Study of the dose rate effect of 180 nm nMOSFETs

NASA Astrophysics Data System (ADS)

He, Bao-Ping; Yao, Zhi-Bin; Sheng, Jiang-Kun; Wang, Zu-Jun; Huang, Shao-Yan; Liu, Min-Bo; Xiao, Zhi-Gang

2015-01-01

Radiation induced offstate leakage in the shallow trench isolation regions of SIMC 0.18 μm nMOSFETs is studied as a function of dose rate. A “true” dose rate effect (TDRE) is observed. Increased damage is observed at low dose rate (LDR) than at high dose rate (HDR) when annealing is taken into account. A new method of simulating radiation induced degradation in shallow trench isolation (STI) is presented. A comparison of radiation induced offstate leakage current in test nMOSFETs between total dose irradiation experiments and simulation results exhibits excellent agreement. The investigation results imply that the enhancement of the leakage current may be worse for the dose rate encountered in the environment of space.

Comparison of 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.

Genetic susceptibility: radiation effects relevant to space travel.

PubMed

Peng, Yuanlin; Nagasawa, Hatsumi; Warner, Christy; Bedford, Joel S

2012-11-01

Genetic variation in the capacity to repair radiation damage is an important factor influencing both cellular and tissue radiosensitivity variation among individuals as well as dose rate effects associated with such damage. This paper consists of two parts. The first part reviews some of the available data relating to genetic components governing such variability among individuals in susceptibility to radiation damage relevant for radiation protection and discusses the possibility and extent to which these may also apply for space radiations. The second part focuses on the importance of dose rate effects and genetic-based variations that influence them. Very few dose rate effect studies have been carried out for the kinds of radiations encountered in space. The authors present here new data on the production of chromosomal aberrations in noncycling low passage human ATM+/+ or ATM+/- cells following irradiations with protons (50 MeV or 1 GeV), 1 GeV(-1) n iron ions and gamma rays, where doses were delivered at a high dose rate of 700 mGy(-1) min, or a lower dose rate of 5 mGy min(-1). Dose responses were essentially linear over the dose ranges tested and not significantly different for the two cell strains. Values of the dose rate effectiveness factor (DREF) were expressed as the ratio of the slopes of the dose-response curves for the high versus the lower (5 mGy min(-1)) dose rate exposures. The authors refer to this as the DREF5. For the gamma ray standard, DREF5 values of approximately two were observed. Similar dose rate effects were seen for both energies of protons (DREF5 ≈ 2.2 in both cases). For 1 GeV(-1) n iron ions [linear energy transfer (LET) ≈ 150 keV μ(-1)], the DREF5 was not 1 as might have been expected on the basis of LET alone but was approximately 1.3. From these results and conditions, the authors estimate that the relative biological effectiveness for 1 GeV(-1) n iron ions for high and low dose rates, respectively, were about 10 and 15 rather than around 20 for low dose rates, as has been assumed by most recommendations from radiation protection organizations for charged particles of this LET. The authors suggest that similar studies using appropriate animal models of carcinogenesis would be valuable.

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…

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.

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.

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.

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.

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.

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

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.

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.

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.

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

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

NASA Technical Reports Server (NTRS)

Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

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.

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

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.

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.

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;

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.

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.

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.

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.

Estimation of the Dose and Dose Rate Effectiveness Factor

NASA Technical Reports Server (NTRS)

Chappell, L.; Cucinotta, F. A.

2013-01-01

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

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.

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.

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.

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

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

“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

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.

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.

Nuclear Radiation Degradation Study on HD Camera Based on CMOS Image Sensor at Different Dose Rates.

PubMed

Wang, Congzheng; Hu, Song; Gao, Chunming; Feng, Chang

2018-02-08

In this work, we irradiated a high-definition (HD) industrial camera based on a commercial-off-the-shelf (COTS) CMOS image sensor (CIS) with Cobalt-60 gamma-rays. All components of the camera under test were fabricated without radiation hardening, except for the lens. The irradiation experiments of the HD camera under biased conditions were carried out at 1.0, 10.0, 20.0, 50.0 and 100.0 Gy/h. During the experiment, we found that the tested camera showed a remarkable degradation after irradiation and differed in the dose rates. With the increase of dose rate, the same target images become brighter. Under the same dose rate, the radiation effect in bright area is lower than that in dark area. Under different dose rates, the higher the dose rate is, the worse the radiation effect will be in both bright and dark areas. And the standard deviations of bright and dark areas become greater. Furthermore, through the progressive degradation analysis of the captured image, experimental results demonstrate that the attenuation of signal to noise ratio (SNR) versus radiation time is not obvious at the same dose rate, and the degradation is more and more serious with increasing dose rate. Additionally, the decrease rate of SNR at 20.0, 50.0 and 100.0 Gy/h is far greater than that at 1.0 and 10.0 Gy/h. Even so, we confirm that the HD industrial camera is still working at 10.0 Gy/h during the 8 h of measurements, with a moderate decrease of the SNR (5 dB). The work is valuable and can provide suggestion for camera users in the radiation field.

Nuclear Radiation Degradation Study on HD Camera Based on CMOS Image Sensor at Different Dose Rates

PubMed Central

Wang, Congzheng; Hu, Song; Gao, Chunming; Feng, Chang

2018-01-01

In this work, we irradiated a high-definition (HD) industrial camera based on a commercial-off-the-shelf (COTS) CMOS image sensor (CIS) with Cobalt-60 gamma-rays. All components of the camera under test were fabricated without radiation hardening, except for the lens. The irradiation experiments of the HD camera under biased conditions were carried out at 1.0, 10.0, 20.0, 50.0 and 100.0 Gy/h. During the experiment, we found that the tested camera showed a remarkable degradation after irradiation and differed in the dose rates. With the increase of dose rate, the same target images become brighter. Under the same dose rate, the radiation effect in bright area is lower than that in dark area. Under different dose rates, the higher the dose rate is, the worse the radiation effect will be in both bright and dark areas. And the standard deviations of bright and dark areas become greater. Furthermore, through the progressive degradation analysis of the captured image, experimental results demonstrate that the attenuation of signal to noise ratio (SNR) versus radiation time is not obvious at the same dose rate, and the degradation is more and more serious with increasing dose rate. Additionally, the decrease rate of SNR at 20.0, 50.0 and 100.0 Gy/h is far greater than that at 1.0 and 10.0 Gy/h. Even so, we confirm that the HD industrial camera is still working at 10.0 Gy/h during the 8 h of measurements, with a moderate decrease of the SNR (5 dB). The work is valuable and can provide suggestion for camera users in the radiation field. PMID:29419782

An accurate derivation of the air dose-rate and the deposition concentration distribution by aerial monitoring in a low level contaminated area

NASA Astrophysics Data System (ADS)

Nishizawa, Yukiyasu; Sugita, Takeshi; Sanada, Yukihisa; Torii, Tatsuo

2015-04-01

Since 2011, MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan) have been conducting aerial monitoring to investigate the distribution of radioactive cesium dispersed into the atmosphere after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), Tokyo Electric Power Company. Distribution maps of the air dose-rate at 1 m above the ground and the radioactive cesium deposition concentration on the ground are prepared using spectrum obtained by aerial monitoring. The radioactive cesium deposition is derived from its dose rate, which is calculated by excluding the dose rate of the background radiation due to natural radionuclides from the air dose-rate at 1 m above the ground. The first step of the current method of calculating the dose rate due to natural radionuclides is calculate the ratio of the total count rate of areas where no radioactive cesium is detected and the count rate of regions with energy levels of 1,400 keV or higher (BG-Index). Next, calculate the air dose rate of radioactive cesium by multiplying the BG-Index and the integrated count rate of 1,400 keV or higher for the area where the radioactive cesium is distributed. In high dose-rate areas, however, the count rate of the 1,365-keV peak of Cs-134, though small, is included in the integrated count rate of 1,400 keV or higher, which could cause an overestimation of the air dose rate of natural radionuclides. We developed a method for accurately evaluating the distribution maps of natural air dose-rate by excluding the effect of radioactive cesium, even in contaminated areas, and obtained the accurate air dose-rate map attributed the radioactive cesium deposition on the ground. Furthermore, the natural dose-rate distribution throughout Japan has been obtained by this method.

Dose and dose rate effects of whole-body gamma-irradiation: I. Lymphocytes and lymphoid organs

NASA Technical Reports Server (NTRS)

Pecaut, M. J.; Nelson, G. A.; Gridley, D. S.

2001-01-01

The major goal of part I of this study was to compare varying doses and dose rates of whole-body gamma-radiation on lymphoid cells and organs. C57BL/6 mice (n = 75) were exposed to 0, 0.5, 1.5, and 3.0 Gy gamma-rays (60Co) at 1 cGy/min (low-dose rate, LDR) and 80 cGy/min (high-dose rate, HDR) and euthanized 4 days later. A significant dose-dependent loss of spleen mass was observed with both LDR and HDR irradiation; for the thymus this was true only with HDR. Decreasing leukocyte and lymphocyte numbers occurred with increasing dose in blood and spleen at both dose rates. The numbers (not percentages) of CD3+ T lymphocytes decreased in the blood in a dose-dependent manner at both HDR and LDR. Splenic T cell counts decreased with dose only in HDR groups; percentages increased with dose at both dose rates. Dose-dependent decreases occurred in CD4+ T helper and CD8+ T cytotoxic cell counts at HDR and LDR. In the blood the percentages of CD4+ cells increased with increasing dose at both dose rates, whereas in the spleen the counts decreased only in the HDR groups. The percentages of the CD8+ population remained stable in both blood and spleen. CD19+ B cell counts and percentages in both compartments declined markedly with increasing HDR and LDR radiation. NK1.1+ natural killer cell numbers and proportions remained relatively stable. Overall, these data indicate that the observed changes were highly dependent on the dose, but not dose rate, and that cells in the spleen are more affected by dose rate than those in blood. The results also suggest that the response of lymphocytes in different body compartments may be variable.

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

NASA Astrophysics Data System (ADS)

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

2015-02-01

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

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

PubMed

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

2000-02-01

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

Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson’s disease: a dose-finding study

PubMed Central

Rosenblad, Carl; af Edholm Arvidsson, Karolina; Wictorin, Klas; Keywood, Charlotte; Shankar, Bavani; Lowe, David A.; Björklund, Anders; Widner, Håkan

2015-01-01

In advanced stages of Parkinson’s disease, serotonergic terminals take up l-DOPA and convert it to dopamine. Abnormally released dopamine may participate in the development of l-DOPA-induced dyskinesias. Simultaneous activation of 5-HT1A and 5-HT1B receptors effectively blocks l-DOPA-induced dyskinesias in animal models of dopamine depletion, justifying a clinical study with eltoprazine, a 5-HT1A/B receptor agonist, against l-DOPA-induced dyskinesias in patients with Parkinson’s disease. A double-blind, randomized, placebo-controlled and dose-finding phase I/IIa study was conducted. Single oral treatment with placebo or eltoprazine, at 2.5, 5 and 7.5 mg, was tested in combination with a suprathreshold dose of l-DOPA (Sinemet®) in 22 patients with Parkinson’s disease (16 male/six female; 66.6 ± 8.8 years old) with l-DOPA-induced dyskinesias. A Wilcoxon Signed Ranked Test was used to compare each eltoprazine dose level to paired randomized placebo on the prespecified primary efficacy variables; area under the curve scores on Clinical Dyskinesia Rating Scale for 3 h post-dose and maximum change of Unified Parkinson’s Disease Rating Scale part III for 3 h post-dose. Secondary objectives included effects on maximum Clinical Dyskinesia Rating Scale score, area under the curve of Rush Dyskinesia Rating Scale score for 3 h post-dose, mood parameters measured by Hospital Anxiety Depression Scale and Montgomery Asberg Depression Rating Scale along with the pharmacokinetics, safety and tolerability profile of eltoprazine. A mixed model repeated measures was used for post hoc analyses of the area under the curve and peak Clinical Dyskinesia Rating Scale scores. It was found that serum concentrations of eltoprazine increased in a dose-proportional manner. Following levodopa challenge, 5 mg eltoprazine caused a significant reduction of l-DOPA-induced dyskinesias on area under the curves of Clinical Dyskinesia Rating Scale [–1.02(1.49); P = 0.004] and Rush Dyskinesia Rating Scale [–0.15(0.23); P = 0.003]; and maximum Clinical Dyskinesia Rating Scale score [–1.14(1.59); P = 0.005]. The post hoc analysis confirmed these results and also showed an antidyskinetic effect of 7.5 mg eltoprazine. Unified Parkinson’s Disease Rating Scale part III scores did not differ between the placebo and eltoprazine treatments. The most frequent adverse effects after eltoprazine were nausea and dizziness. It can be concluded that a single dose, oral treatment with eltoprazine has beneficial antidyskinetic effects without altering normal motor responses to l-DOPA. All doses of eltoprazine were well tolerated, with no major adverse effects. Eltoprazine has a favourable risk-benefit and pharmacokinetic profile in patients with Parkinson’s disease. The data support further clinical studies with chronic oral eltoprazine to treat l-DOPA-induced-dyskinesias. PMID:25669730

Human Papillomavirus Vaccine Effectiveness Against Incident Genital Warts Among Female Health-Plan Enrollees, United States.

PubMed

Hariri, Susan; Schuler, Megan S; Naleway, Allison L; Daley, Matthew F; Weinmann, Sheila; Crane, Bradley; Newcomer, Sophia R; Tolsma, Dennis; Markowitz, Lauri E

2018-02-01

We examined the effectiveness of human papillomavirus vaccination by dose number and spacing against incident genital warts in a cohort of 64,517 female health-plan enrollees in the United States during 2006-2012. Eligible recipients were classified into groups by regimen: 0, 1, 2 (<6 months apart), 2 (≥6 months apart), or 3 doses. They were followed until a genital wart diagnosis, loss to follow-up, or the end of study. Propensity score weights were used to balance baseline differences across groups. To account for latent genital warts before vaccination, we applied 6- and 12-month buffer periods from last and first vaccine dose, respectively. Incidence rates and hazard ratios were calculated using Poisson regression and Cox models. The propensity score-weighted incidence rate per 100,000 person-years was 762 among unvaccinated participants. Using 6- and 12-month buffer periods, respectively, incidence rates were 641 and 257 for 1 dose, 760 and 577 for the 2-dose (<6-month interval) regimen, 313 and 194 for the 2-dose (≥6-month interval) regimen, and 199 and 162 among 3-dose vaccinees; vaccine effectiveness was 68% and 76% for the 2-dose (≥6-month interval) regimen and 77% and 80% in 3-dose vaccinees compared with unvaccinated participants. Vaccine effectiveness was not significant among vaccinees receiving 1-dose and 2-dose (<6-month interval) regimens compared with unvaccinated participants. Our findings contribute to a better understanding of the real-world effectiveness of HPV vaccination. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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.

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.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

4D radiobiological modelling of the interplay effect in conventionally and hypofractionated lung tumour IMRT.

PubMed

Selvaraj, J; Uzan, J; Baker, C; Nahum, A

2015-01-01

To study the impact of the interplay between respiration-induced tumour motion and multileaf collimator leaf movements in intensity-modulated radiotherapy (IMRT) as a function of number of fractions, dose rate on population mean tumour control probability ([Formula: see text]) using an in-house developed dose model. Delivered dose was accumulated in a voxel-by-voxel basis inclusive of tumour motion over the course of treatment. The effect of interplay on dose and [Formula: see text] was studied for conventionally and hypofractionated treatments using digital imaging and communications in medicine data sets. Moreover, the effect of dose rate on interplay was also studied for single-fraction treatments. Simulations were repeated several times to obtain [Formula: see text] for each plan. The average variation observed in mean dose to the target volumes were -0.76% ± 0.36% for the 20-fraction treatment and -0.26% ± 0.68% and -1.05% ± 0.98% for the three- and single-fraction treatments, respectively. For the 20-fraction treatment, the drop in [Formula: see text] was -1.05% ± 0.39%, whereas for the three- and single-fraction treatments, it was -2.80% ± 1.68% and -4.00% ± 2.84%, respectively. By reducing the dose rate from 600 to 300 MU min(-1) for the single-fraction treatments, the drop in [Formula: see text] was reduced by approximately 1.5%. The effect of interplay on [Formula: see text] is negligible for conventionally fractionated treatments, whereas considerable drop in [Formula: see text] is observed for the three- and single-fraction treatments. Reduced dose rate could be used in hypofractionated treatments to reduce the interplay effect. A novel in silico dose model is presented to determine the impact of interplay effect in IMRT treatments on [Formula: see text].

4D radiobiological modelling of the interplay effect in conventionally and hypofractionated lung tumour IMRT

PubMed Central

Uzan, J; Baker, C; Nahum, A

2015-01-01

Objective: To study the impact of the interplay between respiration-induced tumour motion and multileaf collimator leaf movements in intensity-modulated radiotherapy (IMRT) as a function of number of fractions, dose rate on population mean tumour control probability () using an in-house developed dose model. Methods: Delivered dose was accumulated in a voxel-by-voxel basis inclusive of tumour motion over the course of treatment. The effect of interplay on dose and was studied for conventionally and hypofractionated treatments using digital imaging and communications in medicine data sets. Moreover, the effect of dose rate on interplay was also studied for single-fraction treatments. Simulations were repeated several times to obtain for each plan. Results: The average variation observed in mean dose to the target volumes were −0.76% ± 0.36% for the 20-fraction treatment and −0.26% ± 0.68% and −1.05% ± 0.98% for the three- and single-fraction treatments, respectively. For the 20-fraction treatment, the drop in was −1.05% ± 0.39%, whereas for the three- and single-fraction treatments, it was −2.80% ± 1.68% and −4.00% ± 2.84%, respectively. By reducing the dose rate from 600 to 300 MU min−1 for the single-fraction treatments, the drop in was reduced by approximately 1.5%. Conclusion: The effect of interplay on is negligible for conventionally fractionated treatments, whereas considerable drop in is observed for the three- and single-fraction treatments. Reduced dose rate could be used in hypofractionated treatments to reduce the interplay effect. Advances in knowledge: A novel in silico dose model is presented to determine the impact of interplay effect in IMRT treatments on . PMID:25251400

Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

PubMed Central

Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

2014-01-01

Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate γ-Irradiation

PubMed Central

Osipov, A. N.; Klokov, D. Y.; Elakov, A. L.; Rozanova, O. M.; Zaichkina, S. I.; Aptikaeva, G. F.; Akhmadieva, A. Kh.

2004-01-01

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to γ-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20–61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level γ-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation. PMID:19330145

Continuing evaluation of bipolar linear devices for total dose bias dependency and ELDRS effects

NASA Technical Reports Server (NTRS)

McClure, Steven S.; Gorelick, Jerry L.; Yui, Candice; Rax, Bernard G.; Wiedeman, Michael D.

2003-01-01

We present results of continuing efforts to evaluate total dose bias dependency and ELDRS effects in bipolar linear microcircuits. Several devices were evaluated, each exhibiting moderate to significant bias and/or dose rate dependency.

Dose equivalent rate constants and barrier transmission data for nuclear medicine facility dose calculations and shielding design.

PubMed

Kusano, Maggie; Caldwell, Curtis B

2014-07-01

A primary goal of nuclear medicine facility design is to keep public and worker radiation doses As Low As Reasonably Achievable (ALARA). To estimate dose and shielding requirements, one needs to know both the dose equivalent rate constants for soft tissue and barrier transmission factors (TFs) for all radionuclides of interest. Dose equivalent rate constants are most commonly calculated using published air kerma or exposure rate constants, while transmission factors are most commonly calculated using published tenth-value layers (TVLs). Values can be calculated more accurately using the radionuclide's photon emission spectrum and the physical properties of lead, concrete, and/or tissue at these energies. These calculations may be non-trivial due to the polyenergetic nature of the radionuclides used in nuclear medicine. In this paper, the effects of dose equivalent rate constant and transmission factor on nuclear medicine dose and shielding calculations are investigated, and new values based on up-to-date nuclear data and thresholds specific to nuclear medicine are proposed. To facilitate practical use, transmission curves were fitted to the three-parameter Archer equation. Finally, the results of this work were applied to the design of a sample nuclear medicine facility and compared to doses calculated using common methods to investigate the effects of these values on dose estimates and shielding decisions. Dose equivalent rate constants generally agreed well with those derived from the literature with the exception of those from NCRP 124. Depending on the situation, Archer fit TFs could be significantly more accurate than TVL-based TFs. These results were reflected in the sample shielding problem, with unshielded dose estimates agreeing well, with the exception of those based on NCRP 124, and Archer fit TFs providing a more accurate alternative to TVL TFs and a simpler alternative to full spectral-based calculations. The data provided by this paper should assist in improving the accuracy and tractability of dose and shielding calculations for nuclear medicine facility design.

Laser-based irradiation apparatus and method to measure the functional dose-rate response of semiconductor devices

DOEpatents

Horn, Kevin M [Albuquerque, NM

2008-05-20

A broad-beam laser irradiation apparatus can measure the parametric or functional response of a semiconductor device to exposure to dose-rate equivalent infrared laser light. Comparisons of dose-rate response from before, during, and after accelerated aging of a device, or from periodic sampling of devices from fielded operational systems can determine if aging has affected the device's overall functionality. The dependence of these changes on equivalent dose-rate pulse intensity and/or duration can be measured with the apparatus. The synchronized introduction of external electrical transients into the device under test can be used to simulate the electrical effects of the surrounding circuitry's response to a radiation exposure while exposing the device to dose-rate equivalent infrared laser light.

Effects of Beta-blockers on Punished Responding and on Heart Rate in Pigeons

DTIC Science & Technology

1986-06-17

in pigeons. The present study attempted to confirm that fmding, to compare the effects of propranolol, metoprolol , and atenolol with that of...occurred at approximately 15% iii of the high unpunished response rates. Propranolol, atenolol, and metoprolol doses from 1.0 to 10.0 mg!kg, i.m. and...and, to a somewhat lesser extent, metoprolol produced large dose-related decreases. Atenolol’s effect was small. Chlordiazepoxide increased heart rate

A study on dosimetric properties of electronic portal imaging device and its use as a quality assurance tool in Volumetric Modulated Arc Therapy

PubMed Central

Sukumar, Prabakar; Padmanaban, Sriram; Jeevanandam, Prakash; Syam Kumar, S.A.; Nagarajan, Vivekanandan

2011-01-01

Aim In this study, the dosimetric properties of the electronic portal imaging device were examined and the quality assurance testing of Volumetric Modulated Arc Therapy was performed. Background RapidArc involves the variable dose rate, leaf speed and the gantry rotation. The imager was studied for the effects like dose, dose rate, field size, leaf speed and sag during gantry rotation. Materials and methods A Varian RapidArc machine equipped with 120 multileaf collimator and amorphous silicon detector was used for the study. The characteristics that are variable in RapidArc treatment were studied for the portal imager. The accuracy of a dynamic multileaf collimator position at different gantry angles and during gantry rotation was examined using the picket fence test. The control of the dose rate and gantry speed was verified using a test field irradiating seven strips of the same dose with different dose rate and gantry speeds. The control over leaf speed during arc was verified by irradiating four strips of different leaf speeds with the same dose in each strip. To verify the results, the RapidArc test procedure was compared with the X-Omat film and verified for a period of 6 weeks using EPID. Results The effect of gantry rotation on leaf accuracy was minimal. The dose in segments showed good agreement with mean deviation of 0.8% for dose rate control and 1.09% for leaf speed control over different gantry speeds. Conclusion The results provided a precise control of gantry speed, dose rate and leaf speeds during RapidArc delivery and were consistent over 6 weeks. PMID:24376989

On the radiation induced degradation of NBR-EPDM rubbers

NASA Astrophysics Data System (ADS)

Chipara, M. D.; Grecu, V. V.; Chipara, M. I.; Ponta, C.; Reyes Romero, J.

1999-05-01

The modification of the elongation at break for NBR-EPDM rubbers subjected to gamma irradiation at various integral doses ranging from 10 to 200 kGy, at different dose rates (0.14, 0.47, 1, 3, 4.7 kGy/h) are reported. The presence of the dose rate effect is noticed.

Effect of Jiangzhi tablet on gastrointestinal propulsive function in mice

NASA Astrophysics Data System (ADS)

Wang, Xiangrong; Geng, Xiuli; Zhao, Jingsheng; Fan, Lili; Zhang, Zhengchen

2018-04-01

This paper aims to study the effect of lipid-lowering tablets on gastric emptying and small intestinal propulsion in mice. Mice were randomly divided into control group, Digestant Pill group, Jiangzhi tablet group, middle dose and small dose, the mice gastric emptying phenolsulfonphthalein, gastric residual rate of phenol red indicator to evaluate the gastric emptying rate, residual rate of detection in mouse stomach; small intestine propulsion and selection of carbon ink as the experimental index. Effects were observed to promote the function of normal mice gastric emptying and intestine. The gastric emptying and small intestinal motor function of normal mice were all promoted by each administration group, and the effect was most obvious in small dose group. The effect of reducing blood lipid on gastrointestinal motility of mice ware obviously enhanced.

Nanocluster irradiation evolution in Fe-9%Cr ODS and ferritic-martensitic alloys

NASA Astrophysics Data System (ADS)

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

2017-12-01

The objective of this study is to evaluate the influence of dose rate and cascade morphology on nanocluster evolution in a model Fe-9%Cr oxide dispersion strengthened steel and the commercial ferritic/martensitic (F/M) alloys HCM12A and HT9. We present a large, systematic data set spanning the three alloys, three irradiating particle types, four orders of magnitude in dose rate, and doses ranging 1-100 displacements per atom over 400-500 °C. Nanoclusters are characterized using atom probe tomography. ODS oxide nanoclusters experience partial dissolution after irradiation due to inverse Ostwald ripening, while F/M nanoclusters undergo Ostwald ripening. Damage cascade morphology is indicative of nanocluster number density evolution. Finally, the effects of dose rate on nanocluster morphology provide evidence for a temperature dilation theory, which purports that a negative temperature shift is necessary for higher dose rate irradiations to emulate nanocluster evolution in lower dose rate irradiations.

External dose assessment in the Ukraine following the Chernobyl accident

NASA Astrophysics Data System (ADS)

Frazier, Remi Jordan Lesartre

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

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

PubMed Central

Sanders, Charles L.

2012-01-01

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

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; McCann, Una; Jesse, Robert

2011-12-01

This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Participants were 18 adults (17 hallucinogen-naïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up. Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.

Chasing Ghosts in Space Radiobiology Research: The Lost Focus on Non-Targeted Effects

NASA Astrophysics Data System (ADS)

Cucinotta, Francis; Saganti, Premkumar; Cacao, Eliedonna

2016-07-01

The doses and dose-rates of astronaut exposures to galactic cosmic rays (GCR) are accurately known, and lead to particle hits per cell nucleus from high charge and energy (HZE) particles of much less than one hit per cell per week. A large number of experiments have shown that additivity of biological effects is a valid assumption for space radiation exposures, while experiments at higher doses and dose-rates than occur in space continue to be a focus of the majority of space radiobiology research. Furthermore HZE particle exposures with mono-energetic particles manifest themselves as a mixed-radiation field due to the contributions of delta-rays and the random impact parameter of a particles track core to DNA and non-DNA targets in cells and tissues. The mixed-field manifestation of mono-energetic HZE particle exposures is well known from theoretical studies of microdosimetry and track structure. Additional mixed-field effects occur for single species experiments due to nuclear fragmentation in particle accelerator beam-lines and biological samples along with energy straggling. In contrast to these well known aspects of space radiobiology there are many open questions on the contribution of non-targeted effects to low dose and dose-rate exposures. Non-targeted effects (NTEs) include bystander effects and genomic instability, and have been shown to be the most important outstanding question for reducing uncertainties in space radiation cancer risk assessment. The dose-rate and radiation quality dependence of NTE's has not been established, while there is an over-arching need to develop 21st century experimental models of human cancer risk. We review possible mechanisms of NTE's and how new experiments to address these issues could be designed.

Dose-Rate Effects in Breaking DNA Strands by Short Pulses of Extreme Ultraviolet Radiation.

PubMed

Vyšín, Luděk; Burian, Tomáš; Ukraintsev, Egor; Davídková, Marie; Grisham, Michael E; Heinbuch, Scott; Rocca, Jorge J; Juha, Libor

2018-05-01

In this study, we examined dose-rate effects on strand break formation in plasmid DNA induced by pulsed extreme ultraviolet (XUV) radiation. Dose delivered to the target molecule was controlled by attenuating the incident photon flux using aluminum filters as well as by changing the DNA/buffer-salt ratio in the irradiated sample. Irradiated samples were examined using agarose gel electrophoresis. Yields of single- and double-strand breaks (SSBs and DSBs) were determined as a function of the incident photon fluence. In addition, electrophoresis also revealed DNA cross-linking. Damaged DNA was inspected by means of atomic force microscopy (AFM). Both SSB and DSB yields decreased with dose rate increase. Quantum yields of SSBs at the highest photon fluence were comparable to yields of DSBs found after synchrotron irradiation. The average SSB/DSB ratio decreased only slightly at elevated dose rates. In conclusion, complex and/or clustered damages other than cross-links do not appear to be induced under the radiation conditions applied in this study.

Dose-response characteristics of an amorphous silicon EPID.

PubMed

Winkler, Peter; Hefner, Alfred; Georg, Dietmar

2005-10-01

Electronic portal imaging devices (EPIDs) were originally developed for the purpose of patient setup verification. Nowadays, they are increasingly used as dosimeters (e.g., for IMRT verification and linac-specific QA). A prerequisite for any clinical dosimetric application is a detailed understanding of the detector's dose-response behavior. The aim of this study is to investigate the dosimetric properties of an amorphous silicon EPID (Elekta IVIEWGT) with respect to three photon beam qualities: 6, 10, and 25 MV. The EPID showed an excellent temporal stability on short term as well as on long term scales. The stability throughout the day was strongly influenced by warming up, which took several hours and affected EPID response by 2.5%. Ghosting effects increased the sensitivity of the EPID. They became more pronounced with decreasing time intervals between two exposures as well as with increasing dose. Due to ghosting, changes in pixel sensitivity amounted up to 16% (locally) for the 25 MV photon beam. It was observed that the response characteristics of our EPID depended on dose as well as on dose rate. Doubling the dose rate increased the EPID sensitivity by 1.5%. This behavior was successfully attributed to a dose per frame effect, i.e., a nonlinear relationship between the EPID signal and the dose which was delivered to the panel between two successive readouts. The sensitivity was found to vary up to 10% in the range of 1 to 1000 monitor units. This variation was governed by two independent effects. For low doses, the EPID signal was reduced due to the linac's changing dose rate during startup. Furthermore, the detector reading was influenced by intrabeam variations of EPID sensitivity, namely, an increase of detector response during uniform exposure. For the beam qualities which were used, the response characteristics of the EPID did not depend on energy. Differences in relative dose-response curves resulted from energy dependent temporal output characteristics of the accelerator. If ghosting is prevented from affecting the results and all dose-response effects are properly corrected for, the EPID signal becomes independent of dose rate, dose, and exposure time.

Analysis of Potassium in Bricks--Determining the Dose Rate from {sup 40}K for Thermoluminescence Dating

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

Musilek, Ladislav; Polach, Tomas; Trojek, Tomas

2008-08-07

Thermoluminescence (TL) dating is based on accumulating the natural radiation dose in the material of a dated artefact (brick, pottery, etc.), and comparing the dose accumulated during the lifetime of the object with the dose rate within the sample collected for TL measurement. Determining the dose rate from natural radionuclides in materials is one of the most important and most difficult parts of the technique. The most important radionuclides present are usually nuclides of the uranium and thorium decay series and {sup 40}K. An analysis of the total potassium concentration enables us to determine the {sup 40}K content effectively, andmore » from this it is possible to calculate the dose rate originating from this radiation source. X-ray fluorescence (XRF) analysis can be used to determine the potassium concentration in bricks rapidly and efficiently. The procedure for analysing potassium, examples of results of dose rate calculation and possible sources of error are described here.« less

Multi-scale simulation of radiation damage accumulation and subsequent hardening in neutron-irradiated α-Fe

DOE PAGES

Dunn, Aaron; Dingreville, Remi; Capolungo, Laurent

2015-11-27

A hierarchical methodology is introduced to predict the effects of radiation damage and irradiation conditions on the yield stress and internal stress heterogeneity developments in polycrystalline α-Fe. Simulations of defect accumulation under displacement cascade damage conditions are performed using spatially resolved stochastic cluster dynamics. The resulting void and dislocation loop concentrations and average sizes are then input into a crystal plasticity formulation that accounts for the change in critical resolved shear stress due to the presence of radiation induced defects. The simulated polycrystalline tensile tests show a good match to experimental hardening data over a wide range of irradiation doses.more » With this capability, stress heterogeneity development and the effect of dose rate on hardening is investigated. The model predicts increased hardening at higher dose rates for low total doses. By contrast, at doses above 10 –2 dpa when cascade overlap becomes significant, the model does not predict significantly different hardening for different dose rates. In conclusion, the development of such a model enables simulation of radiation damage accumulation and associated hardening without relying on experimental data as an input under a wide range of irradiation conditions such as dose, dose rate, and temperature.« less

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models.

PubMed

Schwarte, Sebastian; Bremer, Michael; Fruehauf, Joerg; Sorge, Yanina; Skubich, Susanne; Hoffmann, Matthias W

2007-09-01

Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.

Measurements of air dose rates in and around houses in the Fukushima Prefecture in Japan after the Fukushima accident.

PubMed

Matsuda, Norihiro; Mikami, Satoshi; Sato, Tetsuro; Saito, Kimiaki

2017-01-01

Measurements of air dose rates for 192 houses in a less contaminated area (<0.5 μSv h -1 ) of the Fukushima Prefecture in Japan were conducted in both living rooms and/or bedrooms using optically stimulated luminescence (OSL) dosimeters and around the houses via a man-borne survey at intervals of several meters. The relation of the two air dose rates (inside and outside) for each house, including the background from natural radionuclides, was divided into several categories, determined by construction materials (light and heavy) and floor number, with the dose reduction factors being expressed as the ratio of the dose inside to that outside the house. For wooden and lightweight steel houses (classed as light), the dose rates inside and outside the houses showed a positive correlation and linear regression with a slope-intercept form due to the natural background, although the degree of correlation was not very high. The regression coefficient, i.e., the average dose reduction factor, was 0.38 on the first floor and 0.49 on the second floor. It was found that the contribution of natural radiation cannot be neglected when we consider dose reduction factors in less contaminated areas. The reductions in indoor dose rates are observed because a patch of ground under each house is not contaminated (this is the so-called uncontaminated effect) since the shielding capability of light construction materials is typically low. For reinforced steel-framed concrete houses (classed as heavy), the dose rates inside the houses did not show a correlation with those outside the houses due to the substantial shielding capability of these materials. The average indoor dose rates were slightly higher than the arithmetic mean value of the outdoor dose rates from the natural background because concrete acts as a source of natural radionuclides. The characteristics of the uncontaminated effect were clarified through Monte Carlo simulations. It was found that there is a great variation in air dose rates even within one house, depending on the height of the area and its closeness to the outside boundary. Measurements of outdoor dose rates required consideration of local variations depending on the environment surrounding each house. The representative value was obtained from detailed distributions of air dose rates around the house, as measured by a man-borne survey. Therefore, it is imperative to recognize that dose reduction factors fluctuate in response to various factors such as the size and shape of a house, construction materials acting as a shield and as sources, position (including height) within a room, floor number, total number of floors, and surrounding environment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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

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

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

2015-06-15

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

Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis

PubMed Central

Wang, Wei-Hong; Huang, Jia-Qing; Zheng, Ge-Fan; Xia, Harry Hua-Xiang; Wong, Wai-Man; Lam, Shiu-Kum; Wong, Benjamin Chun-Yu

2005-01-01

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H2RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H2RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis. PMID:15996033

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

NASA Astrophysics Data System (ADS)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Basu, Ananda; Szeri, Andrew J.

2016-11-01

Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected - usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches.

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.

Radiation induced degradation of xanthan gum in aqueous solution

NASA Astrophysics Data System (ADS)

Hayrabolulu, Hande; Demeter, Maria; Cutrubinis, Mihalis; Güven, Olgun; Şen, Murat

2018-03-01

In our previous study, we have investigated the effect of gamma rays on xanthan gum in the solid state and it was determined that dose rate was an important factor effecting the radiation degradation of xanthan gum. In the present study, in order to provide a better understanding of how ionizing radiation effect xanthan gum, we have investigated the effects of ionizing radiation on aqueous solutions of xanthan at various concentrations (0.5-4%). Xanthan solutions were irradiated with gamma rays in air, at ambient temperature, at different dose rates (0.1-3.3-7.0 kGy/h) and doses (2.5-50 kGy). Change in their molecular weights was followed by size exclusion chromatography (SEC). Chain scission yield (G(S)), and degradation rate constants (k) were calculated. It was determined that, solution concentration was a factor effecting the degradation chemical yield and degradation rate of xanthan gum. Chain scission reactions were more effective for lower solution concentrations.

Environmental standards for ionizing radiation: theoretical basis for dose-response curves.

PubMed Central

Upton, A C

1983-01-01

The types of injury attributable to ionizing radiation are subdivided, for purposes of risk assessment and radiological protection, into two broad categories: stochastic effects and nonstochastic effects. Stochastic effects are viewed as probablistic phenomena, varying in frequency but not severity as a function of the dose, without any threshold; nonstochastic effects are viewed as deterministic phenomena, varying in both frequency and severity as a function of the dose, with clinical thresholds. Included among stochastic effects are heritable effects (mutations and chromosome aberrations) and carcinogenic effects. Both types of effects are envisioned as unicellular phenomena which can result from nonlethal injury of individual cells, without the necessity of damage to other cells. For the induction of mutations and chromosome aberrations in the low-to-intermediate dose range, the dose-response curve with high-linear energy transfer (LET) radiation generally conforms to a linear nonthreshold relationship and varies relatively little with the dose rate. In contrast, the curve with low-LET radiation generally conforms to a linear-quadratic relationship, rising less steeply than the curve with high-LET radiation and increasing in slope with increasing dose and dose rate. The dose-response curve for carcinogenic effects varies widely from one type of neoplasm to another in the intermediate-to-high dose range, in part because of differences in the way large doses of radiation can affect the promotion and progression of different neoplasms. Information about dose-response relations for low-level irradiation is fragmentary but consistent, in general, with the hypothesis that the neoplastic transformation may result from mutation, chromosome aberration or genetic recombination in a single susceptible cell. PMID:6653536

Cardiovascular effects of constant rate infusions of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized at equipotent doses of sevoflurane.

PubMed

Moran-Muñoz, Rafael; Valverde, Alexander; Ibancovichi, J A; Acevedo-Arcique, Carlos M; Recillas-Morales, Sergio; Sanchez-Aparicio, Pedro; Osorio-Avalos, Jorge; Chavez-Monteagudo, Julio Raul

2017-07-01

This study evaluated the cardiovascular effects of a constant rate infusion (CRI) of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized with sevoflurane at equipotent doses. Treatments consisted of T1-Lidocaine [loading dose 2 mg/kg body weight (BW), IV, and CRI of 100 μg/kg BW per min] at 1.4% end-tidal of sevoflurane (FE SEV ); T2-Dexmedetomidine (loading dose 2 μg/kg BW, IV, and CRI of 2 μg/kg BW per hour) and FE SEV 1.1%; and T3-Lidocaine-Dexmedetomidine using the same doses of T1 and T2 and FE SEV 0.8%. Constant rate infusion of lidocaine did not induce any cardiovascular changes; lidocaine and dexmedetomidine resulted in cardiovascular effects similar to dexmedetomidine alone. These effects were characterized by a significant ( P < 0.001) decrease in heart rate, cardiac output, cardiac index, oxygen delivery, and pulmonary vascular resistance index, and a significant ( P < 0.001) increase in mean and diastolic arterial pressure, systemic vascular resistance index, pulmonary arterial occlusion pressure and oxygen extraction ratio, compared with baseline values. In conclusion, a CRI of lidocaine combined with dexmedetomidine produces significant cardiovascular changes similar to those observed with dexmedetomidine alone.

Peri-interventional antibiotic prophylaxis only vs continuous low-dose antibiotic treatment in patients with JJ stents: a prospective randomised trial analysing the effect on urinary tract infections and stent-related symptoms.

PubMed

Moltzahn, Felix; Haeni, Katharina; Birkhäuser, Frédéric D; Roth, Beat; Thalmann, George N; Zehnder, Pascal

2013-02-01

To evaluate the antibiotic treatment regime in patients with indwelling JJ stents, the benefits and disadvantages of a peri-interventional antibiotic prophylaxis were compared with those of a continuous low-dose antibiotic treatment in a prospective randomised trial. In all, 95 patients were randomised to either receive peri-interventional antibiotic prophylaxis during stent insertion only (group A, 44 patients) or to additionally receive a continuous low-dose antibiotic treatment until stent removal (group B, 51). Evaluations for urinary tract infections (UTI), stent-related symptoms (SRSs) and drug side-effects were performed before stent insertion and consecutively after 1, 2 and 4 weeks and/or at stent withdrawal. All patients received a peri-interventional antibiotic prophylaxis with 1.2 g amoxicillin/clavulanic acid. Amoxicillin/clavulanic acid (625 mg) once daily was administered for continuous low-dose treatment (group B). Primary endpoints were the overall rates of UTIs and SRSs. Secondary endpoints were the rates and severity of drug side-effects. Neither the overall UTI rates (group A: 9% vs group B: 10%), nor the rates of febrile UTIs (group A: 7% vs group B: 6%) were different between the groups. Similarly, SRS rates did not differ (group A: 98% vs group B: 96%). Antibiotic side-effect symptoms were to be increased in patients treated with low-dose antibiotics. A continuous antibiotic low-dose treatment during the entire JJ stent-indwelling time does not reduce the quantity or severity of UTIs and has no effect on SRSs either compared with a peri-interventional antibiotic prophylaxis only. © 2012 BJU International.

Mechanical properties of carbon steel depending on the rate of the dose build-up of nitrogen and argon ions

NASA Astrophysics Data System (ADS)

Vorob'ev, V. L.; Bykov, P. V.; Bayankin, V. Ya.; Shushkov, A. A.; Vakhrushev, A. V.

2014-08-01

The effect of pulsed irradiation with argons and nitrogen ions on the mechanical properties, morphology, and structure of the surface layers of carbon steel St3 (0.2% C, 0.4% Mn, 0.15% Si, and Fe for balance) has been investigated depending on the rate of dose build-up at an average ion current density of 10, 20, and 40 μA/cm2. It has been established that the fatigue life and microhardness of surface layers increase in the entire studied range of dose build-up rates. This seems to be due to the hardening of the surface layers, which resulted from the generation of radiation defects and the irradiation-dynamic effect of fast ions. The sample irradiated by argon ions at the lowest of the selected dose build-up rates j av = 10 μA/cm2 withstands the largest number of cycles to failure.

SU-E-T-13: Comparison of Dose Rates with and without Gold Backing of USC #9 Radioactive Eye Plaque Using MCNP5.

