selection of a single pair of threshold linear energy transfer (LET) and asymptotic cross-section values, were compared to the results of an integration over the cross-section curves versus LET. The integration gave lower upset rates than the use of the selected values of the SEU parameters. Since the integration approach is more accurate and eliminates the need for an arbitrary definition of threshold LET and asymptotic cross section, it is recommended for all error rate predictions where experimental sigma-versus-LET curves are available.

Long-term risk in a recently active volcanic system: Evaluation of doses and indoor radiological risk in the quaternary Vulsini Volcanic District (Central Italy)

NASA Astrophysics Data System (ADS)

Capaccioni, B.; Cinelli, G.; Mostacci, D.; Tositti, L.

2012-12-01

Volcanic rocks in the Vulsini Volcanic District (Central Italy) contain high concentrations of 238U, 232Th and 40K due to subduction-related metasomatic enrichment of incompatible elements in the mantle source coupled with magma differentiation within the upper crust. Due to their favorable mechanical properties they have been extensively used for construction since the Etruscan age. In the old buildings of the Bolsena village, one of the most populated ancient village in the area, the major source of indoor radioactivity is 222Rn, a radioactive noble gas descendant of 238U. Direct 222Rn indoor measurements have detected extremely high values in the old center due to the combined effect of building materials, radon fluxes from the volcanic basement and low air exchange rates. In these cases the evaluated risk of developing lung cancer within a 75 year lifetime reaches up to 40% for ever smokers. Simulations of "standard rooms" built with different tuffs and lavas collected from the Vulsini Volcanic District have also provided estimations of the effective doses and lifetime risk for radiogenic cancer. Other than by the method adopted for calculation, the total evaluated risk for each volcanic rock depends on different parameters, such as: radionuclide content, radon emanation power, occupancy factor and air exchange rate. Occupancy factor and air exchange rate appear as the only controlling parameters able to mitigate the indoor radiological risk.

Influence of gamma-ray skyshine on nuclear facilities design

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

Ohta, M.; Tsuji, M.; Kimura, Y.

1986-01-01

In safety analysis of nuclear facilities, skyshine dose rate at site boundary is one of the most important shielding design problems. For nuclear power stations in Japan, the skyshine dose rate at the site boundary has been specified not to exceed 5 mR/yr by the authorities, including total dose contribution from all structures on site, and this guide is commonly applied to other nuclear fuel cycle facilities. Therefore the design criterion dose of each structure on site is, considering plot planning, shielding condition, and so on, defined as a value <5 mR/yr. The purpose of this study is to investigatemore » how skyshine dose standards or other factors have an influence on the design of nuclear facilities, in a parametric survey of gamma-ray skyshine.« less

“Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs

PubMed Central

Barrett, Frederick S.; Schlienz, Nicolas J.; Lembeck, Natalie; Waqas, Muhammad; Vandrey, Ryan

2018-01-01

Abstract Introduction: Cannabis has been historically classified as a hallucinogen. However, subjective cannabis effects do not typically include hallucinogen-like effects. Empirical reports of hallucinogen-like effects produced by cannabis in controlled settings, particularly among healthy research volunteers, are rare and have mostly occurred after administration of purified Δ-9 tetrahydrocannabinol (THC) rather than whole plant cannabis. Methods: The case of a healthy 30-year-old male who experienced auditory and visual hallucinations in a controlled laboratory study after inhaling vaporized cannabis that contained 25 mg THC (case dose) is presented. Ratings on the Hallucinogen Rating Scale (HRS) following the case dose are compared with HRS ratings obtained from the participant after other doses of cannabis and with archival HRS data from laboratory studies involving acute doses of cannabis, psilocybin, dextromethorphan (DXM), and salvinorin A. Results: Scores on the Volition subscale of the HRS were greater for the case dose than for the maximum dose administered in any other comparison study. Scores on the Intensity and Perception subscales were greater for the case dose than for the maximum dose of cannabis, psilocybin, or salvinorin A. Scores on the Somaesthesia subscale were greater for the case dose than for the maximum dose of DXM, salvinorin A, or cannabis. Scores on the Affect and Cognition subscales for the case dose were significantly lower than for the maximum doses of psilocybin and DXM. Conclusion: Acute cannabis exposure in a healthy adult male resulted in self-reported hallucinations that rated high in magnitude on several subscales of the HRS. However, the hallucinatory experience in this case was qualitatively different than that typically experienced by participants receiving classic and atypical hallucinogens, suggesting that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action. This type of adverse event needs to be considered in the clinical use of cannabis. PMID:29682608

Exposure-Response Modeling to Characterize the Relationship Between Ixekizumab Serum Drug Concentrations and Efficacy Responses at Week 12 in Patients With Moderate to Severe Plaque Psoriasis.

