Dose properties of a laser accelerated electron beam and prospects for clinical application.

PubMed

Kainz, K K; Hogstrom, K R; Antolak, J A; Almond, P R; Bloch, C D; Chiu, C; Fomytskyi, M; Raischel, F; Downer, M; Tajima, T

2004-07-01

Laser wakefield acceleration (LWFA) technology has evolved to where it should be evaluated for its potential as a future competitor to existing technology that produces electron and x-ray beams. The purpose of the present work is to investigate the dosimetric properties of an electron beam that should be achievable using existing LWFA technology, and to document the necessary improvements to make radiotherapy application for LWFA viable. This paper first qualitatively reviews the fundamental principles of LWFA and describes a potential design for a 30 cm accelerator chamber containing a gas target. Electron beam energy spectra, upon which our dose calculations are based, were obtained from a uniform energy distribution and from two-dimensional particle-in-cell (2D PIC) simulations. The 2D PIC simulation parameters are consistent with those reported by a previous LWFA experiment. According to the 2D PIC simulations, only approximately 0.3% of the LWFA electrons are emitted with an energy greater than 1 MeV. We studied only the high-energy electrons to determine their potential for clinical electron beams of central energy from 9 to 21 MeV. Each electron beam was broadened and flattened by designing a dual scattering foil system to produce a uniform beam (103%>off-axis ratio>95%) over a 25 x 25 cm2 field. An energy window (deltaE) ranging from 0.5 to 6.5 MeV was selected to study central-axis depth dose, beam flatness, and dose rate. Dose was calculated in water at a 100 cm source-to-surface distance using the EGS/BEAM Monte Carlo algorithm. Calculations showed that the beam flatness was fairly insensitive to deltaE. However, since the falloff of the depth-dose curve (R10-R90) and the dose rate both increase with deltaE, a tradeoff between minimizing (R10-R90) and maximizing dose rate is implied. If deltaE is constrained so that R10-R90 is within 0.5 cm of its value for a monoenergetic beam, the maximum practical dose rate based on 2D PIC is approximately 0.1 Gy min(-1) for a 9 MeV beam and 0.03 Gy min(-1) for a 15 MeV beam. It was concluded that current LWFA technology should allow a table-top terawatt (T3) laser to produce therapeutic electron beams that have acceptable flatness, penetration, and falloff of depth dose; however, the dose rate is still 1%-3% of that which would be acceptable, especially for higher-energy electron beams. Further progress in laser technology, e.g., increasing the pulse repetition rate or number of high energy electrons generated per pulse, is necessary to give dose rates acceptable for electron beams. Future measurements confirming dosimetric calculations are required to substantiate our results. In addition to achieving adequate dose rate, significant engineering developments are needed for this technology to compete with current electron acceleration technology. Also, the functional benefits of LWFA electron beams require further study and evaluation.

Intravenous Sedation with Low-Dose Dexmedetomidine: Its Potential for Use in Dentistry

PubMed Central

Ogawa, Sachie; Seino, Hiroaki; Ito, Hiroshi; Yamazaki, Shinya; Ganzberg, Steven; Kawaai, Hiroyoshi

2008-01-01

This study investigated the physiologic and sedative parameters associated with a low-dose infusion of dexmedetomidine (Dex). Thirteen healthy volunteers were sedated with Dex at a loading dose of 6 mcg/kg/h for 5 minutes and a continuous infusion dose of 0.2 mcg/kg/h for 25 minutes. The recovery process was observed for 60 minutes post infusion. The tidal volume decreased significantly despite nonsignificant changes in respiratory rate, minute ventilation, oxygen saturation, and end-tidal carbon dioxide. The mean arterial pressure and heart rate also decreased significantly but within clinically acceptable levels. Amnesia to pin prick was present in 69% of subjects. A Trieger dot test plot error ratio did not show a significant change at 30 minutes post infusion despite a continued significant decrease in bispectral index. We conclude that sedation with a low dose of Dex appears to be safe and potentially efficacious for young healthy patients undergoing dental procedures. PMID:18788843

The impact of different algorithms for ideal body weight on screening for hydroxychloroquine retinopathy in women.

PubMed

Browning, David J; Lee, Chong; Rotberg, David

2014-01-01

To determine how algorithms for ideal body weight (IBW) affect hydroxychloroquine dosing in women. This was a retrospective study of 520 patients screened for hydroxychloroquine retinopathy. Charts were reviewed for sex, height, weight, and daily dose. The outcome measures were ranges of IBW across algorithms; rates of potentially toxic dosing; height thresholds below which 400 mg/d dosing is potentially toxic; and rates for which actual body weight (ABW) was less than IBW. Women made up 474 (91%) of the patients. The IBWs for a height varied from 30-34 pounds (13.6-15.5 kg) across algorithms. The threshold heights below which toxic dosing occurred varied from 62-70 inches (157.5-177.8 cm). Different algorithms placed 16%-98% of women in the toxic dosing range. The proportion for whom dosing should have been based on ABW rather than IBW ranged from 5%-31% across algorithms. Although hydroxychloroquine dosing should be based on the lesser of ABW and IBW, there is no consensus about the definition of IBW. The Michaelides algorithm is associated with the most frequent need to adjust dosing; the Metropolitan Life Insurance, large frame, mean value table with the least frequent need. No evidence indicates that one algorithm is superior to others.

Potential impact of clinical use of noninvasive FFRCT on radiation dose exposure and downstream clinical event rate.

PubMed

Bilbey, Nicolas; Blanke, Philipp; Naoum, Christopher; Arepalli, Chesnel Dey; Norgaard, Bjarne Linde; Leipsic, Jonathon

2016-01-01

This study aims to determine the potential impact of introducing noninvasive fractional flow reserve based on coronary computed tomography angiography (CTA) into clinical practice, with respect to radiation dose exposure and downstream event rate. We modeled a population of 1000 stable, symptomatic patients with suspected coronary artery disease, using the disease prevalence from the CONFIRM registry to estimate the pretest likelihood. Four potential clinical pathways were modeled based on the first noninvasive diagnostic test performed: (1) dobutamine echo; (2) single-photon emission computerized tomography (SPECT); (3) coronary CTA; and (4) CTA+FFRCT and leading to possible invasive coronary angiography. The posttest likelihood of testing positive/negative by each test was based on the presenting disease burden and diagnostic accuracy of each test. The dobutamine echo pathway resulted in the lowest radiation dose of 5.4 mSv, with 4.0 mSv from angiography and 1.4 mSv from percutaneous coronary intervention (PCI). The highest dose was with SPECT, with 26.5 mSv. The coronary computed tomography angiography (cCTA) pathway demonstrated a dose of 14.2 mSv, 3.7 mSv from cCTA, 7.7 mSv from angiography, and 2.8 mSv from PCI. The CTA+FFRCT pathway exhibited a radiation dose of 9.7 mSv, 3.7 mSv for cCTA, 4.2 mSv for angiography, and 1.8 mSv for PCI. Radiation dose exposure for CTA+FFRCT was lower than for SPECT (P<.001). The CTA+FFRCT pathway resulted in the lowest projected death/myocardial infarction rate at 1 year (2.44%) while the dobutamine stress pathway had the highest 1-year event rate (2.84%). Our analysis suggests that integrating FFRCT into the CTA clinical pathway may result in reduced cumulative radiation exposure, while promoting favorable clinical outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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

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

2010-06-01

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

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

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.

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

PubMed Central

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

2013-01-01

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

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

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

Real-time dosimetry in radiotherapy using tailored optical fibers

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

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.

Novel spectrometers for environmental dose rate monitoring.

PubMed

Kessler, P; Behnke, B; Dabrowski, R; Dombrowski, H; Röttger, A; Neumaier, S

2018-07-01

A new generation of dosemeters, based on the scintillators LaBr 3 , CeBr 3 and SrI 2 , read out with conventional photomultipliers, to be used in the field of environmental gamma-radiation monitoring, was investigated. The main features of these new instruments and especially their outdoor performance, studied by long-term investigations under real weather conditions, are presented. The systems were tested at the reference sites for environmental radiation of the Physikalisch-Technische Bundesanstalt. The measurements are compared with that of well characterized classical dose rate reference instruments to demonstrate the suitability of new spectrometers for environmental dose rate monitoring even in adverse weather conditions. Their potential to replace the (mainly Geiger Müller based) dose rate meters operated in about 5000 European early waning network stations as well as in environmental radiation monitoring in general is shown. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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.

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

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

Howe, G.R.

1997-03-01

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

Cost comparison of unit dose and traditional drug distribution in a long-term-care facility.

PubMed

Lepinski, P W; Thielke, T S; Collins, D M; Hanson, A

1986-11-01

Unit dose and traditional drug distribution systems were compared in a 352-bed long-term-care facility by analyzing nursing time, medication-error rate, medication costs, and waste. Time spent by nurses in preparing, administering, charting, and other tasks associated with medications was measured with a stop-watch on four different nursing units during six-week periods before and after the nursing home began using unit dose drug distribution. Medication-error rate before and after implementation of the unit dose system was determined by patient profile audits and medication inventories. Medication costs consisted of patient billing costs (acquisition cost plus fee) and cost of medications destroyed. The unit dose system required a projected 1507.2 hours less nursing time per year. Mean medication-error rates were 8.53% and 0.97% for the traditional and unit dose systems, respectively. Potential annual savings because of decreased medication waste with the unit dose system were $2238.72. The net increase in cost for the unit dose system was estimated at $615.05 per year, or approximately $1.75 per patient. The unit dose system appears safer and more time-efficient than the traditional system, although its costs are higher.

A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice

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

Walker, Mary K., E-mail: mwalker@salud.unm.edu; Boberg, Jason R.; Walsh, Mary T.