PubMed

Aryal, P; Molloy, J

2012-06-01

To show the effect of gold backing on dose rates for the USC #9 radioactive eye plaque. An I125 source (IsoAid model IAI-125A) and gold backing was modeled using MCNP5 Monte Carlo code. A single iodine seed was simulated with and without gold backing. Dose rates were calculated in two orthogonal planes. Dose calculation points were structured in two orthogonal planes that bisect the center of the source. A 2×2 cm matrix of spherical points of radius 0.2 mm was created in a water phantom of 10 cm radius. 0.2 billion particle histories were tracked. Dose differences with and without the gold backing were analyzed using Matlab. The gold backing produced a 3% increase in the dose rate near the source surface (<1mm) relative to that without the backing. This was presumably caused by fluorescent photons from the gold. At distances between 1 and 2 cm, the gold backing reduced the dose rate by up to 12%, which we attribute to a lack of scatter resulting from the attenuation from the gold. Dose differences were most pronounced in the radial direction near the source center but off axis. The dose decreased by 25%, 65% and 81% at 1, 2, and 3 mm off axis at a distance of 1 mm from the source surface. These effects were less pronounced in the perpendicular dimension near the source tip, where maximum dose decreases of 2% were noted. I 125 sources embedded directly into gold troughs display dose differences of 2 - 90%, relative to doses without the gold backing. This is relevant for certain types of plaques used in treatment of ocular melanoma. Large dose reductions can be observed and may have implications for scleral dose reduction. © 2012 American Association of Physicists in Medicine.

Effect of Ion Flux (Dose Rate) in Source-Drain Extension Ion Implantation for 10-nm Node FinFET and Beyond on 300/450mm Platforms

NASA Astrophysics Data System (ADS)

Shen, Ming-Yi

The improvement of wafer equipment productivity has been a continuous effort of the semiconductor industry. Higher productivity implies lower product price, which economically drives more demand from the market. This is desired by the semiconductor manufacturing industry. By raising the ion beam current of the ion implanter for 300/450mm platforms, it is possible to increase the throughput of the ion implanter. The resulting dose rate can be comparable to the performance of conventional ion implanters or higher, depending on beam current and beam size. Thus, effects caused by higher dose rate must be investigated further. One of the major applications of ion implantation (I/I) is source-drain extension (SDE) I/I for the silicon FinFET device. This study investigated the dose rate effects on the material properties and device performance of the 10-nm node silicon FinFET. In order to gain better understanding of the dose rate effects, the dose rate study is based on Synopsys Technology CAD (TCAD) process and device simulations that are calibrated and validated using available structural silicon fin samples. We have successfully shown that the kinetic monte carlo (KMC) I/I simulation can precisely model both the silicon amorphization and the arsenic distribution in the fin by comparing the KMC simulation results with TEM images. The results of the KMC I/I simulation show that at high dose rate more activated arsenic dopants were in the source-drain extension (SDE) region. This finding matches with the increased silicon amorphization caused by the high dose-rate I/I, given that the arsenic atoms could be more easily activated by the solid phase epitaxial regrowth process. This increased silicon amorphization led to not only higher arsenic activation near the spacer edge, but also less arsenic atoms straggling into the channel. Hence, it is possible to improve the throughput of the ion implanter when the dopants are implanted at high dose rate if the same doping level with a lower wafer dose can be achieved. In addition, the leakage current might also be reduced due to less undesired dopants in the channel. However, the twin defects from the problematic Si{111} recrystallization is well-known to cause excessive leakage current to the FinFET. This drawback can offset the benefits of the high dose rate I/I mentioned above. This work produced the first attempt at simulating the electrical impact of twin defects on advanced-node (10 nm) FinFET device performance. It was found that the high dose-rate I/I causes more twin defects in the silicon fin, and the physical locations of these defects were close to the channel. The defects undesirably induced trap-assisted band-to-band tunneling near the drain, which increased the leakage current. This issue could be mitigated by using asymmetrical gate overlap/underlap design or thicker spacer for SDE I/I so that the twin defects are not located in the depletion region near the drain.

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

PubMed

Kum, Oyeon

2018-06-01

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

Radiation Pneumopathy in the Rat After Intravenous Application of {sup 188}Re-Labeled Microspheres

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

Liepe, Knut; Faulhaber, Diana; Wunderlich, Gerd

2011-10-01

Purpose: To determine the dose dependence and kinetics of pneumopathy after systemic administration of rhenium-188 ({sup 188}Re)-labeled microspheres in a rat model. Methods and Materials: {sup 188}Re-microspheres were injected intravenously into adult Wistar rats (n = 54, age, 8 {+-} 2 months). The rats were divided into 6 groups according to the intended absorbed dose in the lung (maximum 60 Gy). Gamma camera scans were used to estimate the individual whole lung doses. One control group (n = 5) received nonlabeled microspheres. The breathing rate was measured before and weekly after the treatment using whole body plethysmography until 24 weeks.more » An increase in the breathing rate by 20% compared with the individual pretreatment control value was defined as the quantal endpoint for dose-effect analyses. Results: A biphasic increase in the breathing rate was observed. The first impairment of lung function occurred in Weeks 3-6. For late changes, the interval to onset was clearly dose dependent and was 17 weeks (10-30 Gy) and 10 weeks (50-60 Gy), respectively. The incidence of the response was highly dependent on the estimated lung dose. The median effective dose for an early and late response was virtually identical (19.9 {+-} 0.6 Gy and 20.4 {+-} 3.1 Gy, respectively). A significant correlation was found between the occurrence of an early and a late effect in the same rat, suggesting a strong consequential component. Conclusions: The effects of radiolabeled microspheres can be studied longitudinally in a rat model, using changes in the breathing rate as the functional, clinically relevant response. The isoeffective doses from the present study using radionuclide administration and those from published investigations of homogeneous external beam radiotherapy are almost similar.« less

In vitro fungicidal effects of methylene blue at 625-nm.

PubMed

Guffey, J Stephen; Payne, William; Roegge, Wilson

2017-11-01

The aim of the study is to confirm the effectiveness of photodynamic therapy (PDT) as a significant inhibitor of Trichophyton rubrum (T. rubrum) and to determine the most appropriate dose and rate of delivery. Trichophyton rubrum is the most common dermatophyte worldwide, responsible for the majority of superficial fungal infections. The traditional treatment of T. rubrum has known adverse effects. An alternative treatment is warranted. Photosensitised T. rubrum specimens were treated with 625-nm light at doses of 3, 12, 24, 40 and 60 J/cm 2 . Colony counts were performed and compared to untreated controls. Doses of 24, 40 and 60 J/cm 2 all produced kill rates of over 94%. A lower rate of delivery (7.80 mW/cm 2 ) was shown to be a greater inhibitor of T. rubrum than a higher rate of delivery (120 mW/cm 2 ). Photodynamic therapy with methylene blue (MB) at 625 nm using a low rate of delivery at doses of 24, 40 and 60 J/cm 2 is an effective inhibitor of T. rubrum. A rate of delivery of 7.80 mW/cm 2 is a significantly greater inhibitor of T. rubrum than a rate of 120 mW/cm 2 when applying 625-nm light in PDT using MB. © 2017 Blackwell Verlag GmbH.

Prototype Operational Advances for Atmospheric Radiation Dose Rate Specification

NASA Astrophysics Data System (ADS)

Tobiska, W. K.; Bouwer, D.; Bailey, J. J.; Didkovsky, L. V.; Judge, K.; Garrett, H. B.; Atwell, W.; Gersey, B.; Wilkins, R.; Rice, D.; Schunk, R. W.; Bell, D.; Mertens, C. J.; Xu, X.; Crowley, G.; Reynolds, A.; Azeem, I.; Wiltberger, M. J.; Wiley, S.; Bacon, S.; Teets, E.; Sim, A.; Dominik, L.

2014-12-01

Space weather's effects upon the near-Earth environment are due to dynamic changes in the energy transfer processes from the Sun's photons, particles, and fields. The coupling between the solar and galactic high-energy particles, the magnetosphere, and atmospheric regions can significantly affect humans and our technology as a result of radiation exposure. Space Environment Technologies (SET) has developed innovative, new space weather observations that will become part of the toolset that is transitioned into operational use. One prototype operational system for providing timely information about the effects of space weather is SET's Automated Radiation Measurements for Aerospace Safety (ARMAS) system. ARMAS will provide the "weather" of the radiation environment to improve aircraft crew and passenger safety. Through several dozen flights the ARMAS project has successfully demonstrated the operation of a micro dosimeter on commercial aviation altitude aircraft that captures the real-time radiation environment resulting from Galactic Cosmic Rays and Solar Energetic Particles. The real-time radiation exposure is computed as an effective dose rate (body-averaged over the radiative-sensitive organs and tissues in units of microsieverts per hour); total ionizing dose is captured on the aircraft, downlinked in real-time via Iridium satellites, processed on the ground into effective dose rates, compared with NASA's Langley Research Center (LaRC) most recent Nowcast of Atmospheric Ionizing Radiation System (NAIRAS) global radiation climatology model runs, and then made available to end users via the web and smart phone apps. We are extending the dose measurement domain above commercial aviation altitudes into the stratosphere with a collaborative project organized by NASA's Armstrong Flight Research Center (AFRC) called Upper-atmospheric Space and Earth Weather eXperiment (USEWX). In USEWX we will be flying on the ER-2 high altitude aircraft a micro dosimeter for effective dose rate measurements and a thermal neutron monitor to characterize Single Event Effects (SEEs) in avionics. In this presentation we describe recent ARMAS and USEWX advances that will ultimately provide operational users with real-time dose and dose rate data for human tissue and avionics exposure risk mitigation.

Tolerance to effects of high-dose oral δ9-tetrahydrocannabinol and plasma cannabinoid concentrations in male daily cannabis smokers.

PubMed

Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schwope, David M; Darwin, William D; Kelly, Deanna L; McMahon, Robert P; Liu, Fang; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

2013-01-01

Oral cannabinoids are taken for medicinal or recreational purposes, yet little is known about tolerance to their effects after high-dose extended exposure. The development of tolerance to effects of around-the-clock oral synthetic Δ9-tetrahydrocannabinol (THC) (20 mg every 3.5-6 h) was evaluated in 13 healthy male daily cannabis smokers residing on a secure research unit: 40 mg on Day 1; 100 mg on Days 2-4; 120 mg on Days 5-6. Systolic and diastolic blood pressure (BP), heart rate, and symptoms of subjective intoxication (100 mm visual-analogue scales, VAS) were assessed the morning of Day 1 (before any oral THC), and on Days 2, 4 and 6, every 30 min for 3 h after the first morning THC dose. Morning subjective intoxication ratings increased from Days 1 to 2, and then declined on Days 4 and 6. The morning THC dose increased intoxication ratings on Day 2, but had less effect on Days 4 and 6, a pattern consistent with tolerance. THC lowered BP and increased heart rate over the six days. Plasma THC and 11-OH-THC concentrations increased significantly over the first five days of dosing. Six days of around-the-clock, oral THC produced tolerance to subjective intoxication, but not to cardiovascular effects.

The effects of different dosage levels of hepatitis B vaccine as booster on anti-HBs-negative children 5–15 y after primary immunization; China, 2009–2010

PubMed Central

Chen, Yongdi; Lv, Huakun; Gu, Hua; Cui, Fujiang; Wang, Fuzhen; Yao, Jun; Xia, Shichang; Liang, Xiaofeng

2014-01-01

The changes in lgG antibody levels to hepatitis B surface antigen (HBsAg) and in antibody to HBsAg (anti-HBs) seroconversion rates due to different dosages of hepatitis B vaccine (HepB) were compared in 2106 children. Children who had been previously vaccinated as infants with HepB were revaccinated at 5–15 y of age, after which the antibody titers were determined. After the first booster dose, the anti-HBs seroconversion rate (defined as an anti-HBs ≥10 mIU/ml) with 10 μg of HepB (93.6%) was significantly greater than the rate with 5 µg of HepB (90.3%) (P < 0.05); the anti-HBs seroconversion rate in 10–15-y-old boys vaccinated with 10 μg of HepB (90.9%) was significantly greater than the rate with 5 µg of HepB (84.3%) (P < 0.05). The anti-HBs seroconversion rates after the third booster dose with 5 or 10 μg of HepB were greater than those after the first booster dose (99.6% and 99.7%, vs. 90.3% and 93.6%, P < 0.05); as was the corresponding GMTs (658 ± 4 mIU/ml and 2599 ± 3 mIU/ml, vs. 255 ± 11 mIU/ml and 877 ± 11 mIU/ml [P < 0.05]). The immunization effects of booster vaccination with 3 doses of HepB with 5 or 10 µg are effective; a single booster dose with 10 µg of HepB for 10–15-y-old boys and with 5 or 10 µg of HepB for 5–9 y old boys and for 5–15-y-old girls are effective in generating protective antibody against HBV; however, for anti-HBs-negative children after a single dose of booster, 3 doses are needed. PMID:24192508

The effects of different dosage levels of hepatitis B vaccine as booster on anti-HBs-negative children 5-15 y after primary immunization; China, 2009-2010.

PubMed

Chen, Yongdi; Lv, Huakun; Gu, Hua; Cui, Fujiang; Wang, Fuzhen; Yao, Jun; Xia, Shichang; Liang, Xiaofeng

2014-01-01

The changes in lgG antibody levels to hepatitis B surface antigen (HBsAg) and in antibody to HBsAg (anti-HBs) seroconversion rates due to different dosages of hepatitis B vaccine (HepB) were compared in 2106 children. Children who had been previously vaccinated as infants with HepB were revaccinated at 5-15 y of age, after which the antibody titers were determined. After the first booster dose, the anti-HBs seroconversion rate (defined as an anti-HBs ≥10 mIU/ml) with 10 μg of HepB (93.6%) was significantly greater than the rate with 5 µg of HepB (90.3%) (P<0.05); the anti-HBs seroconversion rate in 10-15-y-old boys vaccinated with 10 μg of HepB (90.9%) was significantly greater than the rate with 5 µg of HepB (84.3%) (P<0.05). The anti-HBs seroconversion rates after the third booster dose with 5 or 10 μg of HepB were greater than those after the first booster dose (99.6% and 99.7%, vs. 90.3% and 93.6%, P<0.05); as was the corresponding GMTs (658 ± 4 mIU/ml and 2599 ± 3 mIU/ml, vs. 255 ± 11 mIU/ml and 877 ± 11 mIU/ml [P<0.05]). The immunization effects of booster vaccination with 3 doses of HepB with 5 or 10 µg are effective; a single booster dose with 10 µg of HepB for 10-15-y-old boys and with 5 or 10 µg of HepB for 5-9 y old boys and for 5-15-y-old girls are effective in generating protective antibody against HBV; however, for anti-HBs-negative children after a single dose of booster, 3 doses are needed.

High dose-per-pulse electron beam dosimetry: Commissioning of the Oriatron eRT6 prototype linear accelerator for preclinical use.

PubMed

Jaccard, Maud; Durán, Maria Teresa; Petersson, Kristoffer; Germond, Jean-François; Liger, Philippe; Vozenin, Marie-Catherine; Bourhis, Jean; Bochud, François; Bailat, Claude

2018-02-01

The Oriatron eRT6 is an experimental high dose-per-pulse linear accelerator (linac) which was designed to deliver an electron beam with variable dose-rates, ranging from a few Gy/min up to hundreds of Gy/s. It was built to study the radiobiological effects of high dose-per-pulse/dose-rate electron beam irradiation, in the context of preclinical and cognitive studies. In this work, we report on the commissioning and beam monitoring of the Oriatron eRT6 prototype linac. The beam was characterized in different steps. The output stability was studied by performing repeated measurements over a period of 20 months. The relative output variations caused by changing beam parameters, such as the temporal electron pulse width, the pulse repetition frequency and the pulse amplitude were also analyzed. Finally, depth dose curves and field sizes were measured for two different beam settings, resulting in one beam with a conventional radiotherapy dose-rate and one with a much higher dose-rate. Measurements were performed with Gafchromic EBT3 films and with a PTW Advanced Markus ionization chamber. In addition, we developed a beam current monitoring system based on the signals from an induction torus positioned at the beam exit of the waveguide and from a graphite beam collimator. The stability of the output over repeated measurements was found to be good, with a standard deviation smaller than 1%. However, non-negligible day-to-day variations of the beam output were observed. Those output variations showed different trends depending on the dose-rate. The analysis of the relative output variation as a function of various beam parameters showed that in a given configuration, the dose-rate could be reliably varied over three orders of magnitude. Interdependence effects on the output variation between the parameters were also observed. The beam energy and field size were found to be slightly dose-rate-dependent and suitable mainly for small animal irradiation. The beam monitoring system was able to measure in a reproducible way the total charge of electrons that exit the machine, as long as the electron pulse amplitude remains above a given threshold. Furthermore, we were able to relate the charge measured with the monitoring system to the absorbed dose in a solid water phantom. The Oriatron eRT6 was successfully commissioned for preclinical use and is currently in full operation, with studies being performed on the radiobiological effects of high dose-per-pulse irradiation. © 2017 American Association of Physicists in Medicine.

Efficacy and Safety of OnabotulinumtoxinA Treatment of Forehead Lines: A Multicenter, Randomized, Dose-Ranging Controlled Trial.

PubMed

Solish, Nowell; Rivers, Jason K; Humphrey, Shannon; Muhn, Channy; Somogyi, Chris; Lei, Xiaofang; Bhogal, Meetu; Caulkins, Carrie

2016-03-01

Various onabotulinumtoxinA doses are effective in treating forehead lines (FHL), with a trend toward lower doses. To evaluate efficacy and safety of onabotulinumtoxinA dose-ranging treatment of FHL when the frontalis area and glabellar complex are treated together. Adults with moderate-to-severe FHL received onabotulinumtoxinA 40 U (FHL, 20 U; glabellar lines [GL], 20 U), 30 U (FHL, 10 U; GL, 20 U), or placebo. Response was assessed at weeks 1, 2, day 30, and monthly to day 180. Coprimary efficacy end points were investigator- and subject-assessed Facial Wrinkle Scale scores of none or mild (day 30). Patient-reported outcomes, onset/duration of effect, and adverse events (AEs) were evaluated. Responder rates (investigator/subject, respectively) were 40-U group, 91.2%/89.5%; 30-U group, 86.4%/81.4%; placebo, 1.7%/5.1%. OnabotulinumtoxinA resulted in significantly greater responder rates than placebo (p < .001). Adverse events were mild to moderate and similar between groups (most common AEs: nasopharyngitis [4.6%] and headache [4.0%]). Treatment of FHL with onabotulinumtoxinA 40 and 30 U (in frontalis and glabellar complex muscles) was tolerable, effective, and sustained. Both doses significantly reduced FHL severity; however, the 40-U dose demonstrated a trend toward greater sustained benefit and longer duration of effect versus the 30-U dose, with similar AE rates.

Evaluation of forest decontamination using radiometric measurements.

PubMed

Cresswell, Alan J; Kato, Hiroaki; Onda, Yuichi; Nanba, Kenji

2016-11-01

An experiment has been conducted to evaluate the additional dose reduction by clear felling contaminated forestry in Fukushima Prefecture, Japan, and using the timber to cover the areas with wood chips. A portable gamma spectrometry system, comprising a backpack containing a 3 × 3″ NaI(Tl) detector with digital spectrometer and GPS receiver, has been used to map dose rate and radionuclide activity concentrations before, after and at stages during this experiment. The data show the effect of the different stages of the experiment on dose rate at different locations around the site. The spectrometric data have allowed the assessment of the contributions of natural and anthropogenic radionuclides to the dose rate at different parts of the site before and after the experiment. This has clearly demonstrated the value of radiometric methods in evaluating remediation, and the effect of other environmental processes. The value of spectrometric methods which directly measure radionuclide concentrations has also been shown, especially through the identification of the contribution of natural and anthropogenic activity to the measured dose rate. The experiment has shown that clearing trees and applying wood chips can reduce dose rates by 10-15% beyond that achieved by just clearing the forest litter and natural redistribution of radiocaesium. Copyright © 2016 Elsevier Ltd. All rights reserved.

Psilocybin occasioned mystical-type experiences: Immediate and persisting dose-related effects

PubMed Central

Griffiths, R. R.; Johnson, M.W.; Richards, W. A.; Richards, B.D.; McCann, U.; Jesse, R.

2012-01-01

Rationale This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Objectives This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Methods Participants were 18 adults (17 hallucinogen-naïve). Five 8-hour sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (9 participants each). Placebo was scheduled quasi-randomly. During sessions volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up. Results Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Conclusions Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood and behavior. Implications for therapeutic trials are discussed. PMID:21674151

Maximum dose rate is a determinant of hypothyroidism after 131I therapy of Graves' disease but the total thyroid absorbed dose is not.

PubMed

Krohn, Thomas; Hänscheid, Heribert; Müller, Berthold; Behrendt, Florian F; Heinzel, Alexander; Mottaghy, Felix M; Verburg, Frederik A

2014-11-01

The determinants of successful (131)I therapy of Graves' disease (GD) are unclear. To relate dosimetry parameters to outcome of therapy to identify significant determinants eu- and/or hypothyroidism after (131)I therapy in patients with GD. A retrospective study in which 206 Patients with GD treated in University Hospital between November 1999 and January 2011. All received (131)I therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Post-therapy dosimetric thyroid measurements were performed twice daily until discharge. From these measurements, thyroid (131)I half-life, the total thyroid absorbed dose, and the maximum dose rate after (131)I administration were calculated. In all, 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after (131)I therapy. In univariate analysis, nonhyperthyroid and hyperthyroid patients only differed by sex. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal (131)I half-life, and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (P < .001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.

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

Harrison, F.L.; Rice, D.W. Jr.

The usefulness of sister chromatid exchange (SCE) induction as a measure of low-level radiation effect was examined in a benthic marine worm, Neanthes arenaceodentata. Larvae were exposed to /sup 60/Co radiation for 12 to 24 h at total doses ranging from 0.5 to 309 R and at dose rates from 0.04 to 13 R/h. Animals exposed at intermediate dose rates (0.5, 0.6, 1.25, 2.0, and 2.5 R/h) had SCE frequencies per chromosome about twice that of those receiving no radiation (controls), whereas those exposed at the higher dose rates (7.0 and 13 R/h) had SCE frequencies lower than the controls.more » Animals exposed at the lower dose rates (0.04 and 0.1 R/h) had lower SCE frequencies than those exposed at intermediate dose rates (and higher SCE frequencies than controls). The length of chromosome pair number one differed among metaphase spreads and was used as an index of chromosome condensation in a given metaphase. Because there is a possibility that chromosome morphology may affect the ability to resolve SCEs, morphology will be monitored in future studies. A preliminary experiment was performed to assess the effects of 2.2 and 11.5 R/h for 24 h on growth and development. Larvae observed at 6 and 17 d after irradiation did not have significantly different numbers of abnormal larvae or survival rates.« less

Gamma Radiation Doses In Sweden

NASA Astrophysics Data System (ADS)

Almgren, Sara; Barregârd, Lars; Isaksson, Mats

2008-08-01

Gamma dose rate measurements were performed in one urban and one rural area using thermoluminescence dosimeters (TLD) worn by 46 participants and placed in their dwellings. The personal effective dose rates were 0.096±0.019(1 SD) and 0.092±0.016(1 SD)μSv/h in the urban and rural area, respectively. The corresponding dose rates in the dwellings were 0.11±0.042(1 SD) and 0.091±0.026(1 SD)μSv/h. However, the differences between the areas were not significant. The values were higher in buildings made of concrete than of wood and higher in apartments than in detached houses. Also, 222Rn measurements were performed in each dwelling, which showed no correlation with the gamma dose rates in the dwellings.

SU-F-T-301: Planar Dose Pass Rate Inflation Due to the MapCHECK Measurement Uncertainty Function

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

Bailey, D; Spaans, J; Kumaraswamy, L

Purpose: To quantify the effect of the Measurement Uncertainty function on planar dosimetry pass rates, as analyzed with Sun Nuclear Corporation analytic software (“MapCHECK” or “SNC Patient”). This optional function is toggled on by default upon software installation, and automatically increases the user-defined dose percent difference (%Diff) tolerance for each planar dose comparison. Methods: Dose planes from 109 IMRT fields and 40 VMAT arcs were measured with the MapCHECK 2 diode array, and compared to calculated planes from a commercial treatment planning system. Pass rates were calculated within the SNC analytic software using varying calculation parameters, including Measurement Uncertainty onmore » and off. By varying the %Diff criterion for each dose comparison performed with Measurement Uncertainty turned off, an effective %Diff criterion was defined for each field/arc corresponding to the pass rate achieved with MapCHECK Uncertainty turned on. Results: For 3%/3mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.8–1.1% average, depending on plan type and calculation technique, for an average pass rate increase of 1.0–3.5% (maximum +8.7%). For 2%, 2 mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.7–1.2% average, for an average pass rate increase of 3.5–8.1% (maximum +14.2%). The largest increases in pass rate are generally seen with poorly-matched planar dose comparisons; the MapCHECK Uncertainty effect is markedly smaller as pass rates approach 100%. Conclusion: The Measurement Uncertainty function may substantially inflate planar dose comparison pass rates for typical IMRT and VMAT planes. The types of uncertainties incorporated into the function (and their associated quantitative estimates) as described in the software user’s manual may not accurately estimate realistic measurement uncertainty for the user’s measurement conditions. Pass rates listed in published reports or otherwise compared to the results of other users or vendors should clearly indicate whether the Measurement Uncertainty function is used.« less

Novel Radiobiological Gamma Index for Evaluation of 3-Dimensional Predicted Dose Distribution

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

Sumida, Iori, E-mail: sumida@radonc.med.osaka-u.ac.jp; Yamaguchi, Hajime; Kizaki, Hisao

2015-07-15

Purpose: To propose a gamma index-based dose evaluation index that integrates the radiobiological parameters of tumor control (TCP) and normal tissue complication probabilities (NTCP). Methods and Materials: Fifteen prostate and head and neck (H&N) cancer patients received intensity modulated radiation therapy. Before treatment, patient-specific quality assurance was conducted via beam-by-beam analysis, and beam-specific dose error distributions were generated. The predicted 3-dimensional (3D) dose distribution was calculated by back-projection of relative dose error distribution per beam. A 3D gamma analysis of different organs (prostate: clinical [CTV] and planned target volumes [PTV], rectum, bladder, femoral heads; H&N: gross tumor volume [GTV], CTV,more » spinal cord, brain stem, both parotids) was performed using predicted and planned dose distributions under 2%/2 mm tolerance and physical gamma passing rate was calculated. TCP and NTCP values were calculated for voxels with physical gamma indices (PGI) >1. We propose a new radiobiological gamma index (RGI) to quantify the radiobiological effects of TCP and NTCP and calculate radiobiological gamma passing rates. Results: The mean RGI gamma passing rates for prostate cases were significantly different compared with those of PGI (P<.03–.001). The mean RGI gamma passing rates for H&N cases (except for GTV) were significantly different compared with those of PGI (P<.001). Differences in gamma passing rates between PGI and RGI were due to dose differences between the planned and predicted dose distributions. Radiobiological gamma distribution was visualized to identify areas where the dose was radiobiologically important. Conclusions: RGI was proposed to integrate radiobiological effects into PGI. This index would assist physicians and medical physicists not only in physical evaluations of treatment delivery accuracy, but also in clinical evaluations of predicted dose distribution.« less

The New Radiobiology: Returning to Our Roots

PubMed Central

Ulsh, Brant A.

2012-01-01

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

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

PubMed

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

2017-06-15

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

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

[The Dose Effect of Isocenter Selection during IMRT Dose Verification with the 2D Chamber Array].

PubMed

Xie, Chuanbin; Cong, Xiaohu; Xu, Shouping; Dai, Xiangkun; Wang, Yunlai; Han, Lu; Gong, Hanshun; Ju, Zhongjian; Ge, Ruigang; Ma, Lin

2015-03-01

To investigate the dose effect of isocenter difference during IMRT dose verification with the 2D chamber array. The samples collected from 10 patients were respectively designed for IMRT plans, the isocenter of which was independently defined as P(o), P(x) and P(y). P(o) was fixed on the target center and the other points shifted 8cm from the target center in the orientation of x/y. The PTW729 was used for 2D dose verification in the 3 groups which beams of plans were set to 0 degrees. The γ-analysis passing rates for the whole plan and each beam were gotten using the different standards in the 3 groups, The results showed the mean passing rate of γ-analysis was highest in the P(o) group, and the mean passing rate of the whole plan was better than that of each beam. In addition, it became worse with the increase of dose leakage between the leaves in P(y) group. Therefore, the determination of isocenter has a visible effect for IMRT dose verification of the 2D chamber array, The isocenter of the planning design should be close to the geometric center of target.

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

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

Kurnaz, Asli; Kuecuekoemeroglu, B.; Okumusoglu, N. T.

In this study, it was determined environmental gamma radiation dose rate for some counties of Trabzon-Turkey. A detailed ambient gamma dose measurement has been performed in the seven counties of Trabzon, using a portable environmental survey meter (NaI detector, INSPECTOR 1000). The measurements were performed indoor and outdoor of buildings and also at each spot, a reading was taken at 1 m above ground level. The dose rates varied from 42.69 nGy/h and 140.91 nGy/h for indoor gamma dose and 27.84 nGy/h and 121.80 nGy/h for outdoor gamma dose . Average indoor and outdoor gamma dose rates were ascertained tomore » be 71.05 nGy/h and 60.20 nGy/h, respectively. The annual effective doses were calculated from indoor and outdoor gamma doses to be 348.56 muSv/y and 73.83 muSv/y, respectively.« less

Dosimetric characterization of the (60)Co BEBIG Co0.A86 high dose rate brachytherapy source using PENELOPE.

PubMed

Guerrero, Rafael; Almansa, Julio F; Torres, Javier; Lallena, Antonio M

2014-12-01

(60)Co sources are being used as an alternative to (192)Ir sources in high dose rate brachytherapy treatments. In a recent document from AAPM and ESTRO, a consensus dataset for the (60)Co BEBIG (model Co0.A86) high dose rate source was prepared by using results taken from different publications due to discrepancies observed among them. The aim of the present work is to provide a new calculation of the dosimetric characteristics of that (60)Co source according to the recommendations of the AAPM and ESTRO report. Radial dose function, anisotropy function, air-kerma strength, dose rate constant and absorbed dose rate in water have been calculated and compared to the results of previous works. Simulations using the two different geometries considered by other authors have been carried out and the effect of the cable density and length has been studied. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

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

Atomoxetine Increased Effect over Time in Adults with Attention-Deficit/Hyperactivity Disorder Treated for up to 6 Months: Pooled Analysis of Two Double-Blind, Placebo-Controlled, Randomized Trials.

PubMed

Wietecha, Linda A; Clemow, David B; Buchanan, Andrew S; Young, Joel L; Sarkis, Elias H; Findling, Robert L

2016-07-01

Changes in the magnitude of efficacy throughout 26 weeks of atomoxetine treatment, along with impact of dosing, were evaluated in adults with ADHD from two randomized, double-blind, placebo-controlled studies. Pooled placebo (n = 485) and atomoxetine (n = 518) patients, dosed 25, 40, 60, 80 (target dose), or 100 mg daily, were assessed. Change from baseline in Conners' Adult ADHD Rating Scale-Investigator Rated Scale: Screening Version (CAARS) total ADHD symptoms score and Adult ADHD Investigator Symptom Rating Scale (AISRS) total score were analyzed using mixed-model repeated measures, with least squares mean change, effect size, and response rate calculated at 1, 2, 4, 8, 12, 16, 22, and 26 weeks. Decreases on CAARS for atomoxetine- versus placebo-treated patients were consistently statistically significantly greater at every time point beginning at one week (P ≤ 0.006, 0.28 effect size). By 4 weeks, comparison was -13.19 compared with -8.84 (P < 0.0001, 0.45 effect size). By 26 weeks, mean change was -15.42 versus -9.71 (0.52 effect size); increase in effect size over time was most pronounced in the 80 mg group (0.82 effect size). AISRS demonstrated similar results. Atomoxetine response rate (CAARS 50% decrease) continued to increase throughout 26 weeks. Atomoxetine treatment in adults with ADHD was associated with small effect sizes after 4 weeks and moderate effect sizes by 6 months of treatment. The data support increased effect size and response rate over time during longer-term treatment at target dose. © 2016 Eli Lilly and Company. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Early effects comparison of X-rays delivered at high-dose-rate pulses by a plasma focus device and at low dose rate on human tumour cells.

PubMed

Virelli, A; Zironi, I; Pasi, F; Ceccolini, E; Nano, R; Facoetti, A; Gavoçi, E; Fiore, M R; Rocchi, F; Mostacci, D; Cucchi, G; Castellani, G; Sumini, M; Orecchia, R

2015-09-01

A comparative study has been performed on the effects of high-dose-rate (DR) X-ray beams produced by a plasma focus device (PFMA-3), to exploit its potential medical applications (e.g. radiotherapy), and low-DR X-ray beams produced by a conventional source (XRT). Experiments have been performed at 0.5 and 2 Gy doses on a human glioblastoma cell line (T98G). Cell proliferation rate and potassium outward currents (IK) have been investigated by time lapse imaging and patch clamp recordings. The results showed that PFMA-3 irradiation has a greater capability to reduce the proliferation rate activity with respect to XRT, while it does not affect IK of T98G cells at any of the dose levels tested. XRT irradiation significantly reduces the mean IK amplitude of T98G cells only at 0.5 Gy. This work confirms that the DR, and therefore the source of radiation, is crucial for the planning and optimisation of radiotherapy applications. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum.

PubMed

Johnson, Matthew W; MacLean, Katherine A; Reissig, Chad J; Prisinzano, Thomas E; Griffiths, Roland R

2011-05-01

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 min for 60 min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 min (first time point) and definite subjective effects were no longer present at approximately 20 min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2(A)) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Dose reduction of risperidone and olanzapine can improve cognitive function and negative symptoms in stable schizophrenic patients: A single-blinded, 52-week, randomized controlled study.

PubMed

Zhou, Yanling; Li, Guannan; Li, Dan; Cui, Hongmei; Ning, Yuping

2018-05-01

The long-term effects of dose reduction of atypical antipsychotics on cognitive function and symptomatology in stable patients with schizophrenia remain unclear. We sought to determine the change in cognitive function and symptomatology after reducing risperidone or olanzapine dosage in stable schizophrenic patients. Seventy-five stabilized schizophrenic patients prescribed risperidone (≥4 mg/day) or olanzapine (≥10 mg/day) were randomly divided into a dose-reduction group ( n=37) and a maintenance group ( n=38). For the dose-reduction group, the dose of antipsychotics was reduced by 50%; for the maintenance group, the dose remained unchanged throughout the whole study. The Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery were measured at baseline, 12, 28, and 52 weeks. Linear mixed models were performed to compare the Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects and MATRICS Consensus Cognitive Battery scores between groups. The linear mixed model showed significant time by group interactions on the Positive and Negative Syndrome Scale negative symptoms, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, attention/vigilance, working memory and total score of MATRICS Consensus Cognitive Battery (all p<0.05). Post hoc analyses showed significant improvement in Positive and Negative Syndrome Scale negative subscale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, working memory and total score of MATRICS Consensus Cognitive Battery for the dose reduction group compared with those for the maintenance group (all p<0.05). This study indicated that a risperidone or olanzapine dose reduction of 50% may not lead to more severe symptomatology but can improve speed of processing, working memory and negative symptoms in patients with stabilized schizophrenia.

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

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.

Biological effects of low energy nitrogen ion implantation on Jatropha curcas L. seed germination

NASA Astrophysics Data System (ADS)

Xu, Gang; Wang, Xiao-teng; Gan, Cai-ling; Fang, Yan-qiong; Zhang, Meng

2012-09-01

To explore the biological effects of nitrogen ion beam implantation on dry Jatropha curcas seed, a beam of N+ with energy of 25 keV was applied to treat the dry seed at six different doses. N+ beam implantation greatly decreased germination rate and seedling survival rate. The doses within the range of 12 × 1016 to 15 × 1016 ions cm-2 severely damaged the seeds: total antioxidant capacity (TAC), germination rate, seedling survival rate, reduced ascorbate acid (HAsA) and reduced glutathione (GSH) contents, and most of the tested antioxidases activity (i.e. catalase (CAT), ascorbate peroxidase (APX) and superoxide dismutase (SOD)) reached their lowest levels. At a dose of 18 × 1016 ion cm-2, biological repair took place: moderate increases were found in TAC, germination rate, seedling survival rate, HAsA and GSH contents, and some antioxidant enzyme activities (i.e. CAT, APX, SOD and GPX). The dose of 18 × 1016 ions cm-2 may be the optimum dose for use in dry J. curcas seed mutation breeding. CAT, HAsA and GSH contributed to the increase of TAC, but CAT was the most important. POD performed its important role as seed was severely damaged. The main role of the HAsA-GSH cycle appeared to be for regeneration of HAsA.

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

NASA Astrophysics Data System (ADS)

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

1986-08-01

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

Effects of Methylphenidate on Sleep Functioning in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Becker, Stephen P; Froehlich, Tanya E; Epstein, Jeffery N

2016-06-01

To examine the effects of stimulant medication on the sleep functioning of children with attention-deficit/hyperactivity disorder (ADHD) and identify predictors of sleep problems as a side effect of taking stimulant medication. One hundred sixty-three stimulant-naïve children (72% boys) aged 7 to 11 years diagnosed with ADHD (120 with ADHD predominantly inattentive type, 43 with ADHD combined type) participated in a 4-week, randomized, double-blind, placebo-controlled trial of once-daily (long-acting) methylphenidate (MPH). Parents completed weekly side-effect ratings including an item related to sleep problems. Ten percent of patients had parent-rated sleep problems before the initiation of medication. Rates of parent-rated sleep problems during MPH titration generally increased with increasing MPH dose (placebo: 8%; low dose: 18%; medium dose: 15%; high dose: 25%). Differences emerged between children with (n = 16) or without (n = 147) preexisting sleep problems. Although 23% of children without preexisting sleep problems went on to have sleep problems at the highest MPH dose, only 37.5% of children with preexisting sleep problems still had sleep problems at the highest MPH dose. Lower weight and lower body mass index (BMI) were associated with increased sleep problems during MPH titration. This study demonstrated a general association between increased MPH dose and increased sleep problems in children with ADHD, particularly for children of lower weight/BMI. However, a substantial proportion of children with preexisting sleep difficulties no longer had sleep problems on the highest MPH dose, which may help explain mixed findings reported to date in studies examining the impact of MPH on sleep functioning in children with ADHD and suggests that MPH dose titration should not be avoided solely on the basis of a child's premorbid sleep problems. Future research is needed to replicate and extend these findings to more specific domains of sleep functioning and to identify differences between children with persistent or improved sleep functioning as a result of MPH use.

External dose-rate conversion factors of radionuclides for air submersion, ground surface contamination and water immersion based on the new ICRP dosimetric setting.

PubMed

Yoo, Song Jae; Jang, Han-Ki; Lee, Jai-Ki; Noh, Siwan; Cho, Gyuseong

2013-01-01

For the assessment of external doses due to contaminated environment, the dose-rate conversion factors (DCFs) prescribed in Federal Guidance Report 12 (FGR 12) and FGR 13 have been widely used. Recently, there were significant changes in dosimetric models and parameters, which include the use of the Reference Male and Female Phantoms and the revised tissue weighting factors, as well as the updated decay data of radionuclides. In this study, the DCFs for effective and equivalent doses were calculated for three exposure settings: skyshine, groundshine and water immersion. Doses to the Reference Phantoms were calculated by Monte Carlo simulations with the MCNPX 2.7.0 radiation transport code for 26 mono-energy photons between 0.01 and 10 MeV. The transport calculations were performed for the source volume within the cut-off distances practically contributing to the dose rates, which were determined by a simplified calculation model. For small tissues for which the reduction of variances are difficult, the equivalent dose ratios to a larger tissue (with lower statistical errors) nearby were employed to make the calculation efficient. Empirical response functions relating photon energies, and the organ equivalent doses or the effective doses were then derived by the use of cubic-spline fitting of the resulting doses for 26 energy points. The DCFs for all radionuclides considered important were evaluated by combining the photon emission data of the radionuclide and the empirical response functions. Finally, contributions of accompanied beta particles to the skin equivalent doses and the effective doses were calculated separately and added to the DCFs. For radionuclides considered in this study, the new DCFs for the three exposure settings were within ±10 % when compared with DCFs in FGR 13.

External dose-rate conversion factors of radionuclides for air submersion, ground surface contamination and water immersion based on the new ICRP dosimetric setting

PubMed Central

Yoo, Song Jae; Jang, Han-Ki; Lee, Jai-Ki; Noh, Siwan; Cho, Gyuseong

2013-01-01

For the assessment of external doses due to contaminated environment, the dose-rate conversion factors (DCFs) prescribed in Federal Guidance Report 12 (FGR 12) and FGR 13 have been widely used. Recently, there were significant changes in dosimetric models and parameters, which include the use of the Reference Male and Female Phantoms and the revised tissue weighting factors, as well as the updated decay data of radionuclides. In this study, the DCFs for effective and equivalent doses were calculated for three exposure settings: skyshine, groundshine and water immersion. Doses to the Reference Phantoms were calculated by Monte Carlo simulations with the MCNPX 2.7.0 radiation transport code for 26 mono-energy photons between 0.01 and 10 MeV. The transport calculations were performed for the source volume within the cut-off distances practically contributing to the dose rates, which were determined by a simplified calculation model. For small tissues for which the reduction of variances are difficult, the equivalent dose ratios to a larger tissue (with lower statistical errors) nearby were employed to make the calculation efficient. Empirical response functions relating photon energies, and the organ equivalent doses or the effective doses were then derived by the use of cubic-spline fitting of the resulting doses for 26 energy points. The DCFs for all radionuclides considered important were evaluated by combining the photon emission data of the radionuclide and the empirical response functions. Finally, contributions of accompanied beta particles to the skin equivalent doses and the effective doses were calculated separately and added to the DCFs. For radionuclides considered in this study, the new DCFs for the three exposure settings were within ±10 % when compared with DCFs in FGR 13. PMID:23542764

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer: A Randomized Trial Comparing Two Radiation Doses

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

Jakobsen, Anders, E-mail: anders.jakobsen@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2012-11-15

Purpose: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation. Methods and Materials: The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of {<=}5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; armmore » B). Concomitant chemotherapy, uftoral 300 mg/m{sup 2} and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0). Results: The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04). Conclusions: This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.« less

Biological effects of α-radiation exposure by (241)Am in Arabidopsis thaliana seedlings are determined both by dose rate and (241)Am distribution.