PubMed

Chigutsa, Emmanuel; de Mendizabal, Nieves Velez; Chua, Laiyi; Heathman, Michael; Friedrich, Stuart; Jackson, Kimberley; Reich, Kristian

2018-06-07

Ixekizumab, a high-affinity monoclonal antibody, selectively targets interleukin-17A and has been shown to be efficacious in the treatment of moderate to severe psoriasis. The objective was to describe the relationship between ixekizumab concentrations and efficacy response (static Physician Global Assessment [sPGA] and the Psoriasis Activity and Severity Index [PASI) scores] after 12 weeks of ixekizumab treatment in psoriasis patients from 3 phase 3 studies. Data from 2888 psoriasis patients randomized to receive placebo or 80 mg ixekizumab every 2 weeks or every 4 weeks were analyzed. Separate logistic regression models describing the relationship between ixekizumab concentrations and sPGA or PASI scores at week 12 were used to determine the probability of patients achieving a response and to investigate the impact of various patient factors other than drug concentrations on response rates. Both dosing regimens were efficacious, with higher rates of response achieved with the higher range of observed ixekizumab concentrations after every-2-week dosing. Although higher bodyweight, palmoplantar involvement, lower baseline disease state, or high baseline C-reactive protein were associated with slightly lower response rates, the magnitude of effect of these factors on sPGA(0,1) response was small, with all subgroups able to achieve high levels of response. Other factors tested had no effect including age, sex, and antidrug antibody status. Logistic regression modeling of ixekizumab concentration and efficacy data accurately identified the proportion of responders using sPGA or PASI end points. The higher concentration ranges achieved with 80 mg every 2 weeks versus every 4 weeks were associated with higher response levels. © 2018, The American College of Clinical Pharmacology.

Dose rate estimation of the Tohoku hynobiid salamander, Hynobius lichenatus, in Fukushima.

PubMed

Fuma, Shoichi; Ihara, Sadao; Kawaguchi, Isao; Ishikawa, Takahiro; Watanabe, Yoshito; Kubota, Yoshihisa; Sato, Youji; Takahashi, Hiroyuki; Aono, Tatsuo; Ishii, Nobuyoshi; Soeda, Haruhi; Matsui, Kumi; Une, Yumi; Minamiya, Yukio; Yoshida, Satoshi

2015-05-01

The radiological risks to the Tohoku hynobiid salamanders (class Amphibia), Hynobius lichenatus due to the Fukushima Dai-ichi Nuclear Power Plant accident were assessed in Fukushima Prefecture, including evacuation areas. Aquatic egg clutches (n = 1 for each sampling date and site; n = 4 in total), overwintering larvae (n = 1-5 for each sampling date and site; n = 17 in total), and terrestrial juveniles or adults (n = 1 or 3 for each sampling date and site; n = 12 in total) of H. lichenatus were collected from the end of April 2011 to April 2013. Environmental media such as litter (n = 1-5 for each sampling date and site; n = 30 in total), soil (n = 1-8 for each sampling date and site; n = 31 in total), water (n = 1 for each sampling date and site; n = 17 in total), and sediment (n = 1 for each sampling date and site; n = 17 in total) were also collected. Activity concentrations of (134)Cs + (137)Cs were 1.9-2800, 0.13-320, and 0.51-220 kBq (dry kg) (-1) in the litter, soil, and sediment samples, respectively, and were 0.31-220 and <0.29-40 kBq (wet kg)(-1) in the adult and larval salamanders, respectively. External and internal absorbed dose rates to H. lichenatus were calculated from these activity concentration data, using the ERICA Assessment Tool methodology. External dose rates were also measured in situ with glass dosimeters. There was agreement within a factor of 2 between the calculated and measured external dose rates. In the most severely contaminated habitat of this salamander, a northern part of Abukuma Mountains, the highest total dose rates were estimated to be 50 and 15 μGy h(-1) for the adults and overwintering larvae, respectively. Growth and survival of H. lichenatus was not affected at a dose rate of up to 490 μGy h(-1) in the previous laboratory chronic gamma-irradiation experiment, and thus growth and survival of this salamander would not be affected, even in the most severely contaminated habitat in Fukushima Prefecture. However, further studies of the adult salamanders may be required in order to examine whether the most severe radioactive contamination has any effects on sensitive endpoints, since the estimated highest dose rate to the adults exceeded some of the guidance dose rates proposed by various organisations and programmes for the protection of amphibians, which range from 4 to 400 μGy h(-1). Conversely, at one site in Nakadori, a moderately contaminated region in Fukushima Prefecture, the dose rate to the adult salamanders in spring of 2012 was estimated to be 0.2 μGy h(-1). Estimated dose rates to the overwintering larvae in spring of 2012 were 1 and 0.2 μGy h(-1) at one site in Nakadori, and in Aizu, a less contaminated region in Fukushima Prefecture, respectively. These results suggest that there is a low risk that H. lichenatus will be affected by radioactive contamination in these districts, though further studies on dose rate estimation are required for definitive risk characterisation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The subjective experience of trauma and subsequent PTSD in a sample of undocumented immigrants.