Oral gavage dosing can induce stress and potentially confound experimental measurements, particularly when blood pressure and heart rate are endpoints of interest. Thus, we developed a pill formulation that mice would voluntarily consume and tested the hypothesis that pill dosing would be significantly less stressful than oral gavage. C57Bl/6 male mice were singly housed and on four consecutive days were exposed to an individual walking into the room (week 1, control), a pill being placed into the cage (week 2), and a dose of water via oral gavage (week 3). Blood pressure and heart rate were recorded by radiotelemetry continuouslymore » for 5 h after treatment, and feces collected 6–10 h after treatment for analysis of corticosterone metabolites. Both pill and gavage dosing significantly increased mean arterial pressure (MAP) during the first hour, compared to control. However, the increase in MAP was significantly greater after gavage and remained elevated up to 5 h, while MAP returned to normal within 2 h after a pill. Neither pill nor gavage dosing significantly increased heart rate during the first hour, compared to control; however, pill dosing significantly reduced heart rate while gavage significantly increased heart rate 2–5 h post dosing. MAP and heart rate did not differ 24 h after dosing. Lastly, only gavage dosing significantly increased fecal corticosterone metabolites, indicating a systemic stress response via activation of the hypothalamic–pituitary–adrenal axis. These data demonstrated that this pill dosing method of mice is significantly less stressful than oral gavage. -- Highlights: ► Developed a novel oral dosing method using a pill that mice will readily consume. ► Assessed stress by blood pressure, heart rate, and fecal corticosterone metabolites. ► Demonstrated that pill dosing is significantly less stressful than oral gavage.« less

Risk of anaphylaxis after vaccination in children and adults

PubMed Central

McNeil, Michael M.; Weintraub, Eric S.; Duffy, Jonathan; Sukumaran, Lakshmi; Jacobsen, Steven J.; Klein, Nicola P.; Hambidge, Simon J.; Lee, Grace M.; Jackson, Lisa A.; Irving, Stephanie A.; King, Jennifer P.; Kharbanda, Elyse O.; Bednarczyk, Robert A.; DeStefano, Frank

2015-01-01

Background Anaphylaxis is a potentially life-threatening allergic reaction. The risk of anaphylaxis after vaccination has not been well described in adults or with newer vaccines in children. Objective We sought to estimate the incidence of anaphylaxis after vaccines and describe the demographic and clinical characteristics of confirmed cases of anaphylaxis. Methods Using health care data from the Vaccine Safety Datalink, we determined rates of anaphylaxis after vaccination in children and adults. We first identified all patients with a vaccination record from January 2009 through December 2011 and used diagnostic and procedure codes to identify potential anaphylaxis cases. Medical records of potential cases were reviewed. Confirmed cases met the Brighton Collaboration definition for anaphylaxis and had to be determined to be vaccine triggered. We calculated the incidence of anaphylaxis after all vaccines combined and for selected individual vaccines. Results We identified 33 confirmed vaccine-triggered anaphylaxis cases that occurred after 25,173,965 vaccine doses. The rate of anaphylaxis was 1.31 (95% CI, 0.90-1.84) per million vaccine doses. The incidence did not vary significantly by age, and there was a nonsignificant female predominance. Vaccine-specific rates included 1.35 (95% CI, 0.65-2.47) per million doses for inactivated trivalent influenza vaccine (10 cases, 7,434,628 doses given alone) and 1.83 (95% CI, 0.22-6.63) per million doses for inactivated monovalent influenza vaccine (2 cases, 1,090,279 doses given alone). The onset of symptoms among cases was within 30 minutes (8 cases), 30 to less than 120 minutes (8 cases), 2 to less than 4 hours (10 cases), 4 to 8 hours (2 cases), the next day (1 case), and not documented (4 cases). Conclusion Anaphylaxis after vaccination is rare in all age groups. Despite its rarity, anaphylaxis is a potentially life-threatening medical emergency that vaccine providers need to be prepared to treat. PMID:26452420

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.

Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia.

PubMed

Pierce, Dwayne A; Russell, Greg; Pirkle, James L

2015-12-01

Hyperkalemia is a potentially life-threatening condition that is common in kidney disease patients. Insulin is used to treat hyperkalemia, but may cause hypoglycemia, especially in kidney disease when insulin may be metabolized more slowly. We compared the rates of hypoglycemia in patients with low estimated glomerular filtration rate (eGFR) using high versus low doses of insulin for hyperkalemia to determine if lower doses of insulin would decrease the incidence of hypoglycemia. This was a retrospective study of hospitalized patients receiving intravenous insulin for hyperkalemia during a 6-month period. Patients with low eGFR were analyzed based on how much insulin they received: high dose (10 units, n = 78) versus low dose (5 units, n = 71). Postdose nadir blood glucose values were examined for up to 8 hours after the dose. The percentage of hypoglycemia (blood glucose ≤70 mg/dl) and a subset of severe hypoglycemia (blood glucose <50 mg/dl) were then reported for each dose group. A total of 149 doses were identified in patients with low eGFR. The rates of hypoglycemia were 16.7% and 19.7% (P = 0.79), respectively, among high-dose (n = 78) and low-dose (n = 71) groups. Rates of severe hypoglycemia were 8.9% and 7.0%, respectively (P = 0.90). More than 28% of hypoglycemic episodes with high doses occurred after 4 hours (median = 2.5 hours) compared with 14.3% with low doses (median = 2.38 hours). There was no difference in the rate of hypoglycemia or severe hypoglycemia between high or low doses of insulin in patients with low eGFR. We recommend monitoring up to 6 hours after insulin use in hyperkalemia. © The Author(s) 2015.

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.

Outpatient Prescribing Errors and the Impact of Computerized Prescribing

PubMed Central

Gandhi, Tejal K; Weingart, Saul N; Seger, Andrew C; Borus, Joshua; Burdick, Elisabeth; Poon, Eric G; Leape, Lucian L; Bates, David W

2005-01-01

Background Medication errors are common among inpatients and many are preventable with computerized prescribing. Relatively little is known about outpatient prescribing errors or the impact of computerized prescribing in this setting. Objective To assess the rates, types, and severity of outpatient prescribing errors and understand the potential impact of computerized prescribing. Design Prospective cohort study in 4 adult primary care practices in Boston using prescription review, patient survey, and chart review to identify medication errors, potential adverse drug events (ADEs) and preventable ADEs. Participants Outpatients over age 18 who received a prescription from 24 participating physicians. Results We screened 1879 prescriptions from 1202 patients, and completed 661 surveys (response rate 55%). Of the prescriptions, 143 (7.6%; 95% confidence interval (CI) 6.4% to 8.8%) contained a prescribing error. Three errors led to preventable ADEs and 62 (43%; 3% of all prescriptions) had potential for patient injury (potential ADEs); 1 was potentially life-threatening (2%) and 15 were serious (24%). Errors in frequency (n=77, 54%) and dose (n=26, 18%) were common. The rates of medication errors and potential ADEs were not significantly different at basic computerized prescribing sites (4.3% vs 11.0%, P=.31; 2.6% vs 4.0%, P=.16) compared to handwritten sites. Advanced checks (including dose and frequency checking) could have prevented 95% of potential ADEs. Conclusions Prescribing errors occurred in 7.6% of outpatient prescriptions and many could have harmed patients. Basic computerized prescribing systems may not be adequate to reduce errors. More advanced systems with dose and frequency checking are likely needed to prevent potentially harmful errors. PMID:16117752

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

PubMed

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

2004-01-01

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

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.

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

Indoor terrestrial gamma dose rate mapping in France: a case study using two different geostatistical models.

PubMed

Warnery, E; Ielsch, G; Lajaunie, C; Cale, E; Wackernagel, H; Debayle, C; Guillevic, J

2015-01-01

Terrestrial gamma dose rates show important spatial variations in France. Previous studies resulted in maps of arithmetic means of indoor terrestrial gamma dose rates by "departement" (French district). However, numerous areas could not be characterized due to the lack of data. The aim of our work was to obtain more precise estimates of the spatial variability of indoor terrestrial gamma dose rates in France by using a more recent and complete data base and geostatistics. The study was based on the exploitation of 97,595 measurements results distributed in 17,404 locations covering all of France. Measurements were done by the Institute for Radioprotection and Nuclear Safety (IRSN) using RPL (Radio Photo Luminescent) dosimeters, exposed during several months between years 2011 and 2012 in French dentist surgeries and veterinary clinics. The data used came from dosimeters which were not exposed to anthropic sources. After removing the cosmic rays contribution in order to study only the telluric gamma radiation, it was decided to work with the arithmetic means of the time-series measurements, weighted by the time-exposure of the dosimeters, for each location. The values varied between 13 and 349 nSv/h, with an arithmetic mean of 76 nSv/h. The observed statistical distribution of the gamma dose rates was skewed to the right. Firstly, ordinary kriging was performed in order to predict the gamma dose rate on cells of 1*1 km(2), all over the domain. The second step of the study was to use an auxiliary variable in estimates. The IRSN achieved in 2010 a classification of the French geological formations, characterizing their uranium potential on the bases of geology and local measurement results of rocks uranium content. This information is georeferenced in a map at the scale 1:1,000,000. The geological uranium potential (GUP) was classified in 5 qualitative categories. As telluric gamma rays mostly come from the progenies of the (238)Uranium series present in rocks, this information, which is exhaustive throughout France, could help in estimating the telluric gamma dose rates. Such an approach is possible using multivariate geostatistics and cokriging. Multi-collocated cokriging has been performed on 1*1 km(2) cells over the domain. This model used gamma dose rate measurement results and GUP classes. Our results provide useful information on the variability of the natural terrestrial gamma radiation in France ('natural background') and exposure data for epidemiological studies and risk assessment from low dose chronic exposures. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

SU-E-T-586: Optimal Determination of Tolerance Level for Radiation Dose Delivery Verification in An in Vivo Dosimetry System

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

Chen, Y; Souri, S; Gill, G

Purpose: To statistically determine the optimal tolerance level in the verification of delivery dose compared to the planned dose in an in vivo dosimetry system in radiotherapy. Methods: The LANDAUER MicroSTARii dosimetry system with screened nanoDots (optically stimulated luminescence dosimeters) was used for in vivo dose measurements. Ideally, the measured dose should match with the planned dose and falls within a normal distribution. Any deviation from the normal distribution may be redeemed as a mismatch, therefore a potential sign of the dose misadministration. Randomly mis-positioned nanoDots can yield a continuum background distribution. A percentage difference of the measured dose tomore » its corresponding planned dose (ΔD) can be used to analyze combined data sets for different patients. A model of a Gaussian plus a flat function was used to fit the ΔD distribution. Results: Total 434 nanoDot measurements for breast cancer patients were collected across a period of three months. The fit yields a Gaussian mean of 2.9% and a standard deviation (SD) of 5.3%. The observed shift of the mean from zero is attributed to the machine output bias and calibration of the dosimetry system. A pass interval of −2SD to +2SD was applied and a mismatch background was estimated to be 4.8%. With such a tolerance level, one can expect that 99.99% of patients should pass the verification and at most 0.011% might have a potential dose misadministration that may not be detected after 3 times of repeated measurements. After implementation, a number of new start breast cancer patients were monitored and the measured pass rate is consistent with the model prediction. Conclusion: It is feasible to implement an optimal tolerance level in order to maintain a low limit of potential dose misadministration while still to keep a relatively high pass rate in radiotherapy delivery verification.« less

Individualized Radiation Dose Escalation Based on the Decrease in Tumor FDG Uptake and Normal Tissue Constraints Improve Survival in Patients With Esophageal Carcinoma.