PubMed

Biermans, Geert; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Saenen, Eline; Van Hees, May; Wannijn, Jean; Vangronsveld, Jaco; Cuypers, Ann

2015-11-01

Human activity has led to an increasing amount of radionuclides in the environment and subsequently to an increased risk of exposure of the biosphere to ionising radiation. Due to their high linear energy transfer, α-emitters form a threat to biota when absorbed or integrated in living tissue. Among these, (241)Am is of major concern due to high affinity for organic matter and high specific activity. This study examines the dose-dependent biological effects of α-radiation delivered by (241)Am at the morphological, physiological and molecular level in 14-day old seedlings of Arabidopsis thaliana after hydroponic exposure for 4 or 7 days. Our results show that (241)Am has high transfer to the roots but low translocation to the shoots. In the roots, we observed a transcriptional response of reactive oxygen species scavenging and DNA repair pathways. At the physiological and morphological level this resulted in a response which evolved from redox balance control and stable biomass at low dose rates to growth reduction, reduced transfer and redox balance decline at higher dose rates. This situation was also reflected in the shoots where, despite the absence of a transcriptional response, the control of photosynthesis performance and redox balance declined with increasing dose rate. The data further suggest that the effects in both organs were initiated in the roots, where the highest dose rates occurred, ultimately affecting photosynthesis performance and carbon assimilation. Though further detailed study of nutrient balance and (241)Am localisation is necessary, it is clear that radionuclide uptake and distribution is a major parameter in the global exposure effects on plant performance and health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.

PubMed

Chen, Jing-Xu; Su, Yun-Ai; Bian, Qing-Tao; Wei, Li-He; Zhang, Rong-Zhen; Liu, Yan-Hong; Correll, Christoph; Soares, Jair C; Yang, Fu-De; Wang, Shao-Li; Zhang, Xiang-Yang

2015-08-01

Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of gamma irradiation on quality of dried potato

NASA Astrophysics Data System (ADS)

Wang, J.; Chao, Y.

2003-03-01

The objectives of this study were to obtain the effect of gamma irradiation on the quality of dried potato. Experiments were conducted to study the influence of different doses, air temperatures, slice thickness of potatoes on the dehydration rate, appearance quality ( L-values), vitamin C content, and the rehydration ratio of dried potatoes. The greater the dose, the higher the dehydration rate, the lesser the vitamin C content, and the lower the rehydration ratio. The L-values for low-dose irradiation was greater than that for non-irradiated potatoes.

Spacecraft shielding for a Mars mission

NASA Astrophysics Data System (ADS)

O'Brien, K.

Calculations of the effective radiation dose due to cosmic rays in the interplanetary medium between Earth and Mars show that, as in the atmosphere above the Pfotzer Maximum, the dose rate increases with increasing wall thickness. An unshielded space crew member would receive almost 70 rem (0.70 Sv) a year. The effect of a typically proposed composite space-craft hull of aluminum and polyethylene would increase the dose rate by a few percent. However, 100 g/cm2 of almost any light material would more than double the cosmic radiation exposure of the crew.

Behavioral effects of microwaves: relationship of total dose and dose rate

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

O'Connor, M.E.; Strattan, R.

1988-10-01

The goal of the research was to compare the relationship of whole-body averaged specific absorption rate (SAR) and specific absorption (SA) to determine whether dose rate or dose was the better predictor of biological effects. Sperm-positive Long-Evans female rats were exposed to 2450-MHz CW microwave radiation for 1-3 hours at approximately 10 W/kg. The maternal subjects were then observed for natural delivery of their litters. Sensitivity to thermally induced seizures and huddling were studied in the offspring. Analyses revealed that there were no statistically significant differences between exposed and control offspring on the behavioral indices. The behavior did not appearmore » to be affected by prenatal exposure to microwave radiation at this level. The huddle sizes became smaller as the pups aged both in exposed and control offspring.« less

WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

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

Chang, S; Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina; Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC

Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression andmore » cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide the added clinical benefit of improving treatment therapeutic ratio. Animal Studies were performed within the LCCC Animal Studies Core Facility at the University of North Carolina at Chapel Hill. The LCCC Animal Studies Core is supported in part by an NCI Center Core Support Grant (CA16086) to the UNC Lineberger Comprehensive Cancer Center.« less

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.

Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.

PubMed

Jensen, Kevin P; DeVito, Elise E; Valentine, Gerald; Gueorguieva, Ralitza; Sofuoglu, Mehmet

2016-07-01

Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration.

The effect of variable-dose diazepam on dreaming and emergence phenomena in 400 cases of ketamine-fentanyl anaesthesia.

PubMed

Grace, R F

2003-09-01

This randomised double-blind field study compared 400 anaesthetics using diazepam (0, 0.025, 0.5, 0.1, 0.175 mg.kg-1) with ketamine (1 mg.kg-1) and fentanyl (1 microg.kg-1) in Melanesian patients. Dreams were very common and generally positive in nature. A minimum of 0.1 mg.kg-1 of diazepam was needed to significantly reduce dreaming when compared with water (67.5% vs. 94.6%; p < 0.0001), and to significantly lower median (95% CI) emergence delirium scores (4 (3-4) vs. 6 (5-7)). Gender and age did not affect the rate of dreaming. Increasing the dose of diazepam did not improve the dream experience. Patient satisfaction scores were similar between groups. Increases in blood pressure and heart rate were greater in dreamers than in non-dreamers. All groups had high rate-pressure products but this was highest when diazepam was not used. Higher diazepam doses significantly reduced the increase in blood pressure and heart rate at 3 and 6 min postketamine. When used with ketamine and fentanyl, 0.1 mg.kg-1 of diazepam has favourable psychic and cardiovascular effects. Lower diazepam doses generally had little effect whereas larger doses did not enhance the benefits further.

X-Ray-Induced Chromosome Aberrations in Mouse Dictyate Oocytes. II. Fractionation and Dose Rate Effects

PubMed Central

Brewen, J. G.; Payne, H. S.; Adler, I. D.

1977-01-01

Split-dose experiments were done on maturing dictyate oocytes to determine if the magnitude of the first dose influenced the "rejoining time" of radiation-induced chromosomal lesions. A total dose of 400r was split into various combinations with varying fractionation intervals. The data derived from analyzing interchanges indicate that there is no difference in the rejoining time whether the first dose was 100, 200, or 300r. It thus appears that the radiation dose in the ranges studied does not significantly alter the rate of repair of the chromosomal lesions. This conclusion is contrary to that which has been propounded to explain the nonlinear dose curves obtained for specific locus mutations. Chronic 60Co γ-ray exposures were given to female mice over an 8-day period. The exposures were delivered during the period of peak sensitivity, i.e., 8–16 days prior to ovulation. The doses given were 117, 240, 348, and 483r. The aberration yields observed were dramatically lower than for comparable doses of acute X rays even when the RBE of γ rays compared with X rays is taken into account. The large drop in yields at the low dose rates is interpreted as resulting from a large two-track component in the acute curve, and as being independent of effects on repair systems. PMID:604163

The effects of caffeine in women during aerobic-dance bench stepping.

PubMed

Ahrens, Jennifer N; Lloyd, Lisa K; Crixell, Sylvia H; Walker, John L

2007-02-01

People of all ages and fitness levels participate regularly in aerobic-dance bench stepping (ADBS) to increase fitness and control body weight. Any reasonable method for enhancing the experience or effectiveness of ADBS would be beneficial. This study examined the acute effects of a single dose of caffeine on physiological responses during ADBS in women. When compared with a placebo, neither a 3- nor a 6-mg/kg dose of caffeine altered physiological responses or rating of perceived exertion (RPE) in 20 women (age 19-28 y) of average fitness level, not habituated to caffeine, while they performed an ADBS routine. Since neither dose of caffeine had any effect on VO2, VCO2, minute ventilation, respiratory-exchange ratio, rate of energy expenditure, heart rate, or RPE during ADBS exercise, it would not be prudent for a group exercise leader to recommend caffeine to increase energy cost or decrease perception of effort in an ADBS session. Furthermore, caffeine ingestion should not interfere with monitoring intensity using heart rate or RPE during ADBS.

Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone.

PubMed

Tompkins, David Andrew; Lanier, Ryan K; Harrison, Joseph A; Strain, Eric C; Bigelow, George E

2010-07-01

Prescription opioid abuse has risen dramatically in the United States as clinicians have increased opioid prescribing for alleviation of both acute and chronic pain. Opioid analgesics with decreased risk for abuse are needed. Preclinical and clinical studies have shown that opioids combined with ultra-low-dose naltrexone (NTX) may have increased analgesic potency and have suggested reduced abuse or dependence liability. This study addressed whether addition of ultra-low-dose naltrexone might decrease the abuse liability of oxycodone (OXY) in humans. This double-blind, placebo-controlled study systematically examined the subjective and physiological effects of combining oral OXY and ultra-low NTX doses in 14 experienced opioid abusers. Seven acute drug conditions given at least 5 days apart were compared in a within-subject crossover design: placebo, OXY 20 mg, OXY 40 mg, plus each of the active OXY doses combined with 0.0001 and 0.001 mg NTX. The methods were sensitive to detecting opioid effects on abuse liability indices, with significant differences between all OXY conditions and placebo as well as between 20 and 40 mg OXY doses on positive subjective ratings (e.g., "I feel a good drug effect" or "I like the drug"), on observer- and participant-rated opioid agonist effects, and on a drug-versus-money value rating. There were no significant differences or evident trends associated with the addition of either NTX dose on any abuse liability indices. The addition of ultra-low-dose NTX to OXY did not decrease abuse liability of acutely administered OXY in experienced opioid abusers.

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

NASA Astrophysics Data System (ADS)

Hajdas, Wojtek; Mrigakshi, Alankrita; Xiao, Hualin

2017-04-01

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

Responding for sucrose and wheel-running reinforcement: effect of D-amphetamine.

PubMed

Belke, T W; Oldford, A C; Forgie, M Y; Beye, J A

2005-07-01

The present study assessed the effect of D-amphetamine on responding maintained by wheel-running and sucrose reinforcement. Six male albino Wistar rats were placed in running wheels and exposed to a fixed-interval 30-s schedule that produced either a drop of 5% sucrose solution or the opportunity to run for 15 s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. Doses of 0.25, 0.5, 1.0, 1.5, and 3.0 mg/kg D-amphetamine were administered by i.p. injection 20 min prior to a session. As the dose increased, index of curvature values decreased toward zero and rate-dependency plots revealed increases in lower rates early in the interval and decreases in higher rates toward the end of the interval. Effects were similar in the presence of both stimuli. However, an analysis of post-reinforcement pauses and local response rates broken down by transitions revealed a differential effect. As the dose increased, local response rates following a wheel-running reinforcer were affected more than those following a sucrose reinforcer.

Effects of 100MeV protons delivered at 0.5 or 1cGy/min on the in vivo induction of early and delayed chromosomal damage.

PubMed

Rithidech, Kanokporn Noy; Honikel, Louise M; Reungpatthanaphong, Paiboon; Tungjai, Montree; Golightly, Marc; Whorton, Elbert B

2013-08-30

Little is known about in vivo cytogenetic effects of protons delivered at the dose and dose rates encountered in space. We determined the effects of 100MeV protons, one of the most abundant type of protons produced during solar particle events (SPE), on the induction of chromosome aberrations (CAs) in bone marrow (BM) cells collected at early (3 and 24h) and late (6 months) time-points from groups of BALB/cJ mice (a known radiosensitive strain) exposed whole-body to 0 (sham-controls), 0.5, or 1.0Gy of 100MeV protons, delivered at 0.5 or 1.0cGy/min. These doses and dose-rates are comparable to those produced during SPE events. Additionally, groups of mice were exposed to 0 or 1Gy of (137)Cs γ rays (delivered at 1cGy/min) as a reference radiation. The kinetics of formation/reduction of gamma-histone 2-AX (γH2AX) were determined in BM cells collected at 1.5, 3, and 24h post-irradiation to assess the early-response. There were five mice per treatment-group per harvest-time. Our data indicated that the kinetics of γH2AX formation/reduction differed, depending on the dose and dose rate of protons. Highly significant numbers of abnormal cells and chromatid breaks (p<0.01), related to those in sham-control groups, were detected in BM cells collected at each time-point, regardless of dose or dose-rate. The finding of significant increases in the frequencies of delayed non-clonal and clonal CAs in BM cells collected at a late time-point from exposed mice suggested that 0.5 or 1Gy of 100MeV protons is capable of inducing genomic instability in BM cells. However, the extent of effects induced by these two low dose rates was comparable. Further, the results showed that the in vivo cytogenetic effects induced by 1Gy of 100MeV protons or (137)Cs γ rays (delivered at 1cGy/min) were similar. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Thecua, Elise; Lecomte, Fabienne; Vicentini, Claire; Abi-Rached, Henry; Mortier, Laurent; Mordon, Serge

2018-04-18

Topical photodynamic therapy is an established treatment modality for various dermatological conditions, including actinic keratosis. In Europe, the approved protocols for photodynamic therapy of actinic keratosis involve irradiation with either an Aktilite CL 128 lamp or daylight, whereas irradiation with the Blu-U illuminator is approved in the United States. Many other protocols using irradiation by a variety of light sources are also clinically efficient. This paper aims to compare 10 different protocols with clinically proven efficacy for photodynamic therapy of actinic keratosis and the available spectral irradiance of the light source. Effective irradiance, effective light dose, and local damage are compared. We also investigate whether there is an association between the complete response rate at 3 months and the effective light dose or local damage. The effective irradiance, also referred to as protoporphyrin IX-weighted irradiance, is obtained by integrating the spectral irradiance weighted by the normalized absorption spectrum of protoporphyrin IX over the wavelength. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose. Local damage, defined as the total cumulative singlet oxygen molecules produced during treatment, is estimated using mathematical modeling of the photodynamic therapy process. This modeling is based on an iterative procedure taking into account the spatial and temporal variations in the protoporphyrin IX absorption spectrum during treatment. The protocol for daylight photodynamic therapy on a clear sunny day, the protocol for daylight photodynamic therapy on an overcast day, the photodynamic therapy protocol for a white LED lamp for operating rooms and the photodynamic therapy protocol for the Blu-U illuminator perform better than the six other protocols-all involving red light illumination-in terms of both effective light dose and local damage. However, no association between the complete response rate at 3 months and the effective light dose or local damage was found. Protocols that achieve high complete response rates at 3 months and low pain scores should be preferred regardless of the effective light dose and local damage. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Observation of dose-rate dependence in a Fricke dosimeter irradiated at low dose rates with monoenergetic X-rays.

PubMed

O'Leary, Mel; Boscolo, Daria; Breslin, Nicole; Brown, Jeremy M C; Dolbnya, Igor P; Emerson, Chris; Figueira, Catarina; Fox, Oliver J L; Grimes, David Robert; Ivosev, Vladimir; Kleppe, Annette K; McCulloch, Aaron; Pape, Ian; Polin, Chris; Wardlow, Nathan; Currell, Fred J

2018-03-16

Absolute measurements of the radiolytic yield of Fe3+ in a ferrous sulphate dosimeter formulation (6 mM Fe2+), with a 20 keV x-ray monoenergetic beam, are reported. Dose-rate suppression of the radiolytic yield was observed at dose rates lower than and different in nature to those previously reported with x-rays. We present evidence that this effect is most likely to be due to recombination of free radicals radiolytically produced from water. The method used to make these measurements is also new and it provides radiolytic yields which are directly traceable to the SI standards system. The data presented provides new and exacting tests of radiation chemistry codes.

Effectiveness of previous mumps vaccination during a summer camp outbreak.

PubMed

Schaffzin, Joshua K; Pollock, Lynn; Schulte, Cynthia; Henry, Kyle; Dayan, Gustavo; Blog, Debra; Smith, Perry

2007-10-01

Mumps is a vaccine-preventable disease that may cause outbreaks. In July 2005, an outbreak of mumps occurred during a children's summer camp in upstate New York. An investigation was initiated to describe the cases and evaluate vaccine effectiveness. A retrospective cohort study was conducted among 541 children from the United States and abroad who attended a 1- or 2-month overnight summer camp. Patients with mumps were interviewed; serologic analysis was conducted for 6 case patients. Vaccine effectiveness was calculated by retrospective review of immunization records for 507 attendees who were eligible for vaccination and had verified immunization history. Thirty-one camp attendees were identified as having mumps (attack rate: 5.7%); 5 (83%) of 6 patients tested had positivity for mumps immunoglobulin M. Of the 507 participants (including 29 patients) with available immunization history, 440 (including 16 [87%] patients) were 2-dose recipients of mumps vaccine (attack rate: 3.6%); 46 participants (including 4 [9%] patients) were 1-dose recipients (attack rate: 8.7%); and 21 (including 9 [4%] patients) were unvaccinated (attack rate: 42.9%). Vaccine effectiveness was 92% for 2 doses and 80% for 1 dose. Outbreaks of mumps in settings such as summer camps can occur despite high vaccination rates. Vaccine effectiveness for 2 mumps vaccinations was greater than vaccine effectiveness for 1 mumps vaccination. Therefore, recommendation of 2 mumps vaccinations for summer camp participants continues to be appropriate. Control of mumps disease relies on broad vaccination coupled with correct clinical diagnosis and strict control measures.

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

PubMed

Li, Gang; Xu, Jiayun; Zhang, Jie

2015-01-01

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

Dose assessment of digital tomosynthesis in pediatric imaging

NASA Astrophysics Data System (ADS)

Gislason, Amber; Elbakri, Idris A.; Reed, Martin

2009-02-01

We investigated the potential for digital tomosynthesis (DT) to reduce pediatric x-ray dose while maintaining image quality. We utilized the DT feature (VolumeRadTM) on the GE DefiniumTM 8000 flat panel system installed in the Winnipeg Children's Hospital. Facial bones, cervical spine, thoracic spine, and knee of children aged 5, 10, and 15 years were represented by acrylic phantoms for DT dose measurements. Effective dose was estimated for DT and for corresponding digital radiography (DR) and computed tomography (CT) patient image sets. Anthropomorphic phantoms of selected body parts were imaged by DR, DT, and CT. Pediatric radiologists rated visualization of selected anatomic features in these images. Dose and image quality comparisons between DR, DT, and CT determined the usefulness of tomosynthesis for pediatric imaging. CT effective dose was highest; total DR effective dose was not always lowest - depending how many projections were in the DR image set. For the cervical spine, DT dose was close to and occasionally lower than DR dose. Expert radiologists rated visibility of the central facial complex in a skull phantom as better than DR and comparable to CT. Digital tomosynthesis has a significantly lower dose than CT. This study has demonstrated DT shows promise to replace CT for some facial bones and spinal diagnoses. Other clinical applications will be evaluated in the future.

Assessment of the point-source method for estimating dose rates to members of the public from exposure to patients with 131I thyroid treatment

DOE PAGES

Dewji, Shaheen Azim; Bellamy, Michael B.; Hertel, Nolan E.; ...

2015-09-01

The U.S. Nuclear Regulatory Commission (USNRC) initiated a contract with Oak Ridge National Laboratory (ORNL) to calculate radiation dose rates to members of the public that may result from exposure to patients recently administered iodine-131 ( 131I) as part of medical therapy. The main purpose was to compare dose rate estimates based on a point source and target with values derived from more realistic simulations that considered the time-dependent distribution of 131I in the patient and attenuation of emitted photons by the patient’s tissues. The external dose rate estimates were derived using Monte Carlo methods and two representations of themore » Phantom with Movable Arms and Legs, previously developed by ORNL and the USNRC, to model the patient and a nearby member of the public. Dose rates to tissues and effective dose rates were calculated for distances ranging from 10 to 300 cm between the phantoms and compared to estimates based on the point-source method, as well as to results of previous studies that estimated exposure from 131I patients. The point-source method overestimates dose rates to members of the public in very close proximity to an 131I patient but is a broadly accurate method of dose rate estimation at separation distances of 300 cm or more at times closer to administration.« less

Individual differences in the reinforcing and punishing effects of nicotine in rhesus monkeys.

PubMed

Koffarnus, Mikhail N; Winger, Gail

2015-07-01

The relatively weak reinforcing effects of nicotine in experimental studies have been attributed to possible aversive effects or the need to space nicotine administrations over time to expose reinforcing effects. This study was designed to determine if the response-maintaining effects of nicotine are increased when availability is spaced through time, and whether nicotine is an effective punisher of remifentanil-maintained responding. Compared to a cocaine reference dose, nicotine dose and timeout (TO) value were varied in eight rhesus monkeys responding for intravenous (i.v.) nicotine on varying fixed-ratio (FR) schedules of reinforcement.The aversive effects of nicotine were evaluated in four animals choosing between a standard dose of remifentanil alone or in combination with one of several doses of nicotine. In three of eight self-administration monkeys, 0.01 mg/kg/inj nicotine did not maintain responding at any FR value. In the other five animals, nicotine-maintained response rates increased with either FR or TO values to a certain point, and then slowed. Maximum nicotine-maintained response rates were much slower than those maintained by cocaine, and demand for nicotine was less than demand for cocaine. Nicotine was an effective punisher of remifentanil-maintained responding at doses ranging from 0.01 to 0.3 mg/kg/inj. Lower punishing dose seemed to be related to the absence of reinforcing effects within subject. There are an order of magnitude individual differences in sensitivity to both the reinforcing and punishing effects of nicotine, and this drug may be unique in being a weak positive reinforcer in small doses and aversive in large doses.

Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential

PubMed Central

Reissig, Chad J.; Harrison, Joseph A.; Carter, Lawrence P.; Griffiths, Roland R.

2014-01-01

Rationale Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. Objectives This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Methods Placebo, inhaled alprazolam (0.5, 1, 2 mg), and oral alprazolam (1, 2, 4 mg) were administered under double-blind, double-dummy conditions using a cross-over design in 14 healthy participants with histories of drug abuse. Participant and observer ratings, and behavioral and cognitive performance measures were assessed repeatedly during 9 hour sessions. Results Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 minutes after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., “drug liking”) were similar across the two routes. On other measures (e.g., sedation and performance) the routes were equipotent. Conclusions The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low. PMID:25199955

Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential.

PubMed

Reissig, Chad J; Harrison, Joseph A; Carter, Lawrence P; Griffiths, Roland R

2015-03-01

Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Placebo, inhaled alprazolam (0.5, 1, and 2 mg), and oral alprazolam (1, 2, and 4 mg) were administered under double-blind, double-dummy conditions using a crossover design in 14 healthy participants with histories of drug abuse. Participant and observer ratings and behavioral and cognitive performance measures were assessed repeatedly during 9-h sessions. Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer-lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 min after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose-response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., "drug liking") were similar across the two routes. On other measures (e.g., sedation and performance), the routes were equipotent. The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low.

Evidence for the changing regimens of acetylcysteine.

PubMed

Chiew, Angela L; Isbister, Geoffrey K; Duffull, Stephen B; Buckley, Nicholas A

2016-03-01

Paracetamol overdose prior to the introduction of acetylcysteine was associated with significant morbidity. Acetylcysteine is now the mainstay of treatment for paracetamol poisoning and has effectively reduced rates of hepatotoxicity and death. The current three-bag intravenous regimen with an initial high loading dose was empirically derived four decades ago and has not changed since. This regimen is associated with a high rate of adverse effects due mainly to the high initial peak acetylcysteine concentration. Furthermore, there are concerns that the acetylcysteine concentration is not adequate for 'massive' overdoses and that the dose and duration may need to be altered. Various novel regimens have been proposed, looking to address these issues. Many of these modified regimens aim to decrease the rate of adverse reactions by slowing the loading dose and thereby decrease the peak concentration. We used a published population pharmacokinetic model of acetylcysteine to simulate these modified regimens. We determined mean peak and 20 h acetylcysteine concentrations and area under the under the plasma concentration-time curve to compare these regimens. Those regimens that resulted in a lower peak acetylcysteine concentration have been shown in studies to have a lower rate of adverse events. However, these studies were too small to show whether they are as effective as the traditional regimen. Further research is still needed to determine the optimum dose and duration of acetylcysteine that results in the fewest side-effects and treatment failures. Indeed, a more patient-tailored approach might be required, whereby the dose and duration are altered depending on the paracetamol dose ingested or paracetamol concentrations. © 2015 The British Pharmacological Society.

Toward an ozone standard to protect vegetation based on effective dose: A review of deposition resistances and a possible metric

Treesearch

W. J. Massman

2004-01-01

Present air quality standards to protect vegetation from ozone are based on measured concentrations (i.e., exposure) rather than on plant uptake rates (or dose). Some familiar cumulative exposure-based indices include SUM06, AOT40, and W126. However, plant injury is more closely related to dose, or more appropriately to effective dose, than to exposure. This study...

Some cosmic radiation dose measurements aboard flights connecting Zagreb Airport.

PubMed

Vuković, B; Radolić, V; Lisjak, I; Vekić, B; Poje, M; Planinić, J

2008-02-01

When primary particles from space, mainly protons, enter the atmosphere, they produce interactions with air nuclei, and cosmic-ray showers are induced. The radiation field at aircraft altitude is complex, with different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard A320 and ATR40 aircraft was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter; the neutron dose was measured with the neutron dosimeter consisted of LR-115 track detector and boron foil BN-1 or 10B converter. The estimated occupational effective dose for the aircraft crew (A320) working 500 h per year was 1.64 mSv. Another experiment was performed at the flights Zagreb-Paris-Buenos Aires and reversely, when one measured non-neutron cosmic radiation dose; for 26.7 h of flight, the MINI 6100 dosimeter gave an average dose rate of 2.3 microSv/h and the TLD dosimeter registered the dose equivalent of 75 microSv or the average dose rate of 2.7 microSv/h; the neutron dosimeter gave the dose rate of 2.4 microSv/h. In the same month, February 2005, a traveling to Japan (24-h-flight: Zagreb-Frankfurt-Tokyo and reversely) and the TLD-100 measurement showed the average dose rate of 2.4microSv/h; the neutron dosimeter gave the dose rate of 2.5 microSv/h. Comparing dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level, we could conclude that the neutron component carried about 50% of the total dose, that was near other known data.

Impact of gamma radiation on the eruption rate of rat incisors

NASA Astrophysics Data System (ADS)

El-Faramawy, Nabil; El-Haddad, Khaled; Ali, Mohamed; Talaat, Mona

2015-09-01

The present work aims to test the effect of gamma radiation on the rate of eruption of rat incisors. One hundred and five adult male albino rats were used and irradiated at different gamma doses. The effects of irradiation were investigated by numerical measurements of eruption rate, histological investigation using light microscope and spectral analysis using Fourier Transform Infra-Red (FTIR). No detectable changes were observed in the groups with smaller radiation doses. There was a significant decrease in the eruption rate starting from the 4 Gy radiation dose. The observation of histological sections revealed disturbance in cellular elements responsible for eruption as well as periodontal disturbance in the samples irradiated with 4 and 6 Gy. FTIR Spectroscopy of control group and the group irradiated by 0.5 Gy showed similar absorption bands with minor differences. However, samples irradiated by 1 Gy showed significant changes in both molecular structure and conformation related to carbonates and hydroxyl groups. From the previous results, it could be concluded that gamma irradiation negatively affects the eruption rate of the rat incisors especially with higher doses.

Effects of an injectable trace mineral supplement on first-service conception rate of dairy cows.

PubMed

Vanegas, J A; Reynolds, J; Atwill, E R

2004-11-01

A total of 825 dairy cows from a commercial dairy farm in central California were used to evaluate effects of one or 2 doses of an injectable trace mineral supplement containing 20 mg/mL of zinc, 20 mg/mL of manganese, 5 mg/mL of selenium, and 10 mg/mL of copper on first-service conception rate. Cows were randomly allocated into treatment or control group to either a single dose (experiment 1) or a double dose (experiment 2) of injected supplement. Allocation was based on days in lactation for experiment 1 and the length of gestation periods for experiment 2. In experiment 1, cows 38 to 45 d in lactation (n = 190) received a single dose of 5 mL of injected supplement. Similar cows were used as controls (n = 227). In experiment 2, cows and pregnant heifers received an initial injection of 5 mL of the mineral supplement from 2 to 3 wk precalving (n = 186). An equal dose was repeated 38 to 45 d in lactation. A similar group of cows and pregnant heifers served as controls for experiment 2 (n = 222). Health and reproductive events postcalving were recorded. In experiment 1, the odds of first-service conception were not significantly different for cows receiving a one-dose regimen of minerals compared with untreated control cows; conception rates were 26.8 and 27.5% for experiment 1 treatment and control groups, respectively. In experiment 1, the odds of first-service conception were significantly lower (odds ratio = 0.66) for cows and heifers given the 2-dose regimen of minerals compared with untreated controls; overall conception rates were 21.5 and 31.5% for experiment 2 treatment and control groups, respectively. In this intensively managed dairy herd, a single dose of injected trace minerals before breeding had no beneficial effects on first-service conception rate. However, dairy cows receiving a dose of trace minerals before calving and another dose before breeding had lower conception at first service.

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

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

Ahmed, S; Ahmed, S; Ahmed, F

2016-06-15

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

Radiation Parameters of High Dose Rate Iridium -192 Sources

NASA Astrophysics Data System (ADS)

Podgorsak, Matthew B.

A lack of physical data for high dose rate (HDR) Ir-192 sources has necessitated the use of basic radiation parameters measured with low dose rate (LDR) Ir-192 seeds and ribbons in HDR dosimetry calculations. A rigorous examination of the radiation parameters of several HDR Ir-192 sources has shown that this extension of physical data from LDR to HDR Ir-192 may be inaccurate. Uncertainty in any of the basic radiation parameters used in dosimetry calculations compromises the accuracy of the calculated dose distribution and the subsequent dose delivery. Dose errors of up to 0.3%, 6%, and 2% can result from the use of currently accepted values for the half-life, exposure rate constant, and dose buildup effect, respectively. Since an accuracy of 5% in the delivered dose is essential to prevent severe complications or tumor regrowth, the use of basic physical constants with uncertainties approaching 6% is unacceptable. A systematic evaluation of the pertinent radiation parameters contributes to a reduction in the overall uncertainty in HDR Ir-192 dose delivery. Moreover, the results of the studies described in this thesis contribute significantly to the establishment of standardized numerical values to be used in HDR Ir-192 dosimetry calculations.

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

PubMed Central

Rejas, Danny

2017-01-01

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

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

PubMed

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

2017-10-01

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

Long-term effects of ionizing radiation after the Chernobyl accident: Possible contribution of historic dose.

PubMed

Omar-Nazir, Laila; Shi, Xiaopei; Moller, Anders; Mousseau, Timothy; Byun, Soohyun; Hancock, Samuel; Seymour, Colin; Mothersill, Carmel

2018-08-01

The impact of the Chernobyl NPP accident on the environment is documented to be greater than expected, with higher mutation rates than expected at the current, chronic low dose rate. In this paper we suggest that the historic acute exposure and resulting non-targeted effects (NTE) such as delayed mutations and genomic instability could account at least in part for currently measured mutation rates and provide an initial test of this concept. Data from Møller and Mousseau on the phenotypic mutation rates of Chernobyl birds 9-11 generations post the Chernobyl accident were used and the reconstructed dose response for mutations was compared with delayed reproductive death dose responses (as a measure of genomic instability) in cell cultures exposed to a similar range of doses. The dose to birds present during the Chernobyl NPP accident was reconstructed through the external pathway due to Cs-137 with an estimate of the uncertainty associated with such reconstruction. The percentage of Chernobyl birds several generations after the accident without mutations followed the general shape of the clonogenic survival percentage of the progeny of irradiated cells, and it plateaued at low doses. This is the expected result if NTE of radiation are involved. We suggest therefore, that NTE induced by the historic dose may play a role in generating mutations in progeny many generations following the initial disaster. Copyright © 2018 Elsevier Inc. All rights reserved.

Cosmic radiation dose in aircraft--a neutron track etch detector.

PubMed

Vuković, B; Radolić, V; Miklavcić, I; Poje, M; Varga, M; Planinić, J

2007-01-01

Cosmic radiation bombards us at high altitude by ionizing particles. The radiation environment is a complex mixture of charged particles of solar and galactic origin, as well as of secondary particles produced in interaction of the galactic cosmic particles with the nuclei of atmosphere of the Earth. The radiation field at aircraft altitude consists of different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard ATR 42 and A 320 aircrafts (flight level of 8 and 11 km, respectively) was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter. The estimated occupational effective dose for the aircraft crew (A 320) working 500 h per year was 1.64 mSv. Other experiments, or dose rate measurements with the neutron dosimeter, consisting of LR-115 track detector and boron foil BN-1 or 10B converter, were performed on five intercontinental flights. Comparison of the dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level showed that the neutron component carried about 50% of the total dose. The dose rate measurements on the flights from the Middle Europe to the South and Middle America, then to Korea and Japan, showed that the flights over or near the equator region carried less dose rate; this was in accordance with the known geomagnetic latitude effect.

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

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.

Radionuclide concentrations in soil and lifetime cancer risk due to gamma radioactivity in Kirklareli, Turkey.

PubMed

Taskin, H; Karavus, M; Ay, P; Topuzoglu, A; Hidiroglu, S; Karahan, G

2009-01-01

The objective of this study is to evaluate and map soil radionuclides' activity concentrations and environmental outdoor gamma dose rates (terrestrial and cosmic) in Kirklareli, Turkey. The excess lifetime cancer risks are also calculated. Outdoor gamma dose rates were determined in 230 sampling stations and soil samples were taken from 177 locations. The coordinates of the readings were determined by the Global Positioning System (GPS). The outdoor gamma dose rates were determined by Eberline smart portable device (ESP-2) and measurements were taken in air for two minutes at 1m from the ground. The average outdoor gamma dose rate was 118+/-34nGyh(-1). Annual effective gamma dose of Kirklareli was 144microSv and the excess lifetime cancer risk of 5.0x10(-4). Soil samples were analyzed by gamma spectroscopy. The average 226Ra, 238U, 232Th, 137Cs, and 40K activities were 37+/-18Bqkg(-1), 28+/-13Bqkg(-1), 40+/-18Bqkg(-1), 8+/-5Bqkg(-1) and 667+/-281Bqkg(-1), respectively. The average soil radionuclides' concentrations of Kirklareli were within the worldwide range although some extreme values had been determined. Annual effective gamma doses and the excess lifetime risks of cancer were higher than the world's average.

SU-E-J-169: The Dosimetric and Temporal Effects of Respiratory-Gated Radiation Therapy in Lung Cancer Patients

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

Rouabhi, O; Gross, B; Xia, J

2015-06-15

Purpose: To evaluate the dosimetric and temporal effects of high dose rate treatment mode for respiratory-gated radiation therapy in lung cancer patients. Methods: Treatment plans from five lung cancer patients (3 nongated (Group 1), 2 gated at 80EX-80IN (Group 2)) were retrospectively evaluated. The maximum tumor motions range from 6–12 mm. Using the same planning criteria, four new treatment plans, corresponding to four gating windows (20EX–20IN, 40EX–40IN, 60EX–60IN, and 80EX–80IN), were generated for each patient. Mean tumor dose (MTD), mean lung dose (MLD), and lung V20 were used to assess the dosimetric effects. A MATLAB algorithm was developed to computemore » treatment time by considering gantry rotation time, time to position collimator leaves, dose delivery time (scaled relative to the gating window), and communication overhead. Treatment delivery time for each plan was estimated using a 500 MU/min dose rate for the original plans and a 1500 MU/min dose rate for the gated plans. Results: Differences in MTD were less than 1Gy across plans for all five patients. MLD and lung V20 were on average reduced between −16.1% to −6.0% and −20.0% to −7.2%, respectively for non-gated plans when compared with the corresponding gated plans, and between − 5.8% to −4.2% and −7.0% to −5.4%, respectively for plans originally gated at 80EX–80IN when compared with the corresponding 20EX-20IN to 60EX– 60IN gated plans. Treatment delivery times of gated plans using high dose rate were reduced on average between −19.7% (−1.9min) to −27.2% (−2.7min) for originally non-gated plans and −15.6% (−0.9min) to −20.3% (−1.2min) for originally 80EX-80IN gated plans. Conclusion: Respiratory-gated radiation therapy in lung cancer patients can reduce lung toxicity, while maintaining tumor dose. Using a gated high-dose-rate treatment, delivery time comparable to non-gated normal-dose-rate treatment can be achieved. This research is supported by Siemens Medical Solutions USA, Inc.« less

Evaluation of indoor radon equilibrium factor using CFD modeling and resulting annual effective dose

NASA Astrophysics Data System (ADS)

Rabi, R.; Oufni, L.

2018-04-01

The equilibrium factor is an important parameter for reasonably estimating the population dose from radon. However, the equilibrium factor value depended mainly on the ventilation rate and the meteorological factors. Therefore, this study focuses on investigating numerically the influence of the ventilation rate, temperature and humidity on equilibrium factor between radon and its progeny. The numerical results showed that ventilation rate, temperature and humidity have significant impacts on indoor equilibrium factor. The variations of equilibrium factor with the ventilation, temperature and relative humidity are discussed. Moreover, the committed equivalent doses due to 218Po and 214Po radon short-lived progeny were evaluated in different tissues of the respiratory tract of the members of the public from the inhalation of indoor air. The annual effective dose due to radon short lived progeny from the inhalation of indoor air by the members of the public was investigated.

Impact of the vaginal applicator and dummy pellets on the dosimetry parameters of Cs-137 brachytherapy source.

PubMed

Sina, Sedigheh; Faghihi, Reza; Meigooni, Ali S; Mehdizadeh, Simin; Mosleh Shirazi, M Amin; Zehtabian, Mehdi

2011-05-19

In this study, dose rate distribution around a spherical 137Cs pellet source, from a low-dose-rate (LDR) Selectron remote afterloading system used in gynecological brachytherapy, has been determined using experimental and Monte Carlo simulation techniques. Monte Carlo simulations were performed using MCNP4C code, for a single pellet source in water medium and Plexiglas, and measurements were performed in Plexiglas phantom material using LiF TLD chips. Absolute dose rate distribution and the dosimetric parameters, such as dose rate constant, radial dose functions, and anisotropy functions, were obtained for a single pellet source. In order to investigate the effect of the applicator and surrounding pellets on dosimetric parameters of the source, the simulations were repeated for six different arrangements with a single active source and five non-active pellets inside central metallic tubing of a vaginal cylindrical applicator. In commercial treatment planning systems (TPS), the attenuation effects of the applicator and inactive spacers on total dose are neglected. The results indicate that this effect could lead to overestimation of the calculated F(r,θ), by up to 7% along the longitudinal axis of the applicator, especially beyond the applicator tip. According to the results obtained in this study, in a real situation in treatment of patients using cylindrical vaginal applicator and using several active pellets, there will be a large discrepancy between the result of superposition and Monte Carlo simulations.

Comparison of monoenergetic photon organ dose rate coefficients for stylized and voxel phantoms submerged in air

DOE PAGES

Bellamy, Michael B.; Hiller, Mauritius M.; Dewji, Shaheen A.; ...

2016-02-01

As part of a broader effort to calculate effective dose rate coefficients for external exposure to photons and electrons emitted by radionuclides distributed in air, soil or water, age-specific stylized phantoms have been employed to determine dose coefficients relating dose rate to organs and tissues in the body. In this article, dose rate coefficients computed using the International Commission on Radiological Protection reference adult male voxel phantom are compared with values computed using the Oak Ridge National Laboratory adult male stylized phantom in an air submersion exposure geometry. Monte Carlo calculations for both phantoms were performed for monoenergetic source photonsmore » in the range of 30 keV to 5 MeV. Furthermore, these calculations largely result in differences under 10 % for photon energies above 50 keV, and it can be expected that both models show comparable results for the environmental sources of radionuclides.« less

Comparison of monoenergetic photon organ dose rate coefficients for stylized and voxel phantoms submerged in air

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

Bellamy, Michael B.; Hiller, Mauritius M.; Dewji, Shaheen A.

As part of a broader effort to calculate effective dose rate coefficients for external exposure to photons and electrons emitted by radionuclides distributed in air, soil or water, age-specific stylized phantoms have been employed to determine dose coefficients relating dose rate to organs and tissues in the body. In this article, dose rate coefficients computed using the International Commission on Radiological Protection reference adult male voxel phantom are compared with values computed using the Oak Ridge National Laboratory adult male stylized phantom in an air submersion exposure geometry. Monte Carlo calculations for both phantoms were performed for monoenergetic source photonsmore » in the range of 30 keV to 5 MeV. Furthermore, these calculations largely result in differences under 10 % for photon energies above 50 keV, and it can be expected that both models show comparable results for the environmental sources of radionuclides.« less

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

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

PubMed

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

2017-02-01

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

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.

Effects of sublethal fenitrothion ingestion on cholinesterase inhibition, standard metabolism, thermal preference, and prey-capture ability in the Australian central bearded dragon (Pogona vitticeps, Agamidae).

PubMed

Bain, David; Buttemer, William A; Astheimer, Lee; Fildes, Karen; Hooper, Michael J

2004-01-01

The central bearded dragon (Pogona vitticeps) is a medium-sized lizard that is common in semiarid habitats in Australia and that potentially is at risk of fenitrothion exposure from use of the chemical in plague locust control. We examined the effects of single sublethal doses of this organophosphate (OP; low dose = 2.0 mg/kg; high dose = 20 mg/kg; control = vehicle alone) on lizard thermal preference, standard metabolic rate, and prey-capture ability. We also measured activities of plasma total cholinesterase (ChE) and acetylcholinesterase before and at 0, 2, 8, 24, 120, and 504 h after OP dosing. Predose plasma total ChE activity differed significantly between sexes and averaged 0.66 +/- 0.06 and 0.45 +/- 0.06 micromol/min/ml for males and females, respectively. Approximately 75% of total ChE activity was attributable to butyrylcholinesterase. Peak ChE inhibition reached 19% 2 h after OP ingestion in the low-dose group, and 68% 8 h after ingestion in high-dose animals. Neither OP doses significantly affected diurnal body temperature, standard metabolic rate, or feeding rate. Plasma total ChE levels remained substantially depressed up to 21 d after dosing in the high-dose group, making this species a useful long-term biomonitor of OP exposure in its habitat.

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

PubMed

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

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.

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

PubMed

El-Jaby, Samy

2016-06-01

A recent paper published in Life Sciences in Space Research (El-Jaby and Richardson, 2015) presented estimates of the secondary neutron ambient and effective dose equivalent rates, in air, from surface altitudes up to suborbital altitudes and low Earth orbit. These estimates were based on MCNPX (LANL, 2011) (Monte Carlo N-Particle eXtended) radiation transport simulations of galactic cosmic radiation passing through Earth's atmosphere. During a recent review of the input decks used for these simulations, a systematic error was discovered that is addressed here. After reassessment, the neutron ambient and effective dose equivalent rates estimated are found to be 10 to 15% different, though, the essence of the conclusions drawn remains unchanged. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Temperature dependency of the repair of sublethal damage in cultured fish cells

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

Mitani, H.; Egami, N.

1984-01-01

Established culture fish cells, CAF-MMMI, derived form the goldfish, Carassium auratus, were able to grow and form colonies over a temperature range from 20 to 33/sup 0/ C. While the growth rate of these cells was dependent on incubation temperature, colony formation had no effect on cell survival after ..gamma.. irradiation at high dose rates. The lethal effect of ..gamma.. rays was decreased at low dose rates at 20-33/sup 0/ C, but not at 6/sup 0/ C. Similarly, split-dose experiments showed that recovery from sublethal damage occurred at the higher temperatures, but not at 6/sup 0/ C. These data aremore » consistent with the in vivo data on the effect of temperature on the radiosensitivity and repair of sublethal damage reported previously for live fish.« less

Characterizing low dose and dose rate effects in rodent and human neural stem cells exposed to proton and gamma irradiation.