PubMed

Rasmussen, Andrew; Rosenfeld, Barry; Reeves, Kim; Keller, Allen S

2007-02-01

Although a subjective component of trauma is commonly recognized in diagnosing posttraumatic stress disorder (PTSD), there are few studies that specifically address Criterion A2, and none addressing this issue among undocumented immigrants. We assessed 212 arriving undocumented immigrants with diverse trauma histories to investigate concordance between objective and subjective factors of trauma (Criteria A1 and A2) and across different types of trauma and PTSD. Concordance between Criteria A1 and A2 varied, with highest rates found for political violence. Interpersonal violence in general was associated with higher rates of PTSD. We identified a dose-response effect for PTSD, but this was not dependent on other events (i.e., other doses) meeting Criterion A2. Discussion focuses on Criterion A within the phenomenology of PTSD and the need to gauge subjective interpretations of trauma events among this population.

A new treatment planning formalism for catheter-based beta sources used in intravascular brachytherapy.

PubMed

Patel, N S; Chiu-Tsao, S T; Tsao, H S; Harrison, L B

2001-01-01

Intravascular brachytherapy (IVBT) is an emerging modality for the treatment of atherosclerotic lesions in the artery. As part of the refinement in this rapidly evolving modality of treatment, the current simplistic dosimetry approach based on a fixed-point prescription must be challenged by future rigorous dosimetry method employing image-based three-dimensional (3D) treatment planning. The goals of 3D IVBT treatment planning calculations include (1) achieving high accuracy in a slim cylindrical region of interest, (2) accounting for the edge effect around the source ends, and (3) supporting multiple dwell positions. The formalism recommended by Task Group 60 (TG-60) of the American Association of Physicists in Medicine (AAPM) is applicable for gamma sources, as well as short beta sources with lengths less than twice the beta particle range. However, for the elongated beta sources and/or seed trains with lengths greater than twice the beta range, a new formalism is required to handle their distinctly different dose characteristics. Specifically, these characteristics consist of (a) flat isodose curves in the central region, (b) steep dose gradient at the source ends, and (c) exponential dose fall-off in the radial direction. In this paper, we present a novel formalism that evolved from TG-60 in maintaining the dose rate as a product of four key quantities. We propose to employ cylindrical coordinates (R, Z, phi), which are more natural and suitable to the slim cylindrical shape of the volume of interest, as opposed to the spherical coordinate system (r, theta, phi) used in the TG-60 formalism. The four quantities used in this formalism include (1) the distribution factor, H(R, Z), (2) the modulation function, M(R, Z), (3) the transverse dose function, h(R), and (4) the reference dose rate at 2 mm along the perpendicular bisector, D(R0=2 mm, Z0=0). The first three are counterparts of the geometry factor, the anisotropy function and the radial dose function in the TG-60 formalism, respectively. The reference dose rate is identical to that recommended by TG-60. The distribution factor is intended to resemble the dose profile due to the spatial distribution of activity in the elongated beta source, and it is a modified Fermi-Dirac function in mathematical form. The utility of this formalism also includes the slow-varying nature of the modulation function, allowing for more accurate treatment planning calculations based on interpolation. The transverse dose function describes the exponential fall-off of the dose in the radial direction, and an exponential or a polynomial can fit it. Simultaneously, the decoupling nature of these dose-related quantities facilitates image-based 3D treatment planning calculations for long beta sources used in IVBT. The new formalism also supports the dosimetry involving multiple dwell positions required for lesions longer than the source length. An example of the utilization of this formalism is illustrated for a 90Y coil source in a carbon dioxide-filled balloon. The pertinent dosimetric parameters were generated and tabulated for future use.

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

[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.

Thalidomide treatment in cutaneous lesions of systemic lupus erythematosus: a multicenter study in China.