PubMed

Ma, Jinbo; Wang, Zhaoyang; Wang, Chengde; Chen, Ercheng; Dong, Yaozong; Song, Yipeng; Wang, Wei; You, Dong; Jiang, Wei; Zang, Rukun

2017-02-01

To determine whether individualized radiation dose escalation after planned chemoradiation based on the decrease in tumor and normal tissue constraints can improve survival in patients with esophageal carcinoma. From August 2005 to December 2010, 112 patients with squamous esophageal carcinoma were treated with radical concurrent chemoradiation. Patients received positron emission tomography-computer tomography scan twice, before radiation and after radiation dose of 50.4 Gy. All patients were noncomplete metabolic response groups according to the Response Evaluation Criteria in solid tumors. Only 52 patients with noncomplete metabolic response received individualized dose escalation based on tumor and normal tissue constraints. Survival and treatment failure were observed and analyzed using SPSS (13.0). The rate of complete metabolic response for patients with noncomplete metabolic response after dose escalation reached 17.3% (9 of 52). The 2-year overall survival rates for patients with noncomplete metabolic response in the conventional and dose-escalation groups were 20.5% and 42.8%, respectively( P = .001). The 2-year local control rates for patients were 35.7% and 76.2%, respectively ( P = .002). When patients were classified into partial metabolic response and no metabolic response, 2-year overall survival rates for patients with partial metabolic response were significantly different in conventional and dose-escalation groups (33.8% vs 78.4%; P = .000). The 2-year overall survival rates for patients with no metabolic response in two groups (8.6% vs 15.1%) did not significantly differ ( P = .917). Individualized radiation dose escalation has the potential to improve survival in patients with esophageal carcinoma according to increased rate of complete metabolic response. However, further trials are needed to confirm this and to identify patients who may benefit from dose escalation.

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.

Radiation dosimetry properties of smartphone CMOS sensors.

PubMed

Van Hoey, Olivier; Salavrakos, Alexia; Marques, Antonio; Nagao, Alexandre; Willems, Ruben; Vanhavere, Filip; Cauwels, Vanessa; Nascimento, Luana F

2016-03-01

During the past years, several smartphone applications have been developed for radiation detection. These applications measure radiation using the smartphone camera complementary metal-oxide-semiconductor sensor. They are potentially useful for data collection and personal dose assessment in case of a radiological incident. However, it is important to assess these applications. Six applications were tested by means of irradiations with calibrated X-ray and gamma sources. It was shown that the measurement stabilises only after at least 10-25 min. All applications exhibited a flat dose rate response in the studied ambient dose equivalent range from 2 to 1000 μSv h(-1). Most applications significantly over- or underestimate the dose rate or are not calibrated in terms of dose rate. A considerable energy dependence was observed below 100 keV but not for the higher energy range more relevant for incident scenarios. Photon impact angle variation gave a measured signal variation of only about 10 %. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

X-ray emission as a potential hazard during ultrashort pulse laser material processing

NASA Astrophysics Data System (ADS)

Legall, Herbert; Schwanke, Christoph; Pentzien, Simone; Dittmar, Günter; Bonse, Jörn; Krüger, Jörg

2018-06-01

In laser machining with ultrashort laser pulses unwanted X-ray radiation in the keV range can be generated when a critical laser intensity is exceeded. Even if the emitted X-ray dose per pulse is low, high laser repetition rates can lead to an accumulation of X-ray doses beyond exposure safety limits. For 925 fs pulse duration at a center wavelength of 1030 nm, the X-ray emission was investigated up to an intensity of 2.6 × 1014 W/cm2. The experiments were performed in air with a thin disk laser at a repetition rate of 400 kHz. X-ray spectra and doses were measured for various planar target materials covering a wide range of the periodic table from aluminum to tungsten. Without radiation shielding, the measured radiation doses at this high repetition rate clearly exceed the regulatory limits. Estimations for an adequate radiation shielding are provided.

Significance of manipulating tumour hypoxia and radiation dose rate in terms of local tumour response and lung metastatic potential, referring to the response of quiescent cell populations

PubMed Central

Masunaga, S; Matsumoto, Y; Kashino, G; Hirayama, R; Liu, Y; Tanaka, H; Sakurai, Y; Suzuki, M; Kinashi, Y; Maruhashi, A; Ono, K

2010-01-01

The purpose of this study was to evaluate the influence of manipulating intratumour oxygenation status and radiation dose rate on local tumour response and lung metastases following radiotherapy, referring to the response of quiescent cell populations within irradiated tumours. B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation at high dose rate (HDR) or reduced dose rate (RDR) following treatment with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the quiescent (Q) and total (proliferating + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Following HDR irradiation, nicotinamide and MTH enhanced the sensitivity of the total and Q-cell populations, respectively. The decrease in sensitivity at RDR irradiation compared with HDR irradiation was slightly inhibited by MTH, especially in Q cells. Without γ-ray irradiation, nicotinamide treatment tended to reduce the number of lung metastases. With γ-rays, in combination with nicotinamide or MTH, especially the former, HDR irradiation decreased the number of metastases more remarkably than RDR irradiation. Manipulating both tumour hypoxia and irradiation dose rate have the potential to influence lung metastasis. The combination with the acute hypoxia-releasing agent nicotinamide may be more promising in HDR than RDR irradiation in terms of reducing the number of lung metastases. PMID:20739345

Indoor radon, geogenic radon surrogates and geology - Investigations on their correlation.

PubMed

Friedmann, H; Baumgartner, A; Bernreiter, M; Gräser, J; Gruber, V; Kabrt, F; Kaineder, H; Maringer, F J; Ringer, W; Seidel, C; Wurm, G

2017-01-01

The indoor radon concentration was measured in most houses in a couple of municipalities in Austria. At the same time the activity concentration of radium in soil, the soil gas radon concentration, the permeability of the ground and the ambient dose equivalent rate were also measured and the geological situations (geological units) were recorded too. From the indoor radon concentration and different house and living parameters a radon potential (Austrian radon potential) was derived which should represent the radon concentration in a standard room. Another radon potential (Neznal radon potential) was calculated from the soil gas radon concentration and the permeability. The aim of the investigation was to correlate all the different variables and to test if the use of surrogate data (e.g. geological information, ambient dose equivalent rate, etc.) can be used to judge the radon risk for an area without performing numerous indoor measurements. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of gut microbiota in the regulation of standard metabolic rate in female Periplaneta americana.

PubMed

Ayayee, Paul A; Ondrejech, Andrew; Keeney, George; Muñoz-Garcia, Agustí

2018-01-01

Insect gut microbiota contribute significantly to host nutritional ecology. Disrupting insect gut microbial assemblages impacts nutrient provisioning functions, and can potentially affect host standard metabolic rate (SMR), a measure of host energy balance. In this study, we evaluated the effect of disrupting gut microbial assemblages on the SMR of female Periplaneta americana cockroaches fed dog food (DF, high protein/carbohydrate (p/c) ratio), and cellulose-amended dog food (CADF, 30% dog food, 70% cellulose, low p/c ratio) diets, supplemented with none, low, or high antibiotic doses. Bacterial loads decreased significantly between diet types ( P = 0.04) and across antibiotic doses ( P = 0.04). There was a significant diet type x antibiotic dose interaction on SMR of females on both diets ( P = 0.05) by the end of the seven-day experimental period. In CADF-fed females, SMR decreased linearly with decreasing bacterial load. However, SMR of DF-fed females on the low dose was significantly higher than those in the control and high dose groups. This is interpreted as a diet-dependent response by low dose DF-fed females to the loss of nutritional services provided by gut bacteria. Severe reductions in bacterial load at high doses reduced SMR of females on both diet types. This study provides insights into the potential role of gut bacteria as modulators of host energy expenditure under varying dietary conditions.