PubMed

Tseng, Bertrand P; Lan, Mary L; Tran, Katherine K; Acharya, Munjal M; Giedzinski, Erich; Limoli, Charles L

2013-01-01

Past work has shown that exposure to gamma rays and protons elicit a persistent oxidative stress in rodent and human neural stem cells (hNSCs). We have now adapted these studies to more realistic exposure scenarios in space, using lower doses and dose rates of these radiation modalities, to further elucidate the role of radiation-induced oxidative stress in these cells. Rodent neural stem and precursor cells grown as neurospheres and human neural stem cells grown as monolayers were subjected to acute and multi-dosing paradigms at differing dose rates and analyzed for changes in reactive oxygen species (ROS), reactive nitrogen species (RNS), nitric oxide and superoxide for 2 days after irradiation. While acute exposures led to significant changes in both cell types, hNSCs in particular, exhibited marked and significant elevations in radiation-induced oxidative stress. Elevated oxidative stress was more significant in hNSCs as opposed to their rodent counterparts, and hNSCs were significantly more sensitive to low dose exposures in terms of survival. Combinations of protons and γ-rays delivered as lower priming or higher challenge doses elicited radioadaptive changes that were associated with improved survival, but in general, only under conditions where the levels of reactive species were suppressed compared to cells irradiated acutely. Protective radioadaptive effects on survival were eliminated in the presence of the antioxidant N-acetylcysteine, suggesting further that radiation-induced oxidative stress could activate pro-survival signaling pathways that were sensitive to redox state. Data corroborates much of our past work and shows that low dose and dose rate exposures elicit significant changes in oxidative stress that have functional consequences on survival.

[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.

Amphetamine self-administration in light and moderate drinkers.

PubMed

Stanley, Matthew D; Poole, Mégan M; Stoops, William W; Rush, Craig R

2011-03-01

Light and moderate drinkers respond differently to the effects of abused drugs, including stimulants such as amphetamine. The purpose of this study was to determine whether light and moderate drinkers differ in their sensitivity to the reinforcing and subjective effects of d-amphetamine. We hypothesized that moderate drinkers (i.e., participants that reported consuming at least seven alcohol-containing beverages per week) would be more sensitive to the reinforcing and positive subject-rated effects of d-amphetamine than light drinkers. Data from four studies that employed similar d-amphetamine self-administration procedures and subject-rated drug-effect measures were included in the analysis. Light (n = 17) and moderate (n = 16) drinkers sampled placebo, low (8 to 10 mg), and high (16 to 20 mg) doses of oral d-amphetamine administered in eight capsules. Following sampling sessions, participants worked for a maximum of eight capsules, each containing 12.5% of the previously sampled dose, on a modified progressive-ratio schedule of reinforcement. Both active doses of d-amphetamine functioned as a reinforcer in the moderate drinkers, while only the high dose did so in the light drinkers. The moderate drinkers worked for significantly more capsules that contained the high dose of d-amphetamine than did the light drinkers. d-Amphetamine produced prototypical stimulant-like subjective effects (e.g., dose-dependent increases in ratings of Good Effects; Like Drug and Willing to Take Again). Moderate drinkers reported significantly greater subjective effects than the light drinkers. These results are consistent with those from previous laboratory experiments and suggest that moderate alcohol consumption may increase vulnerability to the abuse-related effects of stimulants. Copyright © 2010 by the Research Society on Alcoholism.

Estimation of external dose by car-borne survey in Kerala, India.

PubMed

Hosoda, Masahiro; Tokonami, Shinji; Omori, Yasutaka; Sahoo, Sarata Kumar; Akiba, Suminori; Sorimachi, Atsuyuki; Ishikawa, Tetsuo; Nair, Raghu Ram; Jayalekshmi, Padmavathy Amma; Sebastian, Paul; Iwaoka, Kazuki; Akata, Naofumi; Kudo, Hiromi

2015-01-01

A car-borne survey was carried out in Kerala, India to estimate external dose. Measurements were made with a 3-in × 3-in NaI(Tl) scintillation spectrometer from September 23 to 27, 2013. The routes were selected from 12 Panchayats in Karunagappally Taluk which were classified into high level, mid-level and low level high background radiation (HBR) areas. A heterogeneous distribution of air kerma rates was seen in the dose rate distribution map. The maximum air kerma rate, 2.1 μGy/h, was observed on a beach sand surface. 232Th activity concentration for the beach sand was higher than that for soil and grass surfaces, and the range of activity concentration was estimated to be 0.7-2.3 kBq/kg. The contribution of 232Th to air kerma rate was over 70% at the measurement points with values larger than 0.34 μGy/h. The maximum value of the annual effective dose in Karunagappally Taluk was observed around coastal areas, and it was estimated to be 13 mSv/y. More than 30% of all the annual effective doses obtained in this survey exceeded 1 mSv/y.

Dissociable effects of the noncompetitive NMDA receptor antagonists ketamine and MK-801 on intracranial self-stimulation in rats

PubMed Central

Hillhouse, Todd M.; Porter, Joseph H.; Negus, S. Stevens

2014-01-01

Rationale The noncompetitive NMDA antagonist ketamine produces rapid antidepressant effects in treatment-resistant patients suffering from major depressive and bipolar disorders. However, abuse liability is a concern. Objectives This study examined abuse-related effects of keta-mine using intracranial self-stimulation (ICSS) in rats. The higher-affinity NMDA antagonist MK-801 and the monoamine reuptake inhibitor cocaine were examined for comparison. Methods Male Sprague Dawley rats were implanted with electrodes targeting the medial forebrain bundle and trained to respond to brain stimulation under a frequency–rate ICSS procedure. The first experiment compared the potency and time course of ketamine (3.2–10.0 mg/kg) and MK-801 (0.032–0.32 mg/kg). The second experiment examined effects of repeated dosing with ketamine (3.2–20.0 mg/kg/day) and acute cocaine (10.0 mg/kg). Results Following acute administration, ketamine (3.2–10 mg/kg) produced only dose- and time-dependent depressions of ICSS and failed to produce an abuse-related facilitation of ICSS at any dose or pretreatment time. In contrast, MK-801 (0.032–0.32 mg/kg) produced a mixed profile of rate-increasing and rate-decreasing effects; ICSS facilitation was especially prominent at an intermediate dose of 0.18 mg/kg. Repeated dosing with ketamine produced dose-dependent tolerance to the rate-decreasing effects of ketamine (10.0 and 18.0 mg/kg) but failed to unmask expression of ICSS facilitation. Termination of ketamine treatment failed to produce withdrawal-associated decreases in ICSS. As reported previously, 10.0 mg/kg cocaine facilitated ICSS. Conclusions The dissociable effects of ketamine and MK-801 suggest differences in the pharmacology of these nominally similar NMDA antagonists. Failure of ketamine to facilitate ICSS contrasts with other evidence for the abuse liability of ketamine. PMID:24522331

Opioid antagonism of cannabinoid effects: differences between marijuana smokers and nonmarijuana smokers.

PubMed

Haney, Margaret

2007-06-01

In non-human animals, opioid antagonists block the reinforcing and discriminative-stimulus effects of Delta(9)-tetrahydrocannabinol (THC), while in human marijuana smokers, naltrexone (50 mg) enhances the reinforcing and subjective effects of THC. The objective of this study was to test a lower, more opioid-selective dose of naltrexone (12 mg) in combination with THC. The influence of marijuana-use history and sex was also investigated. Naltrexone (0, 12 mg) was administered 30 min before oral THC (0-40 mg) or methadone (0-10 mg) capsules, and subjective effects, task performance, pupillary diameter, and cardiovascular parameters were assessed in marijuana smoking (Study 1; n=22) and in nonmarijuana smoking (Study 2; n=21) men and women. The results show that in marijuana smokers, low-dose naltrexone blunted the intoxicating effects of a low THC dose (20 mg), while increasing ratings of anxiety at a higher THC dose (40 mg). In nonmarijuana smokers, low-dose naltrexone shifted THC's effects in the opposite direction, enhancing the intoxicating effects of a low THC dose (2.5 mg) and decreasing anxiety ratings following a high dose of THC (10 mg). There were no sex differences in these interactions, although among nonmarijuana smokers, men were more sensitive to the effects of THC alone than women. To conclude, a low, opioid-selective dose of naltrexone blunted THC intoxication in marijuana smokers, while in nonmarijuana smokers, naltrexone enhanced THC intoxication. These data demonstrate that the interaction between opioid antagonists and cannabinoid agonists varies as a function of marijuana use history.

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

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

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

Cost-effectiveness of hepatitis A vaccination in Indonesia.

PubMed

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

2014-01-01

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

Cost-effectiveness of hepatitis A vaccination in Indonesia

PubMed Central

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

2014-01-01

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

Organ and effective dose rate coefficients for submersion exposure in occupational settings

DOE PAGES

Veinot, K. G.; Y-12 National Security Complex, Oak Ridge, TN; Dewji, S. A.; ...

2017-08-24

External dose coefficients for environmental exposure scenarios are often computed using assumption on infinite or semi-infinite radiation sources. For example, in the case of a person standing on contaminated ground, the source is assumed to be distributed at a given depth (or between various depths) and extending outwards to an essentially infinite distance. In the case of exposure to contaminated air, the person is modeled as standing within a cloud of infinite, or semi-infinite, source distribution. However, these scenarios do not mimic common workplace environments where scatter off walls and ceilings may significantly alter the energy spectrum and dose coefficients.more » In this study, dose rate coefficients were calculated using the International Commission on Radiological Protection (ICRP) reference voxel phantoms positioned in rooms of three sizes representing an office, laboratory, and warehouse. For each room size calculations using the reference phantoms were performed for photons, electrons, and positrons as the source particles to derive mono-energetic dose rate coefficients. Since the voxel phantoms lack the resolution to perform dose calculations at the sensitive depth for the skin, a mathematical phantom was developed and calculations were performed in each room size with the three source particle types. Coefficients for the noble gas radionuclides of ICRP Publication 107 (e.g., Ne, Ar, Kr, Xe, and Rn) were generated by folding the corresponding photon, electron, and positron emissions over the mono-energetic dose rate coefficients. Finally, results indicate that the smaller room sizes have a significant impact on the dose rate per unit air concentration compared to the semi-infinite cloud case. For example, for Kr-85 the warehouse dose rate coefficient is 7% higher than the office dose rate coefficient while it is 71% higher for Xe-133.« less

Organ and effective dose rate coefficients for submersion exposure in occupational settings

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

Veinot, K. G.; Y-12 National Security Complex, Oak Ridge, TN; Dewji, S. A.

External dose coefficients for environmental exposure scenarios are often computed using assumption on infinite or semi-infinite radiation sources. For example, in the case of a person standing on contaminated ground, the source is assumed to be distributed at a given depth (or between various depths) and extending outwards to an essentially infinite distance. In the case of exposure to contaminated air, the person is modeled as standing within a cloud of infinite, or semi-infinite, source distribution. However, these scenarios do not mimic common workplace environments where scatter off walls and ceilings may significantly alter the energy spectrum and dose coefficients.more » In this study, dose rate coefficients were calculated using the International Commission on Radiological Protection (ICRP) reference voxel phantoms positioned in rooms of three sizes representing an office, laboratory, and warehouse. For each room size calculations using the reference phantoms were performed for photons, electrons, and positrons as the source particles to derive mono-energetic dose rate coefficients. Since the voxel phantoms lack the resolution to perform dose calculations at the sensitive depth for the skin, a mathematical phantom was developed and calculations were performed in each room size with the three source particle types. Coefficients for the noble gas radionuclides of ICRP Publication 107 (e.g., Ne, Ar, Kr, Xe, and Rn) were generated by folding the corresponding photon, electron, and positron emissions over the mono-energetic dose rate coefficients. Finally, results indicate that the smaller room sizes have a significant impact on the dose rate per unit air concentration compared to the semi-infinite cloud case. For example, for Kr-85 the warehouse dose rate coefficient is 7% higher than the office dose rate coefficient while it is 71% higher for Xe-133.« less

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

PubMed

Sakai, K

2018-01-01

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

Three-Dimensional Radiobiologic Dosimetry: Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging–Based Internal Dosimetry

PubMed Central

Prideaux, Andrew R.; Song, Hong; Hobbs, Robert F.; He, Bin; Frey, Eric C.; Ladenson, Paul W.; Wahl, Richard L.; Sgouros, George

2010-01-01

Phantom-based and patient-specific imaging-based dosimetry methodologies have traditionally yielded mean organ-absorbed doses or spatial dose distributions over tumors and normal organs. In this work, radiobiologic modeling is introduced to convert the spatial distribution of absorbed dose into biologically effective dose and equivalent uniform dose parameters. The methodology is illustrated using data from a thyroid cancer patient treated with radioiodine. Methods Three registered SPECT/CT scans were used to generate 3-dimensional images of radionuclide kinetics (clearance rate) and cumulated activity. The cumulated activity image and corresponding CT scan were provided as input into an EGSnrc-based Monte Carlo calculation: The cumulated activity image was used to define the distribution of decays, and an attenuation image derived from CT was used to define the corresponding spatial tissue density and composition distribution. The rate images were used to convert the spatial absorbed dose distribution to a biologically effective dose distribution, which was then used to estimate a single equivalent uniform dose for segmented volumes of interest. Equivalent uniform dose was also calculated from the absorbed dose distribution directly. Results We validate the method using simple models; compare the dose-volume histogram with a previously analyzed clinical case; and give the mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for an illustrative case of a pediatric thyroid cancer patient with diffuse lung metastases. The mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for the tumor were 57.7, 58.5, and 25.0 Gy, respectively. Corresponding values for normal lung tissue were 9.5, 9.8, and 8.3 Gy, respectively. Conclusion The analysis demonstrates the impact of radiobiologic modeling on response prediction. The 57% reduction in the equivalent dose value for the tumor reflects a high level of dose nonuniformity in the tumor and a corresponding reduced likelihood of achieving a tumor response. Such analyses are expected to be useful in treatment planning for radionuclide therapy. PMID:17504874

Discriminative-stimulus effects of zolpidem, triazolam, pentobarbital, and caffeine in zolpidem-trained humans.

PubMed

Rush, C R; Baker, R W; Rowlett, J K

2000-02-01

Six non-drug-abusing humans were trained to discriminate 15 mg zolpidem in the present experiment. After participants acquired discrimination, a range of doses of zolpidem (2.5-15.0 mg), triazolam (0.0625-0.3750 mg), pentobarbital (25-150 mg), caffeine (100-600 mg), and placebo were tested to determine whether they shared discriminative-stimulus effects with 15 mg zolpidem. The participant-rated and performance-impairing effects of zolpidem, triazolam, pentobarbital, and caffeine were assessed concurrently. Triazolam and pentobarbital dose dependently increased zolpidem-appropriate responding. Caffeine occasioned low levels of zolpidem-appropriate responding. Zolpidem, triazolam, and pentobarbital, but not caffeine, generally produced a similar constellation of participant-rated drug effects (e.g., increased scores for the Pentobarbital, Chlorpromazine, and Alcohol Group subscale on the Addiction Research Center Inventory) and dose dependently impaired performance. These results suggest that humans can reliably discriminate zolpidem. Despite its unique benzodiazepine-receptor binding profile, the discriminative-stimulus, participant-rated, and performance-impairing effects of zolpidem are similar to those of the barbiturates and benzodiazepines.

Subjective and physiological effects, and expired carbon monoxide concentrations in frequent and occasional cannabis smokers following smoked, vaporized, and oral cannabis administration.

PubMed

Newmeyer, Matthew N; Swortwood, Madeleine J; Abulseoud, Osama A; Huestis, Marilyn A

2017-06-01

Although smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. Few studies directly compare cannabis' subjective and physiological effects following multiple administration routes. Subjective and physiological effects, and expired carbon monoxide (CO) were evaluated in frequent and occasional cannabis users following placebo (0.001% Δ 9 -tetrahydrocannabinol [THC]), smoked, vaporized, and oral cannabis (6.9% THC, ∼54mg). Participants' subjective ratings were significantly elevated compared to placebo after smoking and vaporization, while only occasional smokers' ratings were significantly elevated compared to placebo after oral dosing. Frequent smokers' maximum ratings were significantly different between inhaled and oral routes, while no differences in occasional smokers' maximum ratings between active routes were observed. Additionally, heart rate increases above baseline 0.5h after smoking (mean 12.2bpm) and vaporization (10.7bpm), and at 1.5h (13.0bpm) and 3h (10.2bpm) after oral dosing were significantly greater than changes after placebo, with no differences between frequent and occasional smokers. Finally, smoking produced significantly increased expired CO concentrations 0.25-6h post-dose compared to vaporization. All participants had significant elevations in subjective effects after smoking and vaporization, but only occasional smokers after oral cannabis, indicating partial tolerance to subjective effects with frequent exposure. There were no differences in occasional smokers' maximum subjective ratings across the three active administration routes. Vaporized cannabis is an attractive alternative for medicinal administrations over smoking or oral routes; effects occur quickly and doses can be titrated with minimal CO exposure. These results have strong implications for safety and abuse liability assessments. Published by Elsevier B.V.

Effect of the dose of exogenous fibrolytic enzyme preparations on preingestive fiber hydrolysis, ruminal fermentation, and in vitro digestibility of bermudagrass haylage.

PubMed

Romero, J J; Zarate, M A; Adesogan, A T

2015-01-01

Our objectives were to evaluate the effects of the dose rates of 5 Trichoderma reesei and Aspergillus oryzae exogenous fibrolytic enzymes (EFE; 1A, 2A, 11C, 13D, and 15D) on in vitro digestibility, fermentation characteristics, and preingestive hydrolysis of bermudagrass haylage and to identify the optimal dose of each EFE for subsequent in vitro and in vivo studies. In experiment 1, EFE were diluted in citrate-phosphate buffer (pH 6) and applied in quadruplicate in each of 2 runs at 0× (control), 0.5×, 1×, 2×, and 3×; where 1× was the respective manufacturer-recommended dose (2.25, 2.25, 10, 15, and 15g of EFE/kg of dry matter). The suspension was incubated for 24h at 25°C and for a further 24h at 39°C after the addition of ruminal fluid. In experiment 2, a similar approach to that in experiment 1 was used to evaluate simulated preingestive effects, except that sodium azide (0.02% wt/vol) was added to the EFE solution. The suspension was incubated for 24h at 25°C and then 15mL of water was added before filtration to extract water-soluble compounds. For both experiments, data for each enzyme were analyzed separately as a completely randomized block design with a model that included effects of EFE dose, run, and their interaction. In experiment 1, increasing the EFE dose rate nonlinearly increased the DM digestibility of 1A, 2A, 11C, and 13D and the neutral detergent fiber digestibility (NDFD) of 1A, 2A, 11C, and 13D. Optimal doses of 1A, 2A, 11C, 13D, and 15D, as indicated by the greatest increases in NDFD at the lowest dose tested, were 2×, 2×, 1×, 0.5×, and 0.5×, respectively. Increasing the dose rate of 2A, 11C, and 13D nonlinearly increased concentrations of total volatile fatty acids and propionate (mM), decreased their acetate-to-propionate ratios and linearly decreased those of samples treated with 1A and 15D. In experiment 2, increasing the dose rate of each EFE nonlinearly decreased concentrations of netural detergent fiber; also, increasing the dose rate of 1A, 2A, 11C, and 1D nonlinearly increased concentrations of water-soluble carbohydrates and free ferulic acid (μg/g). Application of increasing doses of the EFE increased NDF hydrolysis, NDFD, and ruminal fluid fermentation of bermudagrass haylage, but the optimal dose varied with the EFE. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

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

Fasola, Carolina E.; Jones, Jennifer C.; Huang, Derek D.

2013-08-01

Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: Atmore » a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.« less

Effectiveness of using low rate fluoroscopy to reduce an examiner's radiation dose during lumbar nerve root block.

PubMed

Yamane, Kentaro; Kai, Nobuo; Mazaki, Tetsuro; Miyamoto, Tadashi; Matsushita, Tomohiro

2018-06-13

Long-term exposure to radiation can lead to gene mutations and increase the risk of cancer. Low rate fluoroscopy has the potential to reduce the radiation exposure for both the examiner and the patient during various fluoroscopic procedures. The purpose of this study was to evaluate the impact of low rate fluoroscopy on reducing an examiner's radiation dose during nerve root block. A total of 101 lumbar nerve root block examinations were performed at our institute during a 6-month period. During the first 3 months, low rate fluoroscopy was performed at 7.5 frames/s (FPS) in 54 examinations, while 47 were performed at 15 FPS during the last 3 months. The examiner wore a torso protector, a neck protector, radiation protection gloves, and radiation protection glasses. Optically stimulated luminescence (OSL) dosimeter badges were placed on both the inside and the outside of each protector. The dosimeters were exchanged every month. Radiation doses (mSv) were measured as the integrated radiation quantity every month from the OSL dosimeters. The effective and equivalent doses for the hands, skin, and eyes were investigated. The mean monthly equivalent doses were significantly lower both inside and outside the hand protector for the 7.5 FPS versus 15 FPS (inside; P = 0.021, outside; P = 0.024). There were no significant differences between the two groups for the mean monthly calculated effective dose for each protector's condition. Radiation exposure was significantly reduced for the skin on the examiner's hand when using low rate fluoroscopy at 7.5 FPS, with no noticeable decrease in image quality or prolonged fluoroscopy time. Copyright © 2018. Published by Elsevier B.V.

Verification of shielding effect by the water-filled materials for space radiation in the International Space Station using passive dosimeters

NASA Astrophysics Data System (ADS)

Kodaira, S.; Tolochek, R. V.; Ambrozova, I.; Kawashima, H.; Yasuda, N.; Kurano, M.; Kitamura, H.; Uchihori, Y.; Kobayashi, I.; Hakamada, H.; Suzuki, A.; Kartsev, I. S.; Yarmanova, E. N.; Nikolaev, I. V.; Shurshakov, V. A.

2014-01-01

The dose reduction effects for space radiation by installation of water shielding material ("protective curtain") of a stack board consisting of the hygienic wipes and towels have been experimentally evaluated in the International Space Station by using passive dosimeters. The averaged water thickness of the protective curtain was 6.3 g/cm2. The passive dosimeters consisted of a combination of thermoluminescent detectors (TLDs) and plastic nuclear track detectors (PNTDs). Totally 12 passive dosimeter packages were installed in the Russian Service Module during late 2010. Half of the packages were located at the protective curtain surface and the other half were at the crew cabin wall behind or aside the protective curtain. The mean absorbed dose and dose equivalent rates are measured to be 327 μGy/day and 821 μSv/day for the unprotected packages and 224 μGy/day and 575 μSv/day for the protected packages, respectively. The observed dose reduction rate with protective curtain was found to be 37 ± 7% in dose equivalent, which was consistent with the calculation in the spherical water phantom by PHITS. The contributions due to low and high LET particles were found to be comparable in observed dose reduction rate. The protective curtain would be effective shielding material for not only trapped particles (several 10 MeV) but also for low energy galactic cosmic rays (several 100 MeV/n). The properly utilized protective curtain will effectively reduce the radiation dose for crew living in space station and prolong long-term mission in the future.

Radiation damage in room-temperature data acquisition with the PILATUS 6M pixel detector.

PubMed

Rajendran, Chitra; Dworkowski, Florian S N; Wang, Meitian; Schulze-Briese, Clemens

2011-05-01

The first study of room-temperature macromolecular crystallography data acquisition with a silicon pixel detector is presented, where the data are collected in continuous sample rotation mode, with millisecond read-out time and no read-out noise. Several successive datasets were collected sequentially from single test crystals of thaumatin and insulin. The dose rate ranged between ∼ 1320 Gy s(-1) and ∼ 8420 Gy s(-1) with corresponding frame rates between 1.565 Hz and 12.5 Hz. The data were analysed for global radiation damage. A previously unreported negative dose-rate effect is observed in the indicators of global radiation damage, which showed an approximately 75% decrease in D(1/2) at sixfold higher dose rate. The integrated intensity decreases in an exponential manner. Sample heating that could give rise to the enhanced radiation sensitivity at higher dose rate is investigated by collecting data between crystal temperatures of 298 K and 353 K. UV-Vis spectroscopy is used to demonstrate that disulfide radicals and trapped electrons do not accumulate at high dose rates in continuous data collection.

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

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

PubMed

Kastritis, E; Gavriatopoulou, M; Roussou, M; Fotiou, D; Ziogas, D C; Migkou, M; Eleutherakis-Papaiakovou, E; Panagiotidis, I; Kanellias, N; Psimenou, E; Papadopoulou, E; Pamboucas, C; Manios, E; Gakiopoulou, H; Ntalianis, A; Tasidou, A; Giannouli, S; Terpos, E; Dimopoulos, M A

2017-06-16

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Effects of acute buspirone administration on inhibitory control and sexual discounting in cocaine users.

PubMed

Strickland, Justin C; Bolin, B Levi; Romanelli, Michael R; Rush, Craig R; Stoops, William W

2017-01-01

Cocaine users display deficits in inhibitory control and make impulsive choices that may increase risky behavior. Buspirone is an anxiolytic that activates dopaminergic and serotonergic systems and improves impulsive choice (i.e., reduces sexual risk-taking intent) in cocaine users when administered chronically. We evaluated the effects of acutely administered buspirone on inhibitory control and impulsive choice. Eleven subjects with a recent history of cocaine use completed this within-subject, placebo-controlled study. Subjects performed two cued go/no-go and a sexual risk delay-discounting task following oral administration of buspirone (10 and 30 mg), triazolam (0.375 mg; positive control), and placebo (negative control). Physiological and psychomotor performance and subject-rated data were also collected. Buspirone failed to change inhibitory control or impulsive choice; however, slower reaction times were observed at the highest dose tested. Buspirone did not produce subject-rated drug effects but dose-dependently decreased diastolic blood pressure. Triazolam impaired psychomotor performance and increased ratings of positive subject-rated effects (e.g., Like Drug). These findings indicate that acutely administered buspirone has little impact on behavioral measures of inhibitory control and impulsive sexual decision-making. Considering previous findings with chronic dosing, these findings highlight that the behavioral effects of buspirone differ as a function of dosing conditions. Copyright © 2017 John Wiley & Sons, Ltd.

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.

Common Errors in the Calculation of Aircrew Doses from Cosmic Rays

NASA Astrophysics Data System (ADS)

O'Brien, Keran; Felsberger, Ernst; Kindl, Peter

2010-05-01

Radiation doses to air crew are calculated using flight codes. Flight codes integrate dose rates over the aircraft flight path, which were calculated by transport codes or obtained by measurements from take off at a specific airport to landing at another. The dose rates are stored in various ways, such as by latitude and longitude, or in terms of the geomagnetic vertical cutoff. The transport codes are generally quite satisfactory, but the treatment of the boundary conditions is frequently incorrect. Both the treatment of solar modulation and of the effect of the geomagnetic field are often defective, leading to the systematic overestimate of the crew doses.

Total dose dependency and ELDRS effects on bipolar linear devices

NASA Technical Reports Server (NTRS)

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

2002-01-01

The use of bipolar linear devices is prevalent in most satellite and some space applications. However, degradation as a result of low dose irradiations known as ELDERS (effects of enhanced low dose rate sensitivity) is a major concern when selecting flight hardware. Many studies and reports have been conducted on this possible phenomenon as well as their responsible physical mechanisms.

Total Dose Effects on Error Rates in Linear Bipolar Systems

NASA Technical Reports Server (NTRS)

Buchner, Stephen; McMorrow, Dale; Bernard, Muriel; Roche, Nicholas; Dusseau, Laurent

2007-01-01

The shapes of single event transients in linear bipolar circuits are distorted by exposure to total ionizing dose radiation. Some transients become broader and others become narrower. Such distortions may affect SET system error rates in a radiation environment. If the transients are broadened by TID, the error rate could increase during the course of a mission, a possibility that has implications for hardness assurance.

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

PubMed

Cuttler, Jerry M; Pollycove, Myron

2009-01-01

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

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

PubMed Central

Cuttler, Jerry M.; Pollycove, Myron

2009-01-01

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

Dedicated high dose rate 192Ir brachytherapy radiation fields for in vitro cell exposures at variable source-target cell distances: killing of mammalian cells depends on temporal dose rate fluctuation

NASA Astrophysics Data System (ADS)

Veigel, Cornelia; Hartmann, Günther H.; Fritz, Peter; Debus, Jürgen; Weber, Klaus-Josef

2017-02-01

Afterloading brachytherapy is conducted by the stepwise movement of a radioactive source through surgically implanted applicator tubes where at predefined dwell positions calculated dwell times optimize spatial dose delivery with respect to a planned dose level. The temporal exposure pattern exhibits drastic fluctuations in dose rate at a given coordinate and within a single treatment session because of the discontinuous and repeated source movement into the target volume. This could potentially affect biological response. Therefore, mammalian cells were exposed as monolayers to a high dose rate 192Ir source by utilizing a dedicated irradiation device where the distance between a planar array of radioactive source positions and the plane of the cell monolayer could be varied from 2.5 mm to 40 mm, thus varying dose rate pattern for any chosen total dose. The Gammamed IIi afterloading system equipped with a nominal 370 GBq (10 Ci) 192-Ir source was used to irradiate V79 Chinese hamster lung fibroblasts from both confluent and from exponential growth phase with dose up to 12 Gy (at room temperature, total exposure not exceeding 1 h). For comparison, V79 cells were also exposed to 6 MV x-rays from a clinical linear accelerator (dose rate of 2.5 Gy min-1). As biological endpoint, cell survival was determined by standard colony forming assay. Dose measurements were conducted with a diamond detector (sensitive area 7.3 mm2), calibrated by means of 60Co radiation. Additionally, dose delivery was simulated by Monte Carlo calculations using the EGSnrc code system. The calculated secondary electron fluence spectra at the cell location did not indicate a significant change of radiation quality (i.e. higher linear energy transfer) at the lower distances. Clonogenic cell survival curves obtained after brachytherapy exhibited an altered biological response compared to x-rays which was characterized by a significant reduction of the survival curve shoulder when dose rate fluctuations were high. Therefore, also for the time scale of the present investigation, cellular effects of radiation are not invariant to the temporal pattern in dose rate. We propose that with high dose rate variation the cells activate less efficiently their DNA damage response than after continuous irradiation.

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

PubMed

Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

2013-02-01

Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The Dose Effects of Short-Term Dronabinol (Oral THC) Maintenance in Daily Cannabis Users

PubMed Central

Vandrey, Ryan; Stitzer, Maxine L.; Mintzer, Miriam Z.; Huestis, Marilyn A.; Murray, Jeannie A.; Lee, Dayong

2012-01-01

BACKGROUND Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. METHODS Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120 mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked 5 puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad-libitum cannabis use. RESULTS Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120 mg doses. CONCLUSIONS Dronabinol’s ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg per day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. PMID:22921474

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

PubMed

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

2015-05-01

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

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.

PubMed

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

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

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

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

2015-05-01

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

Dose-Rate Dependence of High-Dose Health Effects in Humans from Photon Radiation with Application to Radiological Terrorism

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

Strom, Daniel J.

2005-01-14

In 1981, as part of a symposium entitled ''The Control of Exposure of the Public to Ionizing Radiation in the Event of Accident or Attack,'' Lushbaugh, H?bner, and Fry published a paper examining ''radiation tolerance'' of various human health endpoints as a function of dose rate. This paper may not have received the notice it warrants. The health endpoints examined by Lushbaugh et al. were the lethal dose that will kill 50% of people within 60 days of exposure without medical care (LD50/60); severe bone marrow damage in healthy men; severe bone marrow damage in leukemia patients; temporary sterility (azoospermia);more » reduced male fertility; and late effects such as cancer. Their analysis was grounded in extensive clinical experience and anchored to a few selected data points, and based on the 1968 dose-rate dependence theory of J.L. Bateman. The Lushbaugh et al. paper did not give predictive equations for the relationships, although they were implied in the text, and the relationships were presented in a non-intuitive way. This work derives the parameters needed in Bateman's equation for each health endpoint, tabulates the results, and plots them in a more conventional manner on logarithmic scales. The results give a quantitative indication of how the human organism can tolerate more radiation dose when it is delivered at lower dose rates. For example, the LD50/60 increases from about 3 grays (300 rads) when given at very high dose rates to over 10 grays (1,000 rads) when given at much lower dose rates over periods of several months. The latter figure is borne out by the case of an individual who survived for at least 19 years after receiving doses in the range of 9 to 17 grays (900-1700 rads) over 106 days. The Lushbaugh et al. work shows the importance of sheltering when confronted with long-term exposure to radiological contamination such as would be expected from a radiological dispersion event, reactor accident, or ground-level nuclear explosion.« less

Comparison of Effects Produced by Nicotine and the α4β2-Selective Agonist 5-I-A-85380 On Intracranial Self-Stimulation in Rats

PubMed Central

Freitas, Kelen; Carroll, F. Ivy; Negus, S. Stevens

2015-01-01

Intracranial self-stimulation (ICSS) is one type of preclinical procedure for research on pharmacological mechanisms that mediate abuse potential of drugs acting at various targets including nicotinic acetylcholine receptors (nAChRs). This study compared effects of the non-selective nAChR agonist nicotine (0.032-1.0 mg/kg) and the α4β2-selective nAChR agonist 5-I-A-85380 (0.01-1.0 mg/kg) on ICSS in male Sprague-Dawley rats. Rats were implanted with electrodes targeting the medial forebrain bundle at the level of the lateral hypothalamus and trained to respond under a fixed-ratio 1 schedule for a range of brain stimulation frequencies (158-56 Hz). A broad range of 5-I-A-85380 doses produced an abuse-related increase (or “facilitation”) of low ICSS rates maintained by low brain-stimulation frequencies, and this effect was blocked by both the nonselective nAChR antagonist mecamylamine and the selective α4β2 antagonist dihyrdo-ß-erythroidine (DHßE). Conversely, nicotine produced weaker ICSS facilitation across a narrower range of doses, and higher nicotine doses decreased high rates of ICSS maintained by high brain- stimulation frequencies. The rate-decreasing effects of a high nicotine dose were blocked by mecamylamine but not DHßE. Chronic nicotine treatment produced selective tolerance to rate-decreasing effects of nicotine but did not alter ICSS rate-increasing effects of nicotine. These results suggest that α4β2 receptors are sufficient to mediate abuse-related rate-increasing effects of nAChR agonists in this ICSS procedure. Conversely, nicotine effects at non-α4β2 nAChRs appear to oppose and limit abuse-related effects mediated by α4β2 receptors, although tolerance can develop to these non-α4β2 effects. Selective α4β2 agonists may have higher abuse potential than nicotine. PMID:26461167

Effect of the embolization material in the dose calculation for stereotactic radiosurgery of arteriovenous malformations

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

Galván de la Cruz, Olga Olinca; Lárraga-Gutiérrez, José Manuel, E-mail: jlarraga@innn.edu.mx; Laboratorio de Física Médica, Instituto Nacional de Neurología y Neurocirugía

2013-07-01

It is reported in the literature that the material used in an embolization of an arteriovenous malformation (AVM) can attenuate the radiation beams used in stereotactic radiosurgery (SRS) up to 10% to 15%. The purpose of this work is to assess the dosimetric impact of this attenuating material in the SRS treatment of embolized AVMs, using Monte Carlo simulations assuming clinical conditions. A commercial Monte Carlo dose calculation engine was used to recalculate the dose distribution of 20 AVMs previously planned with a pencil beam dose calculation algorithm. Dose distributions were compared using the following metrics: average, minimal and maximummore » dose of AVM, and 2D gamma index. The effect in the obliteration rate was investigated using radiobiological models. It was found that the dosimetric impact of the embolization material is less than 1.0 Gy in the prescription dose to the AVM for the 20 cases studied. The impact in the obliteration rate is less than 4.0%. There is reported evidence in the literature that embolized AVMs treated with SRS have low obliteration rates. This work shows that there are dosimetric implications that should be considered in the final treatment decisions for embolized AVMs.« less

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

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

Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi

2012-09-15

Purpose: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. Methods: Step-and-shoot IMRT plans optimized at a reference phase weremore » extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10% faster or slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing period irregularities. When {+-}20% variation of target motion amplitude was present as breathing irregularity, the two delivery methods show compatible plan quality if the dose distribution of CDRT delivery is renormalized. Conclusions: Delivery of 4D-IMRT treatment plans, stemmed from 3D step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate regulation. Comparison of cumulative dose distribution indicates that the preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT strategy, as it compensates the interplay between patient breathing irregularity and tracking delivery without compromising the segment-weight modulation.« less

Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

NASA Technical Reports Server (NTRS)

Kumagai, Kazuhiro; Reid, Ian A.

1994-01-01

We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

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

PubMed

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

2002-01-01

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

Biological effective dose for comparison and combination of external beam and low-dose rate interstitial brachytherapy prostate cancer treatment plans

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

Jani, Ashesh B.; Hand, Christopher M.; Lujan, Anthony E.

2004-03-31

We report a methodology for comparing and combining dose information from external beam radiotherapy (EBRT) and interstitial brachytherapy (IB) components of prostate cancer treatment using the biological effective dose (BED). On a prototype early-stage prostate cancer patient treated with EBRT and low-dose rate I-125 brachytherapy, a 3-dimensional dose distribution was calculated for each of the EBRT and IB portions of treatment. For each component of treatment, the BED was calculated on a point-by-point basis to produce a BED distribution. These individual BED distributions could then be summed for combined therapies. BED dose-volume histograms (DVHs) of the prostate, urethra, rectum, andmore » bladder were produced and compared for various combinations of EBRT and IB. Transformation to BED enabled computation of the relative contribution of each modality to the prostate dose, as the relative weighting of EBRT and IB was varied. The BED-DVHs of the prostate and urethra demonstrated dramatically increased inhomogeneity with the introduction of even a small component of IB. However, increasing the IB portion relative to the EBRT component resulted in lower dose to the surrounding normal structures, as evidenced by the BED-DVHs of the bladder and rectum. Conformal EBRT and low-dose rate IB conventional dose distributions were successfully transformed to the common 'language' of BED distributions for comparison and for merging prostate cancer radiation treatment plans. The results of this analysis can assist physicians in quantitatively determining the best combination and weighting of radiation treatment modalities for individual patients.« less

Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle - an update.

PubMed

Konold, Timm; Arnold, Mark E; Austin, Anthony R; Cawthraw, Saira; Hawkins, Steve A C; Stack, Michael J; Simmons, Marion M; Sayers, A Robin; Dawson, Michael; Wilesmith, John W; Wells, Gerald A H

2012-12-05

To provide information on dose-response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of the bovine prion protein gene on disease incidence and revises estimates of effective oral exposure. Following interim published results, two further cattle, one dosed with 100 mg and culled at 127 months post exposure and the other dosed with 10 mg and culled at 110 months post exposure, developed BSE. Both had a similar pathological phenotype to previous cases. Based on attack rate and incubation period distribution according to dose, the dose estimate at which 50% of confirmed cases would be clinically affected was revised to 0.15 g of the brain homogenate used in the experiment, with a 95% confidence interval of 0.03-0.79 g. Neither the full open reading frame nor the promoter region of the prion protein gene of dosed cattle appeared to influence susceptibility to BSE, but this may be due to the sample size. Oral exposure of cattle to a large range of doses of a BSE brainstem homogenate produced disease in all dose groups. The pathological presentation resembled natural disease. The attack rate and incubation period were dependent on the dose.

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

Radiation protection issues in galactic cosmic ray risk assessment

NASA Technical Reports Server (NTRS)

Sinclair, W. K.

1994-01-01

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

Radiation protection issues in galactic cosmic ray risk assessment.

PubMed

Sinclair, W K

1994-01-01

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

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.

Low doses of glyphosate enhance growth, CO2 assimilation, stomatal conductance and transpiration in sugarcane and eucalyptus.

PubMed

Nascentes, Renan F; Carbonari, Caio A; Simões, Plinio S; Brunelli, Marcela C; Velini, Edivaldo D; Duke, Stephen O

2018-05-01

Sublethal doses of herbicides can enhance plant growth and stimulate other process, an effect known as hormesis. The magnitude of hormesis is dependent on the plant species, the herbicide and its dose, plant development stage and environmental parameters. Glyphosate hormesis is well established, but relatively little is known of the mechanism of this phenomenon. The objective of this study was to determine if low doses of glyphosate that cause growth stimulation in sugarcane and eucalyptus concomitantly stimulate CO 2 assimilation. Shoot dry weight in both species increased at both 40 and 60 days after application of 6.2 to 20.2 g a.e. ha -1 glyphosate. The level of enhanced shoot dry weight was 11 to 37%, depending on the time after treatment and the species. Concomitantly, CO 2 assimilation, stomatal conductance and transpiration were increased by glyphosate doses similar to those that caused growth increases. Glyphosate applied at low doses increased the dry weight of sugarcane and eucalyptus plants in all experiments. This hormetic effect was related to low dose effects on CO 2 assimilation rate, stomatal conductance and transpiration rate, indicating that low glyphosate doses enhance photosynthesis of plants. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Space weather effects measured in atmospheric radiation on aircraft

NASA Astrophysics Data System (ADS)

Tobiska, W. K.; Bouwer, D.; Bailey, J. J.; Didkovsky, L. V.; Judge, K.; Wieman, S. R.; Atwell, W.; Gersey, B.; Wilkins, R.; Rice, D.; Schunk, R. W.; Bell, L. D.; Mertens, C. J.; Xu, X.; Wiltberger, M. J.; Wiley, S.; Teets, E.; Shea, M. A.; Smart, D. F.; Jones, J. B. L.; Crowley, G.; Azeem, S. I.; Halford, A. J.

2016-12-01

Space weather's effects upon the near-Earth environment are due to dynamic changes in the energy transfer processes from the Sun's photons, particles, and fields. Of the domains that are affected by space weather, the coupling between the solar and galactic high-energy particles, the magnetosphere, and atmospheric regions can significantly affect humans and our technology as a result of radiation exposure. Since 2013 Space Environment Technologies (SET) has been conducting observations of the atmospheric radiation environment at aviation altitudes using a small fleet of six instruments. The objective of this work is to improve radiation risk management in air traffic operations. Under the auspices of the Automated Radiation Measurements for Aerospace Safety (ARMAS) and Upper-atmospheric Space and Earth Weather eXperiment (USEWX) projects our team is making dose rate measurements on multiple aircraft flying global routes. Over 174 ARMAS and USEWX flights have successfully demonstrated the operation of a micro dosimeter on commercial aviation altitude aircraft that captures the radiation environment resulting from Galactic Cosmic Rays (GCRs), Solar Energetic Protons (SEPs), and outer radiation belt energetic electrons. The real-time radiation exposure is measured as an absorbed dose rate in silicon and then computed as an ambient dose equivalent rate for reporting dose relevant to radiative-sensitive organs and tissue in units of microsieverts per hour. ARMAS total ionizing absorbed dose is captured on the aircraft, downlinked in real-time, processed on the ground into ambient dose equivalent rates, compared with NASA's Langley Research Center (LaRC) most recent Nowcast of Atmospheric Ionizing Radiation System (NAIRAS) global radiation climatology model runs, and then made available to end users. Dose rates from flight altitudes up to 56,700 ft. are shown for flights across the planet under a variety of space weather conditions. We discuss several space weather effects on the atmospheric radiation environment, including the levels of GCR background radiation, small SEP events, and possible EMIC wave driven energetic electrons from the outer radiation belt creating "radiation" clouds in the troposphere.