PubMed

Wang, Dandan; Chen, Haifeng; Wang, Shiying; Zou, Yaohong; Li, Jing; Pan, Jieping; Wang, Xiangdang; Ren, Tianli; Zhang, Yu; Chen, Zhiwei; Feng, Xuebing; Sun, Lingyun

2016-06-01

Thalidomide is effective for treating severe cutaneous lupus patients. The aim of this study was to observe the optimum effective and maintenance doses of thalidomide to maximize clinical benefit and minimize side effects for patients with cutaneous lupus in China. Sixty-nine patients with lupus rash from eight hospitals in China were enrolled and treated with different doses of thalidomide. We started the dose of thalidomide at 25 mg daily and gradually increased administration dose once a week until erythema was markedly improved. The effective and maintenance doses were documented. The size of skin lesions was noted once a week. Systemic lupus erythematosus disease activity index (SLEDAI) score, levels of erythrocyte sedimentation rate (ESR), and serum TNF-α were measured before and after treatment. The remission rates were evaluated weekly until 8 weeks. Sixty-eight percent of patients showed an effective dose of 50 mg daily; another 13, 10, and 9 % of patients had an effective dose of 100, 75, and 25 mg daily, respectively. The maintenance dose was 50 mg daily for 71 % of the patients, and 100, 75, and 25 mg daily for 9, 14, and 6 % of the patients. SLEDAI score and serum ESR levels significantly decreased 4 weeks after thalidomide treatment. At the end of the fourth week, the rates of complete remission, partial remission, and no response were 56 % (n = 39), 41 % (n = 28), and 3 % (n = 2). At the eighth week, the rate of total remission rose up to 100 %. The most common side effects were drowsiness and constipation. No peripheral neuropathy was observed in these patients. Thalidomide at a dose of 50 mg daily may offer a better benefit to risk ratio in the treatment of Chinese cutaneous lupus patients.

A mathematical model for the effects of radiation to the induced cancer in mice

NASA Astrophysics Data System (ADS)

Wada, Takahiro; Manabe, Yuichiro; Bando, Masako

We have been studying biological effects of radiation in terms of mathematical models. There are two main objects that we need to study: mutation and cancer. We proposed the Whack-A-Mole (WAM) model which takes account of the repair effects to study radiation induced mutations. We applied it to the mutation of several species including Drosophila and mice, and succeeded to reproduce the dose and dose-rate dependence of the mutation rates. Here, as a next step, we study the effects of low dose-rate radiation to an induced cancer in mice. In the experiment, they divided their mice in four groups and kept them under constant gamma-ray radiations with different dose rate for each group since the birth. On the 35th day, chemical carcinogen was given to each mouse and they observed the occurrence and the growth of cancer for one year. Our mathematical model consists of two stages. The first stage describes a multiple-step carcinogenesis and the second stage describes its growth. We assume that the carcinogenesis starts with the chemical carcinogen and that the rate of the following processes depends on the dose rate as it does in the WAM model. We found some irregularities in the data, however, the overall fit is satisfactory. This work was supported by JSPS KAKENHI Grant Number JP16H04637.

Functional Data Analysis in NTCP Modeling: A New Method to Explore the Radiation Dose-Volume Effects

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

Benadjaoud, Mohamed Amine, E-mail: mohamedamine.benadjaoud@gustaveroussy.fr; Université Paris sud, Le Kremlin-Bicêtre; Institut Gustave Roussy, Villejuif

2014-11-01

Purpose/Objective(s): To describe a novel method to explore radiation dose-volume effects. Functional data analysis is used to investigate the information contained in differential dose-volume histograms. The method is applied to the normal tissue complication probability modeling of rectal bleeding (RB) for patients irradiated in the prostatic bed by 3-dimensional conformal radiation therapy. Methods and Materials: Kernel density estimation was used to estimate the individual probability density functions from each of the 141 rectum differential dose-volume histograms. Functional principal component analysis was performed on the estimated probability density functions to explore the variation modes in the dose distribution. The functional principalmore » components were then tested for association with RB using logistic regression adapted to functional covariates (FLR). For comparison, 3 other normal tissue complication probability models were considered: the Lyman-Kutcher-Burman model, logistic model based on standard dosimetric parameters (LM), and logistic model based on multivariate principal component analysis (PCA). Results: The incidence rate of grade ≥2 RB was 14%. V{sub 65Gy} was the most predictive factor for the LM (P=.058). The best fit for the Lyman-Kutcher-Burman model was obtained with n=0.12, m = 0.17, and TD50 = 72.6 Gy. In PCA and FLR, the components that describe the interdependence between the relative volumes exposed at intermediate and high doses were the most correlated to the complication. The FLR parameter function leads to a better understanding of the volume effect by including the treatment specificity in the delivered mechanistic information. For RB grade ≥2, patients with advanced age are significantly at risk (odds ratio, 1.123; 95% confidence interval, 1.03-1.22), and the fits of the LM, PCA, and functional principal component analysis models are significantly improved by including this clinical factor. Conclusion: Functional data analysis provides an attractive method for flexibly estimating the dose-volume effect for normal tissues in external radiation therapy.« less

Factors Influencing Male Plutella xylostella (Lepidoptera: Plutellidae) Capture Rates in Sex Pheromone-Baited Traps on Canola in Western Canada.