Contribution of time-activity pattern and microenvironment to black carbon (BC) inhalation exposure and potential internal dose among elementary school children

NASA Astrophysics Data System (ADS)

Jeong, Hyeran; Park, Donguk

2017-09-01

The aims of this study were to quantify the contributions of activities or microenvironments (MEs) to daily total exposure to and potential dose of black carbon (BC). Daily BC exposures (24-h) were monitored using a micro-aethalometer micoAeth AE51 with forty school-aged children living in an urban area in Korea from August 2015 to January 2016. The children's time-activity patterns and the MEs they visited were investigated by means of a time-activity diary (TAD) and follow-up interviews with the children and their parents. Potential inhaled dose was estimated by multiplying the airborne BC concentrations (μg/m3) we monitored for the time the children spent in a particular ME by the inhalation rate (IR, m3/h) for the time-activity performed. The contribution of activities and MEs to overall daily exposure to and potential dose of BC was quantified. Overall mean daily potential dose was equal to 24.1 ± 10.6 μg/day (range: 6.6-46.3 μg/day). The largest contribution to BC exposure and potential dose (51.9% and 41.7% respectively) occurred in the home thanks to the large amount of time spent there. Transportation was where children received the most intense exposure to (14.8%) and potential dose (20.2%) of BC, while it accounted for 7.6% of daily time. School on weekdays during the semester was responsible for 20.3% of exposure and 22.5% of potential dose. Contribution to BC exposure and potential dose was altered by several time-activity parameters, such as type of day (weekdays vs. weekends; school days vs. holidays), season, and gender. Traveling by motor vehicle and subway showed more elevated exposure or potential dose intensity on weekdays or school days, probably influenced by the increased surrounding traffic volumes on these days compared to on weekends or holidays. This study may be used to prioritize targets for minimizing children's exposure to BC and to indicate outcomes of BC control strategies.

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

PubMed

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

2016-06-01

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

A model for evaluating radiological impacts on organisms other than man for use in post-closure assessments of geological repositories for radioactive wastes.

PubMed

Thorn, M C; Kelly, M; Rees, J H; Sánchez-Friera, P; Calvez, M

2002-09-01

Bioaccumulation and dosimetric models have been developed that allow the computation of dose rates to a wide variety of plants and animals in the context of the deep geological disposal of solid radioactive wastes. These dose rates can be compared with the threshold dose rates at which significant deleterious effects have been observed in field and laboratory observations. This provides a general indication of whether effects on ecosystems could be observable, but does not quantify the level of those effects. To address this latter issue, two indicator organisms were identified and exposure-response relationships were developed for endpoints of potential interest (mortality in conifers and the induction of skeletal malformations in rodents irradiated in utero). The bioaccumulation, dosimetry and exposure-response models were implemented and used to evaluate the potential significance of radionuclide releases from a proposed deep geological repository for radioactive wastes in France. This evaluation was undertaken in the context of a programme of assessment studies being performed by the Agence nationale pour la gestion des déchets radioactifs (ANDRA).

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.

Technical basis for implementation of remote reading capabilities for radiological control instruments at tank farms

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

PIERSON, R.M.

1999-10-27

This document provides the technical basis for use of remote reading capabilities with radiological control instruments at River Protection Project facilities. The purpose of this document is to evaluate applications of remote reading capabilities with Radiological Control instrumentation to allow continuous monitoring of radiation dose rates at River Protection Project (RPP) facilities. In addition this document provides a technical basis and implementing guidelines for remote monitoring of dose rates and their potential contribution to maintaining radiation exposures ALARA.

Magnetic resonance imaging in prostate brachytherapy: Evidence, clinical end points to data, and direction forward.

PubMed

Pugh, Thomas J; Pokharel, Sajal S

The integration of multiparametric MRI into prostate brachytherapy has become a subject of interest over the past 2 decades. MRI directed high-dose-rate and low-dose-rate prostate brachytherapy offers the potential to improve treatment accuracy and standardize postprocedure quality. This article reviews the evidence to date on MRI utilization in prostate brachytherapy and postulates future pathways for MRI integration. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

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

Zhu, Yuanyuan; Munro, Catherine J.; Olszta, Matthew J.

In this work, we showcase that through precise control of the electron dose rate, state-of-the-art large solid angle energy dispersive X-ray spectroscopy (EDS) mapping in aberration-corrected scanning transmission electron microscope (STEM) is capable of faithful and unambiguous chemical characterization of the Pt and Pd distribution in a peptide-mediated nanosystem. This low-dose-rate recording scheme adds another dimension of flexibility to the design of elemental mapping experiments, and holds significant potential for extending its application to a wide variety of beam sensitive hybrid nanostructures.

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

What timing of vaccination is potentially dangerous for children younger than 2 years?

PubMed

Gras, Pauline; Bailly, Anne-Charlotte; Lagrée, Marion; Dervaux, Benoit; Martinot, Alain; Dubos, François

2016-08-02

Vaccine-preventable diseases still occur although measured coverage rates at 2 y of age are high. The occurrence of these diseases may be explained in part by untimely, that is, late vaccination. Our objective was to identify potentially dangerous vaccination delays for each dose of each vaccine in children younger than 2 y. A 3-round Delphi process was conducted by e-mail. We recruited 37 French experts in vaccines for children: 16 from the Infovac-France group and 21 from the French study group for pediatric infectious diseases. Items were generated by a literature review for the 10 vaccine doses recommended before 2 y of age. Item reduction in round 1 and 2 and any consensus in round 3 used a 70% consensus cutoff. The mean participation rate was 79%. Delays that should not be exceeded were identified for all vaccine doses. The 70% consensus was reached for 6 of the 10 vaccine doses: 15 d after the recommended date for the first 2 doses of the diphtheria-tetanus-acellular pertussis-inactivated polio vaccine/Haemophilus influenzae b vaccine and for the second dose of the pneumococcal conjugate vaccine, 1 month for the meningococcal C vaccine and for the first dose of the measles-mumps-rubella vaccine, and 11 y of age for completion of the hepatitis B vaccination. This Delphi process identified potentially dangerous vaccination delays for children to the age of 2 y. These can be used as new indicators in further studies of vaccine effectiveness and can help to improve the quality of vaccine protection in children.

SU-E-T-145: Beam Characteristics of Flattening Filter Free Beams Including Low Dose Rate Setting

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

Uehara, K; Ogata, T; Nakayama, M

2015-06-15

Purpose: In commissioning of volumetric modulated arc therapy (VMAT), it is necessary to evaluate the beam characteristics of various dose rate settings with potential to use. The aim of this study is to evaluate the beam characteristics of flattened and flattening filter free (FFF) including low dose rate setting. Methods: We used a Varian TrueBeam with Millennium 120 MLC. Both 6 and 10 MV beams with or without flattening filter were used for this study. To evaluate low-dose rate FFF beams, specially-designed leaf sequence files control out-of-field MLC leaf pair at constant dose rate ranging from 80 to 400 MU/min.more » For dose rate from 80 MU/min to the maximum usable value of all energies, beam output were measured using ionization chamber (CC04, IBA). The ionization chamber was inserted into water equivalent phantom (RT3000-New, R-tech), and the phantom was set with SAD of 100cm. The beam profiles were performed using the 2D diode array (Profiler2, Sun Nuclear). The SSD was set to 90cm and a combined 30cmx30cmx9cm phantom which consisted of solid water slabs was put on the device. All measurement were made using 100MU irradiation for 10cmx10cm jaw-defined field size with a gantry angle of 0°. Results: In all energies, the dose rate dependences with beam output and variation coefficient were within 0.2% and 0.07%, respectively. The flatness and symmetry exhibited small variations (flatness ≤0.1 point and symmetry≤0.3 point at absolute difference). Conclusion: We had studied the characteristics of flattened and FFF beam over the 80 MU/min. Our results indicated that the beam output and profiles of FFF of TrueBeam linac were highly stable at low dose rate setting.« less

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.

SU-F-T-345: Quasi-Dead Beams: Clinical Relevance and Implications for Automatic Planning

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

Price, R; Veltchev, I; Lin, T

Purpose: Beam direction selection for fixed-beam IMRT planning is typically a manual process. Severe dose-volume limits on critical structures in the thorax often result in atypical selection of beam directions as compared to other body sites. This work demonstrates the potential consequences as well as clinical relevance. Methods: 21 thoracic cases treated with 5–7 beam directions, 6 cases including non-coplanar arrangements, with fractional doses of 150–411cGy were analyzed. Endpoints included per-beam modulation scaling factor (MSF), variation from equal weighting, and delivery QA passing rate. Results: During analysis of patient-specific delivery QA a sub-standard passing rate was found for a singlemore » 5-field plan (90.48% of pixels evaluated passing 3% dose, 3mm DTA). During investigation it was found that a single beam demonstrated a MSF of 34.7 and contributed only 2.7% to the mean dose of the target. In addition, the variation from equal weighting for this beam was 17.3% absolute resulting in another beam with a MSF of 4.6 contributing 41.9% to the mean dose to the target; a variation of 21.9% from equal weighting. The average MSF for the remaining 20 cases was 4.0 (SD 1.8) with an average absolute deviation of 2.8% from equal weighting (SD 3.1%). Conclusion: Optimization in commercial treatment planning systems typically results in relatively equally weighted beams. Extreme variation from this can result in excessively high MSFs (very small segments) and potential decreases in agreement between planned and delivered dose distributions. In addition, the resultant beam may contribute minimal dose to the target (quasi-dead beam); a byproduct being increased treatment time and associated localization uncertainties. Potential ramifications exist for automatic planning algorithms should they allow for user-defined beam directions. Additionally, these quasi-dead beams may be embedded in the libraries for model-based systems potentially resulting in inefficient and less accurate deliveries.« less

M-Rated Video Games and Aggressive or Problem Behavior among Young Adolescents

ERIC Educational Resources Information Center

Olson, Cheryl K.; Kutner, Lawrence A.; Baer, Lee; Beresin, Eugene V.; Warner, Dorothy E.; Nicholi, Armand M., II

2009-01-01

This research examined the potential relationship between adolescent problem behaviors and amount of time spent with violent electronic games. Survey data were collected from 1,254 7th and 8th grade students in two states. A "dose" of exposure to Mature-rated games was calculated using Entertainment Software Rating Board ratings of…

Directional interstitial brachytherapy from simulation to application

NASA Astrophysics Data System (ADS)

Lin, Liyong

Organs at risk (OAR) are sometimes adjacent to or embedded in or overlap with the clinical target volume (CTV) to be treated. The purpose of this PhD study is to develop directionally low energy gamma-emitting interstitial brachytherapy sources. These sources can be applied between OAR to selectively reduce hot spots in the OARs and normal tissues. The reduction of dose over undesired regions can expand patient eligibility or reduce toxicities for the treatment by conventional interstitial brachytherapy. This study covers the development of a directional source from design optimization to construction of the first prototype source. The Monte Carlo code MCNP was used to simulate the radiation transport for the designs of directional sources. We have made a special construction kit to assemble radioactive and gold-shield components precisely into D-shaped titanium containers of the first directional source. Directional sources have a similar dose distribution as conventional sources on the treated side but greatly reduced dose on the shielded side, with a sharp dose gradient between them. A three-dimensional dose deposition kernel for the 125I directional source has been calculated. Treatment plans can use both directional and conventional 125I sources at the same source strength for low-dose-rate (LDR) implants to optimize the dose distributions. For prostate tumors, directional 125I LDR brachytherapy can potentially reduce genitourinary and gastrointestinal toxicities and improve potency preservation for low risk patients. The combination of better dose distribution of directional implants and better therapeutic ratio between tumor response and late reactions enables a novel temporary LDR treatment, as opposed to permanent or high-dose-rate (HDR) brachytherapy for the intermediate risk T2b and high risk T2c tumors. Supplemental external-beam treatments can be shortened with a better brachytherapy boost for T3 tumors. In conclusion, we have successfully finished the design optimization and construction of the first prototype directional source. Potential clinical applications and potential benefits of directional sources have been shown for prostate and breast tumors.