Effect of combined heat and radiation on microbial destruction

NASA Technical Reports Server (NTRS)

Fisher, D. A.; Pflug, I. J.

1977-01-01

A series of experiments at several levels of relative humidity and radiation dose rates was carried out using spores of Bacillus subtilis var. niger to evaluate the effect of heat alone, radiation alone, and a combination of heat and radiation. Combined heat and radiation treatment of microorganisms yields a destruction rate greater than the additive rates of the independent agents. The synergistic mechanism shows a proportional dependency on radiation dose rate, an Arrhenius dependence on temperature, and a dependency on relative humidity. Maximum synergism occurs under conditions where heat and radiation individually destroy microorganisms at approximately equal rates. Larger synergistic advantage is possible at low relative humidities rather than at high relative humidities.

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

[Inhibitory effect of human lactoferrin (neolactoferrin) on the growth of transplantable tumor in the uterine cervix of mice].

PubMed

Kobliakov, V A; Antoshina, E E; Gor'kova, T G; Gol'dman, I L; Trukhanova, L S; Sadchikova, E R

2012-01-01

There was studied effect of recombinant form of human breast milk component-lactoferrin, received from milk of goats-producers (neolactoferrin), on growth of transplantable tumor of the cervix in mice (TTC-5). Neolactoferrin in dose of 100 mg/kg and 200 mg/kg of animals' mass inhibited the rate of tumor growth. The most effective was the dose of 200 mg/kg, which was entered a week before transplantation. In contrast to the control group, in groups where neolactoferrin was entered it was fixed resorption of TTC-5 in 6 mice. Repeated transplantation TTC-5 to these mice led to reducing of the rate of tumor growth and increasing of duration of their lives. To investigate if tumor-braking effect neolactoferrin connected with direct effect on the tumor or due to the general effect of the organism, TTC-5 cells were transformed in culture and they were exposed by neolactoferrin in dose of 10 and 100 mkg/ml. In investigated doses neolactoferrin did not influence on tumor cells growth. There is discussed possible mechanism of anti-tumor effect of neolactoferrin.

Radiosensitivity study and radiation effects on morphology characterization of grey oyster mushroom Pleurotus sajor-caju

NASA Astrophysics Data System (ADS)

Rashid, Rosnani Abdul; Daud, Fauzi; Senafi, Sahidan; Awang, Mat Rasol; Mohamad, Azhar; Mutaat, Hassan Hamdani; Maskom, Mohd Meswan

2014-09-01

Radiosensitive dosage and morphology characterization of irradiated grey oyster mushroom Pleurotus sajor-caju by gamma rays was investigated due to effects of irradiation. In order to establish the effect, mycelium of P. sajor-caju was irradiated by gamma rays at dose 0.1 to 8.0 kGy with dose rate 0.227 Gy sec-1. The irradiation of mycelia was carried out at the radiation facility in Malaysian Nuclear Agency. The radiosensitivity study was performed by evaluating the percentage of survival irradiated mycelia. The lethal dose of the mycelium P. sajor-caju was determined at 4.0 kGy and LD50 to be equal at 2.2 kGy. The radiation effects on morphology were evaluated based on growth rate of irradiated mycelia, mycelia types, colonization period on substrate, morphology of fruit bodies and yields. The results shown growth rate of irradiated mycelium was slightly lower than the control and decreased as the dose increased. Irradiation was found can induced the primordia formation on PDA and the BE of irradiated seed is higher than to control. The irradiation is proven to be useful for generating new varieties of mushroom with commercial value to the industry.

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.

Hemopoietic Response to Low Dose-Rates of Ionizing Radiation Shows Stem Cell Tolerance and Adaptation

PubMed Central

Fliedner, Theodor M.; Graessle, Dieter H.; Meineke, Viktor; Feinendegen, Ludwig E.

2012-01-01

Chronic exposure of mammals to low dose-rates of ionizing radiation affects proliferating cell systems as a function of both dose-rate and the total dose accumulated. The lower the dose-rate the higher needs to be the total dose for a deterministic effect, i.e., tissue reaction to appear. Stem cells provide for proliferating, maturing and functional cells. Stem cells usually are particularly radiosensitive and damage to them may propagate to cause failure of functional cells. The paper revisits 1) medical histories with emphasis on the hemopoietic system of the victims of ten accidental chronic radiation exposures, 2) published hematological findings of long-term chronically gamma-irradiated rodents, and 3) such findings in dogs chronically exposed in large life-span studies. The data are consistent with the hypothesis that hemopoietic stem and early progenitor cells have the capacity to tolerate and adapt to being repetitively hit by energy deposition events. The data are compatible with the “injured stem cell hypothesis”, stating that radiation–injured stem cells, depending on dose-rate, may continue to deliver clones of functional cells that maintain homeostasis of hemopoiesis throughout life. Further studies perhaps on separated hemopoietic stem cells may unravel the molecular-biology mechanisms causing radiation tolerance and adaptation. PMID:23304110

The role of single-shot metronidazole in the prevention of Clostridium difficile infection following ileostomy reversal surgery.

PubMed

Fernandes, Roland; Robinson, Paul; Rangarajan, Karan; Scott, Sophie; Angco, Laura

2017-05-01

Symptomatic infection with Clostridium difficile is strongly linked to antibiotic use and rates are higher for colorectal surgery. In February 2015, trust policy for antibiotic prophylaxis of ileostomy reversal surgery was changed from three doses of metronidazole plus cefuroxime to single-dose metronidazole, in a bid to reduce rates of Clostridium difficile infection. A retrospective cohort study was conducted at a single, large hospital trust between February 2014 and February 2016, before and after change in antimicrobial policy. Theatre data, clinical notes and pathology results were all reviewed. Outcome data, patient age, gender, length of operation and hospital stay were extracted. One hundred three patients underwent ileostomy reversal surgery between February 2014 and February 2015. All received cefuroxime together with metronidazole at induction of anaesthesia followed by two further post-operative doses as operative prophylaxis. Ninety-six patients underwent ileostomy reversal surgery between February 2015 and February 2016. All received single-dose metronidazole at induction as prophylaxis. Post-operative diarrhoea was significantly reduced in patients given single-dose metronidazole compared with patients managed with multiple dose, dual antibiotic therapy (32 vs 12.5%, P 0.001). Rates of CDI were also significantly reduced in patients given single-dose metronidazole (6.8 vs 1%, P 0.038). Single-dose, pre-operative metronidazole is effective at reducing post-operative diarrhoea and CDI in ileostomy reversal surgery compared with multiple-dose cefuroxime plus metronidazole. Metronidazole may be effective as a prophylactic antibiotic against CDI in colonic surgery.

Biology relevant to space radiation

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

Fry, R J.M.

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

Total Dose Effects on Single Event Transients in Digital CMOS and Linear Bipolar Circuits

NASA Technical Reports Server (NTRS)

Buchner, S.; McMorrow, D.; Sibley, M.; Eaton, P.; Mavis, D.; Dusseau, L.; Roche, N. J-H.; Bernard, M.

2009-01-01

This presentation discusses the effects of ionizing radiation on single event transients (SETs) in circuits. The exposure of integrated circuits to ionizing radiation changes electrical parameters. The total ionizing dose effect is observed in both complementary metal-oxide-semiconductor (CMOS) and bipolar circuits. In bipolar circuits, transistors exhibit grain degradation, while in CMOS circuits, transistors exhibit threshold voltage shifts. Changes in electrical parameters can cause changes in single event upset(SEU)/SET rates. Depending on the effect, the rates may increase or decrease. Therefore, measures taken for SEU/SET mitigation might work at the beginning of a mission but not at the end following TID exposure. The effect of TID on SET rates should be considered if SETs cannot be tolerated.

The role of nicotinic receptor alpha 7 subunits in nicotine discrimination.

PubMed

Stolerman, I P; Chamberlain, S; Bizarro, L; Fernandes, C; Schalkwyk, L

2004-03-01

The subtypes of nicotinic receptors at which the behavioural effects of nicotine originate are not fully understood. The experiments described here use mice lacking the alpha7 subunit of nicotinic receptors to investigate the role of alpha7-containing receptors in nicotine discrimination. Wild-type and alpha7-knockout mice were trained in a two-lever nicotine discrimination procedure using a tandem schedule of food reinforcement. Mutant mice exhibited baseline rates of lever-pressing as low as 52.2% of rates in wild-type controls (n=21-24). Mutant and wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) at a similar rate (n=10-12) and reached similar final levels of accuracy (71.9 +/- 4.4% and 90.8 +/- 3.1% after 60 training sessions for 0.4 and 0.8 mg/kg training doses, respectively, in mutant mice, as compared with 75.0 +/- 6.5% and 87.6 +/- 4.8% for wild types). The genotypes exhibited similar steep dose-response curves for nicotine discrimination. In both genotypes, dose-response curves for mice trained with 0.8 mg/kg of nicotine were displaced three- to four-fold to the right as compared with those for the mice trained with the smaller dose. The predominant effect of nicotine on the overall rate of responding was a reduction at the largest doses tested and there was no difference between the genotypes. The results suggest that nicotinic receptors containing the alpha7 subunit do not contribute to the discriminative stimulus or response-rate-depressant effects of nicotine, although they may regulate baseline rates of operant responding.

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.

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

Combined experimental and Monte Carlo verification of brachytherapy plans for vaginal applicators

NASA Astrophysics Data System (ADS)

Sloboda, Ron S.; Wang, Ruqing

1998-12-01

Dose rates in a phantom around a shielded and an unshielded vaginal applicator containing Selectron low-dose-rate sources were determined by experiment and Monte Carlo simulation. Measurements were performed with thermoluminescent dosimeters in a white polystyrene phantom using an experimental protocol geared for precision. Calculations for the same set-up were done using a version of the EGS4 Monte Carlo code system modified for brachytherapy applications into which a new combinatorial geometry package developed by Bielajew was recently incorporated. Measured dose rates agree with Monte Carlo estimates to within 5% (1 SD) for the unshielded applicator, while highlighting some experimental uncertainties for the shielded applicator. Monte Carlo calculations were also done to determine a value for the effective transmission of the shield required for clinical treatment planning, and to estimate the dose rate in water at points in axial and sagittal planes transecting the shielded applicator. Comparison with dose rates generated by the planning system indicates that agreement is better than 5% (1 SD) at most positions. The precision thermoluminescent dosimetry protocol and modified Monte Carlo code are effective complementary tools for brachytherapy applicator dosimetry.

Effectiveness of a Third Dose of MMR Vaccine for Mumps Outbreak Control.

PubMed

Cardemil, Cristina V; Dahl, Rebecca M; James, Lisa; Wannemuehler, Kathleen; Gary, Howard E; Shah, Minesh; Marin, Mona; Riley, Jacob; Feikin, Daniel R; Patel, Manisha; Quinlisk, Patricia

2017-09-07

The effect of a third dose of the measles-mumps-rubella (MMR) vaccine in stemming a mumps outbreak is unknown. During an outbreak among vaccinated students at the University of Iowa, health officials implemented a widespread MMR vaccine campaign. We evaluated the effectiveness of a third dose for outbreak control and assessed for waning immunity. Of 20,496 university students who were enrolled during the 2015-2016 academic year, mumps was diagnosed in 259 students. We used Fisher's exact test to compare unadjusted attack rates according to dose status and years since receipt of the second MMR vaccine dose. We used multivariable time-dependent Cox regression models to evaluate vaccine effectiveness, according to dose status (three vs. two doses and two vs. no doses) after adjustment for the number of years since the second dose. Before the outbreak, 98.1% of the students had received at least two doses of MMR vaccine. During the outbreak, 4783 received a third dose. The attack rate was lower among the students who had received three doses than among those who had received two doses (6.7 vs. 14.5 cases per 1000 population, P<0.001). Students had more than nine times the risk of mumps if they had received the second MMR dose 13 years or more before the outbreak. At 28 days after vaccination, receipt of the third vaccine dose was associated with a 78.1% lower risk of mumps than receipt of a second dose (adjusted hazard ratio, 0.22; 95% confidence interval, 0.12 to 0.39). The vaccine effectiveness of two doses versus no doses was lower among students with more distant receipt of the second vaccine dose. Students who had received a third dose of MMR vaccine had a lower risk of mumps than did those who had received two doses, after adjustment for the number of years since the second dose. Students who had received a second dose of MMR vaccine 13 years or more before the outbreak had an increased risk of mumps. These findings suggest that the campaign to administer a third dose of MMR vaccine improved mumps outbreak control and that waning immunity probably contributed to propagation of the outbreak. (Funded by the Centers for Disease Control and Prevention.).

The in vivo efficacy of neuraminidase inhibitors cannot be determined from the decay rates of influenza viral titers observed in treated patients

NASA Astrophysics Data System (ADS)

Palmer, John; Dobrovolny, Hana M.; Beauchemin, Catherine A. A.

2017-01-01

Antiviral therapy is a first line of defence against new influenza strains. Current pandemic preparations involve stock- piling oseltamivir, an oral neuraminidase inhibitor (NAI), so rapidly determining the effectiveness of NAIs against new viral strains is vital for deciding how to use the stockpile. Previous studies have shown that it is possible to extract the drug efficacy of antivirals from the viral decay rate of chronic infections. In the present work, we use a nonlinear mathematical model representing the course of an influenza infection to explore the possibility of extracting NAI drug efficacy using only the observed viral titer decay rates seen in patients. We first show that the effect of a time-varying antiviral concentration can be accurately approximated by a constant efficacy. We derive a relationship relating the true treatment dose and time elapsed between doses to the constant drug dose required to approximate the time- varying dose. Unfortunately, even with the simplification of a constant drug efficacy, we show that the viral decay rate depends not just on drug efficacy, but also on several viral infection parameters, such as infection and production rate, so that it is not possible to extract drug efficacy from viral decay rate alone.

Radiation response of industrial materials: Dose-rate and morphology implications

NASA Astrophysics Data System (ADS)

Berejka, Anthony J.

2007-08-01

Industrial uses of ionizing radiation mostly rely upon high current, high dose-rate (100 kGy/s) electron beam (EB) accelerators. To a lesser extent, industry uses low dose-rate (2.8 × 10-3 kGy/s) radioactive Cobalt-60 as a gamma source, generally for some rather specific purposes, as medical device sterilization and the treatment of food and foodstuffs. There are nearly nine times as many (∼1400) high current EB units in commercial operation than gamma sources (∼160). However, gamma sources can be easily scaled-down so that much research on materials effects is conducted using gamma radiation. Likewise, laboratories are more likely to have very low beam current and consequently low dose-rate accelerators such as Van de Graaff generators and linear accelerators. With the advent of very high current EB accelerators, X-ray processing has become an industrially viable option. With X-rays from high power sources, dose-rates can be modulated based upon accelerator power and the attenuation of the X-ray by the distance of the material from the X-ray target. Dose and dose-rate dependence has been found to be of consequence in several commercial applications which can employ the use of ionizing radiation. The combination of dose and dose-rate dependence of the polymerization and crosslinking of wood impregnants and of fiber composite matrix materials can yield more economically viable results which have promising commercial potential. Monomer and oligomer structure also play an important role in attaining these desirable results. The influence of morphology is shown on the radiation response of olefin polymers, such as ethylene, propylene and isobutylene polymers and their copolymers. Both controlled morphology and controlled dose-rate have commercial consequences. These are also impacted both by the adroit selection of materials and through the possible use of X-ray processing.

Comparative efficacy of continuous and pulse dose terbinafine regimes in toenail dermatophytosis: A randomized double-blind trial.

PubMed

Yadav, Pravesh; Singal, Archana; Pandhi, Deepika; Das, Shukla

2015-01-01

Dermatophytes are the most frequently implicated agents in toenail onychomycosis and oral terbinafine has shown the best cure rates in this condition. The pharmacokinetics of terbinafine favors its efficacy in pulse dosing. To compare the efficacy of terbinafine in continuous and pulse dosing schedules in the treatment of toenail dermatophytosis. Seventy-six patients of potassium hydroxide (KOH) and culture positive dermatophyte toenail onychomycosis were randomly allocated to two treatment groups receiving either continuous terbinafine 250 mg daily for 12 weeks or 3 pulses of terbinafine (each of 500 mg daily for a week) repeated every 4 weeks. Patients were followed up at 4, 8 and 12 weeks during treatment and post-treatment at 24 weeks. At each visit, a KOH mount and culture were performed. In each patient, improvement in a target nail was assessed using a clinical score; total scores for all nails and global assessments by physician and patient were also recorded. Mycological, clinical and complete cure rates, clinical effectivity and treatment failure rates were then compared. The declines in target nail and total scores from baseline were significant at each follow-up visit in both the treatment groups. However, the inter-group difference was statistically insignificant. The same was true for global assessment indices, clinical effectivity as well as clinical, mycological, and complete cure rates. The short follow-up in our study may have led to lower cure rates being recorded. Terbinafine in pulse dosing is as effective as continuous dosing in the treatment of dermatophyte toenail onychomycosis.

Evaluation of ambient dose equivalent rates influenced by vertical and horizontal distribution of radioactive cesium in soil in Fukushima Prefecture.

PubMed

Malins, Alex; Kurikami, Hiroshi; Nakama, Shigeo; Saito, Tatsuo; Okumura, Masahiko; Machida, Masahiko; Kitamura, Akihiro

2016-01-01

The air dose rate in an environment contaminated with (134)Cs and (137)Cs depends on the amount, depth profile and horizontal distribution of these contaminants within the ground. This paper introduces and verifies a tool that models these variables and calculates ambient dose equivalent rates at 1 m above the ground. Good correlation is found between predicted dose rates and dose rates measured with survey meters in Fukushima Prefecture in areas contaminated with radiocesium from the Fukushima Dai-ichi Nuclear Power Plant accident. This finding is insensitive to the choice for modeling the activity depth distribution in the ground using activity measurements of collected soil layers, or by using exponential and hyperbolic secant fits to the measurement data. Better predictions are obtained by modeling the horizontal distribution of radioactive cesium across an area if multiple soil samples are available, as opposed to assuming a spatially homogeneous contamination distribution. Reductions seen in air dose rates above flat, undisturbed fields in Fukushima Prefecture are consistent with decrement by radioactive decay and downward migration of cesium into soil. Analysis of remediation strategies for farmland soils confirmed that topsoil removal and interchanging a topsoil layer with a subsoil layer result in similar reductions in the air dose rate. These two strategies are more effective than reverse tillage to invert and mix the topsoil. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2012-01-03

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

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.

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

PubMed

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

2015-10-01

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

NOTE: Investigating the potential of polymer gel dosimetry for interventional radiology: first results

NASA Astrophysics Data System (ADS)

Antoniou, P. E.; Bousbouras, P.; Sandaltzopoulos, R.; Kaldoudi, E.

2008-04-01

Complex interventional radiology (IR) procedures contribute an increasing percentage of the overall medical radiation exposure of the population making accurate dosimetry a challenge. Magnetic resonance (MR) based polymer gel dosimetry has been widely employed in complex dosimetric problems in radiotherapy. The aim of this note is to investigate the feasibility of normoxic gel dosimetry in IR. Dose response, energy dependence and dose rate dependence were investigated in irradiation set-ups relevant to IR for a particular normoxic gel, based on methacrylic acid (MAA) as the monomer and including tetrakis-hydroxy-methyl-phosphonium chloride (THPC) as antioxidant. The gel presents a linear dose response beyond a 25 cGy threshold. No significant energy dependence was observed in the useful range of interventional radiology (80-110 kVp). A linear correlation between the gel response and dose rate was observed in the range of dose rates relevant to IR (5-8 cGy min-1). These results demonstrate a reduction of gel sensitivity at very low dose rate levels. A possible explanation of this effect is suggested.

Low- and high-dose laser irradiation effects on cell migration and destruction

NASA Astrophysics Data System (ADS)

Layton, Elivia; Gallagher, Kyra A.; Zukerman, Sara; Stevens, Brianna; Zhou, Feifan; Liu, Hong; Chen, Wei R.

2018-02-01

Metastases are the cause of more than 90 percent of cancer-related deaths. Current treatment methods, including chemotherapy, radiation, and surgery, fail to target the metastases effectively. One potential treatment for metastatic cancer is laser immunotherapy (LIT). LIT combines the use of a photothermal laser with an immunoadjuvant, Glycated Chitosan (GC). GC combined with single-walled carbon nanotubes (SWNTs) has proven to be a viable alternative to traditional cancer treatment methods, when under irradiation of laser with appropriate wavelength. In this study, the effects of low dose and high dose laser irradiation on metastatic pancreatic cancer cell migration were observed. It was found that low dose irradiation increased the migration rate, but the high dose irradiation significantly decreased the migration rate of the cancer cells. When using LIT, the goal is to kill tumor cells and to prompt the correct immune response. If the tumor were irradiated with a low dose, it would promote metastasis. If the dose of irradiation were too high, it would destroy the entire tumor and the immune response would not recognize the tumor. Therefore, the laser dose plays an important role in LIT, particularly when using SWNT as light absorbing agent. Our results from this study will delineate the optimal laser irradiation dose for destroying tumor cells and at the same time preserve and release tumor antigens as a precursor of antitumor immune response.

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

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.

Low dose or low dose rate ionizing radiation-induced health effect in the human.

PubMed

Tang, Feng Ru; Loganovsky, Konstantin

2018-06-05

The extensive literature review on human epidemiological studies suggests that low dose ionizing radiation (LDIR) (≤100 mSv) or low dose rate ionizing radiation (LDRIR) (<6mSv/H) exposure could induce either negative or positive health effects. These changes may depend on genetic background, age (prenatal day for embryo), sex, nature of radiation exposure, i.e., acute or chronic irradiation, radiation sources (such as atomic bomb attack, fallout from nuclear weapon test, nuclear power plant accidents, 60 Co-contaminated building, space radiation, high background radiation, medical examinations or procedures) and radionuclide components and human epidemiological experimental designs. Epidemiological and clinical studies show that LDIR or LDRIR exposure may induce cancer, congenital abnormalities, cardiovascular and cerebrovascular diseases, cognitive and other neuropsychiatric disorders, cataracts and other eye and somatic pathology (endocrine, bronchopulmonary, digestive, etc). LDIR or LDRIR exposure may also reduce mutation and cancer mortality rates. So far, the mechanisms of LDIR- or LDRIR -induced health effect are poorly understood. Further extensive studies are still needed to clarify under what circumstances, LDIR or LDRIR exposure may induce positive or negative effects, which may facilitate development of new therapeutic approaches to prevent or treat the radiation-induced human diseases or enhance radiation-induced positive health effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Modelling the external radiation exposure from the Chernobyl fallout using data from the Swedish municipality measurement system.

PubMed

Jönsson, Mattias; Tondel, Martin; Isaksson, Mats; Finck, Robert; Wålinder, Robert; Mamour, Afrah; Rääf, Christopher

2017-11-01

In connection with the Chernobyl fallout and the subsequent deposition of radionuclides in Sweden, Swedish municipalities launched a measurement program to monitor the external radiation exposure. This program encompasses measurements of the ambient dose equivalent rate 1 m above ground at selected locations, and repeats those measurements at the same locations at 7-month intervals. Measurement data compiled from the seven locations with the highest deposition were combined with data from aerial surveys since May 1986 of ground deposition of 137 Cs, high-resolution gamma spectrometry performed at four locations in May 1986, and measurements from fixed continuous air gamma rate monitoring stations from 28 April to 15 May 1986. Based on these datasets, a model of the time pattern of the external dose rate in terms of ambient dose equivalent rate from the Chernobyl fallout was developed. The decrease in the ambient dose equivalent rate could, on average, be described by a four-component exponential decay function with effective half-times of 6.8 ± 0.3 d, 104 ± 26 d, 1.0 ± 0.02 y and 5.5 ± 0.09 y, respectively. The predominant contributions to the external dose rate in the first month were from short-lived fission products superseded by 134 Cs and then 137 Cs. Integrated over 70 y and using extrapolation of the curve fits, our model predicts that 137 Cs contributes about 60% and 134 Cs contributes about 30% of the external effective dose at these seven locations. The projected time-integrated 70 y external effective dose to an unshielded person from all nuclides per unit total activity deposition of 137 Cs is estimated to be 0.29 ± 0.0.08 mSv/(kBq m -2 ). These results are in agreement with those found in Chernobyl contaminated Russian forest areas, and emphasize the usefulness of maintaining a long-term and regular measurement program in contaminated areas. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Comparative Study on the Life-Saving Radioprotective Effects of Vitamins A, E, C and Over-the-Counter Multivitamins.

PubMed

Mortazavi, S M J; Rahimi, S; Mosleh-Shirazi, M A; Arjomandi, M; Soleimani, A; Koohi Hossein-Abadi, O; Haghani, M; Alavi, M

2015-06-01

Oral intake of vitamins which present antioxidant characteristics can protect living organisms against oxidative damage caused by exposure to ionizing radiation. It was previously reported that administration of high levels of vitamin C can lead to increased DNA damage through production of hydroxyl radicals from hydrogen peroxide by the Fenton reaction. However, our early experiments did not confirm this hypothesis. The main goal of this study was to determine if high doses of Vit C can show life-saving radioprotective effects. Phase I: Seventy two male Balb/c mice weighing 20-25g were randomly divided into six groups of 12 animals each. Group I; Vit E for five days, Groups II and III; Vit C and Vit A. Group 4; all three vitamins. Group V; an over-the-counter multivitamin. Group VI; none of the above. Phase II: 120 male BALB/c mice weighing 20-25g were randomly divided into 12 groups of 10 each. Group I; Vit A for five days. Groups II-IV; Vit C 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. Group V-VII; Vit E at daily doses of 200 iu/kg, 400 iu/kg, 800 iu/kg, respectively. Group VIII and IX; all three vitamins at low and high doses, respectively. Group X; an over-the-counter multivitamin. Group XI; controls group and Group XII; received pure olive oil. All animals (Phases I and II) were exposed to a lethal dose of gamma rays and the survival rates of the animals were monitored and recorded continuously for 16 days after exposure. Phase I: 14 days after irradiation the survival rate for control group was 33.33%, while the survival rates for the 1st to 5th groups were 45.45%, 81.81%, 50%, 57.14%, and 9.09% , respectively. Phase II: The survival rates in the control group and the group that only received pure olive oil, were 50% and 60%, respectively. Survival rate in the animals received Vit C at daily doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, were 90%, 90% and 90%, respectively. Log rank (Mantel-Cox) test showed statistically significant differences between the survival rates in control irradiated mice (no vitamins) and mice received Vit C at daily doses of 200 mg/kg (P=0.042), 400 mg/kg (P=0.042) and 800 mg/kg (P=0.042). Altogether, findings of this study showed that even high doses of Vit C can show life-saving radioprotective effects. The significant radioprotective effect of Vit C at doses used in this study, opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life-threatening situations such as exposure to lethal doses of ionizing radiation.  The radioprotective effect of Vit A and Vit E seem to be less efficient compared to that of Vit C.

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.

Clomiphene Stair-Step Protocol for Women With Polycystic Ovary Syndrome.

PubMed

Jones, Tiffanny; Ho, Jacqueline R; Gualtieri, Marc; Bruno-Gaston, Janet; Chung, Karine; Paulson, Richard J; Bendikson, Kristin A

2018-01-01

To compare time to ovulation, ovulation rates, and side effect profile of traditional and the stair-step protocol for ovulation induction using clomiphene citrate in women with polycystic ovary syndrome (PCOS). We performed a retrospective study of women seeking care for infertility with a diagnosis of PCOS at a university-based infertility clinic from July 2012 to July 2014. We included patients who were resistant to the initial starting dose of 50 mg clomiphene. The primary outcome was time to ovulation. Secondary outcomes included ovulation rates, clinical pregnancy rates, and mild and moderate-to-severe side effects based on dose. For the traditional protocol, higher doses of clomiphene were used each subsequent month if no ovulation occurred. For the stair-step protocol, higher doses of clomiphene were given 7 days after the last dose if no dominant follicles were seen on ultrasonography. Our study had 80% power to detect a 20% difference in ovulation. One hundred nine patients were included in the analysis with 66 (60.6%) in the traditional and 43 (39.4%) in the stair-step protocol. Age and body mass index were similar between groups. The time to ovulation was decreased in the stair-step protocol group compared with the traditional protocol group (23.1±0.9 days vs 47.5±6.3 days). Ovulation rates were increased in the stair-step group compared with the traditional group at 150 mg (16 [37%] vs 8 [12%], P=.004) and at 200 mg (9 [21%] vs 3 [5%], P=.01). Pregnancy rates were similar between groups once ovulation was achieved (12 [18.1%] vs 7 [16.3%], P=.08). The stair-step protocol had an increased incidence of mild side effects (vasomotor flushes, headaches, gastrointestinal disturbance, mastalgia, changes in mood; 18 [41%] vs 8 [12%]), but there was no difference in the incidence of severe side effects (headaches, visual disturbances). For women with PCOS, the stair-step clomiphene protocol is associated with decreased time to ovulation and increased ovulation rates at higher doses when compared with the traditional protocol.

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.

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate–Dependent Manner

PubMed Central

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR. PMID:29531508

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

Tissue responses to low protracted doses of high let radiations or photons: Early and late damage relevant to radio-protective countermeasures

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

Ainsworth, E.J.; Afzal, S.M.J.; Crouse, D.A.

1988-01-01

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for ..gamma..-radiation. When total doses of 96 or 247 cGy of neutrons or ..gamma.. rays were givenmore » as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and ..gamma..-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. 63 refs., 6 figs., 7 tabs.« less

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

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.

Preliminary Analysis of the Multisphere Neutron Spectrometer

NASA Technical Reports Server (NTRS)

Goldhagen, P.; Kniss, T.; Wilson, J. W.; Singleterry, R. C.; Jones, I. W.; VanSteveninck, W.

2003-01-01

Crews working on present-day jet aircraft are a large occupationally exposed group with a relatively high average effective dose from galactic cosmic radiation. Crews of future high-speed commercial aircraft flying at higher altitudes would be even more exposed. To help reduce the significant uncertainties in calculations of such exposures, the Atmospheric Ionizing Radiation (AIR) Project, an international collaboration of 15 laboratories, made simultaneous radiation measurements with 14 instruments on five flights of a NASA ER-2 high-altitude aircraft. The primary AIR instrument was a highly sensitive extended-energy multisphere neutron spectrometer with lead and steel shells placed within the moderators of two of its 14 detectors to enhance response at high energies. Detector responses were calculated for neutrons and charged hadrons at energies up to 100 GeV using MCNPX. Neutron spectra were unfolded from the measured count rates using the new MAXED code. We have measured the cosmic-ray neutron spectrum (thermal to greater than 10 GeV), total neutron fluence rate, and neutron effective dose and dose equivalent rates and their dependence on altitude and geomagnetic cutoff. The measured cosmic-ray neutron spectra have almost no thermal neutrons, a large "evaporation" peak near 1 MeV and a second broad peak near 100 MeV which contributes about 69% of the neutron effective dose. At high altitude, geomagnetic latitude has very little effect on the shape of the spectrum, but it is the dominant variable affecting neutron fluence rate, which was 8 times higher at the northernmost measurement location than it was at the southernmost. The shape of the spectrum varied only slightly with altitude from 21 km down to 12 km (56 - 201 grams per square centimeter atmospheric depth), but was significantly different on the ground. In all cases, ambient dose equivalent was greater than effective dose for cosmic-ray neutrons.

Evaluation of the dosimetric properties of a synthetic single crystal diamond detector in high energy clinical proton beams.

PubMed

Mandapaka, A K; Ghebremedhin, A; Patyal, B; Marinelli, Marco; Prestopino, G; Verona, C; Verona-Rinati, G

2013-12-01

To investigate the dosimetric properties of a synthetic single crystal diamond Schottky diode for accurate relative dose measurements in large and small field high-energy clinical proton beams. The dosimetric properties of a synthetic single crystal diamond detector were assessed by comparison with a reference Markus parallel plate ionization chamber, an Exradin A16 microionization chamber, and Exradin T1a ion chamber. The diamond detector was operated at zero bias voltage at all times. Comparative dose distribution measurements were performed by means of Fractional depth dose curves and lateral beam profiles in clinical proton beams of energies 155 and 250 MeV for a 14 cm square cerrobend aperture and 126 MeV for 3, 2, and 1 cm diameter circular brass collimators. ICRU Report No. 78 recommended beam parameters were used to compare fractional depth dose curves and beam profiles obtained using the diamond detector and the reference ionization chamber. Warm-up∕stability of the detector response and linearity with dose were evaluated in a 250 MeV proton beam and dose rate dependence was evaluated in a 126 MeV proton beam. Stem effect and the azimuthal angle dependence of the diode response were also evaluated. A maximum deviation in diamond detector signal from the average reading of less than 0.5% was found during the warm-up irradiation procedure. The detector response showed a good linear behavior as a function of dose with observed deviations below 0.5% over a dose range from 50 to 500 cGy. The detector response was dose rate independent, with deviations below 0.5% in the investigated dose rates ranging from 85 to 300 cGy∕min. Stem effect and azimuthal angle dependence of the diode signal were within 0.5%. Fractional depth dose curves and lateral beam profiles obtained with the diamond detector were in good agreement with those measured using reference dosimeters. The observed dosimetric properties of the synthetic single crystal diamond detector indicate that its behavior is proton energy independent and dose rate independent in the investigated energy and dose rate range and it is suitable for accurate relative dosimetric measurements in large as well as in small field high energy clinical proton beams.

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.

Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

NASA Technical Reports Server (NTRS)

Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

2011-01-01

Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT cells and misrejoined breaks increased in both cell lines. The present study suggests that AT cells begin to rejoin breaks when a certain number of breaks are accumulated and an increased number of exchanges were observed in G0 AT cells, which is similar situation after high-dose-rate irradiation.

Switching to aripiprazole in outpatients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues with risperidone: a randomized, multicentre, open-label study.

PubMed

Ryckmans, V; Kahn, J P; Modell, S; Werner, C; McQuade, R D; Kerselaers, W; Lissens, J; Sanchez, R

2009-05-01

This study evaluated the safety/tolerability and effectiveness of aripiprazole titrated-dose versus fixed-dose switching strategies from risperidone in patients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues. Patients were randomized to an aripiprazole titrated-dose (starting dose 5 mg/day) or fixed-dose (dose 15 mg/day) switching strategy with risperidone down-tapering. Primary endpoint was rate of discontinuation due to adverse events (AEs) during the 12-week study. Secondary endpoints included positive and negative syndrome scale (PANSS), clinical global impressions - improvement of illness scale (CGI-I), preference of medication (POM), subjective well-being under neuroleptics (SWN-K) and GEOPTE (Grupo Español para la Optimización del Tratamiento de la Esquizofrenia) scales. Rates of discontinuations due to AEs were similar between titrated-dose and fixed-dose strategies (3.5% vs. 5.0%; p=0.448). Improvements in mean PANSS total scores were similar between aripiprazole titrated-dose and fixed-dose strategies (-14.8 vs. -17.2; LOCF), as were mean CGI-I scores (2.9 vs. 2.8; p=0.425; LOCF) and SWN-K scores (+8.6 vs.+10.3; OC,+7.8 vs.+9.8; LOCF). Switching can be effectively and safely achieved through a titrated-dose or fixed-dose switching strategy for aripiprazole, with down-titration of risperidone.

Physiological effects following administration of Citrus aurantium for 28 days in rats

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

Hansen, Deborah K., E-mail: deborah.hansen@fda.hhs.gov; George, Nysia I.; White, Gene E.

Background: Since ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats. Method: Female Sprague–Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extractmore » contained 95% synephrine. Doses were 10 or 50 mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats. Results and conclusion: Synephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine.« less

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.

The role of temperature increase rate in combinational hyperthermia chemotherapy treatment

NASA Astrophysics Data System (ADS)

Tang, Yuan; McGoron, Anthony J.

2010-02-01

Hyperthermia in combination with chemotherapy has been widely used in cancer treatment. Our previous study has shown that rapid rate hyperthermia in combination with chemotherapy can synergistically kill cancer cells whereas a sub-additive effect was found when a slow rate hyperthermia was applied. In this study, we explored the basis of this difference. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. P-glycoprotein (P-gp) expression, Caspase 3 activity, and heat shock protein 70 (HSP 70) expression following the two different modes of heating were measured. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. Slow rate hyperthermia was provided by a cell culture incubator. Two sets of thermal doses were delivered by either slow rate or rapid rate hyperthermia. HSP70 expression was highly elevated under low dose slow rate incubator hyperthermia while maintained at the baseline level under the other three treatments. Caspase3 level slightly increased after low dose slow rate incubator hyperthermia while necrotic cell death was found in the other three types of heat treatment. In conclusion, when given at the same thermal dose, slow rate hyperthermia is more likely to induce thermotolerance. Meanwhile, hyperthermia showed a dose dependent capability in reversing P-gp mediated MDR; when MDR is reversed, the combinational treatment induced extensive necrotic cell death. During this process, the rate of heating also played a very important role; necrosis was more dramatic in rapid rate hyperthermia than in slow rate hyperthermia even though they were given at the same dose.

Comparison Between Prospectively Electrocardiogram-Gated High-Pitch Mode and Retrospectively Electrocardiogram-Gated Mode for Dual-Source CT Coronary Angiography.

PubMed

Koplay, Mustafa; Celik, Mahmut; Avcı, Ahmet; Erdogan, Hasan; Demir, Kenan; Sivri, Mesut; Nayman, Alaaddin

2015-01-01

We aimed to report the image quality, relationship between heart rate and image quality, amount of contrast agent given to the patients and radiation doses in coronary CT angiography (CTA) obtained by using high-pitch prospectively ECG-gated "Flash Spiral" technique (method A) or retrospectively ECG-gated technique (method B) using 128×2-slice dual-source CT. A total of 110 patients who were evaluated with method A and method B technique with a 128×2-detector dual-source CT device were included in the study. Patients were divided into three groups based on their heart rates during the procedure, and a relationship between heart rate and image quality were evaluated. The relationship between heart rate, gender and radiation dose received by the patients was compared. A total of 1760 segments were evaluated in terms of image quality. Comparison of the relationship between heart rate and image quality revealed a significant difference between heart rate <60 beats/min group and >75 beats/min group whereas <60 beats/min and 60-75 beats/min groups did not differ significantly. The average effective dose for coronary CTA was calculated as 1.11 mSv (0.47-2.01 mSv) for method A and 8.22 mSv (2.19-12.88 mSv) for method B. Method A provided high quality images with doses as low as <1 mSv in selected patients who have low heart rates with a high negative predictive value to rule out coronary artery disease. Although method B increases the amount of effective dose, it provides high diagnostic quality images for patients who have a high heart rate and arrhythmia which makes it is difficult to obtain images.

The effect of low dose rate irradiation on the tensile properties and microstructure of austenitic stainless steel.

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

Allen, T. R.; Tsai, H.; Cole, J. I.

2002-09-17

To assess the effects of long-term, low-dose-rate neutron exposure on mechanical strength and ductility, tensile properties were measured on 12% and 20% cold-worked Type 316 stainless steel. Samples were prepared from reactor core components retrieved from the EBR-II reactor following final shutdown. Sample locations were chosen to cover a dose range of 1-56 dpa at temperatures from 371-440 C and dose rates from 0.5-5.8 x10{sup -7} dpa/s. These dose rates are approximately an order of magnitude lower than those of typical EBR-II test sample locations. The tensile tests for the 12% CW material were performed at 380 C and 430more » C while those for the 20% CW samples were performed at 370 C. In each case, the tensile test temperature approximately matched the irradiation temperature. To help understand the tensile properties, microstructural samples with similar irradiation history were also examined. The strength and loss of work hardening increase the fastest as a function of irradiation dose for the 12% CW material irradiated at lower temperature. The decrease in ductility with increasing dose occurs more rapidly for the 12% CW material irradiated at lower temperature and the 20% cold-worked material. Post-tensile test fractography indicates that at higher dose, the 20% CW samples begin a shift in fracture mode from purely ductile to mainly small facets and slip bands, suggesting a transition toward channel fracture. The fracture for all of the 12% cold-worked samples was ductile. For both the 12% and 20% CW materials, the yield strength increases correlate with changes in void and loop density and size.« less

Dose-dependent heart rate reducing effect of nizatidine, a histamine H2-receptor antagonist.

PubMed Central

Hinrichsen, H; Halabi, A; Fuhrmann, G; Kirch, W

1993-01-01

1. Twelve healthy subjects were treated in a randomised placebo-controlled crossover study with placebo, 150 mg, 300 mg, and 600 mg nizatidine, 100 mg pirenzepine, and 300 mg nizatidine plus 100 mg pirenzepine for 1 week each. 2. On the seventh treatment day, heart rate, blood pressure, systolic time intervals, impedance cardiographic and Doppler ultrasound variables were measured. 3. Stroke volume and blood pressure were not altered by nizatidine and/or pirenzepine. By contrast, heart rate and cardiac output significantly (P < 0.05) decreased in a dose-dependent manner 1.5 and 3 h after administration of 300 and 600 mg nizatidine. Treatment with 150 mg nizatidine led to similar though non-significant trends. 4. While a slightly insignificant rise in heart rate was detected with pirenzepine alone, heart rate and cardiac output remained unchanged upon combined nizatidine and pirenzepine treatment as compared with placebo and baseline values. 5. In conclusion, nizatidine reduced heart rate and cardiac output in a dose-dependent manner, whereas this negative chronotropic effect was counteracted by concurrent administration of the anti-cholinergic drug pirenzepine. PMID:8099802

Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

NASA Astrophysics Data System (ADS)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for γ-radiation. When total doses of 96 or 247 cGy of neutrons or γ rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and γ-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or γ rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for γ rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

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

A comparison of the central nervous system effects of haloperidol, chlorpromazine and sulpiride in normal volunteers.