PubMed

Miluch, C E; Dosdall, L M; Evenden, M L

2014-12-01

Optimization of male moth trapping rates in sex pheromone-baited traps plays a key role in managing Plutella xylostella (L.). We investigated various ways to increase the attractiveness of pheromone-baited traps to P. xylostella in canola agroecosystems in AB, Canada. Factors tested included pheromone blend and dose, addition of a green leaf volatile to the pheromone at different times during the season, lure type, trap color, and height. The industry standard dose of 100 μg of pheromone (four-component blend) per lure (ConTech Enterprises Inc., Delta, British Columbia [BC], Canada) captured the most moths in the two lure types tested. Traps baited with pheromone released from gray rubber septa captured more males than those baited with red rubber septa. Traps baited with lures in which Z11-16: Ac is the main component attracted significantly more moths than those in which Z11-16: Ald is the main component. The addition of the green leaf volatile, (Z)-3-hexenyl acetate, to pheromone at a range of doses, did not increase moth capture at any point during the canola growing season. Unpainted white traps captured significantly more male moths than pheromone-baited traps that were painted yellow. Trap height had no significant effect on moth capture. Recommendations for monitoring P. xylostella in canola agroecosystems of western Canada include using a pheromone blend with Z11-16: Ac as the main component released from gray rubber septa at a dose of 100 μg. © 2014 Entomological Society of America.

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

Farfan, E.; Jannik, T.

This article describes major studies performed by the Chernobyl Center's International Radioecology Laboratory (Slavutich, Ukraine) on radioecology of murine rodents and shrews inhabiting the Chernobyl Exclusion Zone. The article addresses the long-term (1986-2005) and seasonal dynamics of radioactive contamination of animals, and reviews interspecies differences in radionuclide accumulations and factors affecting the radionuclide accumulations. It is shown that bioavailability of radionuclides in the 'soil-to-plant' chain and a trophic specialization of animals play key roles in determining their actual contamination levels. The total absorbed dose rates in small mammals significantly reduced during the years following the Chernobyl Nuclear Power Plant accident.more » In 1986, the absorbed dose rate reached 1.3-6.0 Gy hr{sup -1} in the central areas of the Chernobyl Exclusion Zone (the 'Red Forest'). In 1988 and 1990, the total absorbed dose rates were 1.3 and 0.42 Gy hr{sup -1}, respectively. In 1995, 2000, and 2005, according to the present study, the total absorbed dose rates rarely exceeded 0.00023, 0.00018, and 0.00015 Gy hr{sup -1}, respectively. Contributions of individual radiation sources into the total absorbed dose are described.« less

Herbicides and plant hormesis.

PubMed

Belz, Regina G; Duke, Stephen O

2014-05-01

Herbicide hormesis is commonly observed at subtoxic doses of herbicides and other phytotoxins. The occurrence and magnitude of this phenomenon are influenced by plant growth stage and physiological status, environmental factors, the endpoint measured and the timing between treatment and endpoint measurement. The mechanism in some cases of herbicide hormesis appears to be related to the target site of the herbicide, whereas in other examples hormesis may be by overcompensation to moderate stress induced by the herbicides or a response to disturbed homeostasis. Theoretically, herbicide hormesis could be used in crop production, but this has been practical only in the case of the use of herbicides as sugar cane 'ripeners' to enhance sucrose accumulation. The many factors that can influence the occurrence, the magnitude and the dose range of hormetic increases in yield for most crops make it too unpredictable and risky as a production practice with the currently available knowledge. Herbicide hormesis can cause undesired effects in situations in which weeds are unintentionally exposed to hormetic doses (e.g. in adjacent fields, when shielded by crop vegetation). Some weeds that have evolved herbicide resistance may have hormetic responses to recommended herbicide application rates. Little is known about such effects under field conditions. A more complete understanding of herbicide hormesis is needed to exploit its potential benefits and to minimize its potential harmful effects in crop production. © 2014 Society of Chemical Industry.