Image-Guided High-Dose Rate Brachytherapy in Cervix Carcinoma Using Balloon Catheter and Belt Immobilization System.

PubMed

Fan, Qiyong; Yeung, Anamaria R; Amdur, Robert; Helmig, Richard; Park, Justin; Li, Jonathan; Kahler, Darren; Liu, Chihray; Lu, Bo

2017-06-01

The efficacy of image-guided high-dose rate brachytherapy for cervical cancer is limited by the ineffective rectal sparing devices available commercially and the potential applicator movement. We developed a novel device using a balloon catheter and a belt immobilization system, serving for rectal dose reduction and applicator immobilization purposes, respectively. The balloon catheter is constructed by gluing a short inflatable tube to a long regular open-end catheter. Contrast agent (10) cm 3 is injected into the inflatable end, which is affixed to the tandem and ring applicator, to displace the posterior vaginal wall. The belt immobilization system consists of a specially designed bracket that can hold and fix itself to the applicator, a diaper-like Velcro fastener package used for connecting the patient's pelvis to the bracket, and a buckle that holds the fasteners to stabilize the whole system. The treatment data for 21 patients with cervical cancer using both balloon catheter and belt immobilization system were retrospectively analyzed. Computed tomography and magnetic resonance images, acquired about 30 minutes apart, were registered to evaluate the effectiveness of the immobilization system. In comparison with a virtual rectal blade, the balloon decreased the rectal point dose by 34% ± 4.2% (from 276 ± 57 to 182 ± 38 cGy), corresponding to an extra sparing distance of 7.9 ± 1.1 mm. The maximum sparing distance variation per patient is 1.4 ± 0.6 mm, indicating the high interfractional reproducibility for rectum sparing. With the immobilization system, the mean translational and rotational displacements of the applicator set are <3 mm and <1.5°, respectively, in all directions. The rectal balloon provides significant dose reduction to the rectum and it may potentially minimize patient discomfort. The immobilization system permits almost no movement of the applicator during treatment. This work has the potential to be promoted as a standardized solution for high-dose rate treatment of cervical cancer.

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.

Modern dosimetric tools for 60Co irradiation at high containment laboratories

PubMed Central

Twardoski, Barri; Feldmann, Heinz; Bloom, Marshall E.; Ward, Joe

2011-01-01

Purpose To evaluate an innovative photo-fluorescent film as a routine dosimetric tool during 60Co irradiations at a high containment biological research laboratory, and to investigate whether manufacturer-provided chamber exposure rates can be used to accurately administer a prescribed dose to biological specimens. Materials and methods Photo-fluorescent, lithium fluoride film dosimeters and National Institutes of Standards and Technology (NIST) transfer dosimeters were co-located in a self-shielded 60Co irradiator and exposed to γ-radiation with doses ranging from 5–85 kGy. Film dose-response relationships were developed for varying temperatures simulating conditions present when irradiating infectious biological specimens. Dose measurement results from NIST transfer dosimeters were compared to doses predicted using manufacturer-provided irradiator chamber exposure rates. Results The film dosimeter exhibited a photo-fluorescent response signal that was consistent and nearly linear in relationship to γ-radiation exposure over a wide dose range. The dosimeter response also showed negligible effects from dose fractionization and humidity. Significant disparities existed between manufacturer-provided chamber exposure rates and actual doses administered. Conclusion This study demonstrates the merit of utilizing dosimetric tools to validate the process of exposing dangerous and exotic biological agents to γ-radiation at high containment laboratories. The film dosimeter used in this study can be utilized to eliminate potential for improperly administering γ-radiation doses. PMID:21961968

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

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Low dose radiation hypersensitivity and clustered DNA damages in human fibroblasts exposed to low dose and dose rate protons or 137CS y-rays

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

Bennett P. V.; Bennett, P.V.; Keszenman, D.J.

Effective radioprotection for human space travelers hinges upon understanding the individual properties of charged particles. A significant fraction of particle radiation astronauts will encounter in space exploratory missions will come from high energy protons in galactic cosmic radiation (GCR) and/or possible exposures to lower energy proton flux from solar particle events (SPEs). These potential exposures present major concerns for NASA and others, in planning and executing long term space exploratory missions. We recently reported cell survival and transformation (acquisition of anchorage-independent growth in soft agar) frequencies in apparently normal NFF-28 primary human fibroblasts exposed to 0-30 cGy of 50MeV, 100MeVmore » (SPE-like), or 1000 MeV (GCR-like) monoenergetic protons. These were modeled after 1989 SPE energies at an SPE-like low dose-rate (LDR) of 1.65 cGy/min or high dose rate (HDR) of 33.3 cGy/min delivered at the NASA Space Radiation Laboratory (NSRL) at BNL.« less

Accelerated heavy particles and the lens. VII: The cataractogenic potential of 450 MeV/amu iron ions

NASA Technical Reports Server (NTRS)

Worgul, B. V.; Brenner, D. J.; Medvedovsky, C.; Merriam, G. R. Jr; Huang, Y.

1993-01-01

PURPOSE. To determine the cataractogenic potential dose of high velocity iron ions as a fixation of dose administered singly or fractionated. The dose is critical to risk assessment and to theories of radiation action and cataractogenesis. METHODS. Twenty-eight-day-old rats were examined by slit-lamp biomicroscopy on a weekly-bi-weekly basis for more than 2 yr after radiation exposure. For the acute exposure study doses of 1, 2, 5, 25, and 50 cGy were evaluated. The fractionated regimens involved total doses of 2, 25, and 50 cGy. The reference radiation consisted of 50, 100, 200, or 700 cGy of 250 kilovolt (peak) x-rays. RESULTS. In accordance with previous findings in the rat using 570 MeV/amu 40Ar ions, the relative biologic effectiveness increased rapidly with decreasing dose, reaching values as high as 100. Unlike 40Ar ions, fractionation of the 56Fe doses did not produce a consistent enhancement at any of the doses examined. CONCLUSIONS. The data support the previous findings of a high cataractogenic potential for high linear energy transfer (LET) radiation. The effectiveness for the production of cataracts increases with decreasing dose relative to x-rays and is independent of dose protraction. Although the present study did not reveal a consistent enhancement of effect when the ions were applied in fractions, the results are consistent with at least one theory of the inverse dose-rate effect observed for high-LET radiation.

Space radiation dose analysis for solar flare of August 1989

NASA Technical Reports Server (NTRS)

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

1990-01-01

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

Space radiation dose analysis for solar flare of August 1989

NASA Astrophysics Data System (ADS)

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

1990-12-01

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

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

PubMed Central

Paul, Sunirmal; Smilenov, Lubomir B.; Elliston, Carl D.; Amundson, Sally A.

2015-01-01

In the event of a nuclear accident or radiological terrorist attack, there will be a pressing need for biodosimetry to triage a large, potentially exposed population and to assign individuals to appropriate treatment. Exposures from fallout are likely, resulting in protracted dose delivery that would, in turn, impact the extent of injury. Biodosimetry approaches that can distinguish such low-dose-rate (LDR) exposures from acute exposures have not yet been developed. In this study, we used the C57BL/6 mouse model in an initial investigation of the impact of low-dose-rate delivery on the transcriptomic response in blood. While a large number of the same genes responded to LDR and acute radiation exposures, for many genes the magnitude of response was lower after LDR exposures. Some genes, however, were differentially expressed (P < 0.001, false discovery rate < 5%) in mice exposed to LDR compared with mice exposed to acute radiation. We identified a set of 164 genes that correctly classified 97% of the samples in this experiment as exposed to acute or LDR radiation using a support vector machine algorithm. Gene expression is a promising approach to radiation biodosimetry, enhanced greatly by this first demonstration of its potential for distinguishing between acute and LDR exposures. Further development of this aspect of radiation biodosimetry, either as part of a complete gene expression biodosimetry test or as an adjunct to other methods, could provide vital triage information in a mass radiological casualty event. PMID:26114327

Prognostic implication of simultaneous anemia and lymphopenia during concurrent chemoradiotherapy in cervical squamous cell carcinoma.