PubMed Central

McClelland, G R; Cooper, S M; Pilgrim, A J

1990-01-01

1. Twelve healthy male volunteers participated in four experimental occasions during each of which they were dosed with one of the following anti-psychotic drugs: chlorpromazine (50 mg), haloperidol (3 mg), sulpiride (400 mg) and placebo. Drugs were allocated to subjects in a double-blind, crossover fashion. 2. The subject's mood state, psychometric performance and electroencephalogram (EEG) were assessed pre-dose, and at 2, 4, 6, 8, 24 and 48 h post-dose. Mood states were assessed using 16 visual analogue scales and psychomotor performance was measured using the following tests: elapsed time estimation, tapping rate, choice reaction times, a rapid information processing task, flash fusion threshold, a manipulative motor task, digit span, body sway and tremor. 3. Chlorpromazine and haloperidol significantly reduced subjective ratings of 'alertness' and 'contentedness', and haloperidol significantly reduced feelings of 'calmness'. Sulpiride did not significantly affect any of the visual analogue scales. 4. All three anti-psychotic drugs had similar EEG effects with peak effect 2 to 4 h postdose. The profile was characterised by an increase in the proportion of slow wave activity (delta and theta) as well as decreased alpha (8-14 Hz) and faster (beta) wave activity. 5. Chlorpromazine reduced tapping rate and increased choice reaction movement times. Haloperidol reduced the flash fusion threshold frequency at 6 h post-dose. Sulpiride prolonged the duration of the manipulative motor task, particularly at 48 h post-dose. 6. All three anti-psychotic drugs impaired performance on the rapid information processing task. Chlorpromazine significantly reduced the number of correct letter pair identifications at 2, 4 and 6 h post-dose, haloperidol at 4, 6, 8, 24 and 48 h post-dose, and sulpiride at 24 h post-dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2288826

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

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Richardson, Richard B.

2015-07-01

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

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

PubMed

El-Jaby, Samy; Richardson, Richard B

2015-07-01

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

Low or High Fractionation Dose {beta}-Radiotherapy for Pterygium? A Randomized Clinical Trial

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

Viani, Gustavo Arruda, E-mail: gusviani@gmail.com; De Fendi, Ligia Issa; Fonseca, Ellen Carrara

2012-02-01

Purpose: Postoperative adjuvant treatment using {beta}-radiotherapy (RT) is a proven technique for reducing the recurrence of pterygium. A randomized trial was conducted to determine whether a low fractionation dose of 2 Gy within 10 fractions would provide local control similar to that after a high fractionation dose of 5 Gy within 7 fractions for surgically resected pterygium. Methods: A randomized trial was conducted in 200 patients (216 pterygia) between February 2006 and July 2007. Only patients with fresh pterygium resected using a bare sclera method and given RT within 3 days were included. Postoperative RT was delivered using a strontium-90more » eye applicator. The pterygia were randomly treated using either 5 Gy within 7 fractions (Group 1) or 2 Gy within 10 fractions (Group 2). The local control rate was calculated from the date of surgery. Results: Of the 216 pterygia included, 112 were allocated to Group 1 and 104 to Group 2. The 3-year local control rate for Groups 1 and 2 was 93.8% and 92.3%, respectively (p = .616). A statistically significant difference for cosmetic effect (p = .034), photophobia (p = .02), irritation (p = .001), and scleromalacia (p = .017) was noted in favor of Group 2. Conclusions: No better local control rate for postoperative pterygium was obtained using high-dose fractionation vs. low-dose fractionation. However, a low-dose fractionation schedule produced better cosmetic effects and resulted in fewer symptoms than high-dose fractionation. Moreover, pterygia can be safely treated in terms of local recurrence using RT schedules with a biologic effective dose of 24-52.5 Gy{sub 10.}.« less

Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study.

PubMed

Ragavendran, J Vaigunda; Laferrière, André; Bennett, Gary J; Ware, Mark A; Gandhi, Wiebke; Bley, Keith; Schweinhardt, Petra; Coderre, Terence J

2016-10-01

This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain. Of 69 healthy subjects aged 18 to 60 years, 23 each were randomly allocated to low-dose (0.04% + 2%) and high-dose (0.1% + 5%) CLON + PTX groups. Both of these groups also received their corresponding placebos in one of 2 treatment periods separated by at least 48 hours. Twenty-three additional subjects received either CLON (0.1%) or PTX (5%) as single drug treatments, in each of 2 treatment periods. Assessment of analgesic efficacy was based on allodynic effects of previous intraepidermal capsaicin injection, as well as postcapsaicin tourniquet-induced pain 50 minutes following capsaicin injection. Visual Analogue Scale (VAS) ratings of pain intensity and the area of dynamic mechanical allodynia were the primary outcome measures, whereas area of punctate mechanical allodynia (PMA) served as a secondary outcome measure. Topical treatments with high- or low-dose combinations significantly reduced VAS ratings compared with corresponding placebo treatments throughout the period of postcapsaicin tourniquet-induced pain. Importantly, the high-dose combination produced lower VAS ratings than CLON alone, which were lower than PTX alone. Results also revealed significant inhibition of postcapsaicin dynamic mechanical allodynia and PMA for the high-dose combination compared with placebo, and of PMA for CLON compared with the low-dose combination. Hence, the present data are supportive of further clinical investigation of the high-dose topical combination of CLON + PTX in complex regional pain syndrome and neuropathic pain patients, for which our preclinical data predict efficacy.

A consistent two-mutation model of bone cancer for two data sets of radium-injected beagles.

PubMed

Bijwaard, H; Brugmans, M J P; Leenhouts, H P

2002-09-01

A two-mutation carcinogenesis model has been applied to model osteosarcoma incidence in two data sets of beagles injected with 226Ra. Taking age-specific retention into account, the following results have been obtained: (1) a consistent and well-fitting solution for all age and dose groups, (2) mutation rates that are linearly dependent on dose rate, with an exponential decrease for the second mutation at high dose rates, (3) a linear-quadratic dose-effect relationship, which indicates that care should be taken when extrapolating linearly, (4) highest cumulative incidences for injection at young adult age, and highest risks for injection doses of a few kBq kg(-1) at these ages, and (5) when scaled appropriately, the beagle model compares fairly well with a description for radium dial painters, suggesting that a consistent model description of bone cancer induction in beagles and humans may be possible.

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

PubMed

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

2018-06-08

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

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception.

PubMed

Shohel, Mohammad; Rahman, Mohammad Mahfuzur; Zaman, Asif; Uddin, Mir Muhammad Nasir; Al-Amin, Md Mamun; Reza, Hasan Mahmud

2014-04-04

Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12-24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given, the more effective it seems to be.

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception

PubMed Central

2014-01-01

Background Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Methods Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Results Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12–24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. Conclusions The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given, the more effective it seems to be. PMID:24708837

Demonstration of an adaptive response to preconditioning Frankliniella occidentalis (Pergande) to sublethal doses of spinosad: a hormetic-dose response.

PubMed

Gong, Youhui; Xu, Baoyun; Zhang, Youjun; Gao, Xiwu; Wu, Qingjun

2015-07-01

Sublethal doses of some insecticides have been reported to either stimulate or reduce the survival and fecundity of insects. Many sublethal-effect studies have been conducted after exposure of only one generation to sublethal insecticides, and there is little information about the sublethal effects on insects after long-term exposure to sublethal insecticides. In this study, changes in biological characteristics were investigated in spinosad-susceptible (Spin-S) and sublethal-spinosad-treated (Spin-Sub) strains of Frankliniella occidentalis (Pergande) after exposure to their corresponding sublethal concentrations of spinosad. The results showed that for the Spin-S strain, the LC10 concentration of spinosad slightly affected the biotic fitness both in parents and offspring of F. occidentalis. The LC25 concentration of spinosad prolonged the development time, reduced the fecundity, and significantly reduced the intrinsic rate of increase, the net reproductive rate and the finite rate of increase in the Spin-S strain. However, the negative effects were not as pronounced in the offspring (F1 generation) as in the parent generation. For the Spin-Sub strain, the LC10 and LC25 concentrations of spinosad had little negative effect on the development and fecundity, and no significant difference was found between the effects of the LC10 and LC25 treatments on the Spin-Sub strain. The Spin-Sub strain exhibited a shorter developmental time, and larger intrinsic rates of increase and net reproductive rates, compared with the corresponding treatments of the Spin-S strain. These findings combined with our previous studies suggest that the biotic fitness increased in the Spin-Sub strain and the strain became more adaptable to sublethal doses of spinosad, compared with the Spin-S strain. Physiological and biochemical adaptation may contribute to these changes after long treatment times at sublethal doses.

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis

PubMed Central

Haney, Margaret; Malcolm, Robert J; Babalonis, Shanna; Nuzzo, Paul A; Cooper, Ziva D; Bedi, Gillinder; Gray, Kevin M; McRae-Clark, Aimee; Lofwall, Michelle R; Sparenborg, Steven; Walsh, Sharon L

2016-01-01

Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ9-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30–5.80% THC). Non-treatment-seeking, healthy cannabis smokers (n=31; 17M, 14 F) completed eight outpatient sessions. CBD was administered 90 min prior to cannabis administration. The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session. A subset of participants (n=8) completed an additional session to measure plasma CBD concentrations after administration of the highest CBD dose (800 mg). Under placebo CBD conditions, active cannabis (1) was self-administered by significantly more participants than placebo cannabis and (2) produced significant, time-dependent increases in ratings of ‘High', ‘Good Effect', ratings of the cannabis cigarette (eg, strength, liking), and heart rate relative to inactive cannabis. CBD, which alone produced no significant psychoactive or cardiovascular effects, did not significantly alter any of these outcomes. Cannabis self-administration, subjective effects, and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules. These findings suggest that oral CBD does not reduce the reinforcing, physiological, or positive subjective effects of smoked cannabis. PMID:26708108

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis.

PubMed

Haney, Margaret; Malcolm, Robert J; Babalonis, Shanna; Nuzzo, Paul A; Cooper, Ziva D; Bedi, Gillinder; Gray, Kevin M; McRae-Clark, Aimee; Lofwall, Michelle R; Sparenborg, Steven; Walsh, Sharon L

2016-07-01

Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ(9)-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30-5.80% THC). Non-treatment-seeking, healthy cannabis smokers (n=31; 17M, 14 F) completed eight outpatient sessions. CBD was administered 90 min prior to cannabis administration. The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session. A subset of participants (n=8) completed an additional session to measure plasma CBD concentrations after administration of the highest CBD dose (800 mg). Under placebo CBD conditions, active cannabis (1) was self-administered by significantly more participants than placebo cannabis and (2) produced significant, time-dependent increases in ratings of 'High', 'Good Effect', ratings of the cannabis cigarette (eg, strength, liking), and heart rate relative to inactive cannabis. CBD, which alone produced no significant psychoactive or cardiovascular effects, did not significantly alter any of these outcomes. Cannabis self-administration, subjective effects, and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules. These findings suggest that oral CBD does not reduce the reinforcing, physiological, or positive subjective effects of smoked cannabis.

An evaluation of some pertinent parameters that influence the dosimetric performance of synthetic diamond detectors

NASA Astrophysics Data System (ADS)

Ade, N.; Nam, T. L.; Mhlanga, S. H.

2013-05-01

Although the near-tissue equivalence of diamond allows the direct measurement of dose for clinical applications without the need for energy-corrections, it is often cited that diamond detectors require pre-irradiation, a procedure necessary to stabilize the response or sensitivity of a diamond detector before dose measurements. In addition it has been pointed out that the relative dose measured with a diamond detector requires dose rate dependence correction and that the angular dependence of a detector could be due to its mechanical design or to the intrinsic angular sensitivity of the detection process. While the cause of instability of response has not been meticulously investigated, the issue of dose rate dependence correction is uncertain as some studies ignored it but reported good results. The aims of this study were therefore to investigate, in particular (1) the major cause of the unstable response of diamond detectors requiring pre-irradiation; (2) the influence of dose rate dependence correction in relative dose measurements; and (3) the angular dependence of the diamond detectors. The study was conducted with low-energy X-rays and electron therapy beams on HPHT and CVD synthesized diamonds. Ionization chambers were used for comparative measurements. Through systematic investigations, the major cause of the unstable response of diamond detectors requiring the recommended pre-irradiation step was isolated and attributed to the presence and effects of ambient light. The variation in detector's response between measurements in light and dark conditions could be as high as 63% for a CVD diamond. Dose rate dependence parameters (Δ values) of 0.950 and 1.035 were found for the HPHT and CVD diamond detectors, respectively. Without corrections based on dose rate dependence, the relative differences between depth-doses measured with the diamond detectors and a Markus chamber for exposures to 7 and 14 MeV electron beams were within 2.5%. A dose rate dependence correction using the Δ values obtained seemed to worsen the performance of the HPHT sample (up to about 3.3%) but it had a marginal effect on the performance of the CVD sample. In addition, the angular response of the CVD diamond detector was shown to be comparable with that of a cylindrical chamber. This study concludes that once the responses of the diamond detectors have been stabilised and they are properly shielded from ambient light, pre-irradiation prior to each measurement is not required. Also, the relative dose measured with the diamond detectors do not require dose rate dependence corrections as the required correction is only marginal and could have no dosimetric significance.

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.

Laser-based irradiation apparatus and methods for monitoring the dose-rate response of semiconductor devices

DOEpatents

Horn, Kevin M [Albuquerque, NM

2006-03-28

A scanned, pulsed, focused laser irradiation apparatus can measure and image the photocurrent collection resulting from a dose-rate equivalent exposure to infrared laser light across an entire silicon die. Comparisons of dose-rate response images or time-delay images from before, during, and after accelerated aging of a device, or from periodic sampling of devices from fielded operational systems allows precise identification of those specific age-affected circuit structures within a device that merit further quantitative analysis with targeted materials or electrical testing techniques. Another embodiment of the invention comprises a broad-beam, dose rate-equivalent exposure apparatus. The broad-beam laser irradiation apparatus can determine if aging has affected the device's overall functionality. This embodiment can be combined with the synchronized introduction of external electrical transients into a device under test to simulate the electrical effects of the surrounding circuitry's response to a radiation exposure.

Effects of γ ray irradiation on Vibrio Qinghaiensis sp. Q67

NASA Astrophysics Data System (ADS)

Wei, Yan; Linping, Kuai

2017-12-01

In order to investigate the luminous responses of γ ray irradiation on Vibrio Qinghaiensis sp. Q67, two γ ray sources, 60Co and 137Cs, were used. Following the dose rates between 0.05Gy/min and 0.2Gy/min of 60Co, the relative luminous value (RLV ) of Q67 was less than 1 after 5 minutes irradiation and inversely related to dose rate. Irradiated 1 hour at dose rates range from 100nGy/h to 10mGy/h of 137Cs, two successive stages in the luminous response were found: hormesis and inhibition. It was found that RLV was interleaved and could not be distinguished until inhibition stage appearance. The time when RLV drops to less than 1 (T0 ) was linear with the logarithm of dose rate. Experimental result indicates that Q67 is sensitive to acute γray radiation, which could be used to monitor γray radiation.

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

PubMed

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

2018-05-15

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

WE-EF-BRA-06: Feasibility of Spatially Modulated Proton Beams for Small Animal Research

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

Lee, E; Meyer, J

Purpose: To investigate the feasibility of proton minibeam radiotherapy (pMBRT) for small animal research. The motivation is to explore with protons the extraordinary normal tissue sparing effects to spatially modulated beams as observed on high flux synchrotron beam lines. We hypothesized that we can design a multi-slit collimator for our proton beam line to produce planar-parallel dose profiles with high modulation in the entrance region and homogenous dose coverage in the overlap of the Bragg peaks. Methods: The high dose rate 50 MeV research proton beamline at the University of Washington was modeled using the TOol for PArticle Simulation (TOPAS)more » Monte Carlo package. A brass collimator was implemented to generate proton minibeams. The collimator consists of an array of 2 cm long slits to cover an area of 2×2 cm{sup 2}. The slit widths (0.1–1 mm), center-to-center (ctc) distances (1–3 mm) and collimator thickness (1–7 cm) were varied to evaluate the effect on dose rate, the peak-to-valley dose ratios (PVDR) and the change of penumbra and peak width (FWHM) with depth. Results: The Bragg peak was at a depth of ∼21 mm. The penumbra and FWHM remained relatively constant to a depth of about 10–15 mm. The PVDR ranged from 1.6 to 26 and the dose rate dropped exponentially with collimator thickness. A uniform dose can be achieved at depth with slightly compromised PVDRs and dose rate. Conclusion: The technical realization of pMBRT is feasible. The simulations have shown that it is possible to obtain uniform dose at depth while modulation is maintained on the entrance side. While the simulated beam widths are larger than on synchrotron generated microbeams the dosimetric advantage could avoid having to interlace two microbeams to achieve uniform dose in the target. The next steps are to build a collimator and verify the simulations experimentally.« less

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

PubMed

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

2017-01-01

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

Temporal variation of dose rate distribution around the Fukushima Daiichi nuclear power station using unmanned helicopter.

PubMed

Sanada, Yukihisa; Orita, Tadashi; Torii, Tatsuo

2016-12-01

Aerial radiological survey using an unmanned aerial vehicle (UAV) was applied to measurement surface contamination around the Fukushima Daiichi nuclear power station (FDNPS). An unmanned helicopter monitoring system (UHMS) was developed to survey the environmental effect of radioactive cesium scattered as a result of the FDNPS accident. The UHMS was used to monitor the area surrounding the FDNPS six times from 2012 to 2015. Quantitative changes in the radioactivity distribution trend were revealed from the results of these monitoring runs. With this information, we found that the actual reduction of dose rate was faster than the one calculated with radiocesium physical half-life. It is indicated that the attenuation effect of radiation by radiocesium penetration in soil is dominant as for reason of reduction of dose rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-10-01

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

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

PubMed

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

2018-02-27

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

Health effects in women exposed to low levels of ionizing radiation

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

Fabrikant, J.I.

1982-06-01

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

The effect of dosing regimen on the pharmacokinetics of risedronate

PubMed Central

Mitchell, David Y; Heise, Mark A; Pallone, Karen A; Clay, Marian E; Nesbitt, John D; Russell, Darrell A; Melson, Chad W

1999-01-01

Aims To examine the effect of timing of a risedronate dose relative to food intake on the rate and extent of risedronate absorption following single-dose, oral administration to healthy male and female volunteers. Methods A single-dose, randomized, parallel study design was conducted with volunteers assigned to four treatment groups (31 or 32 subjects per group, 127 subjects total). Each subject was orally administered 30 mg risedronate. Group 1 was fasted for 10 h prior to and 4 h after dosing (fasted group); Groups 2 and 3 were fasted for 10 h and were dosed 1 and 0.5 h, respectively, before a high-fat breakfast; and Group 4 was dosed 2 h after a standard dinner. Blood and urine samples were collected for 168 h after dosing. Pharmacokinetic parameters were estimated by simultaneous analysis of risedronate serum concentration and urinary excretion rate-time data. Results Extent of risedronate absorption (AUC and Ae) was comparable (P = 0.4) in subjects dosed 2 h after dinner and 0.5 h before breakfast; however, a significantly greater extent of absorption occurred when risedronate was given 1 or 4 h prior to a meal (1.4- to 2.3-fold greater). Administration 0.5, 1, or 4 h prior to a meal resulted in a significantly greater rate of absorption (Cmax 2.8-, 3.5-, and 4.1-fold greater, respectively) when compared with 2 h after dinner. Conclusions The comparable extent of risedronate absorption when administered either 0.5–1 h before breakfast or 2 h after an evening meal support previous clinical studies where risedronate was found to have similar effectiveness using these dosing regimens. This flexibility in the timing of risedronate administration may provide patients an alternative means to achieve the desired efficacy while maintaining their normal daily routine. PMID:10583024

Effects of Epoetin Alfa Titration Practices, Implemented After Changes to Product Labeling, on Hemoglobin Levels, Transfusion Use, and Hospitalization Rates.

PubMed

Molony, Julia T; Monda, Keri L; Li, Suying; Beaubrun, Anne C; Gilbertson, David T; Bradbury, Brian D; Collins, Allan J

2016-08-01

Little is known about epoetin alfa (EPO) dosing at dialysis centers after implementation of the US Medicare prospective payment system and revision of the EPO label in 2011. Retrospective cohort study. Approximately 412,000 adult hemodialysis patients with Medicare Parts A and B as primary payer in 2009 to 2012 to describe EPO dosing and hemoglobin patterns; of these, about 70,000 patients clustered in about 1,300 dialysis facilities to evaluate facility-level EPO titration practices and patient-level outcomes in 2012. Facility EPO titration practices when hemoglobin levels were <10 and >11g/dL (grouped treatment variable) determined from monthly EPO dosing and hemoglobin level patterns. Patient mean hemoglobin levels, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates using a facility-based analysis. Monthly EPO dose and hemoglobin level, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates. Monthly EPO doses declined across all hemoglobin levels, with the greatest decline in patients with hemoglobin levels < 10g/dL (July-October 2011). In 2012, nine distinct facility titration practices were identified. Across groups, mean hemoglobin levels differed slightly (10.5-10.8g/dL) but within-patient hemoglobin standard deviations were similar (∼0.68g/dL). Patients at facilities implementing greater dose reductions and smaller dose escalations had lower hemoglobin levels and higher transfusion rates. In contrast, patients at facilities that implemented greater dose escalations (and large or small dose reductions) had higher hemoglobin levels and lower transfusion rates. There were no clinically meaningful differences in all-cause or cause-specific hospitalization events across groups. Possibly incomplete claims data; excluded small facilities and those without consistent titration patterns; hemoglobin levels reported monthly; inferred facility practice from observed dosing. Following prospective payment system implementation and labeling revisions, EPO doses declined significantly. Under the new label, facility EPO titration practices were associated with mean hemoglobin levels (but not standard deviations) and transfusion use, but not hospitalization rates. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Spectral Behavior of Irradiated Sodium Chloride Crystals Under Europa-Like Conditions

NASA Astrophysics Data System (ADS)

Poston, Michael J.; Carlson, Robert W.; Hand, Kevin P.

2017-12-01

F- and M-color center formation (decay) was observed during (after) irradiation of sodium chloride crystal grains with 10 keV electrons as a function of temperature, radiation dose rate, and radiation dose. The F centers (peak center: 460 nm) were found to form and decay at a faster rate than the M centers (peak center: 720 nm). These effects were influenced by temperature and possibly by irradiation dose rate. Tracking the band depth ratio of the color center features during irradiation could enable age determination of geologically very young features on the surface of Europa and other icy ocean worlds.

Physiological and performance effects of pyridostigmine bromide in healthy volunteers: a dose-response study.

PubMed

Cook, Mary R; Graham, Charles; Sastre, Antonio; Gerkovich, Mary M

2002-07-01

Questions have been raised about the role pyridostigmine bromide (PB) plays in the etiology of Gulf War veterans' illnesses. There is a need to understand better the physiological and behavioral effects of this drug, particularly at the 30-mg/8-h regimen recommended by the US Military. OBJECTIVE. To perform a double-blind, cross-over, dose-response study of PB in 67 healthy, young volunteers (31 women, 36 men). Volunteers were initially trained on a standardized test battery. Supervised administration of placebo (PL) and PB (every 8 h/5 days) occurred in each of two dosing weeks, separated by a non-dosing week. One group received 30 mg PB and PL, and the other 60 mg PB and PL. In each dosing week, the battery was performed after the first pill and again when steady-state plasma PB levels were achieved. PB was associated with an overall improvement in reaction time on tests of memory and attention, and with a reduction in RMS error on a tracking task. PB slowed heart rate and decreased the high frequency component of heart rate variability (HF HRV). Dose-response effects were found only for HF HRV, and RMS error. The extent of cholinesterase inhibition was directly related to the magnitude of the HF HRV decrease, and was predicted by the weight-normalized PB dose. Cholinesterase inhibition was not related to the extent or severity of reported drug side effects. PB does not appear to have detrimental physiological or performance consequences at the recommended 30-mg dose, or at twice that dose, when evaluated under non-stressful laboratory conditions.

Exposure of luminous marine bacteria to low-dose gamma-radiation.

PubMed

Kudryasheva, N S; Petrova, A S; Dementyev, D V; Bondar, A A

2017-04-01

The study addresses biological effects of low-dose gamma-radiation. Radioactive 137 Cs-containing particles were used as model sources of gamma-radiation. Luminous marine bacterium Photobacterium phosphoreum was used as a bioassay with the bioluminescent intensity as the physiological parameter tested. To investigate the sensitivity of the bacteria to the low-dose gamma-radiation exposure (≤250 mGy), the irradiation conditions were varied as follows: bioluminescence intensity was measured at 5, 10, and 20°С for 175, 100, and 47 h, respectively, at different dose rates (up to 4100 μGy/h). There was no noticeable effect of gamma-radiation at 5 and 10°С, while the 20°С exposure revealed authentic bioluminescence inhibition. The 20°С results of gamma-radiation exposure were compared to those for low-dose alpha- and beta-radiation exposures studied previously under comparable experimental conditions. In contrast to ionizing radiation of alpha and beta types, gamma-emission did not initiate bacterial bioluminescence activation (adaptive response). As with alpha- and beta-radiation, gamma-emission did not demonstrate monotonic dose-effect dependencies; the bioluminescence inhibition efficiency was found to be related to the exposure time, while no dose rate dependence was found. The sequence analysis of 16S ribosomal RNA gene did not reveal a mutagenic effect of low-dose gamma radiation. The exposure time that caused 50% bioluminescence inhibition was suggested as a test parameter for radiotoxicity evaluation under conditions of chronic low-dose gamma irradiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis.

PubMed

Xu, Ying; Hackett, Maree; Carter, Gregory; Loo, Colleen; Gálvez, Verònica; Glozier, Nick; Glue, Paul; Lapidus, Kyle; McGirr, Alexander; Somogyi, Andrew A; Mitchell, Philip B; Rodgers, Anthony

2016-04-01

Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5 mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50 mg intra-nasal spray, another assessed 0.1-0.4 mg/kg i.v., and another assessed 0.1-0.5 mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6-7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2-5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis

PubMed Central

Xu, Ying; Hackett, Maree; Carter, Gregory; Gálvez, Verònica; Glozier, Nick; Glue, Paul; Lapidus, Kyle; McGirr, Alexander; Somogyi, Andrew A.; Mitchell, Philip B.; Rodgers, Anthony

2016-01-01

Background: Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. Methods: A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Results: Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50mg intra-nasal spray, another assessed 0.1–0.4mg/kg i.v., and another assessed 0.1–0.5mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6–7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2–5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Conclusion: Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety. PMID:26578082

Low-dose-rate or high-dose-rate brachytherapy in treatment of prostate cancer – between options

PubMed Central

2013-01-01

Purpose Permanent low-dose-rate (LDR-BT) and temporary high-dose-rate (HDR-BT) brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never to be conducted comparing these two forms of brachytherapy, a comparative analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. The aim of this paper is to look for possible similarities and differences between both brachytherapy modalities. Indications and contraindications for monotherapy and for brachytherapy as a boost to external beam radiation therapy (EBRT) are presented. It is suggested that each of these techniques has attributes that advocates for one or the other. First, they represent the extreme ends of the spectrum with respect to dose rate and fractionation, and therefore have inherently different radiobiological properties. Low-dose-rate brachytherapy has the great advantage of being practically a one-time procedure, and enjoys a long-term follow-up database supporting its excellent outcomes and low morbidity. Low-dose-rate brachytherapy has been a gold standard for prostate brachytherapy in low risk patients since many years. On the other hand, HDR is a fairly invasive procedure requiring several sessions associated with a brief hospital stay. Although lacking in significant long-term data, it possesses the technical advantage of control over its postimplant dosimetry (by modulating the source dwell time and position), which is absent in LDR brachytherapy. This important difference in dosimetric control allows HDR doses to be escalated safely, a flexibility that does not exist for LDR brachytherapy. Conclusions Radiobiological models support the current clinical evidence for equivalent outcomes in localized prostate cancer with either LDR or HDR brachytherapy, using current dose regimens. At present, all available clinical data regarding these two techniques suggests that they are equally effective, stage for stage, in providing high tumor control rates. PMID:23634153

Effect of the gamma radiation dose rate on psychrotrophic bacteria, thiobarbituric acid reactive substances, and sensory characteristics of mechanically deboned chicken meat.

PubMed

Brito, Poliana P; Azevedo, Heliana; Cipolli, Kátia M V A B; Fukuma, Henrique T; Mourão, Gerson B; Roque, Cláudio V; Miya, Norma T; Pereira, José L

2011-03-01

Frozen samples of mechanically deboned chicken meat (MDCM) with skin were irradiated with gamma radiation doses of 0.0 kGy (control) and 3 kGy at 2 different radiation dose rates: 0.32 kGy/h (3 kGy) and 4.04 kGy/h (3 kGy). Batches of irradiated and control samples were evaluated during 11 d of refrigerated (2 ± 1 °C) storage for the following parameters: total psychrotrophic bacteria count, thiobarbituric acid reactive substances (TBARS), evaluation of objective color (L*, a*, and b*) and a sensory evaluation (irradiated odor, oxidized odor, pink and brown colors). No statistical difference (P > 0.05) was found amongst the TBARS values obtained for the MDCM samples irradiated with dose rates of 0.32 and 4.04 kGy/h. There was a significant increase (P < 0.05) in the psychrotrophic bacterial count as from the 7th day of refrigerated storage, for the MDCM samples irradiated at the dose rate of 4.04 kGy/h. With respect to the attribute of oxidized odor, the samples irradiated with a dose rate of 0.32 kGy/h showed a stronger intensity and were significantly different (P < 0.05) from the sample irradiated with a dose rate of 4.04 kGy/h on days 0 and 2 of refrigerated storage. Irradiation with a dose rate of 4.04 kGy/h (3 kGy) was shown to be the best condition for the processing of MDCM according to the evaluation of all the variables, under the conditions of this study. Practical Application:  The results obtained for the application of different dose rates of ionizing radiation to mechanically deboned chicken meat will provide the food industry with information concerning the definition of the best processing conditions to maximize the sensory and food quality.

Food, Fun and Fitness Internet program for girls: influencing log-on rate

USDA-ARS?s Scientific Manuscript database

Internet-based interventions hold promise as an effective channel for reaching large numbers of youth. However, log-on rates, a measure of program dose, have been highly variable. Methods to enhance log-on rate are needed. Incentives may be an effective method. This paper reports the effect of reinf...

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

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

PubMed Central

Yasutaka, Tetsuo; Naito, Wataru; Nakanishi, Junko

2013-01-01

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

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

PubMed

Yasutaka, Tetsuo; Naito, Wataru; Nakanishi, Junko

2013-01-01

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

γ irradiation with different dose rates induces different DNA damage responses in Petunia x hybrida cells.

PubMed

Donà, Mattia; Ventura, Lorenzo; Macovei, Anca; Confalonieri, Massimo; Savio, Monica; Giovannini, Annalisa; Carbonera, Daniela; Balestrazzi, Alma

2013-05-15

In plants, there is evidence that different dose rate exposures to gamma (γ) rays can cause different biological effects. The dynamics of DNA damage accumulation and molecular mechanisms that regulate recovery from radiation injury as a function of dose rate are poorly explored. To highlight dose-rate dependent differences in DNA damage, single cell gel electrophoresis was carried out on regenerating Petunia x hybrida leaf discs exposed to LDR (total dose 50 Gy, delivered at 0.33 Gy min(-1)) and HDR (total doses 50 and 100 Gy, delivered at 5.15 Gy min(-1)) γ-ray in the 0-24h time period after treatments. Significant fluctuations of double strand breaks and different repair capacities were observed between treatments in the 0-4h time period following irradiation. Dose-rate-dependent changes in the expression of the PhMT2 and PhAPX genes encoding a type 2 metallothionein and the cytosolic isoform of ascorbate peroxidase, respectively, were detected by Quantitative RealTime-Polymerase Chain Reaction. The PhMT2 and PhAPX genes were significantly up-regulated (3.0- and 0.7-fold) in response to HDR. The results are discussed in light of the potential practical applications of LDR-based treatments in mutation breeding. Copyright © 2013 Elsevier GmbH. All rights reserved.

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.

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

PubMed Central

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

2018-01-01

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

Age, Sex, and Dose Effects of Nonbenzodiazepine Hypnotics on Hip Fracture in Nursing Home Residents.

PubMed

Dore, David D; Zullo, Andrew R; Mor, Vincent; Lee, Yoojin; Berry, Sarah D

2018-04-01

The Food and Drug Administration recommends a reduced dose of nonbenzodiazepine hypnotics in women, yet little is known about the age-, sex-, and dose-specific effects of these drugs on risk of hip fracture, especially among nursing home (NH) residents. We estimated the age-, sex-, and dose-specific effects of nonbenzodiazepine hypnotics on the rate of hip fracture among NH residents. Case-crossover study in US NHs. A total of 691 women and 179 men with hip fracture sampled from all US long-stay NH residents. Measures of patient characteristics were obtained from linked Medicare and the Minimum Data Set (2007-2008). The outcome was hospitalization for hip fracture with surgical repair. We estimated rate ratios (RRs) and 95% confidence intervals (CIs) from conditional logistic regression models for nonbenzodiazepine hypnotics (vs nonuse) comparing 0 to 29 days before hip fracture (hazard period) with 60 to 89 and 120 to 149 days before hip fracture (control periods). We stratified analyses by age, sex, and dose. The average RR of hip fracture was 1.7 (95% CI 1.5-1.9) for any use. The RR of hip fracture was higher for residents aged ≥90 years vs <70 years (2.2 vs 1.3); however, the CIs overlapped. No differences in the effect of the hypnotic on risk of hip fracture were evident by sex. Point estimates for hip fracture were greater with high-dose versus low-dose hypnotics (RR 1.9 vs 1.6 for any use), but these differences were highly compatible with chance. The rate of hip fracture in NH residents due to use of nonbenzodiazepine hypnotics was greater among older patients than among younger patients and, possibly, with higher doses than with lower doses. When clinicians are prescribing a nonbenzodiazepine hypnotic to any NH resident, doses of these drugs should be kept as low as possible, especially among those with advanced age. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

PubMed Central

Sandrini, G; Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G

2007-01-01

Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57–1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82–1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. Conclusion: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf. PMID:17627707

Effects of Different Doses of Irbesartan Combined With Spironolactone on Urinary Albumin Excretion Rate in Elderly Patients With Early Type 2 Diabetic Nephropathy.

PubMed

Chen, Yingying; Liu, Peng; Chen, Xia; Li, Yanan; Zhang, Fengmei; Wang, Yangang

2018-05-01

There is a lack of research on the effect of low dose of angiotensin receptor blockers combined with spironolactone, and the effect of high dose of angiotensin receptor blockers alone on the urinary albumin excretion rate (UAER) in elderly patients with early type 2 diabetic nephropathy (DN). We conducted a prospective, randomized, open-label, parallel-controlled study that included 244 elderly patients with early DN and mild-to-moderate essential hypertension. Patients were randomly divided into 4 groups: low-dose irbesartan (group A), high-dose irbesartan (group B), low-dose irbesartan combined with spironolactone (group C) and high-dose irbesartan combined with spironolactone (group D). Changes in UAER, serum potassium and blood pressure were compared. There were no statistical differences in the baseline characteristics among groups. Furthermore, no significant difference in blood pressure before and after treatment was found among different groups. After 72-week treatment, UAER in group D was lower compared to group A and B (P < 0.05). Meanwhile, compared with group B, UAER in group C decreased significantly (P < 0.05). Additionally, significantly higher serum potassium was found in group D compared to other groups (P < 0.05). Also, group D had the highest count of patients who withdrew from the study due to hyperkalemia compared to other groups (P < 0.05). Our results indicate high-dose irbesartan combined with spironolactone may be more efficient in reducing UAER in elderly patients with early DN, but this treatment could cause hyperkalemia. Low-dose irbesartan combined with spironolactone was shown to be safer and more effective in decreasing UAER compared to high-dose irbesartan. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Evaluation of the stepwise collimation method for the reduction of the patient dose in full spine radiography

NASA Astrophysics Data System (ADS)

Lee, Boram; Lee, Sunyoung; Yang, Injeong; Yoon, Myeonggeun

2014-05-01

The purpose of this study is to evaluate the dose reduction when using the stepwise collimation method for scoliosis patients undergoing full spine radiography. A Monte Carlo simulation was carried out to acquire dose vs. volume data for organs at risk (OAR) in the human body. While the effective doses in full spine radiography were reduced by 8, 15, 27 and 44% by using four different sizes of the collimation, the doses to the skin were reduced by 31, 44, 55 and 66%, indicating that the reduction of the dose to the skin is higher than that to organs inside the body. Although the reduction rates were low for the gonad, being 9, 14, 18 and 23%, there was more than a 30% reduction in the dose to the heart, suggesting that the dose reduction depends significantly on the location of the OARs in the human body. The reduction rate of the secondary cancer risk based on the excess absolute risk (EAR) varied from 0.6 to 3.4 per 10,000 persons, depending on the size of the collimation. Our results suggest that the stepwise collimation method in full spine radiography can effectively reduce the patient dose and the radiation-induced secondary cancer risk.

Effects of arbuscular mycorrhizal inoculation and fertilization on mycorrhizal Statute of Jacaranda mimosifolia D.Don cultivated in nurseries.

PubMed

Zaouchi, Yousr; Bahri, Nada Ben; Rezgui, S; Bettaieb, Taoufik

2013-10-01

The effects of fertilization and the nature of the inoculum as well as the variation of the dose intake of the latter on the level of Jacaranda mimosifolia D.Don mycorhization were tested. Young plants were treated with two inoculums presenting different origins, compositions and modes of application: one is a commercial product containing Glomus irregulare, and the other is a composite indigenous inoculum resulting from trapping five species of genus Glomus and also from multiplication on mycotrophic plants: leek (Allium porrum L.) and vetch (Vicia sativa L.). For each inoculum, two doses were tested and for each dose of inoculum, four levels of fertilization based on a complete commercial fertilizer (Osmocote) were tested: 0 g/plant, 2 g/plant, 4 g/plant, and 6g/plant. Three repetitions were performed for each combination treatment of inoculum/fertilizer. One-year-old young Jacaranda plants, being about 40 cm high, were cultured under greenhouse in 10/12 cm caliber pots. After six months, all the inoculated plants were mycorrhized. According to endomycorrhizal structures found on their roots, plants receiving doses of composite indigenous inoculum reached a more advanced stage of mycorrhization than those treated with the commercial inoculum. The existence of an interaction effect between the inoculum dose and the level of fertilization on Jacaranda mycorhization rate was excluded. These two parameters of variation were studied as simple effects. The increase in commercial inoculum dose had a significant positive influence on the level of Jacaranda plants mycorrhization (P=0.05). The rate of mycorrhization jumped from 12.69% to 21.92%. Nonetheless, for plants receiving increasing doses of composite indigenous inoculum, the level of mycorrhization has varied randomly. In both instances of inoculum treatments, increasing the dose of fertilizer significantly inhibited endomycorrhizal colonization of Jacaranda roots (P=0.01). Thus, the rate of root colonization decreased from 47.43% to 2.41% for plants receiving the composite indigenous inoculums. It decreased from 32.35% to 3.95% for those treated with the commercial inoculum. Mycorrhization had a positive effect on root dry biomass of Jacaranda, as in the case of unfertilize ave the highest rates of colonization. Copyright © 2013. Published by Elsevier SAS.

Antibiotic Dosing in Continuous Renal Replacement Therapy.

PubMed

Shaw, Alexander R; Mueller, Bruce A

2017-07-01

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The effect of low dose rate on metabolomic response to radiation in mice

PubMed Central

Goudarzi, Maryam; Mak, Tytus D.; Chen, Congju; Smilenov, Lubomir B.; Brenner, David J.

2014-01-01

Metabolomics has been shown to have utility in assessing responses to exposure by ionizing radiation (IR) in easily accessible biofluids such as urine. Most studies to date from our laboratory and others have employed γ-irradiation at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at relatively low dose rates (LDR). There are well-documented differences in the biologic responses to LDR compared to HDR, so an important question is to assess LDR effects at the metabolomics level. Our study took advantage of a modern mass spectrometry approach in exploring the effects of dose rate on the urinary excretion levels of metabolites 2 days after IR in mice. A wide variety of statistical tools were employed to further focus on metabolites, which showed responses to LDR IR exposure (0.00309 Gy/min) distinguishable from those of HDR. From a total of 709 detected spectral features, more than 100 were determined to be statistically significant when comparing urine from mice irradiated with 1.1 or 4.45 Gy to that of sham-irradiated mice 2 days post-exposure. The results of this study show that LDR and HDR exposures perturb many of the same pathways such as TCA cycle and fatty acid metabolism, which also have been implicated in our previous IR studies. However, it is important to note that dose rate did affect the levels of particular metabolites. Differences in urinary excretion levels of such metabolites could potentially be used to assess an individual's exposure in a radiobiological event and thus would have utility for both triage and injury assessment. PMID:25047638

Singlet oxygen explicit dosimetry to predict long-term local tumor control for BPD-mediated photodynamic therapy

NASA Astrophysics Data System (ADS)

Kim, Michele M.; Penjweini, Rozhin; Ong, Yi Hong; Zhu, Timothy C.

2017-02-01

Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence, photosensitizer photobleaching rate, and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate (Φ) effects are not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted singlet oxygen [1O2]rx was investigated as a dosimetric quantity for PDT outcome. The ability of [1O2]rx to predict the long-term local tumor control rate (LCR) for BPD-mediated PDT was examined. Mice bearing radioactivelyinduced fibrosarcoma (RIF) tumors were treated with different in-air fluences (250, 300, and 350 J/cm2) and in-air ϕ (75, 100, and150 mW/cm2) with a BPD dose of 1 mg/kg and a drug-light interval of 3 hours. Treatment was delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and BPD concentration was used to calculate [1O2]rx. Φ was calculated for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Kaplan-Meier analyses for LCR were done for an endpoint of tumor volume <= 100 mm3 using four dose metrics: light fluence, photosensitizer photobleaching rate, PDT dose, and [1O2]rx. PDT dose was defined as the product of the timeintegral of photosensitizer concentration and Φ at a 3 mm tumor depth. Preliminary studies show that [1O2]rx better correlates with LCR and is an effective dosimetric quantity that can predict treatment outcome.

American association of poison control centers database characterization of human tilmicosin exposures, 2001-2005.

PubMed

Oakes, Jennifer; Seifert, Steven

2008-12-01

Tilmicosin is a veterinary antibiotic with significant human toxicity at doses commonly used in animals, but the parenteral dose-response relationship has not been well characterized. Human exposures to tilmicosin in the database of the American Association of Poison Control Centers (AAPCC) from 2001 to 2005 were analyzed for demographic associations, exposure dose, clinical effects and outcomes. Over the 5-year period, there were 1,291 single-substance human exposures to tilmicosin. The mean age was 39.1 years, and 80% were male. By route there were 768 (54%) parenteral exposures. Patients with parenteral exposures had a significantly increased likelihood of being seen at a healthcare facility, admission, and admission to an ICU. With nonparenteral exposure, most had no clinical effects or minor effects, and there were no major effects or deaths. With parenteral exposure, moderate effects occurred in 46 (6%), major effects in 2 (0.3%) and there were 4 (0.5%) deaths, two of which were suicides. A dose-response relationship could be demonstrated. Clinical effect durations of up to a week occurred at even the lowest dose range. Over 250 cases of human tilmicosin exposure are reported to poison centers per year and over 150 of those are parenteral. Most exposures produce no or minor effects, but fatalities have occurred with parenteral exposure. The case fatality rate in parenteral exposures is 10 times the case fatality rate for all human exposures in the AAPCC database. Significant adverse and prolonged effects are reported at parenteral doses > 0.5 mL, suggesting that all parenteral exposures should be referred for healthcare facility evaluation.

The effect of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue

NASA Technical Reports Server (NTRS)

Foster, B. R.