Uterine insemination with a standard AI dose in a sow pool system.

PubMed

Peltoniemi, O A T; Alm, K; Andersson, M

2009-06-01

The effect of uterine AI with a standard dose of spermatozoa on fertility of the sow was studied in a field trial. The trial involved a sow pool system with 440 sows using AI as the primary method of breeding. Sows were twice a day checked for oestrus symptoms by back pressure test in front of a boar on days 3-6 after weaning. When in standing heat, sows were randomly allocated into either a uterine insemination group (UTER, n = 157) or standard AI group (CONT, n = 169) and bred accordingly using 3 billion spermatozoa in 80 ml of extender. In both treatment groups, insemination was repeated once if the sow was still receptive 24 h later. Using pregnancy (farrowed or not) and live-born litter size as the outcome variables, a logistic and linear regression approach, respectively, was taken to study the effect of the following factors: treatment (UTER vs CONT), AI operator, breed, satellite herd preceding weaning, parity, weaning-to-oestrus interval and length of lactation. Overall, live-born litter size was 11.3 +/- 2.9, repeat breeding rate 4.2% and farrowing rate 91.2%. In the UTER group, 93.6% of inseminated sows farrowed, whereas farrowing rate for the CONT group was 88.8% (p = 0.13). Intrauterine insemination with a standard AI dose did not result in a significant improvement in the live-born litter size (11.5 +/- 2.8 for the UTER and 11.1 +/- 3.0 for the CONT sows, respectively, p = 0.13). However, the preceding satellite herd had a highly significant effect on the live-born litter size (12.4 +/- 2.6; 11.1 +/- 2.9; 10.8 +/- 2.9 and 10.9 +/- 2.9 for the four satellite herds, p < 0.01). We conclude that uterine insemination did not have a significant effect on live-born litter size and farrowing rate and we also conclude that satellite herd appears to have a major effect on fertility in a sow pool system.

A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study.

PubMed

Hoffmann, Till; Assmann, Alexander; Dierksen, Angelika; Roussel, Elisabeth; Ullrich, Sebastian; Lichtenberg, Artur; Albert, Alexander; Sixt, Stephan

2018-04-18

Although off-label use of recombinant activated factor VII against refractory bleeding is incorporated in current guideline recommendations, safety concerns persist predominantly with respect to thromboembolic complications. We analyzed the safety and efficacy of recombinant activated factor VII at a very low dose in cardiosurgical patients with refractory bleeding. This prospective study includes 1180 cardiosurgical patients at risk of bleeding. Goal-directed substitution was based on real-time laboratory testing and clinical scoring of the bleeding intensity. All patients who fulfilled the criteria for enhanced risk of bleeding (n = 281) were consequently included in the present analysis. Patients in whom refractory bleeding developed despite substitution with specific hemostatic compounds (n = 167) received a single shot of very low-dose recombinant activated factor VII (≤20 μg/kg). Mortality and risk of thromboembolic complications, and freedom from stroke and acute myocardial infarction in particular, were analyzed (vs patients without recombinant activated factor VII) by multivariable logistic and Cox regression analyses, as well as Kaplan-Meier estimates. There was no increase in rates of mortality (30-day mortality 4.2% vs 7.0% with P = .418; follow-up survival 85.6% at 13.0 [interquartile range, 8.4-15.7] months vs 80.7% at 10.2 [interquartile range, 7.2-16.1] months with P = .151), thromboembolic complications (6.6% vs 9.6% with P = .637), renal insufficiency, need for percutaneous coronary intervention, duration of ventilation, duration of hospital stay, or rehospitalization in patients receiving very low-dose recombinant activated factor VII compared with patients not receiving recombinant activated factor VII. Complete hemostasis without any need for further hemostatic treatment was achieved after very low-dose recombinant activated factor VII administration in the majority of patients (up to 88.6% vs 0% with P < .001). The key results were confirmed after adjustment by propensity score-based analyses. When combined with early and specific restoration of hemostatic reserves after cardiac surgery, very low-dose recombinant activated factor VII treatment of refractory bleeding is effective and not associated with any apparent increase in adverse events. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Very low dose gamma irradiation stimulates gaseous exchange and carboxylation efficiency, but inhibits vascular sap flow in groundnut (Arachis hypogaea L.).