PubMed

Cho, Oyeon; Chun, Mison; Oh, Young-Taek; Noh, O Kyu; Chang, Suk-Joon; Ryu, Hee-Sug; Lee, Eun Ju

2017-10-01

Radioresistance often leads to poor survival in concurrent chemoradiotherapy-treated cervical squamous cell carcinoma, and reliable biomarkers can improve prognosis. We compared the prognostic potential of hemoglobin, absolute neutrophil count, and absolute lymphocyte count with that of squamous cell carcinoma antigen in concurrent chemoradiotherapy-treated squamous cell carcinoma. We analyzed 152 patients with concurrent chemoradiotherapy and high-dose-rate intracavitary brachytherapy-treated cervical squamous cell carcinoma. Hemoglobin, absolute neutrophil count, absolute lymphocyte count, and squamous cell carcinoma antigen were quantitated and correlated with survival, using Cox regression, receiver operating characteristic curve analysis, and Kaplan-Meier plots. Both hemoglobin and absolute lymphocyte count in the second week of concurrent chemoradiotherapy (Hb2 and ALC2) and squamous cell carcinoma antigen in the third week of concurrent chemoradiotherapy (mid-squamous cell carcinoma antigen) correlated significantly with disease-specific survival and progression-free survival. The ratio of high-dose-rate intracavitary brachytherapy dose to total dose (high-dose-rate intracavitary brachytherapy ratio) correlated significantly with progression-free survival. Patients with both low Hb2 (≤11 g/dL) and ALC2 (≤639 cells/µL) showed a lower 5-year disease-specific survival rate than those with high Hb2 and/or ALC2, regardless of mid-squamous cell carcinoma antigen (mid-squamous cell carcinoma antigen: ≤4.7 ng/mL; 5-year disease-specific survival rate: 85.5% vs 94.6%, p = 0.0096, and mid-squamous cell carcinoma antigen: >4.7 ng/mL; 5-year disease-specific survival rate: 43.8% vs 66.7%, p = 0.192). When both Hb2 and ALC2 were low, the low high-dose-rate intracavitary brachytherapy ratio (≤0.43) subgroup displayed significantly lower 5-year disease-specific survival rate compared to the subgroup high high-dose-rate intracavitary brachytherapy ratio (>0.43) (62.5% vs 88.2%, p = 0.0067). Patients with both anemia and lymphopenia during concurrent chemoradiotherapy showed poor survival, independent of mid-squamous cell carcinoma antigen, and escalating high-dose-rate intracavitary brachytherapy ratio might improve survival.

Investigation of pulsed IMRT and VMAT for re-irradiation treatments: dosimetric and delivery feasibilities

NASA Astrophysics Data System (ADS)

Lin, Mu-Han; Price, Robert A., Jr.; Li, Jinsheng; Kang, Shengwei; Li, Jie; Ma, C.-M.

2013-11-01

Many tumor cells demonstrate hyperradiosensitivity at doses below ˜50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (˜20 cGy/pulse and effective dose rate 6.7 cGy min-1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min-1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (˜20 cGy arc-1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min-1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10-1.38 HI 1.04-1.10) and the VMAT (CI 1.08-1.26 HI 1.05-1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of the 186 IMRT pulses (fields) were found to exceed 50 cGy maximum PTV dose per pulse while the maximum PTV dose per pulse was within 40 cGy for all the VMAT pulses (arcs). However, for VMAT plans, the dosimetric quality of the entire treatment plan was less superior for the breast cases and large irregular targets. The gamma passing rates for both techniques at the 100 MU min-1 dose rate were at least 94.1% (3%/3 mm) and the point dose measurements agreed with the planned values to within 2.2%. The average root mean square error of the leaf position was 0.93 ± 0.83 mm for IMRT and 0.53 ± 0.48 mm for VMAT based on the Dynalog file analysis. The RMS error of the leaf position was nearly identical for the repeated deliveries of the same plans. In general, both techniques are feasible for PLDR treatments. VMAT was more advantageous for PLDR with more uniform target dose per pulse, especially for centrally located tumors. However, for large, irregular and/or peripheral tumors, IMRT could produce more favorable PLDR plans. By taking the biological benefit of PLDR delivery and the dosimetric benefit of IMRT and VMAT, the proposed methods have a great potential for those previously-irradiated recurrent patients.

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Shuttle radiation dose measurements in the International Space Station orbits

NASA Technical Reports Server (NTRS)

Badhwar, Gautam D.

2002-01-01

The International Space Station (ISS) is now a reality with the start of a permanent human presence on board. Radiation presents a serious risk to the health and safety of the astronauts, and there is a clear requirement for estimating their exposures prior to and after flights. Predictions of the dose rate at times other than solar minimum or solar maximum have not been possible, because there has been no method to calculate the trapped-particle spectrum at intermediate times. Over the last few years, a tissue-equivalent proportional counter (TEPC) has been flown at a fixed mid-deck location on board the Space Shuttle in 51.65 degrees inclination flights. These flights have provided data that cover the expected changes in the dose rates due to changes in altitude and changes in solar activity from the solar minimum to the solar maximum of the current 23rd solar cycle. Based on these data, a simple function of the solar deceleration potential has been derived that can be used to predict the galactic cosmic radiation (GCR) dose rates to within +/-10%. For altitudes to be covered by the ISS, the dose rate due to the trapped particles is found to be a power-law function, rho(-2/3), of the atmospheric density, rho. This relationship can be used to predict trapped dose rates inside these spacecraft to +/-10% throughout the solar cycle. Thus, given the shielding distribution for a location inside the Space Shuttle or inside an ISS module, this approach can be used to predict the combined GCR + trapped dose rate to better than +/-15% for quiet solar conditions.

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.

Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol.

PubMed

Olmstead, Craig; Cruz, Kyle; Stodilka, Robert; Zabel, Pamela; Wolfson, Robert

2015-02-01

Radionuclide therapies, including treatment of neuroendocrine tumors with lutetium-177 (Lu-177) octreotate, often involve hospital admission to minimize radiation exposure to the public. Overnight admission due to Lu-177 octreotate therapy incurs additional cost for the hospital and is an inconvenience for the patient. This study endeavors to characterize the potential radiation risk to caregivers and the public should Lu-177 octreotate therapies be performed on an outpatient basis. Dose rate measurements of radiation emanating from 10 patients were taken 30 min, 4, and 20 h after initiation of Lu-177 octreotate therapy. Instadose radiation dose measurement monitors were also placed around the patients' rooms to assess the potential cumulative radiation exposure during the initial 30 min-4 h after treatment (simulating the hospital-based component of the outpatient model) as well as 4-20 h after treatment (simulating the discharged outpatient portion). The mean recorded dose rate at 30 min, 4, and 20 h after therapy was 20.4, 14.0, and 6.6 μSv/h, respectively. The majority of the cumulative dose readings were below the minimum recordable threshold of 0.03 mSv, with a maximum dose recorded of 0.18 mSv. Given the low dose rate and cumulative levels of radiation measured, the results support that an outpatient Lu-177 octreotate treatment protocol would not jeopardize public safety. Nevertheless, the concept of ALARA still requires that detailed radiation safety protocols be developed for Lu-177 octreotate outpatients to minimize radiation exposure to family members, caregivers, and the general public.

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.

Dose-Escalated Robotic SBRT for Stage I–II Prostate Cancer

PubMed Central

Meier, Robert

2015-01-01

Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I–II prostate cancer. PMID:25905037

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential

PubMed Central

Capel, Rebecca A.; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R.; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J.; Terrar, Derek A.; Burton, Rebecca-Ann B.

2015-01-01

Background Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. Objectives The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. Methods We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the “funny” current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1–30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). Results In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. Conclusions We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. PMID:26025323

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

PubMed

Capel, Rebecca A; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J; Terrar, Derek A; Burton, Rebecca-Ann B

2015-10-01

Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the "funny" current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1-30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

NESHAP Area-Specific Dose-Release Factors for Potential Onsite Member-of-the-Public Locations at SRS using CAP88-PC Version 4.0

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

Trimor, P.

The Environmental Protection Agency (EPA) requires the use of the computer model CAP88-PC to estimate the total effective doses (TED) for demonstrating compliance with 40 CFR 61, Subpart H (EPA 2006), the National Emission Standards for Hazardous Air Pollutants (NESHAP) regulations. As such, CAP88 Version 4.0 was used to calculate the receptor dose due to routine atmospheric releases at the Savannah River Site (SRS). For estimation, NESHAP dose-release factors (DRFs) have been supplied to Environmental Compliance and Area Closure Projects (EC&ACP) for many years. DRFs represent the dose to a maximum receptor exposed to 1 Ci of a specified radionuclidemore » being released into the atmosphere. They are periodically updated to include changes in the CAP88 version, input parameter values, site meteorology, and location of the maximally exposed individual (MEI). In this report, the DRFs were calculated for potential radionuclide atmospheric releases from 13 SRS release points. The three potential onsite MEI locations to be evaluated are B-Area, Three Rivers Landfill (TRL), and Savannah River Ecology Lab Conference Center (SRELCC) with TRL’s onsite workers considered as members-of-the-public, and the potential future constructions of dormitories at SRELCC and Barracks at B-Area. Each MEI location was evaluated at a specified compass sector with different area to receptor distances and was conducted for both ground-level and elevated release points. The analysis makes use of area-specific meteorological data (Viner 2014). The resulting DRFs are compared to the 2014 NESHAP offsite MEI DRFs for three operational areas; A-Area, H-Area, and COS for a release rate of 1 Ci of tritium oxide at 0 ft. elevation. CAP88 was executed again using the 2016 NESHAP MEI release rates for 0 and 61 m stack heights to determine the radionuclide dose at TRL from the center-of-site (COS).« less

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.

The Bebig Valencia-type skin applicators: Dosimetric study and implementation of a dosimetric hybrid technique.