1973-01-01

The problem studied involved cell proliferation in mice thymus undergoing irradiation at a dose rate of 10 roetgens/day for 105 days. Specifically, the aim was to determine wheather or not a steady state of cell population can be established for the indicated period of time and what compensatory mechanisms of cell population are involved.

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

PubMed

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

2005-12-09

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

Radiosensitivity study and radiation effects on morphology characterization of grey oyster mushroom Pleurotus sajor-caju

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

Rashid, Rosnani Abdul; Awang, Mat Rasol; Mohamad, Azhar

2014-09-03

Radiosensitive dosage and morphology characterization of irradiated grey oyster mushroom Pleurotus sajor-caju by gamma rays was investigated due to effects of irradiation. In order to establish the effect, mycelium of P. sajor-caju was irradiated by gamma rays at dose 0.1 to 8.0 kGy with dose rate 0.227 Gy sec{sup −1}. The irradiation of mycelia was carried out at the radiation facility in Malaysian Nuclear Agency. The radiosensitivity study was performed by evaluating the percentage of survival irradiated mycelia. The lethal dose of the mycelium P. sajor-caju was determined at 4.0 kGy and LD{sub 50} to be equal at 2.2 kGy.more » The radiation effects on morphology were evaluated based on growth rate of irradiated mycelia, mycelia types, colonization period on substrate, morphology of fruit bodies and yields. The results shown growth rate of irradiated mycelium was slightly lower than the control and decreased as the dose increased. Irradiation was found can induced the primordia formation on PDA and the BE of irradiated seed is higher than to control. The irradiation is proven to be useful for generating new varieties of mushroom with commercial value to the industry.« less

Radiation Damage in Si Diodes from Short, Intense Ion Pulses

NASA Astrophysics Data System (ADS)

de Leon, S. J.; Ludewigt, B. A.; Persaud, A.; Seidl, P. A.; Schenkel, T.

2017-10-01

The Neutralized Drift Compression Experiment (NDCX-II) at Berkeley Lab is an induction accelerator studying the effects that concentrated ion beams have on various materials. Charged particle radiation damage was the focus of this research - we have characterized a series of Si diodes using an electrometer and calibrated the diodes response using an 241Am alpha source, both before and after exposing the diodes to 1 MeV He ions in the accelerator. The key part here is that the high intensity pulses from NDCX-II (>1010 ions/cm2 per pulse in <20 ns) enabled a systematic study of dose-rate effects. An example of a dose-rate effect in Si diodes is increased accumulation of defects due to damage from ions that bombard them in a short pulse. This accumulated damage leads to a reduction in the charge collection efficiency and an increase in leakage current. Testing dose-rate effects in Si diodes and other semiconductors is a crucial step in designing sustainable instruments that can encounter high doses of radiation, such as high intensity accelerators, fusion energy experiments and space applications and results from short pulses can inform models of radiation damage evolution. This work was supported by the Office of Science of the US Department of Energy under contract DE-AC0205CH11231.

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation.

PubMed

Sanzari, Jenine K; Cengel, Keith A; Wan, X Steven; Rusek, Adam; Kennedy, Ann R

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure.

Acute hematological effects in mice exposed to the expected doses, dose-rates, and energies of solar particle event-like proton radiation

NASA Astrophysics Data System (ADS)

Sanzari, Jenine K.; Cengel, Keith A.; Steven Wan, X.; Rusek, Adam; Kennedy, Ann R.

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during an SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hours post-radiation exposure.

Particle effects on ultraviolet disinfection of coliform bacteria in recycled water.

PubMed

Jolis, D; Lam, C; Pitt, P

2001-01-01

Pilot- and bench-scale coliform inactivation tests with UV irradiation were used to show how suspended solids remaining in filtered secondary effluent affect the efficiency of the UV disinfection process. Observed kinetic inactivation rates decreased with increasing suspended particle sizes of 7 microm or larger present in tertiary effluent. First-order inactivation rates estimated from collimated beam dose-response curves for discrete ranges of UV doses were substantially different, which should caution researchers not to compare inactivation data obtained with largely dissimilar UV doses or suspended particle distributions. A dose of approximately 800 J/m2 was identified as the minimum dose that will consistently meet the California wastewater reclamation coliform criterion when applied to in-line filtration effluent.

Low-dose radiation attenuates chemical mutagenesis in vivo.

PubMed

Kakinuma, Shizuko; Yamauchi, Kazumi; Amasaki, Yoshiko; Nishimura, Mayumi; Shimada, Yoshiya

2009-09-01

The biological effects of low-dose radiation are not only of social concern but also of scientific interest. The radioadaptive response, which is defined as an increased radioresistance by prior exposure to low-dose radiation, has been extensively studied both in vitro and in vivo. Here we briefly review the radioadaptive response with respect to mutagenesis, survival rate, and carcinogenesis in vivo, and introduce our recent findings of cross adaptation in mouse thymic cells, that is, the suppressive effect of repeated low-dose radiation on mutation induction by the alkylating agent N-ethyl-N-nitrosourea.

Effect of low-dose scopolamine on autonomic control of the heart

NASA Technical Reports Server (NTRS)

Raeder, E. A.; Stys, A.; Cohen, R. J.

1997-01-01

Background: In low doses, scopolamine paradoxically enhances parasympathetic outflow to the heart. The mechanisms which mediate this action are not fully understood. Moreover, there are conflicting data regarding the potential role of sympathetic activity. This study in 17 healthy individuals was designed to characterize the influence of low dose transdermal scopolamine on the gain of the baroreflex and respiratory heart rate reflex and to determine the role of sympathetic activity. Methods: The effect of scopolamine was analyzed in the time and frequency domain by computing heart rate variability indices. The gains of the respiratory heart rate reflex and the baroreflex were estimated simultaneously by means of a cardiovascular system identification approach using an optimized autoregressive moving average algorithm. Measurements were repeated in the upright posture to assess the influence of enhanced sympathetic activity. In six subjects ambulatory ECGs were recorded to determine whether there are diurnal variations of the effect of scopolamine. Results: Scopolamine enhances vagal modulation of heart rate through both the respiratory-heart rate reflex and the baroreflex, as the gains of both were augmented by the drug in the supine and in the upright postures. Conclusions: Scopolamine increases parasympathetic cardiac control by augmenting the gain of the respiratory-heart rate and baroreflex. This action is not attenuated in the upright posture when sympathetic tone is increased.

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.

Lhermitte Sign After Chemo-IMRT of Head-and-Neck Cancer: Incidence, Doses, and Potential Mechanisms

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

Pak, Daniel; Vineberg, Karen; Feng, Felix

2012-08-01

Purpose: We have observed a higher rate of Lhermitte sign (LS) after chemo-intensity-modulated radiotherapy (IMRT) of head-and-neck cancer than the published rates after conventional radiotherapy. We hypothesized that the inhomogeneous spinal cord dose distributions produced by IMRT caused a 'bath-and-shower' effect, characterized by low doses in the vicinity of high doses, reducing spinal cord tolerance. Methods and Materials: Seventy-three patients with squamous cell carcinoma of the oropharynx participated in a prospective study of IMRT concurrent with weekly carboplatin and paclitaxel. Of these, 15 (21%) reported LS during at least 2 consecutive follow-up visits. Mean dose, maximum dose, and partial volumemore » and absolute volume (in milliliters) of spinal cord receiving specified doses ({>=}10 Gy, {>=}20 Gy, {>=}30 Gy, and {>=}40 Gy), as well as the pattern of dose distributions at the 'anatomic' spinal cord (from the base of the skull to the aortic arch) and 'plan-related' spinal cord (from the top through the bottom of the planning target volumes), were compared between LS patients and 34 non-LS patients. Results: LS patients had significantly higher spinal cord mean doses, V{sub 30}, V{sub 40}, and absolute volumes receiving 30 Gy or more and 40 Gy or more compared with the non-LS patients (p < 0.05). The strongest predictors of LS were higher V{sub 40} and higher cord volumes receiving 40 Gy or more (p {<=} 0.007). There was no evidence of larger spinal cord volumes receiving low doses in the vicinity of higher doses (bath-and-shower effect) in LS compared with non-LS patients. Conclusions: Greater mean dose, V{sub 30}, V{sub 40}, and cord volumes receiving 30 Gy or more and 40 Gy or more characterized LS compared with non-LS patients. Bath-and-shower effects could not be validated in this study as a potential contributor to LS. The higher-than-expected rates of LS may be because of the specific concurrent chemotherapy agents or more accurate identification of LS in the setting of a prospective study.« less

Comparison of effects produced by nicotine and the α4β2-selective agonist 5-I-A-85380 on intracranial self-stimulation in rats.

PubMed

Freitas, Kelen; Carroll, F Ivy; Negus, S Stevens

2016-02-01

Intracranial self-stimulation (ICSS) is one type of preclinical procedure for research on pharmacological mechanisms that mediate abuse potential of drugs acting at various targets, including nicotinic acetylcholine receptors (nAChRs). This study compared effects of the nonselective nAChR agonist nicotine (0.032-1.0 mg/kg) and the α4β2-selective nAChR agonist 5-I-A-85380 (0.01-1.0 mg/kg) on ICSS in male Sprague-Dawley rats. Rats were implanted with electrodes targeting the medial forebrain bundle at the level of the lateral hypothalamus and trained to respond under a fixed-ratio 1 schedule for a range of brain stimulation frequencies (158-56 Hz). A broad range of 5-I-A-85380 doses produced an abuse-related increase (or "facilitation") of low ICSS rates maintained by low brain-stimulation frequencies, and this effect was blocked by both the nonselective nAChR antagonist mecamylamine and the selective α4β2 antagonist dihyrdo-β-erythroidine (DHβE). Conversely, nicotine produced weaker ICSS facilitation across a narrower range of doses, and higher nicotine doses decreased high rates of ICSS maintained by high brain-stimulation frequencies. The rate-decreasing effects of a high nicotine dose were blocked by mecamylamine but not DHβE. Chronic nicotine treatment produced selective tolerance to rate-decreasing effects of nicotine but did not alter ICSS rate-increasing effects of nicotine. These results suggest that α4β2 receptors are sufficient to mediate abuse-related rate-increasing effects of nAChR agonists in this ICSS procedure. Conversely, nicotine effects at non-α4β2 nAChRs appear to oppose and limit abuse-related effects mediated by α4β2 receptors, although tolerance can develop to these non-α4β2 effects. Selective α4β2 agonists may have higher abuse potential than nicotine. PsycINFO Database Record (c) 2016 APA, all rights reserved.

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

PubMed Central

Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

2016-01-01

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. Trial Registration ClinicalTrials.gov identifier: NCT00465595 PMID:27909165

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

2016-12-01

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. ClinicalTrials.gov identifier: NCT00465595. © The Author(s) 2016.

Absolute x-ray dosimetry on a synchrotron medical beam line with a graphite calorimeter.

PubMed

Harty, P D; Lye, J E; Ramanathan, G; Butler, D J; Hall, C J; Stevenson, A W; Johnston, P N

2014-05-01

The absolute dose rate of the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter. The calorimetry results were compared to measurements from the existing free-air chamber, to provide a robust determination of the absolute dose in the synchrotron beam and provide confidence in the first implementation of a graphite calorimeter on a synchrotron medical beam line. The graphite calorimeter has a core which rises in temperature when irradiated by the beam. A collimated x-ray beam from the synchrotron with well-defined edges was used to partially irradiate the core. Two filtration sets were used, one corresponding to an average beam energy of about 80 keV, with dose rate about 50 Gy/s, and the second filtration set corresponding to average beam energy of 90 keV, with dose rate about 20 Gy/s. The temperature rise from this beam was measured by a calibrated thermistor embedded in the core which was then converted to absorbed dose to graphite by multiplying the rise in temperature by the specific heat capacity for graphite and the ratio of cross-sectional areas of the core and beam. Conversion of the measured absorbed dose to graphite to absorbed dose to water was achieved using Monte Carlo calculations with the EGSnrc code. The air kerma measurements from the free-air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. Absolute measurements of the IMBL dose rate were made using the graphite calorimeter and compared to measurements with the free-air chamber. The measurements were at three different depths in graphite and two different filtrations. The calorimetry measurements at depths in graphite show agreement within 1% with free-air chamber measurements, when converted to absorbed dose to water. The calorimetry at the surface and free-air chamber results show agreement of order 3% when converted to absorbed dose to water. The combined standard uncertainty is 3.9%. The good agreement of the graphite calorimeter and free-air chamber results indicates that both devices are performing as expected. Further investigations at higher dose rates than 50 Gy/s are planned. At higher dose rates, recombination effects for the free-air chamber are much higher and expected to lead to much larger uncertainties. Since the graphite calorimeter does not have problems associated with dose rate, it is an appropriate primary standard detector for the synchrotron IMBL x rays and is the more accurate dosimeter for the higher dose rates expected in radiotherapy applications.

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.

Effects of alfaxalone administered intravenously to healthy yearling loggerhead sea turtles (Caretta caretta) at three different doses.

PubMed

Phillips, Brianne E; Posner, Lysa P; Lewbart, Gregory A; Christiansen, Emily F; Harms, Craig A

2017-04-15

OBJECTIVE To compare physiologic and anesthetic effects of alfaxalone administered IV to yearling loggerhead sea turtles (Caretta caretta) at 3 different doses. DESIGN Randomized crossover study. ANIMALS 9 healthy yearling loggerhead sea turtles. PROCEDURES Animals received each of 3 doses of alfaxalone (3 mg/kg [1.4 mg/lb], 5 mg/kg [2.3 mg/lb], or 10 mg/kg [4.5 mg/lb]) administered IV in randomly assigned order, with a minimum 7-day washout period between doses. Endotracheal intubation was attempted following anesthetic induction, and heart rate, sedation depth, cloacal temperature, and respirations were monitored. Times to first effect, induction, first voluntary muscle movement, first respiration, and recovery were recorded. Venous blood gas analysis was performed at 0 and 30 minutes. Assisted ventilation was performed if apnea persisted 30 minutes following induction. RESULTS Median anesthetic induction time for all 3 doses was 2 minutes. Endotracheal intubation was accomplished in all turtles following induction. Heart rate significantly increased after the 3- and 5-mg/kg doses were administered. Median intervals from alfaxalone administration to first spontaneous respiration were 16, 22, and 54 minutes for the 3-, 5-, and 10-mg/kg doses, respectively, and median intervals to recovery were 28, 46, and 90 minutes, respectively. Assisted ventilation was required for 1 turtle after receiving the 5-mg/kg dose and for 5 turtles after receiving the 10-mg/kg dose. The 10-mg/kg dose resulted in respiratory acidosis and marked hypoxemia at 30 minutes. CONCLUSIONS AND CLINICAL RELEVANCE IV alfaxalone administration to loggerhead sea turtles resulted in a rapid anesthetic induction and dose-dependent duration of sedation. Assisted ventilation is recommended if the 10 mg/kg dose is administered.

High dose-per-pulse electron beam dosimetry - A model to correct for the ion recombination in the Advanced Markus ionization chamber.

PubMed

Petersson, Kristoffer; Jaccard, Maud; Germond, Jean-François; Buchillier, Thierry; Bochud, François; Bourhis, Jean; Vozenin, Marie-Catherine; Bailat, Claude

2017-03-01

The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose-per-pulse electron beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two-voltage-analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen. Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source-to-surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose-response, in beams with varying dose rate/dose-per-pulse, with the chamber together with dose rate/dose-per-pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose-per-pulse (10 -2  ≤ mean dose rate ≤ 10 3 Gy/s, 10 2  ≤ mean dose rate within pulse ≤ 10 7  Gy/s, 10 -4  ≤ dose-per-pulse ≤ 10 1  Gy), which was achieved by independently varying the linac gun grid tension, and the SSD. The results demonstrate how the ion collection efficiency of the chamber decreased as the dose-per-pulse increased, and that the ion recombination was dependent on the dose-per-pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose-per-pulse range, but only for a low polarizing chamber voltage (50 V). However, the two-voltage-analysis method and the Burns & McEwen equation only agreed with the data at low dose-per-pulse values (≤ 10 -2 and ≤ 10 -1  Gy, respectively). An empirical model of the ion recombination in the chamber was found by fitting a logistic function to the data. The ion collection efficiency of the Advanced Markus ionization chamber decreases for measurements in electron beams with increasingly higher dose-per-pulse. However, this chamber is still functional for dose measurements in beams with dose-per-pulse values up toward and above 10 Gy, if the ion recombination is taken into account. Our results show that existing models give a less-than-accurate description of the observed ion recombination. This motivates the use of the presented empirical model for measurements with the Advanced Markus chamber in high dose-per-pulse electron beams, as it enables accurate absorbed dose measurements (uncertainty estimation: 2.8-4.0%, k = 1). The model depends on the dose-per-pulse in the beam, and it is also influenced by the polarizing chamber voltage, with increasing ion recombination with a lowering of the voltage. © 2017 American Association of Physicists in Medicine.

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.

Solar particle dose rate buildup and distribution in critical body organs

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

The effects of oxytocin and atosiban on the modulation of heart rate in pregnant women.

PubMed

Weissman, Amir; Tobia, Rana Swed; Burke, Yechiel Z; Maxymovski, Olga; Drugan, Arie

2017-02-01

To evaluate autonomic modulation of heart rate in pregnant women treated with oxytocin to induce labor and with atosiban (an oxytocin antagonist) to arrest preterm labor. A prospective study with two cohorts: 14 pregnant women treated with atosiban for premature uterine contractions, and 28 women undergoing induction of labor with oxytocin. Computerized analyses of the electrocardiogram were performed with spectral and nonlinear dynamic analyses. Atosiban did not alter any of the variables associated with heart rate variability, whereas oxytocin showed a dose-dependent decrease in heart rate (p < 0.05) and a significant increase in all spectral variables studied (p < 0.01). Atosiban has no adverse effects on the cardiovascular system or the modulation of heart rate. Oxytocin, on the other hand, can cause a dose-dependent bradycardic effect and an increase in the spectral power, thus should be used with caution in certain pregnant women.

Effect of Intrathecal Bupivacaine Dose on the Success of External Cephalic Version for Breech Presentation: A Prospective, Randomized, Blinded Clinical Trial.

PubMed

Chalifoux, Laurie A; Bauchat, Jeanette R; Higgins, Nicole; Toledo, Paloma; Peralta, Feyce M; Farrer, Jason; Gerber, Susan E; McCarthy, Robert J; Sullivan, John T

2017-10-01

Breech presentation is a leading cause of cesarean delivery. The use of neuraxial anesthesia increases the success rate of external cephalic version procedures for breech presentation and reduces cesarean delivery rates for fetal malpresentation. Meta-analysis suggests that higher-dose neuraxial techniques increase external cephalic version success to a greater extent than lower-dose techniques, but no randomized study has evaluated the dose-response effect. We hypothesized that increasing the intrathecal bupivacaine dose would be associated with increased external cephalic version success. We conducted a randomized, double-blind trial to assess the effect of four intrathecal bupivacaine doses (2.5, 5.0, 7.5, 10.0 mg) combined with fentanyl 15 μg on the success rate of external cephalic version for breech presentation. Secondary outcomes included mode of delivery, indication for cesarean delivery, and length of stay. A total of 240 subjects were enrolled, and 239 received the intervention. External cephalic version was successful in 123 (51.5%) of 239 patients. Compared with bupivacaine 2.5 mg, the odds (99% CI) for a successful version were 1.0 (0.4 to 2.6), 1.0 (0.4 to 2.7), and 0.9 (0.4 to 2.4) for bupivacaine 5.0, 7.5, and 10.0 mg, respectively (P = 0.99). There were no differences in the cesarean delivery rate (P = 0.76) or indication for cesarean delivery (P = 0.82). Time to discharge was increased 60 min (16 to 116 min) with bupivacaine 7.5 mg or higher as compared with 2.5 mg (P = 0.004). A dose of intrathecal bupivacaine greater than 2.5 mg does not lead to an additional increase in external cephalic procedural success or a reduction in cesarean delivery.

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

Effects of polyaluminum chloride and lanthanum-modified bentonite on the growth rates of three Cylindrospermopsis raciborskii strains

PubMed Central

van Oosterhout, Frank; Becker, Vanessa; Attayde, José Luiz; Lürling, Miquel

2018-01-01

In tropical and subtropical lakes, eutrophication often leads to nuisance blooms of Cylindrospermopsis raciborskii. In laboratory experiments, we tested the combined effects of flocculant polyaluminum chloride (PAC) and lanthanum-modified bentonite (LMB) on the sinking and growth rates of three C. raciborskii strains. We tested the hypothesis that the combination of PAC and LMB would (1) effectively sink C. raciborskii in a test tube experiment and (2) impair C. raciborskii growth, irrespective of the biomass of the inoculum (bloom) and the strain in the growth experiment. We tested the recommended (LMB1) and a three-times higher dose of LMB (LMB3). The combined addition of PAC and LMB enhanced the sedimentation of all C. raciborskii strains. Moreover, both the PAC and LMB doses decreased the phosphate concentration. PAC and LMB1 decreased the growth rate of all strains, but the efficacy depended on the biomass and strain. The combined addition of PAC and LMB3 inhibited the growth of all strains independently of the biomass and strain. We conclude that a low dose of PAC in combination with the recommended dose of LMB decreases C. raciborskii blooms and that the efficiency of the technique depends on the biomass of the bloom. A higher dose of LMB is needed to obtain a more efficient control of C. raciborskii blooms. PMID:29614118

Effects of polyaluminum chloride and lanthanum-modified bentonite on the growth rates of three Cylindrospermopsis raciborskii strains.

PubMed

Araújo, Fabiana; van Oosterhout, Frank; Becker, Vanessa; Attayde, José Luiz; Lürling, Miquel

2018-01-01

In tropical and subtropical lakes, eutrophication often leads to nuisance blooms of Cylindrospermopsis raciborskii. In laboratory experiments, we tested the combined effects of flocculant polyaluminum chloride (PAC) and lanthanum-modified bentonite (LMB) on the sinking and growth rates of three C. raciborskii strains. We tested the hypothesis that the combination of PAC and LMB would (1) effectively sink C. raciborskii in a test tube experiment and (2) impair C. raciborskii growth, irrespective of the biomass of the inoculum (bloom) and the strain in the growth experiment. We tested the recommended (LMB1) and a three-times higher dose of LMB (LMB3). The combined addition of PAC and LMB enhanced the sedimentation of all C. raciborskii strains. Moreover, both the PAC and LMB doses decreased the phosphate concentration. PAC and LMB1 decreased the growth rate of all strains, but the efficacy depended on the biomass and strain. The combined addition of PAC and LMB3 inhibited the growth of all strains independently of the biomass and strain. We conclude that a low dose of PAC in combination with the recommended dose of LMB decreases C. raciborskii blooms and that the efficiency of the technique depends on the biomass of the bloom. A higher dose of LMB is needed to obtain a more efficient control of C. raciborskii blooms.

Immunological Effect of aGV Rabies Vaccine Administered Using the Essen and Zagreb Regimens: A Double-Blind, Randomized Clinical Trial.

PubMed

Miao, Li; Shi, Liwei; Yang, Yi; Yan, Kunming; Sun, Hongliang; Mo, Zhaojun; Li, Li

2018-04-01

This study evaluated the immunological effect of an aGV rabies virus strain using the Essen and Zagreb immunization programs. A total of 1,944 subjects were enrolled and divided into three groups: the Essen test group, Essen control group, and Zagreb test group. Neutralizing antibody levels and antibody seroconversion rates were determined at 7 and 14 days after the initial inoculations and then 14 days after the final inoculation in all of the subjects. The seroconversion rates for the Essen test group, Essen control group, and Zagreb test group, which were assessed 7 days after the first dosing in a susceptible population, were 35.74%, 26.92%, and 45.49%, respectively, and at 14 days, the seroconversion rates in this population were 100%, 100%, and 99.63%, respectively. At 14 days after the final dosing, the seroconversion rates were 100% in all three of the groups. The neutralizing serum antibody levels of the Essen test group, Essen control group, and Zagreb test group at 7 days after the first dosing in the susceptible population were 0.37, 0.26, and 0.56 IU/mL, respectively, and at 14 days after the initial dosing, these levels were 16.71, 13.85, and 16.80 IU/mL. At 14 days after the final dosing, the neutralizing antibody levels were 22.9, 16.3, and 18.62 IU/mL, respectively. The results of this study suggested that the aGV rabies vaccine using the Essen program resulted in a good serum immune response, and the seroconversion rates and the neutralizing antibody levels generated with the Zagreb regimen were higher than those with the Essen regimen when measured 7 days after the first dose.

The effect of single dose versus two doses of praziquantel on Schistosoma haematobium infection and pathology among school-aged children in Mali.

PubMed

Sacko, M; Magnussen, P; Traoré, M; Landouré, A; Doucouré, A; Reimert, C M; Vennervald, B J

2009-11-01

The aim of this study was to assess the effect of two doses of 40 mg/kg praziquantel with 2 weeks interval versus a standard single dose of 40 mg/kg on cure rates, egg reduction, intensity of infection, and micro-haematuria in Schistosoma haematobium infections. A randomised controlled intervention study was carried out among school-aged children in two different endemic settings with follow-up at 3, 6 and 18 months following drug administration. Differences in cure rates between the two treatment regimens were not significant. However, in high transmission areas, the double treatment regimen was more effective in egg reduction than single treatment regimen and the difference in egg reduction between the two treatments was significant at 3 months (P<0.005), 6 months (P<0.0001) and 18 months (P<0.003) after treatment. There was a significant difference in the effect of the two treatments on prevalence of micro-haematuria at 18-month follow-up in both Koulikoro (P<0.001) and Selingue (P<0.003). The study shows that although no significant difference could be observed in the overall cure-rates between the two treatment regimens, the effect of double treatment was a significant reduction in infection intensity as well as micro-haematuria which may have a great impact in reducing subtle morbidity.

SU-F-T-273: Using a Diode Array to Explore the Weakness of TPS DoseCalculation Algorithm for VMAT and Sliding Window Techniques

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

Park, J; Lu, B; Yan, G

Purpose: To identify the weakness of dose calculation algorithm in a treatment planning system for volumetric modulated arc therapy (VMAT) and sliding window (SW) techniques using a two-dimensional diode array. Methods: The VMAT quality assurance(QA) was implemented with a diode array using multiple partial arcs that divided from a VMAT plan; each partial arc has the same segments and the original monitor units. Arc angles were less than ± 30°. Multiple arcs delivered through consecutive and repetitive gantry operating clockwise and counterclockwise. The source-toaxis distance setup with the effective depths of 10 and 20 cm were used for a diodemore » array. To figure out dose errors caused in delivery of VMAT fields, the numerous fields having the same segments with the VMAT field irradiated using different delivery techniques of static and step-and-shoot. The dose distributions of the SW technique were evaluated by creating split fields having fine moving steps of multi-leaf collimator leaves. Calculated doses using the adaptive convolution algorithm were analyzed with measured ones with distance-to-agreement and dose difference of 3 mm and 3%.. Results: While the beam delivery through static and step-and-shoot techniques showed the passing rate of 97 ± 2%, partial arc delivery of the VMAT fields brought out passing rate of 85%. However, when leaf motion was restricted less than 4.6 mm/°, passing rate was improved up to 95 ± 2%. Similar passing rate were obtained for both 10 and 20 cm effective depth setup. The calculated doses using the SW technique showed the dose difference over 7% at the final arrival point of moving leaves. Conclusion: Error components in dynamic delivery of modulated beams were distinguished by using the suggested QA method. This partial arc method can be used for routine VMAT QA. Improved SW calculation algorithm is required to provide accurate estimated doses.« less

Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

PubMed

Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand

2014-05-01

In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

Americium-241 Decorporation Model

DTIC Science & Technology

2014-10-01

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

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

PubMed

Tanaka, Toshiaki

2017-03-01

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

Psychopharmacology of theobromine in healthy volunteers.

PubMed

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

2013-07-01

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

Psychopharmacology of theobromine in healthy volunteers

PubMed Central

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

2013-01-01

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

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

PubMed

Brooks, Antone L

2015-04-01

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

AN EVALUATION OF THE BASIC CHARACTERISTICS OF A PLASTIC SCINTILLATING FIBRE DETECTOR IN CT RADIATION FIELDS.

PubMed

Terasaki, Kento; Fujibuchi, Toshioh; Toyoda, Takatoshi; Yoshida, Yutaka; Akasaka, Tsutomu; Nohtomi, Akihiro; Morishita, Junji

2016-12-01

The ionisation chamber for computed tomography (CT) is an instrument that is most commonly used to measure the computed tomography dose index. However, it has been reported that the 10 cm effective detection length of the ionisation chamber is insufficient due to the extent of the dose distribution outside the chamber. The purpose of this study was to estimate the basic characteristics of a plastic scintillating fibre (PSF) detector with a long detection length of 50 cm in CT radiation fields. The authors investigated position dependence using diagnostic X-ray equipment and dependencies for energy, dose rate and slice thickness using an X-ray CT system. The PSF detector outputs piled up at a count rate of 10 000 counts ms -1 in dose rate dependence study. With calibration, this detector may be useful as a CT dosemeter with a long detection length except for the measurement at high dose rate. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Sub-dissociative-dose intranasal ketamine for moderate to severe pain in adult emergency department patients.

PubMed

Yeaman, Fiona; Meek, Robert; Egerton-Warburton, Diana; Rosengarten, Pamela; Graudins, Andis

2014-06-01

There are currently no studies assessing effectiveness of sub-dissociative intranasal (IN) ketamine as the initial analgesic for adult patients in the ED. The study aims to examine the effectiveness of sub-dissociative IN ketamine as a primary analgesic agent for adult patients in the ED. This is a prospective, observational study of adult ED patients presenting with severe pain (≥6 on 11-point scale at triage). IN ketamine dose was 0.7 mg/kg, with secondary dose of 0.5 mg/kg at 15 min if pain did not improve. After 6 months, initial dose was increased to 1.0 mg/kg with the same optional secondary dose. The primary outcomes are change in VAS rating at 30 min; percentage of patients reporting clinically significant reduction in VAS (≥20 mm) at 30 min; dose resulting in clinically significant pain reduction. Of the 72 patients available for analysis, median age was 34.5 years and 64% were men. Median initial VAS rating was 76 mm (interquartile range [IQR]: 65-82). Median total dose of IN ketamine for all patients was 0.98 mg/kg (IQR: 0.75-1.15, range: 0.59-1.57). Median reduction in VAS rating at 30 min was 24 mm (IQR: 2-45). Forty (56%, 95% CI: 44.0-66.7) reported VAS reduction ≥20 mm, these patients having had a total median ketamine dose of 0.94 mg/kg (IQR: 0.72-1.04). IN ketamine, at a dose of about 1 mg/kg, was an effective analgesic agent in 56% of study patients. The place of IN ketamine in analgesic guidelines for adults requires further investigation. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Space radiation risks to the central nervous system

NASA Astrophysics Data System (ADS)

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

2014-07-01

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

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

PubMed Central

Puxty, Drew J.; Ramaekers, Johannes G.; de la Torre, Rafael; Farré, Magí; Pizarro, Neus; Pujadas, Mitona; Kuypers, Kim P. C.

2017-01-01

Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol), which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg), combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg). Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS) 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations). Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA. PMID:28744219

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor.

PubMed

Puxty, Drew J; Ramaekers, Johannes G; de la Torre, Rafael; Farré, Magí; Pizarro, Neus; Pujadas, Mitona; Kuypers, Kim P C

2017-01-01

Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT 2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol), which are elevated by MDMA. In order to investigate the role of the 5-HT 2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg), combined with placebo or a single oral dose of the 5-HT 2 receptor blocker ketanserin (40 mg). Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS) 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations). Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT 2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.

Effects of hemodialysis on iodine-131 biokinetics in thyroid carcinoma patients with end-stage chronic renal failure.

PubMed

Yeyin, Nami; Cavdar, Iffet; Uslu, Lebriz; Abuqbeitah, Mohammad; Demir, Mustafa

2016-03-01

Radioiodine therapy could be challenging in chronic renal failure patients requiring hemodialysis. The aim of this study was to establish the effects of hemodialysis on elimination of radioiodine from the body in thyroid carcinoma patients with end-stage chronic renal failure and to determine its effects on environmental radiation dose. Three end-stage chronic renal failure patients (four cases) diagnosed with differentiated thyroid carcinoma requiring radioiodine therapy were included in our study. Each patient was given 50-75 mCi (1850-2775 MBq) iodine-131 with 50% dose reduction. Dose rate measurement was performed at the 2nd, 24th, and 48th hour (immediately before and after hemodialysis) after radioiodine administration. The Geiger-Müller probe was held at 1 m distance at the level of the midpoint of the thorax for the dose rate measurement. The effective half-life of iodine-131 for three patients was found to be 44 h. In conclusion, the amount of radioiodine excreted per hemodialysis session was calculated to be 51.25%.

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

PubMed

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

2007-10-01

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

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

PubMed

Hunt, G J

1997-04-01

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

Impact of Number of Human Papillomavirus Vaccine Doses on Genital Warts Diagnoses Among a National Cohort of U.S. Adolescents.

PubMed

Perkins, Rebecca B; Lin, Mengyun; Wallington, Sherrie F; Hanchate, Amresh

2017-06-01

The impact of fewer than 3 doses of human papillomavirus (HPV) vaccine on genital warts is uncertain. Using the Truven Health Analytics Marketscan administrative database, we compared rates of genital warts among women receiving 0, 1, 2, or 3 doses of HPV vaccine. Females aged 9 to 18 years on January 1, 2007, who were continuously enrolled in the database through December 31, 2013, were included. Patients were assigned an HPV dose state (0, 1, 2, or 3) based on the last recorded dose. The exposure period began on January 1, 2007, or the date of the final HPV dose, and lasted until the first diagnosis of genital warts or December 31, 2013. Multivariable Poisson regression was performed to determine the risk of genital warts associated with vaccine doses. Among 387,906 subjects, mean age and exposure period were 14.73 and 5.64 years, respectively. The proportions of doses received were: 52.1%, 7.8%, 9.4%, and 30.7% for 0, 1, 2, and 3 doses, respectively. The rate of genital warts was 1.97/1000 person-years. Receipt of 0 or 1 dose was associated with more genital warts than 3 doses. The effectiveness of 2 doses following current Centers for Disease Control and Prevention guidelines was similar to 3 doses. The risk of genital warts rose with age. Prevention of genital warts is higher with completion of 3 vaccine doses than with 1 dose, though 2-dose recommendations appear to provide similar protection. Prospective effectiveness studies of recommended 2-dose schedules against clinical endpoints including persistent infection, genital warts, and cervical dysplasia are necessary to ensure long-term protection of vaccinated cohorts.

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

PubMed Central

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

2015-01-01

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

The effect of metoprolol and practolol on lung function and blood pressure in hypertensive asthmatics

PubMed Central

Formgren, H.

1976-01-01

1 The effect of metoprolol, a new β1-adrenoceptor blocking agent, was compared to practolol in the treatment of hypertension in seventeen asthmatics during concurrent optimum bronchodilator therapy with a selective β2-adrenoceptor-stimulant. 2 The two β-adrenoceptor antagonists were given at two dose levels, practolol (200 mg and 400 mg) daily, and metoprolol (100 mg and 200 mg) daily, in a twice-daily dosage schedule, at 12 h intervals, for 17 days. The comparison was made double-blind and a crossover design was used. The drugs were given in randomized order. The study started with a run-in placebo period and there was a washout period on placebo between the treatment periods. Spirometry, blood pressures and heart rates were recorded in a standardized manner. 3 At the lower dose levels no influence on FEV1 was noted, and no difference was found between the two active drugs. At the higher dose level FEV1 was reduced by both β-adrenoceptor-blocking drugs. Four out of twelve patients given the higher dose experienced exacerbation of their asthma. The heart rate fell with both drugs and at both dose levels. During the placebo period a marked increase of heart rate was noted. The blood pressure fell at both dose levels compared to placebo, no difference being recorded between the two drugs. 4 Metoprolol and practolol are equally effective β1-adrenoceptor blocking drugs. In this study it was found that metoprolol could be used in asthmatics who had indications for β-adrenoceptor blockade, provided that the total daily dose did not exceed 100 mg. Optimal bronchodilator treatment with a bronchoselective β-adrenoceptor agonist is an absolute prerequisite in order to avoid the risk of aggravation of asthma. PMID:22216522

Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers.

PubMed

Savage, A P; Adrian, T E; Carolan, G; Chatterjee, V K; Bloom, S R

1987-02-01

The effect of an infusion of two doses of peptide YY (PYY), a novel putative gastrointestinal hormone, has been assessed on mouth to caecum intestinal transit time and on the rate of gastric emptying after ingestion of an inert 200 ml liquid meal thought unlikely to interrupt fasting gastrointestinal motility patterns. A low dose of PYY was chosen to give plasma concentrations within the range seen postprandially in healthy subjects, while the high dose mimicked the raised levels seen in several malabsorptive conditions. During infusion of PYY at 0.18 pmol/kg/min plasma concentrations rose from a basal of 8 +/- 2 pmol/l to 38 +/- 5 pmol/l and at 0.51 pmol/kg/min to 87 +/- 10 pmol/l. Mouth to caecum transit time was delayed from 67 +/- 4 mins on the saline infusion day to 94 +/- 7 mins (p less than 0.01) on the low dose and 192 +/- 9 mins (p less than 0.001) on the high dose infusion day. Time to 50% gastric emptying was prolonged from 37 +/- 8 mins during saline infusion to 63 +/- 10 mins (p less than 0.05) during low and 130 +/- 12 mins (p less than 0.001) during high dose infusion. Thus the infusion of PYY shows a dose related inhibition of mouth to caecum intestinal transit time and of the rate of gastric emptying and suggests this novel hormonal peptide to be of importance in gastrointestinal physiology.

Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers.

PubMed

Heishman, S J; Henningfield, J E

2000-10-01

When administered acutely to nonsmokers, nicotine's effects on performance are inconsistent, perhaps because of suboptimal dosing or initial dysphoria that could interfere with performance. The purpose of this study was to determine if a range of nicotine doses administered for 8 days to nonsmokers would enhance psychomotor and cognitive abilities and to document the development of nicotine tolerance or sensitization. Twelve male volunteers, who reported ever smoking five cigarettes or less, participated in 8 consecutive experimental days in which they were administered four doses of nicotine polacrilex gum each day in this order: 0, 2, 4, and 8 mg. Performance, subjective, and physiological measures were assessed before and after each dose. Plasma nicotine concentration ranged from 6.9 to 11.5 ng/ml following the 8 mg dose. Nicotine increased rate of responding and decreased response time on working memory (digit recall); however, accuracy was impaired. Nicotine also decreased accuracy on visual scanning and attention (two-letter search), and the 8 mg dose impaired gross motor coordination (circular lights). Tolerance did not develop to the performance impairing effects of nicotine. Nicotine produced dose-related increases in ratings of dysphoria and negative mood, including tension, anxiety, nervousness, turning of stomach, and sedation. Tolerance developed to some, but not all, of these aversive effects. Tolerance also was not observed to the increased cardiovascular measures. Although tolerance developed to some of the aversive effects of nicotine, performance enhancement was not observed. These data do not support the hypothesis that nicotine-induced performance enhancement contributes to the reinforcing effects of tobacco use during the early stages of dependence development.

Tritiated water exposure disrupts myofibril structure and induces mis-regulation of eye opacity and DNA repair genes in zebrafish early life stages.

PubMed

Arcanjo, Caroline; Armant, Olivier; Floriani, Magali; Cavalie, Isabelle; Camilleri, Virginie; Simon, Olivier; Orjollet, Daniel; Adam-Guillermin, Christelle; Gagnaire, Béatrice

2018-04-27

Tritium ( 3 H) is a radioactive isotope of hydrogen. In the environment, the most common form of tritium is tritiated water (HTO). The present study aimed to identify early biomarkers of HTO contamination through the use of an aquatic model, the zebrafish (Danio rerio). We used the zebrafish embryo-larvae model to investigate the modes of action of HTO exposure at dose rates of 0.4 and 4 mGy/h, dose rates expected to induce deleterious effects on fish. Zebrafish were exposed to HTO from 3 hpf (hours post fertilization) to 96 hpf. The transcriptomic effects were investigated 24 h and 96 h after the beginning of the contamination, using mRNAseq. Results suggested an impact of HTO contamination, regardless of the dose rate, on genes involved in muscle contraction (tnnt2d, tnni2a.4, slc6a1a or atp2a1l) and eye opacity (crygm2d9, crygmxl1, mipb or lim2.3) after 24 h of contamination. Interestingly, an opposite differential expression was highlighted in genes playing a role in muscle contraction and eye opacity in 24 hpf embryos when comparing dose rates, suggesting an onset of DNA protective mechanisms. The expression of h2afx and ddb2 involved in DNA repair was enhanced in response to HTO exposure. The entrainment of circadian clock and the response to H 2 O 2 signalling pathways were enriched at 96 hpf at 0.4 mGy/h and in both stages after 4 mGy/h. Genes involved in ROS scavenging were differentially expressed only after 24 h of exposure for the lowest dose rate, suggesting the onset of early protective mechanisms against oxidative stress. Effects highlighted on muscle at the molecular scale were confirmed at a higher biological scale, as electron microscopy observations revealed sarcomere impairments in 96 hpf larvae for both dose rates. Together with other studies, the present work provides useful data to better understand modes of action of tritium on zebrafish embryos-larvae. Copyright © 2018 Elsevier B.V. All rights reserved.

Extra dose due to extravehicular activity during the NASA4 mission measured by an on-board TLD system.

PubMed

Deme, S; Apathy, I; Hejja, I; Lang, E; Feher, I

1999-01-01

A microprocessor-controlled on-board TLD system, 'Pille'96', was used during the NASA4 (1997) mission to monitor the cosmic radiation dose inside the Mir Space Station and to measure the extra dose to two astronauts in the course of their extravehicular activity (EVA). For the EVA dose measurements, CaSO4:Dy bulb dosemeters were located in specially designed pockets of the ORLAN spacesuits. During an EVA lasting 6 h, the dose ratio inside and outside Mir was measured. During the EVA, Mir crossed the South Atlantic Anomaly (SAA) three times. Taking into account the influence of these three crossings the mean EVA/internal dose rate ratio was 3.2. Internal dose mapping using CaSO4:Dy dosemeters gave mean dose rates ranging from 9.3 to 18.3 microGy h-1 at locations where the shielding effect was not the same. Evaluation results of the high temperature region of LiF dosemeters are given to estimate the mean LET.

Defining success in clinical trials--profiling pregabalin, the newest AED.