PubMed

Ahuja, Sumedha; Singh, Bhupinder; Gupta, Vijay Kumar; Singhal, R K; Venu Babu, P

2014-02-01

An experiment was carried out to determine the effect of low dose gamma radiation on germination, plant growth, nitrogen and carbon fixation and carbon flow and release characteristics of groundnut. Dry seeds of groundnut variety Trombay groundnut 37A (TG 37A), a radio mutant type developed by Bhabha Atomic Research Centre (BARC), Mumbai, India, were subjected to the pre-sowing treatment of gamma radiation within low to high dose physiological range, i.e., 0.0, 0.0082, 0.0164. 0.0328, 0.0656, 0.1312, 5, 25, 100, 500 Gray (Gy) from a cobalt source ((60)Co). Observations were recorded for the radiation effect on percentage germination, vigour, gas exchange attributes such as photosynthetic rate, stomatal conductance and transpiration rate, chlorophyll content, root exudation in terms of (14)C release, vascular sap flow rate and activities of rate defining carbon and nitrogen assimilating enzymes such as ribulose-1,5-bisphosphate carboxylase (rubisco) and nitrate reductase (NR). Seed germination was increased by 10-25% at the lower doses up to 5 Gy while the improvement in plant vigour in the same dose range was much higher (22-84%) than the unirradiated control. For radiation exposure above 5 Gy, a dose-dependent decline in germination and plant vigour was measured. No significant effect was observed on the photosynthesis at radiation exposure below 5 Gy but above 5 Gy dose there was a decline in the photosynthetic rate. Stomatal conductance and transpiration rate, however, were only inhibited at a high dose of 500 Gy. Leaf rubisco activity and NR activities remained unaffected at all the investigated doses of gamma irradiation. Mean root exudation and sap flow rate of the irradiated plants, irrespective of the dose, was reduced over the unirradiated control more so in a dose-dependent manner. Results indicated that a very low dose of gamma radiation, in centigray to gray range, did not pose any threat and in fact stimulated metabolic functions in such a way to aid growth and development of groundnut plants. It further showed that the radiation threshold for the gas exchange traits and rubisco activity, which ultimately determine the plant health and yield, were higher than compared to the other metabolic attributes and were well beyond 500 Gy and that the dose range above 500 Gy should be targeted to measure lethal effects of radiation on carbon assimilation attributes in leguminous crops, in general, and groundnut in particular.

Dependence of pentobarbital kinetics upon the dose of the drug and its pharmacodynamic effects.

PubMed

Kozlowski, K H; Szaykowski, A; Danysz, A

1977-01-01

Pentobarbital (PB), at dose range of 20--50 mg/kg, displays in rabbits non-linear, dose-dependent kinetics. Pharmacokinetics parameters of drug elimination depend largely upon the dose, while the distribution phase is dose-independent. The rate of disappearance of PB from the central compartment (plasma) decreases with the increase of the dose. The analysis of pharmacodynamic parameters has shown that this dose-dependent retardation of PB elimination is probably caused by an impairment of metabolic processes, resulting from disturbance of the circulatory system. A close correlation has been found between the hypotensive effect of PB and the elimination constant, k13, and also between the hypotensive effect and beta.Vd(extrap), a coefficient proportional to the rate of metabolism of PB [23, 29]. The results indicate the necessity of considering the changes in the functional state of the organism, related to the action of a drug, in pharmacokinetic studies.

Effect of radiocesium transfer on ambient dose rate in forest environments affected by the Fukushima Nuclear Power Plant accident

NASA Astrophysics Data System (ADS)

Kato, H.

2015-12-01

We investigated the transfer of canopy-intercepted radiocesium to the forest floor during 3 years following the Fukushima Daiichi Nuclear Power Plant accident. The cesium-137 (Cs-137) contents in throughfall, stemflow, and litterfall were monitored in two coniferous stands (plantation of Japanese cedar) and a deciduous broad-leaved forest stand (Japanese oak with red pine). We also measured the ambient dose rate (ADR) at different heights in the forest using a survey meter and a portable Ge gamma-ray detector. Total Cs-137 deposition flux from the canopy to forest floor for the mature cedar, young cedar, and the mixed broad-leaved stands were 166 kBq/m2, 174 kBq/m2, and 60 kBq/m2, respectively. These values correspond to 38%, 40% and 13% of total atmospheric input after the accident. The ambient dose rate in forest exhibited height dependency and its vertical distribution varied with forest type and stand age. The ambient dose rate showed an exponential decrease with time for all the forest sites, however the decreasing trend differed depending on the height of dose measurement and forest type. The ambient dose rate at the canopy (approx. 10 m-height) decreased faster than that expected from physical decay of the two radiocesium isotopes, whereas those at the forest floor varied between the three forest stands. The radiocesium deposition via throughfall seemed to increase ambient dose rate during the first 200 days after the accident, however there was no clear relationship between litterfall and ambient dose rate since 400 days after the accident. These data suggested that the ambient dose rate in forest environment varied both spatially and temporally reflecting the transfer of radiocesium from canopy to forest floor. However, further monitoring investigation and analysis are required to determine the effect of litterfall on long-term trend of ambient dose rate in forest environments.