PubMed

Anagnostopoulos, Georgios; Andrássy, Michael; Baltas, Dimos

To determine the relative dose rate distribution in water for the Bebig 20 mm and 30 mm skin applicators and report results in a form suitable for potential clinical use. Results for both skin applicators are also provided in the form of a hybrid Task Group 43 (TG-43) dosimetry technique. Furthermore, the radiation leakage around both skin applicators from the radiation protection point of view and the impact of the geometrical source position uncertainties are studied and reported. Monte Carlo simulations were performed using the MCNP 6.1 general purpose code, which was benchmarked against published dosimetry data for the Bebig Ir2.A85-2 high-dose-rate iridium-192 source, as well as the dosimetry data for the two Elekta skin applicators. Both Bebig skin applicators were modeled, and the dose rate distributions in a water phantom were calculated. The dosimetric quantities derived according to a hybrid TG-43 dosimetry technique are provided with their corresponding uncertainty values. The air kerma rate in air was simulated in the vicinity of each skin applicator to assess the radiation leakage. Results from the Monte Carlo simulations of both skin applicators are presented in the form of figures and relative dose rate tables, and additionally with the aid of the quantities defined in the hybrid TG-43 dosimetry technique and their corresponding uncertainty values. Their output factors, flatness, and penumbra values were found comparable to the Elekta skin applicators. The radiation shielding was evaluated to be adequate. The effect of potential uncertainties in source positioning on dosimetry should be investigated as part of applicator commissioning. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

The role of a microDiamond detector in the dosimetry of proton pencil beams.

PubMed

Gomà, Carles; Marinelli, Marco; Safai, Sairos; Verona-Rinati, Gianluca; Würfel, Jan

2016-03-01

In this work, the performance of a microDiamond detector in a scanned proton beam is studied and its potential role in the dosimetric characterization of proton pencil beams is assessed. The linearity of the detector response with the absorbed dose and the dependence on the dose-rate were tested. The depth-dose curve and the lateral dose profiles of a proton pencil beam were measured and compared to reference data. The feasibility of calibrating the beam monitor chamber with a microDiamond detector was also studied. It was found the detector reading is linear with the absorbed dose to water (down to few cGy) and the detector response is independent of both the dose-rate (up to few Gy/s) and the proton beam energy (within the whole clinically-relevant energy range). The detector showed a good performance in depth-dose curve and lateral dose profile measurements; and it might even be used to calibrate the beam monitor chambers-provided it is cross-calibrated against a reference ionization chamber. In conclusion, the microDiamond detector was proved capable of performing an accurate dosimetric characterization of proton pencil beams. Copyright © 2015. Published by Elsevier GmbH.

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

PubMed

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

2012-11-01

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

Environmental risks of radioactive discharges from a low-level radioactive waste disposal site at Dessel, Belgium.

PubMed

Batlle, J Vives I; Sweeck, L; Wannijn, J; Vandenhove, H

2016-10-01

The potential radiological impact of releases from a low-level radioactive waste (Category A waste) repository in Dessel, Belgium on the local fauna and flora was assessed under a reference scenario for gradual leaching. The potential impact situations for terrestrial and aquatic fauna and flora considered in this study were soil contamination due to irrigation with contaminated groundwater from a well at 70 m from the repository, contamination of the local wetlands receiving the highest radionuclide flux after migration through the aquifer and contamination of the local river receiving the highest radionuclide flux after migration through the aquifer. In addition, an exploratory study was carried out for biota residing in the groundwater. All impact assessments were performed using the Environmental Risk from Ionising Contaminants: Assessment and Management (ERICA) tool. For all scenarios considered, absorbed dose rates to biota were found to be well below the ERICA 10 μGy h -1 screening value. The highest dose rates were observed for the scenario where soil was irrigated with groundwater from the vicinity of the repository. For biota residing in the groundwater well, a few dose rates were slightly above the screening level but significantly below the dose rates at which the smallest effects are observed for those relevant species or groups of species. Given the conservative nature of the assessment, it can be concluded that manmade radionuclides deposited into the environment by the near surface disposal of category A waste at Dessel do not have a significant radiological impact to wildlife. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation

NASA Astrophysics Data System (ADS)

Seed, T. M.; Fritz, T. E.; Tolle, D. V.; Jackson, W. E.

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d -1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d -1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (> 1yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d -1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d -1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation.

Development of a flexible γ-ray detector using a liquid scintillation light guide (LSLG).

PubMed

Nomura, Kiyoshi; Yunoki, Akira; Hara, Masayuki; Morito, Yuko; Fujishima, Akira

2018-04-10

A flexible γ detector using a liquid scintillation light guide (LSLG) was developed. The analyzed pulse height (PHA) spectrum depended on the diameter, length and scintillator concentration of the LSLG, and the distance of a γ ray irradiation point from the head of photomultiplier tube (PMT). From the analysis of PHA spectrum, it was found that the count ratio of two divided channel regions linearly decreases as the distance from the PMT head increases. It was further found that the radiation dose rate can be estimated by setting the flexible LSLG tube to a circular shape since the count rate is proportional to the dose rate measured by a conventional NaI (Tl) scintillation detector. Therefore, a flexible and long LSLG detector using a single PMT is useful for determination of the dose rate and has a potential to detect local contaminations in a certain narrow space. Copyright © 2018. Published by Elsevier Ltd.

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.

ReachScan - an Exposure Assessment Model

EPA Pesticide Factsheets

ReachScan estimates surface water concentrations downstream from industrial sites to assess impacts on the aquatic environment and potential dose rates for humans exposed via ingestion of drinking water and fish.

Evaluation of optimum room entry times for radiation therapists after high energy whole pelvic photon treatments.

PubMed

Ho, Lavine; White, Peter; Chan, Edward; Chan, Kim; Ng, Janet; Tam, Timothy

2012-01-01

Linear accelerators operating at or above 10 MV produce neutrons by photonuclear reactions and induce activation in machine components, which are a source of potential exposure for radiation therapists. This study estimated gamma dose contributions to radiation therapists during high energy, whole pelvic, photon beam treatments and determined the optimum room entry times, in terms of safety of radiation therapists. Two types of technique (anterior-posterior opposing and 3-field technique) were studied. An Elekta Precise treatment system, operating up to 18 MV, was investigated. Measurements with an area monitoring device (a Mini 900R radiation monitor) were performed, to calculate gamma dose rates around the radiotherapy facility. Measurements inside the treatment room were performed when the linear accelerator was in use. The doses received by radiation therapists were estimated, and optimum room entry times were determined. The highest gamma dose rates were approximately 7 μSv/h inside the treatment room, while the doses in the control room were close to background (~0 μSv/h) for all techniques. The highest personal dose received by radiation therapists was estimated at 5 mSv/yr. To optimize protection, radiation therapists should wait for up to11 min after beam-off prior to room entry. The potential risks to radiation therapists with standard safety procedures were well below internationally recommended values, but risks could be further decreased by delaying room entry times. Dependent on the technique used, optimum entry times ranged between 7 to 11 min. A balance between moderate treatment times versus reduction in measured equivalent doses should be considered.

Renal Drug Dosing

PubMed Central

Vogel, Erin A.; Billups, Sarah J.; Herner, Sheryl J.

2016-01-01

Summary Objective The purpose of this study was to compare the effectiveness of an outpatient renal dose adjustment alert via a computerized provider order entry (CPOE) clinical decision support system (CDSS) versus a CDSS with alerts made to dispensing pharmacists. Methods This was a retrospective analysis of patients with renal impairment and 30 medications that are contraindicated or require dose-adjustment in such patients. The primary outcome was the rate of renal dosing errors for study medications that were dispensed between August and December 2013, when a pharmacist-based CDSS was in place, versus August through December 2014, when a prescriber-based CDSS was in place. A dosing error was defined as a prescription for one of the study medications dispensed to a patient where the medication was contraindicated or improperly dosed based on the patient’s renal function. The denominator was all prescriptions for the study medications dispensed during each respective study period. Results During the pharmacist- and prescriber-based CDSS study periods, 49,054 and 50,678 prescriptions, respectively, were dispensed for one of the included medications. Of these, 878 (1.8%) and 758 (1.5%) prescriptions were dispensed to patients with renal impairment in the respective study periods. Patients in each group were similar with respect to age, sex, and renal function stage. Overall, the five-month error rate was 0.38%. Error rates were similar between the two groups: 0.36% and 0.40% in the pharmacist- and prescriber-based CDSS, respectively (p=0.523). The medication with the highest error rate was dofetilide (0.51% overall) while the medications with the lowest error rate were dabigatran, fondaparinux, and spironolactone (0.00% overall). Conclusions Prescriber- and pharmacist-based CDSS provided comparable, low rates of potential medication errors. Future studies should be undertaken to examine patient benefits of the prescriber-based CDSS. PMID:27466041

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

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.

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

PubMed Central

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

2010-01-01

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

Time- and dose-dependent changes in neuronal activity produced by X radiation in brain slices.

PubMed

Pellmar, T C; Schauer, D A; Zeman, G H

1990-05-01

A new method of exposing tissues to X rays in a lead Faraday cage has made it possible to examine directly radiation damage to isolated neuronal tissue. Thin slices of hippocampus from brains of euthanized guinea pigs were exposed to 17.4 ke V X radiation. Electrophysiological recordings were made before, during, and after exposure to doses between 5 and 65 Gy at a dose rate of 1.54 Gy/min. Following exposure to doses of 40 Gy and greater, the synaptic potential was enhanced, reaching a steady level soon after exposure. The ability of the synaptic potential to generate a spike was reduced and damage progressed after termination of the radiation exposure. Recovery was not observed following termination of exposure. These results demonstrate that an isolated neuronal network can show complex changes in electrophysiological properties following moderate doses of ionizing radiation. An investigation of radiation damage directly to neurons in vitro will contribute to the understanding of the underlying mechanisms of radiation-induced nervous system dysfunction.

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

PubMed

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

2015-02-01

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

Emission of ammonia from indoor concrete wall and assessment of human exposure.