PubMed

Ryvlin, P

2005-11-01

The efficacy and safety of pregabalin as adjunctive therapy for patients with partial epilepsy with or without secondary generalization has been established by four randomized, 12-week, double-blind, placebo-controlled trials (n = 1396) and four long-term open-label studies (n = 1480). Patients in the three fixed-dose trials were >/=12 years of age, had >/=6 partial seizures and no 4-week seizure-free period during the 8-week baseline period. Seventy-three per cent of patients were taking >/=2 concomitant antiepileptic drugs. Responder rates across the effective doses (150-600 mg/day) ranged from 14% to 51% and demonstrated a significant dose-response relationship. The most common adverse events were central nervous system related, generally mild or moderate, transient, and tended to be dose related. The fourth placebo-controlled trial compared a fixed dose of pregabalin 600 mg/day with a flexible-dose regimen (150-600 mg/day). Responder rates were greater for both the fixed dose (45.3%, P < 0.001) and flexible dose (31.3%, P < 0.001) when compared with placebo (11.0%). Compared with the fixed-dose group, the flexible-dose patients had a lower incidence of adverse events and study discontinuations. In long-term open-label trials, the efficacy of pregabalin was maintained with respect to 50% responder rates suggesting no obvious tolerance developing over 2 years. Seizure-free rates were 8.9% and 5.8% for the last 6 months and 1 year of pregabalin treatment, respectively. Long-term open-label pregabalin treatment was well tolerated.

The Utility of Low-Dose Aripiprazole for the Treatment of Bipolar II and Bipolar NOS Depression.

PubMed

Kelly, Tammas; Lieberman, Daniel Z

2017-02-01

Despite initial reports of efficacy in bipolar depression, multicenter trials did not show aripiprazole to be better than placebo, possibly because the doses used were too high, leading to lower efficacy and high dropout rates. This study evaluated the effects of low-dose aripiprazole. Extensive clinical experience has suggested that doses beyond 5 mg are rarely efficacious. Data were gathered from patients with bipolar II or bipolar not otherwise specified depression using a retrospective chart review. Efficacy was assessed with the Clinical Global Impression-Improvement score. Patients who had at least 2 trials of aripiprazole were included in a retrospective off-on-off-on experimental design. All patients were on other medications when aripiprazole was started. Patients were treated with doses of 1 to 5 mg. On average, patients were rated improved or very much improved compared with baseline. Sixteen of 211 patients worsened or experienced no change. Forty-four patients (21%) discontinued due to adverse effects. The group of patients who underwent off-on-off-on trials experienced statistically significant improvement when they started and restarted aripiprazole, and statistically significant worsening when they discontinued it. When treating bipolar II or bipolar not otherwise specified depression, low doses of aripiprazole, 5 mg or less, may be more effective and better tolerated than higher ones. Clinicians should start treatment with a very low dose and give patients time to respond.

Seasonal regulation of condensed tannin consumption by free-ranging goats in a semi-arid savanna

PubMed Central

Heitkӧnig, Ignas M. A.; Scogings, Peter F.; Hattas, Dawood; Dziba, Luthando E.; Prins, Herbert H. T.; de Boer, Willem F.

2018-01-01

Although condensed tannins (CTs) are known to reduce forage intake by mammalian herbivores in controlled experiments, few studies have tested these effects in the field. Thus the role of CTs on foraging ecology of free-ranging herbivores is inadequately understood. To investigate the effects of CTs under natural savanna conditions, we pre-dosed groups of goats with polyethylene glycol (PEG, a CT-neutralising chemical), CT powder or water before observing their foraging behaviour. While accounting for the effects of season and time of the day, we tested the hypothesis that herbivores forage in ways that reduce the intake rate (g DM per minute) of CTs. We expected pre-dosing goats with CTs to reduce CT intake rates by (1) consuming diets low in CTs, (2) reducing bite rates, (3) increasing the number of foraging bouts, or (4) reducing the length of foraging bouts. Lastly, (5) expected CT to have no influence the number of dietary forage species. In both wet and dry seasons, pre-dosing goats with CTs resulted in lower CT consumption rates compared to PEG goats which seemed relieved from the stress associated with CT consumption. During dry season, the number of dietary forage species was similar across treatments, although goats that were dosed with PEG significantly increased this number in the wet season. Dosing goats with PEG increased the number and length of browsing bouts compared to goats from the other treatments. Pre-loading goats with PEG also tended to increase bite rates on browse forages, which contributed to increased consumption rates of CTs. Based on the behavioural adjustments made by goats in this study and within the constraints imposed by chemical complexity in savanna systems, we concluded that herbivores under natural conditions foraged in ways that minimised CTs consumption. More research should further elucidate the mechanism through which CTs regulated feeding behaviour. PMID:29293513

Action research regarding the optimisation of radiological protection for nurses during vascular interventional radiology.

PubMed

Mori, Hiroshige

2015-06-01

The optimisation and decision-making processes for radiological protection have been broadened by the introduction of re-examination or feedback after introducing protective measures. In this study, action research was used to reduce the occupational exposure of vascular interventional radiology (IR) nurses. Four radiological protection improvement measures were continuously performed in cooperation with the researchers, nurses and stakeholders, and the nurses' annual effective doses were compared before and after the improvements. First, the dosimetry equipment was changed from one electronic personal dosimeter (EPD) to two silver-activated phosphate glass dosimeters (PGDs). Second, the nurses were educated regarding maintaining a safe distance from the sources of scattered and leakage radiation. Third, portable radiation shielding screens were placed in the IR rooms. Fourth, the x-ray units' pulse rates were reduced by half. On changing the dosimetry method, the two PGDs recorded a 4.4 fold greater dose than the single EPD. Educating nurses regarding radiological protection and reducing the pulse rates by half decreased their effective doses to one-third and two-fifths of the baseline dose, respectively. No significant difference in their doses was detected after the placement of the shielding screens. Therefore, the action research effectively decreased the occupational doses of the vascular IR nurses.

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

PubMed

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

2018-03-30

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

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

PubMed

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

2016-08-02

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

Determination of the effect of different atmospheric composition on the quality of cold stored irradiated apples

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

Okamoto, T.; Harata, J.; Osanai, T.

1972-03-01

Jonathan apples were irradiated with /sup 60/Co gamma rays, in doses of 0 (control), 2.5, 5, 7.5, 10, 50, 100 krad (dose rate: 20 krad/hr), and 50krad (dose rate: 100 krad/hr), and stored at 0 deg C in three controlled atmosphere rooms (oxygen 3 to 5%, carbon dioxide below 0.5%; oxygen 21%, carbon dioxide 2 to 2.5%; oxygen 3 to 5%, carbon dioxide 2 to 2.5%) and in a common refrigerated room for 4.5 months. Irradiation of apples with doses of 10 krsd or more seemed to lower slightly their qualities and the same tendency was obseved in CA apples.more » Generally, the effects of CA storage, especially in 3 to 5% O/sub 2/ and 2 to 2.5% CO/sub 2/, on the qualities of apples, i.e., respiration, organoleptic properties, changes in weight, surface color, were stronger than the irradiation effect. However, it seems to be true that the treatment with doses of about 5 krad is not at all inferior to the other treatment. So, as the pretreatment of CA storage of apples the irradiation dose of about 5 krad may be recommended. (auth)« less

Effects of HMX exposure upon metabolic rate of northern bobwhite quail (Colinus virginianus) in ovo.

PubMed

Liu, Jun; Cox, Stephen B; Beall, Blake; Brunjes, Kristina J; Pan, Xiaoping; Kendall, Ronald J; Anderson, Todd A; McMurry, Scott T; Cobb, George P; Smith, Philip N

2008-05-01

We evaluated the use of the gas exchange rate as an ecologically relevant indicator of chemical stress in avian embryos/eggs. Northern bobwhite quail (Colinus virginianus) were exposed to octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) via feed containing nominal concentrations of 0, 12.5, 50.0, and 125.0 mg kg(-1). Metabolic rates (oxygen consumption) of developing quail eggs were then measured via respirometry to examine potential effects of HMX exposure. Metabolic rates were examined on 5, 9, and 21 d of incubation. Next, concentrations of HMX in embryos/eggs were determined by liquid chromatography-mass spectrometry. Mean (+/-SE) concentrations of HMX in eggs were 21.0+/-5.9, 1113+/-79.0, 3864+/-154.0, and 7426+/-301.1 ng g(-1) in control, low, medium and high dose groups, respectively. There were significant differences in oxygen consumption among the three embryo ages, however differences among the ages were not consistent among dose groups (age x dose group interaction p<0.0001). Oxygen consumption rates did not vary as a function of HMX in embryos (p=0.18). No evidence was observed for alterations of in ovo metabolic rates associated with HMX exposure.

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

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

Scott, Bobby, R., Ph.D.

2003-06-27

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

Depth dependence of absorbed dose, dose equivalent and linear energy transfer spectra of galactic and trapped particles in polyethylene and comparison with calculations of models

NASA Technical Reports Server (NTRS)

Badhwar, G. D.; Cucinotta, F. A.; Wilson, J. W. (Principal Investigator)

1998-01-01

A matched set of five tissue-equivalent proportional counters (TEPCs), embedded at the centers of 0 (bare), 3, 5, 8 and 12-inch-diameter polyethylene spheres, were flown on the Shuttle flight STS-81 (inclination 51.65 degrees, altitude approximately 400 km). The data obtained were separated into contributions from trapped protons and galactic cosmic radiation (GCR). From the measured linear energy transfer (LET) spectra, the absorbed dose and dose-equivalent rates were calculated. The results were compared to calculations made with the radiation transport model HZETRN/NUCFRG2, using the GCR free-space spectra, orbit-averaged geomagnetic transmission function and Shuttle shielding distributions. The comparison shows that the model fits the dose rates to a root mean square (rms) error of 5%, and dose-equivalent rates to an rms error of 10%. Fairly good agreement between the LET spectra was found; however, differences are seen at both low and high LET. These differences can be understood as due to the combined effects of chord-length variation and detector response function. These results rule out a number of radiation transport/nuclear fragmentation models. Similar comparisons of trapped-proton dose rates were made between calculations made with the proton transport model BRYNTRN using the AP-8 MIN trapped-proton model and Shuttle shielding distributions. The predictions of absorbed dose and dose-equivalent rates are fairly good. However, the prediction of the LET spectra below approximately 30 keV/microm shows the need to improve the AP-8 model. These results have strong implications for shielding requirements for an interplanetary manned mission.

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

PubMed Central

Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

2014-01-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

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

Staff Radiation Doses in a Real-Time Display Inside the Angiography Room

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

Sanchez, Roberto, E-mail: rmsanchez.hcsc@salud.madrid.org; Vano, E.; Fernandez, J. M.

MethodsThe evaluation of a new occupational Dose Aware System (DAS) showing staff radiation doses in real time has been carried out in several angiography rooms in our hospital. The system uses electronic solid-state detectors with high-capacity memory storage. Every second, it archives the dose and dose rate measured and is wirelessly linked to a base-station screen mounted close to the diagnostic monitors. An easy transfer of the values to a data sheet permits further analysis of the scatter dose profile measured during the procedure, compares it with patient doses, and seeks to find the most effective actions to reduce operatormore » exposure to radiation.ResultsThe cumulative occupational doses measured per procedure (shoulder-over lead apron) ranged from 0.6 to 350 {mu}Sv when the ceiling-suspended screen was used, and DSA (Digital Subtraction Acquisition) runs were acquired while the personnel left the angiography room. When the suspended screen was not used and radiologists remained inside the angiography room during DSA acquisitions, the dose rates registered at the operator's position reached up to 1-5 mSv/h during fluoroscopy and 12-235 mSv/h during DSA acquisitions. In such case, the cumulative scatter dose could be more than 3 mSv per procedure.ConclusionReal-time display of doses to staff members warns interventionists whenever the scatter dose rates are too high or the radiation protection tools are not being properly used, providing an opportunity to improve personal protection accordingly.« less

On the use of Lineal Energy Measurements to Estimate Linear Energy Transfer Spectra

NASA Technical Reports Server (NTRS)

Adams, David A.; Howell, Leonard W., Jr.; Adam, James H., Jr.

2007-01-01

This paper examines the error resulting from using a lineal energy spectrum to represent a linear energy transfer spectrum for applications in the space radiation environment. Lineal energy and linear energy transfer spectra are compared in three diverse but typical space radiation environments. Different detector geometries are also studied to determine how they affect the error. LET spectra are typically used to compute dose equivalent for radiation hazard estimation and single event effect rates to estimate radiation effects on electronics. The errors in the estimations of dose equivalent and single event rates that result from substituting lineal energy spectra for linear energy spectra are examined. It is found that this substitution has little effect on dose equivalent estimates in interplanetary quiet-time environment regardless of detector shape. The substitution has more of an effect when the environment is dominated by solar energetic particles or trapped radiation, but even then the errors are minor especially if a spherical detector is used. For single event estimation, the effect of the substitution can be large if the threshold for the single event effect is near where the linear energy spectrum drops suddenly. It is judged that single event rate estimates made from lineal energy spectra are unreliable and the use of lineal energy spectra for single event rate estimation should be avoided.

Sol-gel derived copper-doped silica glass as a sensitive material for X-ray beam dosimetry

NASA Astrophysics Data System (ADS)

Capoen, Bruno; Hamzaoui, Hicham El; Bouazaoui, Mohamed; Ouerdane, Youcef; Boukenter, Aziz; Girard, Sylvain; Marcandella, Claude; Duhamel, Olivier

2016-01-01

The light emission from a sol-gel-derived Cu-doped silica glass was studied under 10 keV X-ray irradiation using a fibered setup. Both radioluminescence (RL) and optically stimulated luminescence (OSL) were analyzed at different high dose rates up to 50 Gy/s and for different exposure times, yielding accumulated doses up to 50 kGy (in SiO2). Even if a darkening effect appears at this dose level, the material remains X-sensitive after exposure to several kGy. At low dose rate, the scintillation mechanisms are similar to photoluminescence, involving the Cu+ ions electronic levels, contrary to the nonlinear domain (for dose rates higher than 30 Gy/s). This RL, as well as the OSL, could be exploited in their linear domain to measure doses as high as 3 kGy. A thorough study of the OSL signal has shown that it must be employed with caution in order to take the fading phenomenon and the response dependency on stimulation source intensity into consideration.

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; Jesse, Robert; MacLean, Katherine A; Barrett, Frederick S; Cosimano, Mary P; Klinedinst, Maggie A

2018-01-01

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level ("standard") support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282.

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors

PubMed Central

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; Jesse, Robert; MacLean, Katherine A; Barrett, Frederick S; Cosimano, Mary P; Klinedinst, Maggie A

2017-01-01

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level (“standard”) support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282 PMID:29020861

Morphine tolerance as a function of ratio schedule: response requirement or unit price?

PubMed

Hughes, Christine E; Sigmon, Stacey C; Pitts, Raymond C; Dykstra, Linda A

2005-05-01

Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, l-methadone, and cocaine dose-dependently decreased overall response rates in each of the components. When a rate decreasing dose of morphine was administered daily, tolerance, as measured by an increase in the dose that reduced response rates to 50% of control (i.e., the ED50 value), developed in each of the components; however, the degree of tolerance was smallest in the fixed-ratio 90 component (i.e., the ED50 value increased the least). When the l-methadone dose-effect curve was redetermined during the chronic morphine phase, the degree of cross-tolerance conferred to l-methadone was similar across components, suggesting that behavioral variables may not influence the degree of cross-tolerance between opioids. During the chronic phase, the cocaine dose-effect curve shifted to the right for 2 pigeons and to the left for 1 pigeon, which is consistent with predictions based on the lack of pharmacological similarity between morphine and cocaine. When the morphine, l-methadone, and cocaine dose-effect curves were redetermined after chronic morphine administration ended, the morphine and l-methadone ED50s replicated those obtained prior to chronic morphine administration. The morphine data suggest that the fixed-ratio value (i.e., the absolute output) determines the degree of tolerance and not the unit price.

Natural radionuclides in cigarette tobacco from Serbian market and effective dose estimate from smoke inhalation.

PubMed

Janković Mandić, Ljiljana; Đolić, Maja; Marković, Dragana; Todorović, Dragana; Onjia, Antonije; Dragović, Snežana

2016-01-01

The activity concentrations of natural radionuclides ((40)K, (210)Pb, (210)Po, (226)Ra and (228)Ra) in 17 most frequently used cigarette brands in Serbia and corresponding effective doses due to smoke inhalation are presented. The mean annual effective doses for (210)Pb and (210)Po were estimated to be 47.3 and 724 µSv y(-1) for (210)Pb and (210)Po, respectively. Serbia currently has the highest smoking rate in the world. The results of this study indicate the high contribution of the annual effective dose due to smoke inhalation to the total inhalation dose from natural radionuclides. The more effective implementation of actions for reducing smoking prevalence in Serbia is highly needed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of ferrous-methylthymol blue-polyvinyl alcohol gel dosimeters using nuclear magnetic resonance and optical techniques

NASA Astrophysics Data System (ADS)

Rabaeh, Khalid A.; Eyadeh, Molham M.; Hailat, Tariq F.; Aldweri, Feras M.; Alheet, Samer M.; Eid, Rania M.

2018-07-01

A new composition of Ferrous sulphate-Metheylthymol blue (MTB)-Polyvinyl alcohol (PVA) dosimeter is introduced in this work and evaluated using nuclear magnetic resonance (NMR) and absorbance spectrophotometry techniques. The Fricke-MTB-PVA dosimeters were irradiated using a medical linear accelerator in a cubic water phantom. The dose response of the dosimeters was investigated using NMR in terms of spin-spin relaxation rate (R2), and ultraviolet and visible regions (UV-Vis) spectrophotometry in terms of absorbance. The dosimeter presents a linear dose response for doses up to 20 Gy with UV-Vis and 40 Gy with NMR method. The sample with 0.1 mM MTB, 5% PVA by weight showed highest dose sensitivity for both techniques. The Fricke-MTB-PVA dosimeter developed in this work has a significant advance over the Fricke-MTB-gelatin system: the NMR sensitivity was remarkably improved; the auto-oxidation rate was seven times lower, and no significant dose rate or photon energy effects were observed.

An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults.

PubMed

Kollins, Scott H; Schoenfelder, Erin N; English, Joseph S; Holdaway, Alex; Van Voorhees, Elizabeth; O'Brien, Benjamin R; Dew, Rachel; Chrisman, Allan K

2015-01-01

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10mg oral doses of delta-9-tetrahydocannibinol (THC); and 0mg, 10mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10mg THC+0mg, 10mg, and 40 mg MPH=89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of "Feel Drug," "Good Effects," and "Take Drug Again." THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. Copyright © 2014 Elsevier Inc. All rights reserved.

An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults

PubMed Central

Kollins, Scott H.; Schoenfelder, Erin N.; English, Joseph S.; Holdaway, Alex; Van Voorhees, Elizabeth; O’Brien, Benjamin R.; Dew, Rachel; Chrisman, Allan K.

2014-01-01

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10 mg oral doses of delta-9-tetrahydocannibinol (THC); and 0 mg, 10 mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10 mg THC + 0 mg, 10 mg, and 40 mg MPH = 89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of “Feel Drug,” “Good Effects,” and “Take Drug Again.” THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. PMID:25175495

Neonicotinoids and bumblebees (Bombus terrestris): effects on nectar consumption in individual workers.

PubMed

Thompson, Helen M; Wilkins, Selwyn; Harkin, Sarah; Milner, Sarah; Walters, Keith F A

2015-07-01

The objective of this study was to quantify whether the presence of three different neonicotinoid insecticides (imidacloprid, thiamethoxam or clothianidin) in sucrose solution results in antifeedant effects in individual worker bumblebees (Bombus terrestris), and, if so, whether this effect is reversible if bees are subsequently offered untreated feed. Bees exposed to imidacloprid displayed a significant dose-dependent reduction in consumption at 10 and 100 µg L(-1), which was reversed when untreated feed was offered. No consistent avoidance/antifeedant response to nectar substitute with thiamethoxam was detected at the more field-realistic dose rates of 1 and 10 µg L(-1), and exposure to the very high 100 µg L(-1) dose rate was followed by 100% mortality of experimental insects. No reduction in food intake was recorded at 1 µg clothianidin L(-1), reduced consumption was noted at 10 µg clothianidin L(-1) and 100% mortality occurred when bees were exposed to rates of 100 µg clothianidin L(-1). This study provides evidence of a direct antifeedant effect of imidacloprid and clothianidin in individual bumblebees but highlights that this may be a compound-specific effect. © 2014 Crown copyright. Pest Management Science © 2014 Society of Chemical Industry.

Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin

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

Foote, Matthew, E-mail: matthew_foote@health.qld.gov.a; Harvey, Jennifer; Porceddu, Sandro

Purpose: To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I-III Merkel cell carcinoma (MCC). Patients and Methods: This was a retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and treated with curative-intent RT. Results: Of the 112 evaluable patients, 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; in most cases (71%) this was for subclinical disease in the adjuvant or elective setting, whereas 21 patients (19%)more » were treated with RT to gross nodal disease. With a median follow-up of 3.7 years, the 2-year and 5-year overall survival rates were 72% and 53%, respectively, and the 2-year locoregional control rate was 75%. The in-field relapse rate was 3% for primary disease, and relapse was significantly lower for patients receiving {>=}50Gy (hazard ratio [HR] = 0.22; 95% confidence interval [CI], 0.06-0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes, with dose being significant for nodal gross disease (HR = 0.24; 95% CI, 0.07-0.87). Patients who did not receive elective nodal RT had a much higher rate of nodal relapse compared with those who did (HR = 6.03; 95% CI, 1.34-27.10). Conclusion: This study indicates a dose-response for subclinical and gross MCC. Doses of {>=}50Gy for subclinical disease and {>=}55Gy for gross disease should be considered. The draining nodal basin should be treated in all patients.« less

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences.

PubMed

Carbonaro, Theresa M; Johnson, Matthew W; Hurwitz, Ethan; Griffiths, Roland R

2018-02-01

Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared. This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects. Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Instructions to participants and staff minimized expectancy effects. Various subjective, behavioral, and physiological effects were assessed after drug administration. High doses of both drugs produced similar increases in participant ratings of peak overall drug effect strength, with similar times to maximal effect and time-course. Psilocybin produced orderly dose-related increases on most participant-rated subjective measures previously shown sensitive to hallucinogens. DXM produced increases on most of these same measures. However, the high dose of psilocybin produced significantly greater and more diverse visual effects than DXM including greater movement and more frequent, brighter, distinctive, and complex (including textured and kaleidoscopic) images and visions. Compared to DXM, psilocybin also produced significantly greater mystical-type and psychologically insightful experiences and greater absorption in music. In contrast, DXM produced larger effects than psilocybin on measures of disembodiment, nausea/emesis, and light-headedness. Both drugs increased systolic blood pressure, heart rate, and pupil dilation and decreased psychomotor performance and balance. Psilocybin and DXM produced similar profiles of subjective experiences, with psilocybin producing relatively greater visual, mystical-type, insightful, and musical experiences, and DXM producing greater disembodiment.

Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus.

PubMed

Lujan-Zilbermann, Jorge; Warshaw, Meredith G; Williams, Paige L; Spector, Stephen A; Decker, Michael D; Abzug, Mark J; Heckman, Barb; Manzella, Adam; Kabat, Bill; Jean-Philippe, Patrick; Nachman, Sharon; Siberry, George K

2012-10-01

To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV). P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% ≥ 15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥ 4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% ≥ 15. Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72. In youth infected with HIV with a CD4% ≥ 15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4. Copyright © 2012 Mosby, Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Obtaining the Optimal Dose in Alcohol Dependence Studies

PubMed Central

Wages, Nolan A.; Liu, Lei; O’Quigley, John; Johnson, Bankole A.

2012-01-01

In alcohol dependence studies, the treatment effect at different dose levels remains to be ascertained. Establishing this effect would aid us in identifying the best dose that has satisfactory efficacy while minimizing the rate of adverse events. We advocate the use of dose-finding methodology that has been successfully implemented in the cancer and HIV settings to identify the optimal dose in a cost-effective way. Specifically, we describe the continual reassessment method (CRM), an adaptive design proposed for cancer trials to reconcile the needs of dose-finding experiments with the ethical demands of established medical practice. We are applying adaptive designs for identifying the optimal dose of medications for the first time in the context of pharmacotherapy research in alcoholism. We provide an example of a topiramate trial as an illustration of how adaptive designs can be used to locate the optimal dose in alcohol treatment trials. It is believed that the introduction of adaptive design methods will enable the development of medications for the treatment of alcohol dependence to be accelerated. PMID:23189064

Dose and side effects of sublingual misoprostol for treatment of postpartum hemorrhage: what difference do they make?

PubMed Central

2012-01-01

Background Shivering and fever are common side effects of misoprostol. An unexpectedly high rate of fever above 40°C was documented among Ecuadorian women given treatment with 800mcg of sublingual misoprostol to manage postpartum hemorrhage (PPH) (36%). Much lower rates have been reported elsewhere (0-9%). Methods From February to July 2010, an open-label pilot study was conducted in Quito, Ecuador to determine whether a lower dose--600mcg sublingual misoprostol--would result in a lower incidence of high fever (≥40°C). Rates of shivering and fever with 600mcg sublingual regimen were compared to previously documented rates in Ecuador following PPH treatment with 800mcg sublingual misoprostol. Results The 600mcg dose resulted in a 55% lower rate of high fever compared with the 800mcg regimen (8/50; 16% vs. 58/163; 36%; relative risk 0.45 95% CI 0.23-0.88). Only one woman had severe shivering following the 600mcg dose compared with 19 women in the 800mcg cohort (2% vs. 12%; relative risk 0.17 (0.02-1.25)). No cases of delirium/altered sensorium were reported with the 600mcg dose and women’s assessment of severity/tolerability of shivering and fever was better with the lower dose. Conclusions 600mcg sublingual misoprostol was found to decrease the occurrence of high fever among Ecuadorian women when given to treat PPH. This study however was not powered to examine the efficacy of this treatment regimen and cannot be recommended at this time. Future research is needed to confirm whether other populations, outside of Quito, Ecuador, experience unusually high rates of elevated body temperature following sublingual administration of misoprostol for treatment of PPH. If indeed similar trends are found elsewhere, larger trials to confirm the efficacy of lower dosages may be justified. Trial Registration Clinical trials.gov, Registry No. NCT01080846 PMID:22769055

Dose and side effects of sublingual misoprostol for treatment of postpartum hemorrhage: what difference do they make?

PubMed

León, Wilfrido; Durocher, Jill; Barrera, Gustavo; Pinto, Ernesto; Winikoff, Beverly

2012-07-07

Shivering and fever are common side effects of misoprostol. An unexpectedly high rate of fever above 40°C was documented among Ecuadorian women given treatment with 800mcg of sublingual misoprostol to manage postpartum hemorrhage (PPH) (36%). Much lower rates have been reported elsewhere (0-9%). From February to July 2010, an open-label pilot study was conducted in Quito, Ecuador to determine whether a lower dose--600mcg sublingual misoprostol--would result in a lower incidence of high fever (≥40°C). Rates of shivering and fever with 600mcg sublingual regimen were compared to previously documented rates in Ecuador following PPH treatment with 800mcg sublingual misoprostol. The 600mcg dose resulted in a 55% lower rate of high fever compared with the 800mcg regimen (8/50; 16% vs. 58/163; 36%; relative risk 0.45 95% CI 0.23-0.88). Only one woman had severe shivering following the 600mcg dose compared with 19 women in the 800mcg cohort (2% vs. 12%; relative risk 0.17 (0.02-1.25)). No cases of delirium/altered sensorium were reported with the 600mcg dose and women's assessment of severity/tolerability of shivering and fever was better with the lower dose. 600mcg sublingual misoprostol was found to decrease the occurrence of high fever among Ecuadorian women when given to treat PPH. This study however was not powered to examine the efficacy of this treatment regimen and cannot be recommended at this time. Future research is needed to confirm whether other populations, outside of Quito, Ecuador, experience unusually high rates of elevated body temperature following sublingual administration of misoprostol for treatment of PPH. If indeed similar trends are found elsewhere, larger trials to confirm the efficacy of lower dosages may be justified. Clinical trials.gov, Registry No. NCT01080846.

Novel, single-dose, topical treatment of tinea pedis using terbinafine: results of a dose-finding clinical trial.

PubMed

de Chauvin, Martine Feuilhade; Viguié-Vallanet, Claude; Kienzler, Jean-Luc; Larnier, Catherine

2008-01-01

Tinea pedis is the most common dermatophytosis requiring topical antifungals for at least 1-4 weeks. To determine the effectiveness of a novel topical single dose formulation of terbinafine (film forming solution-FFS) in the treatment of tinea pedis, 344 outpatients from 43 dermatological centres in France and Bulgaria suffering from tinea pedis with possible extension to soles confirmed by mycological examination (direct and culture) were evaluated for efficacy of terbinafine 1%, 5%, 10% FFS in a randomised double blind vehicle controlled parallel group dose finding study. Evaluations were carried out at baseline, 1 and 6 weeks after a single application of FFS. Effective treatment rate based on negative mycology (direct and culture) and minimal signs and symptoms (two or less with only mild recorded) was measured at week 6. Effective treatment rates at week 6 with terbinafine 1%, 5% and 10% FFS were 66%, 70%, 61% compared with 18% with placebo. All three active preparations were shown to be significantly superior to placebo (P < 0.001). Terbinafine 1% and 5% FFS were shown to be non-inferior to terbinafine 10% FFS. Terbinafine 1% FFS is an effective, safe dose for the treatment of tinea pedis. This novel product represents a significant advance with the enhanced compliance and convenience that it offers.

Letrozole combined with low dose highly purified HMG for ovulation induction in clomiphene citrate-resistant infertile Chinese women with polycystic ovary syndrome: a prospective study.

PubMed

Zhao, Yue; Ruan, Xiangyan; Mueck, Alfred O

2017-06-01

There are still open questions about ovulation induction in clomiphene citrate-(CC)-resistant infertile women. Especially little is known about efficacy and safety of letrozole (LTZ) combined with low-dose highly purified human menopausal gonadotropin (Hp-HMG) in women with polycystic ovary syndrome (PCOS). Prospective, single-arm single-center trial in 200 infertile PCOS patients refractory for at least three CC-treatment cycles. Women with hyperandrogenism took Diane-35 for at least 3 months. All patients got LTZ on day 3 for 5 d in combination with Hp-HMG, starting with 75 IU from cycle day 7 and maintained for up to 3 d. The maximum dose was 150 IU. Primary end-points were ongoing and clinical pregnancy rate, secondary end-points mono-follicular development, ovulation rate, OHSS, multiple pregnancy and early pregnancy loss. Major safety end-point was the incidence of adverse events. Within 395 cycles the ongoing pregnancy rate was 28.24%, for cycles 35.23%, for patients 68%. The rate of ovulation per cycle was 97.7%, percentage of mono-follicular development 70.9%. No severe OHSS, multiple pregnancy, local or systemic side effects were seen. LTZ combined with low-dose Hp-HMG is an effective and safe choice for reducing hyperstimulation and increasing pregnancy rate in CC-resistant women with PCOS.

Comparison of Immunogenicity Between Inactivated and Live Attenuated Hepatitis A Vaccines Among Young Adults: A 3-Year Follow-up Study.

PubMed

Liu, Xue-en; Chen, Hai-ying; Liao, Zheng; Zhou, Yisheng; Wen, Hairong; Peng, Shihui; Liu, Yan; Li, Rui; Li, Jie; Zhuang, Hui

2015-10-15

A randomized clinical trial of hepatitis A vaccines (1 or 2 doses of inactivated vaccine [Healive] or 1 dose of live attenuated vaccine [Biovac]) was conducted among adults to evaluate seroprotection rates and geometric mean concentrations of antibody against hepatitis A virus for 36 months. High rates of seroprotection persisted for at least 36 months among adults who received 1 or 2 doses of inactivated hepatitis A vaccine but not among adults who received 1 dose of live attenuated hepatitis A vaccine. The long-term serial monitoring of immunogenicity induced by 1 dose of inactivated hepatitis A vaccine is needed to determine an effective alternative to a 2-dose schedule. NCT01865968. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

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

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

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

Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats.

PubMed

Wiley, Jenny L; Lefever, Timothy W; Marusich, Julie A; Craft, Rebecca M

2017-03-01

Women report greater sensitivity to the subjective effects of Δ 9 -tetrahydrocannabinol (THC). Similarly, female rodents tend to be more sensitive to some pharmacological effects of THC and synthetic cannabinoids. This study examined sex differences in discriminative stimulus and response rate effects of THC and synthetic cannabinoids in rats. A cumulative dosing THC discrimination procedure was utilized to evaluate sex differences in the discriminative stimulus effects of THC and three synthetic cannabinoids: CP47,497, WIN55,212-2, and JWH-018. Sex differences in the effects of these four compounds and a degradant of A-834735 on response rates also were assessed in a food-reinforced discrete dosing procedure. Females required a lower training dose than males for acquisition of the discrimination. Further, THC was more potent at producing rimonabant-reversible discriminative stimulus and response rate effects in females. While synthetic cannabinoids were more potent in producing THC-like effects than was THC in female rats, greater discrepancies were observed in male rats. Similar sensitivity to the response rate-decreasing effects induced by most, but not all (A-834735 degradant), synthetic cannabinoids was seen in both sexes. This study represents one of the first direct comparisons of sex differences in THC discrimination. Females were more sensitive to THC's effects, which may be related, in part, to sex differences in THC metabolism. Synthetic cannabinoids were more potent than THC in both sexes, but were considerably more so in male than in female rats. Future research should emphasize further characterization of sex differences in cannabinoid pharmacology. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats*

PubMed Central

Wiley, Jenny L.; Lefever, Timothy W.; Marusich, Julie A.; Craft, Rebecca M.

2017-01-01

Background Women report greater sensitivity to the subjective effects of Δ9-tetrahydrocannabinol (THC). Similarly, female rodents tend to be more sensitive to some pharmacological effects of THC and synthetic cannabinoids. This study examined sex differences in discriminative stimulus and response rate effects of THC and synthetic cannabinoids in rats. Methods A cumulative dosing THC discrimination procedure was utilized to evaluate sex differences in the discriminative stimulus effects of THC and three synthetic cannabinoids: CP47,497, WIN55,212-2, and JWH-018. Sex differences in the effects of these four compounds and a degradant of A-834735 on response rates also were assessed in a food-reinforced discrete dosing procedure. Results Females required a lower training dose than males for acquisition of the discrimination. Further, THC was more potent at producing rimonabant-reversible discriminative stimulus and response rate effects in females. While synthetic cannabinoids were more potent in producing THC-like effects than was THC in female rats, greater discrepancies were observed in male rats. Similar sensitivity to the response rate-decreasing effects induced by most, but not all (A-834735 degradant), synthetic cannabinoids was seen in both sexes. Conclusions This study represents one of the first direct comparisons of sex differences in THC discrimination. Females were more sensitive to THC’s effects, which may be related, in part, to sex differences in THC metabolism. Synthetic cannabinoids were more potent than THC in both sexes, but were considerably more so in male than in female rats. Future research should emphasize further characterization of sex differences in cannabinoid pharmacology. PMID:28130989

Effect of ketamine dose on self-rated dissociation in patients with treatment refractory anxiety disorders.

PubMed

Castle, Cameron; Gray, Andrew; Neehoff, Shona; Glue, Paul

2017-10-01

Patients receiving ketamine for refractory depression and anxiety report dissociative symptoms in the first 60 min post-dose. The most commonly used instrument to assess this is the Clinician-Administered Dissociative States Scale (CADSS), developed based on the assessment of patients with dissociative symptoms. Its psychometric properties for ketamine-induced dissociation have not been reported. We evaluated these from a study using 0.25-1 mg/kg ketamine and midazolam (as an active control) in 18 patients with treatment-resistant anxiety. Dissociation ratings were increased by ketamine in a dose-dependent manner. In contrast, midazolam showed no effect on ratings of dissociation. For individual CADSS items, the magnitude of change and the ketamine dose at which changes were observed were not homogenous. The Cronbach alpha for the total scale was high (0.937), with acceptable item-rest correlations for almost all individual items. Purposefully removing items to maximise alpha did not lead to meaningful improvements. Acceptable internal consistency was still observed after removing items which lacked evidence of responsiveness at lower doses. The high Cronbach alpha values identified in this study suggests that the CADSS is an internally consistent instrument for evaluating ketamine-induced dissociation in clinical trials in anxiety, although it does not capture symptoms such as thought disorder.

Induction of osteosarcoma and acute myeloid leukaemia in CBA/H mice by the alpha-emitting nuclides, uranium-233, plutonium-239 and amercium-241.

PubMed

Ellender, M; Harrison, J D; Pottinger, H; Thomas, J M

2001-01-01

To compare tumour induction in CBA/H mice, principally osteosarcoma and acute myeloid leukaemia, resulting from exposure to the alpha-emitting nuclides, uranium-233, plutonium-239 and americium-241, and to relate differences between the three nuclides to the pattern of dose delivery within tissues. Each nuclide was administered intraperitoneally in citrate solution to three groups of adult male CBA/H mice at levels of activity which gave estimated life-time average skeletal doses of about 0.25-0.3 Gy, 0.5-1 Gy and 1-2 Gy. Animals were carefully monitored and sacrificed as soon as they showed signs of ill health; tumours were identified by standard histopathological techniques. Statistical modelling by Cox regression showed that, considering all three nuclides together, there was a highly significant increase in risk of death from osteosarcoma or myeloid leukaemia with increasing dose rate. For osteosarcoma, the effect was significantly greater for 239Pu than 241Am, while separate analysis for 233U showed no significant increase with increasing dose rate. For example, the increase in relative risk of death from osteosarcoma for an increase in life-time average dose rate to bone of 1 mGyd(-1) was 4.2 (2.7-6.5) for 239Pu, 2.3 (1.4-3.4) for 241Am and 1.1 (0.4-3.1) for 233U. For myeloid leukaemia, there was no significant difference between 239Pu and 241Am in the effect of dose rate. The increase in relative risk from myeloid leukaemia for an increase in average dose rate of 1 mGyd(-1) was 1.8 (1.1-2.8) for 239Pu, 2.0 (1.4-2.9) for 241Am and 1.5 (0.8-2.7) for 233U. Significant increases in renal and hepatic carcinomas were also recorded in animals exposed to 233U and 241Am, respectively. Studies of the distribution of the nuclides within the skeleton, published separately, have shown differences in their retention in individual bones and within bone. The proportions of decays occurring near to endosteal bone surfaces and throughout bone marrow were in the order: 239Pu> 241Am>233U. For osteosarcoma, the relative effectiveness of the nuclides in terms of average bone dose, in the order 239Pu>241Am>233U, is consistent with the proportion of dose delivered near to endosteal surfaces. For myeloid leukaemia, the greater effectiveness of 239Pu and 241Am than 233U is consistent with their accumulation in marrow.

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

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

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;

Increased Radioresistance to Lethal Doses of Gamma Rays in Mice and Rats after Exposure to Microwave Radiation Emitted by a GSM Mobile Phone Simulator

PubMed Central

Mortazavi, SMJ; Mosleh-Shirazi, MA; Tavassoli, AR; Taheri, M; Mehdizadeh, AR; Namazi, SAS; Jamali, A; Ghalandari, R; Bonyadi, S; Haghani, M; Shafie, M

2013-01-01

The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1st phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2nd phase, 30 male rats were divided into 2 groups of 15 animals. The 1st group received microwave exposure. The 2nd group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response. PMID:23930107

Effects of β-blockers and anxiety on complication rates after acute myocardial infarction.

PubMed

Abu Ruz, Mohannad E; Lennie, Terry A; Moser, Debra K

2011-01-01

Anxiety is common after acute myocardial infarction and increases the number of complications and the length of stay in the hospital. Anxiety-induced activation of the sympathetic nervous system is hypothesized to be an underlying cause of increased complication rates. Little is known about whether use of β-blockers eliminates the effects of anxiety on complication rate and length of stay. To compare number of complications and length of stay among nonanxious and anxious patients receiving β-blockers during hospitalization. A total of 322 patients with acute myocardial infarction participated in this study within 48 hours of hospital admission. Patients completed the Brief Symptom Inventory to assess anxiety level. After discharge, medical records were reviewed to determine use of β-blockers, type and number of complications, and length of stay. Most patients (96%) were treated with less than 200 mg daily of metoprolol. Anxious patients had more complications (mean [SD], 1.43 [0.15] vs 0.73 [.09], P ≤ .01) and longer stays (7.0 [0.49] vs 5.7 [0.36] days, P < .05) than did nonanxious patients. To test whether the dose of β-blocker made a difference, the interaction between daily dose and anxiety score was tested. No interaction was found between metoprolol dose and anxiety score, and no main effect was found for metoprolol dose. Anxious patients had more complications and longer stays than did nonanxious patients. The administration of metoprolol did not eliminate this relationship, perhaps because patients did not receive a sufficient dose of metoprolol to counter the effect of anxiety.

Measuring methylphenidate response in attention-deficit/hyperactvity disorder: how are laboratory classroom-based measures related to parent ratings?

PubMed

Sonuga-Barke, Edmund J S; Coghill, David; DeBacker, Marc; Swanson, James

2009-12-01

Methylphenidate (MPH) is an efficacious and normally well-tolerated treatment for attention-deficit/hyperactivity disorder (ADHD). Although treatment effects are usually assessed using parent-rating scales, these can be supplemented by more objective methods. Here we examine the associations between ratings and one such method, assessments made across the day in the laboratory classroom. Comparison of Methylphenidates in the Analog Classroom Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol. Therapeutic effects were measured using direct observation, scores on a simple math productivity task and parent ratings. Treatment effects were observed on all measures. Laboratory measures were correlated with each other, most strongly between Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP) inattention and Permanent Product Measure of Performance (PERMP). Parental ratings were correlated with classroom measures during the main morning period (1.5-4.5 hours after dosing) and to a lesser extent in the afternoon (6.0-7.5 hours after dosing), but not, by and large, immediately after dosing or in the evening. The morning correlations seemed stronger for female than for male participants. The results suggest that parental ratings and direct observations tap different aspects of MPH response and that both may be required for comprehensive assessment.

Safety of an i.v. β-adrenergic blockade protocol for heart rate optimization before coronary CT angiography.

PubMed

Kassamali, Rahil H; Kim, Daniel H; Patel, Hiten; Raichura, Nitin; Hoey, Edward T D; Hodson, James; Hussain, Shahid

2014-10-01

The purpose of this study was to assess the safety of heart rate optimization by use of β-adrenergic blockade solely by the i.v. route before coronary CT angiography. The records of 679 patients undergoing CT coronary angiography after receiving i.v. β-adrenergic blockade were retrospectively analyzed. Health screening was completed before scanning, and heart rate was optimized by administration of i.v. metoprolol titrated to a maximum of 70 mg to achieve a heart rate less than 65 beats/min. The median i.v. dose was 20 mg (range, 5-70 mg). The 679 patients analyzed had a total of 10 complications (1.47%). Major complications, defined as not resolving with observation and analgesia alone, occurred in only three patients (0.44%). These complications included a second-degree atrioventricular block. A total of 299 patients (44.0%) needed more than 20 mg of i.v. metoprolol to achieve target heart rate. Only three patients needed the maximum i.v. dose of 70 mg metoprolol. Target heart rate was reached successfully in 666 patients (98.1%) with doses of less than 70 mg. This study did not show a statistically significant association between increasing complication frequency and increasing dose. This study showed that high doses of i.v. metoprolol can be used effectively and with a low rate of major complications to control heart rate before coronary CT angiography in correctly screened patients.