Diamond detector in absorbed dose measurements in high‐energy linear accelerator photon and electron beams

PubMed Central

Binukumar, John Pichy; Amri, Iqbal Al; Davis, Cheriyathmanjiyil Antony

2016-01-01

Diamond detectors (DD) are preferred in small field dosimetry of radiation beams because of small dose profile penumbras, better spatial resolution, and tissue‐equivalent properties. We investigated a commercially available ‘microdiamond’ detector in realizing absorbed dose from first principles. A microdiamond detector, type TM 60019 with tandem electrometer is used to measure absorbed doses in water, nylon, and PMMA phantoms. With sensitive volume 0.004 mm3, radius 1.1 mm, thickness 1×10−3mm, the nominal response is 1 nC/Gy. It is assumed that the diamond detector could collect total electric charge (nC) developed during irradiation at 0 V bias. We found that dose rate effect is less than 0.7% for changing dose rate by 500 MU/min. The reproducibility in obtaining readings with diamond detector is found to be ±0.17% (1 SD) (n=11). The measured absorbed doses for 6 MV and 15 MV photons arrived at using mass energy absorption coefficients and stopping power ratios compared well with Nd, water calibrated ion chamber measured absorbed doses within 3% in water, PMMA, and nylon media. The calibration factor obtained for diamond detector confirmed response variation is due to sensitivity due to difference in manufacturing process. For electron beams, we had to apply ratio of electron densities of water to carbon. Our results qualify diamond dosimeter as a transfer standard, based on long‐term stability and reproducibility. Based on micro‐dimensions, we recommend these detectors for pretreatment dose verifications in small field irradiations like stereotactic treatments with image guidance. PACS number(s): 87.56.Da PMID:27074452

Is oral immunotherapy the cure for food allergies?

PubMed

Nowak-Wegrzyn, Anna; Fiocchi, Alessandro

2010-06-01

To review current evidence on food oral immunotherapy (OIT). Desensitized state, defined as the ingestion of a substantial amount of food in the home diet that protects from severe reactions to accidental exposures, can be achieved by approximately 50-75% of the children treated with OIT. The rate of permanent tolerance is unknown; the longer duration of OIT may result in permanent tolerance. Side effects are common both during the initial dose escalation and during home dosing. Most reactions are mild (oral pruritus, abdominal discomfort, and rashes) and decrease in frequency with the longer duration of OIT. Severe reactions treated with epinephrine have been reported during home dosing. Factors associated with increased risk of reactions to previously tolerated doses during home dosing include exercise, viral infection, dosing on empty stomach, menses, and asthma exacerbation. These preliminary data on OIT are encouraging. Additional studies must answer multiple questions including optimal dose, ideal duration of oral/sublingual immunotherapy, degree of protection, efficacy for different ages, severity and type of food allergy responsive to treatment and need for patient protection during home administration. Until these questions are answered in rigorous multicenter randomized and placebo-controlled trials, OIT remains an experimental approach with not sufficiently well established risk-to-benefit ratio.

STUDIES OF COSMIC-RAY MUONS AND NEUTRONS IN A FIVE-STORY CONCRETE BUILDING.

PubMed

Chen, Wei-Lin; Sheu, Rong-Jiun

2018-05-01

This study thoroughly determined the flux and dose rate distributions of cosmic-ray muons and neutrons in a five-story concrete building by comparing measurements with Monte Carlo simulations of cosmic-ray showers. An angular-energy-dependent surface source comprising secondary muons and neutrons at a height of 200 m above ground level was established and verified, which was used to concatenate the shower development in the upper atmosphere with subsequent simulations of radiation transport down to ground level, including the effect of the terrain and studied building. A Berkeley Lab cosmic-ray detector and a highly sensitive Bonner cylinder were used to perform muon and neutron measurements on each building floor. After careful calibration and correction, the measured responses of the two detectors were discovered to be reasonably consistent with the theoretical predictions, thus confirming the validity of the two-step calculation model employed in this study. The annual effective doses from cosmic-ray muons and neutrons on the open roof of the building were estimated to be 115.2 and 35.2 μSv, respectively. Muons and neutrons were attenuated floor-by-floor with different attenuation factors of 0.97 and 0.78, and their resultant dose rates on the first floor of the building were 97.8 and 9.9 μSv, respectively.