PubMed

Bai, Z; Dong, Y; Wang, Z; Zhu, T

2006-04-01

Addition of urea-based antifreeze admixtures during cement mixing can make it possible to produce concrete cement in construction of buildings in cold weather; this, however, has led to increasing indoor air pollution due to continuous transformation and emission from urea to gaseous ammonia in indoor concrete wall. It is believed that ammonia is harmful to human body and exposure to ammonia can cause some serious symptoms such as headaches, burns, and even permanent damage to the eyes and lungs. In order to understand the emission of ammonia from indoor concrete wall in civil building and assess the health risk of people living in these buildings, the experimental pieces of concrete wall were first prepared by concreting cement and urea-based antifreeze admixtures to simulate the indoor wall in civil building in this work. Then environmental chamber was adopted for studying the effect of temperature, relative humility and air exchange rate on emission of ammonia from experimental pieces of concrete wall. Also the field experiment was made at selected rooms in given civil buildings. Exposure and potential dose of adult and children exposed to indoor/outdoor ammonia in summer and in winter are calculated and evaluated by using Scenario Evaluation Approach. The results indicated that high air exchange rate leads to decreased ammonia concentration, and elevation of temperature causes increasing ammonia concentration and volatilizing rate in chamber. The complete emission of ammonia from the wall containing urea-based antifreeze admixtures needs more than 10 years in general. Ventilating or improving air exchange can play a significant role in reducing ammonia concentration in actual rooms in field experiments. Urea-based antifreeze admixtures in concrete wall can give rise to high exposure and potential dose, especially in summer. Generally, adults have a high potential dose than children, while children have personal average dose rate beyond adults in the same conditions.

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.

Digital radiography can reduce scoliosis x-ray exposure

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

Kling, T.F. Jr.; Cohen, M.J.; Lindseth, R.E.

1990-09-01

Digital radiology is a new computerized system of acquiring x-rays in a digital (electronic) format. It possesses a greatly expanded dose response curve that allows a very broad range of x-ray dose to produce a diagnostic image. Potential advantages include significantly reduced radiation exposure without loss of image quality, acquisition of images of constant density irrespective of under or over exposure, and reduced repeat rates for unsatisfactory films. The authors prospectively studied 30 adolescents with scoliosis who had both conventional (full dose) and digital (full, one-half, or one-third dose) x-rays. They found digital made AP and lateral image with allmore » anatomic areas clearly depicted at full and one-half dose. Digital laterals were better at full dose and equal to conventional at one-half dose. Cobb angles were easily measured on all one-third dose AP and on 8 of 10 one-third dose digital laterals. Digital clearly depicted the Risser sign at one-half and one-third dose and the repeat rate was nil in this study, indicating digital compensates well for exposure errors. The study indicates that digital does allow radiation dose to be reduced by at least one-half in scoliosis patients and that it does have improved image quality with good contrast over a wide range of x-ray exposure.« less

Solution or suspension - Does it matter for lipid based systems? In vivo studies of chase dosing lipid vehicles with aqueous suspensions of a poorly soluble drug.

PubMed

Larsen, A T; Holm, R; Müllertz, A

2017-08-01

In this study, the potential of co-administering an aqueous suspension with a placebo lipid vehicle, i.e. chase dosing, was investigated in rats relative to the aqueous suspension alone or a solution of the drug in the lipid vehicle. The lipid investigated in the present study was Labrafil M2125CS and three evaluated poorly soluble model compounds, danazol, cinnarizine and halofantrine. For cinnarizine and danazol the oral bioavailability in rats after chase dosing or dosing the compound dissolved in Labrafil M21515CS was similar and significantly higher than for the aqueous suspension. For halofantrine the chase dosed group had a tendency towards a low bioavailability relative to the Labrafil M2125CS solution, but still a significant higher bioavailability relative to the aqueous suspension. This could be due to factors such as a slower dissolution rate in the intestinal phase of halofantrine or a lower solubility in the colloidal structures formed during digestion, but other mechanisms may also be involved. The study thereby supported the potential of chase dosing as a potential dosing regimen in situations where it is beneficial to have a drug in the solid state, e.g. due to chemical stability issues in the lipid vehicle. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential radiation control of biofouling bacteria on intake filters

NASA Astrophysics Data System (ADS)

Eichholz, Geoffrey G.; Jones, Cynthia G.; Haynes, Harold E.

The biofouling of filters at deep wells supplying water for industrial and drinking water purposes by various iron- and sulfur-reducing bacteria is a wide-spread problem in the United States and can cause serious economic losses. Among the means of control, steam heating or chemical additives can be applied only intermittently and have their own environmental impact. Preliminary studies have shown that installation of a sealed gamma radiation source may provide an alternative solution. Analysis of a range of water samples from contaminated wells identified many of the samples as rich in barsiderocapsa and barpseudomona bacteria. Static and dynamic experiments on water samples at various does and dose rates have shown that these organisms are relatively radiation-sensitive, with a lethal dose in the range of 200-400Gy (20-40kR). Since the main objective is to restrict growth or deposit of plaque on filters, dose rates of the order of 50-75 Gy/hr would be adequate. Such dose rates could be obtained with relatively weak sources, depending on filter dimensions. A conceptual design for such systems has been proposed.

Multiple anatomy optimization of accumulated dose

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

Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V.; Moore, Joseph A.

Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dosemore » variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.« less

Radiation dose response of N channel MOSFET submitted to filtered X-ray photon beam

NASA Astrophysics Data System (ADS)

Gonçalves Filho, Luiz C.; Monte, David S.; Barros, Fabio R.; Santos, Luiz A. P.

2018-01-01

MOSFET can operate as a radiation detector mainly in high-energy photon beams, which are normally used in cancer treatments. In general, such an electronic device can work as a dosimeter from threshold voltage shift measurements. The purpose of this article is to show a new way for measuring the dose-response of MOSFETs when they are under X-ray beams generated from 100kV potential range, which is normally used in diagnostic radiology. Basically, the method consists of measuring the MOSFET drain current as a function of the radiation dose. For this the type of device, it has to be biased with a high value resistor aiming to see a substantial change in the drain current after it has been irradiated with an amount of radiation dose. Two types of N channel device were used in the experiment: a signal transistor and a power transistor. The delivered dose to the device was varied and the electrical curves were plotted. Also, a sensitivity analysis of the power MOSFET response was made, by varying the tube potential of about 20%. The results show that both types of devices have responses very similar, the shift in the electrical curve is proportional to the radiation dose. Unlike the power MOSFET, the signal transistor does not provide a linear function between the dose rate and its drain current. We also have observed that the variation in the tube potential of the X-ray equipment produces a very similar dose-response.

Sperm yield after single layer centrifugation with Androcoll-E is related to the potential fertility of the original ejaculate.

PubMed

Morrell, J M; Stuhtmann, G; Meurling, S; Lundgren, A; Winblad, C; Macias Garcia, B; Johannisson, A

2014-05-01

Many attempts have been made to identify laboratory tests that are predictive of sperm fertility, both to improve the quality of stallion semen doses for artificial insemination (AI) and to identify potential breeding sires if no fertility data are available. Sperm quality at the stud is mostly evaluated by assessing subjective motility, although this parameter can be poorly indicative of fertility. Sperm morphology and chromatin integrity in Swedish stallions are correlated to pregnancy rate after AI. Because single layer centrifugation (SLC) selects for spermatozoa with normal morphology and good chromatin, retrospective analysis was carried out to investigate whether sperm yield after SLC is linked to potential fertility. Commercial semen doses for AI from 24 stallions (five stallions with four ejaculates each, 19 stallions with three ejaculates each; n = 77) obtained during the breeding season were cooled, and sent overnight to the Swedish University of Agricultural Sciences in an insulated box for evaluation, with other doses being sent to studs for commercial AI. On arrival at Swedish University of Agricultural Sciences, the semen was used for SLC and also for evaluation of sperm motility, membrane integrity, chromatin integrity, and morphology. The seasonal pregnancy rates for each stallion were available. The yield of progressively motile spermatozoa after SLC (calculated as a proportion of the initial load) was found to be highly correlated with pregnancy rate (r = 0.75; P < 0.001). Chromatin damage was highly negatively correlated with pregnancy rate (r = -0.69; P < 0.001). Pregnancy rate was also correlated with membrane integrity (r = 0.58; P < 0.01), progressive motility (r = 0.63; P < 0.01), and normal morphology (r = 0.45; P < 0.05). In conclusion, these preliminary results show that sperm yield after SLC is related to the potential fertility of the original ejaculate, and could be an alternative indicator of stallion fertility if breeding data are not available. Single layer centrifugation is fast (30 minutes) and does not require expensive equipment, whereas other assays require a flow cytometer and/or specialist skills. An additional option could be to transport semen doses to a laboratory for SLC if the stud personnel do not want to perform the procedure themselves. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-E-T-400: Evaluation of Shielding and Activation at Two Pencil Beam Scanning Proton Facilities

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

Remmes, N; Mundy, D; Classic, K

2015-06-15

Purpose: To verify acceptably low dose levels around two newly constructed identical pencil beam scanning proton therapy facilities and to evaluate accuracy of pre-construction shielding calculations. Methods: Dose measurements were taken at select points of interest using a WENDI-2 style wide-energy neutron detector. Measurements were compared to pre-construction shielding calculations. Radiation badges with neutron dose measurement capabilities were worn by personnel and also placed at points throughout the facilities. Seven neutron and gamma detectors were permanently installed throughout the facility, continuously logging data. Potential activation hazards have also been investigated. Dose rates near water tanks immediately after prolonged irradiation havemore » been measured. Equipment inside the treatment room and accelerator vault has been surveyed and/or wipe tested. Air filters from air handling units, sticky mats placed outside of the accelerator vault, and water samples from the magnet cooling water loops have also been tested. Results: All radiation badges have been returned with readings below the reporting minimum. Measurements of mats, air filters, cooling water, wipe tests and surveys of equipment that has not been placed in the beam have all come back at background levels. All survey measurements show the analytical shielding calculations to be conservative by at least a factor of 2. No anomalous events have been identified by the building radiation monitoring system. Measurements of dose rates close to scanning water tanks have shown dose rates of approximately 10 mrem/hr with a half-life less than 5 minutes. Measurements around the accelerator show some areas with dose rates slightly higher than 10 mrem/hr. Conclusion: The shielding design is shown to be adequate. Measured dose rates are below those predicted by shielding calculations. Activation hazards are minimal except in certain very well defined areas within the accelerator vault and for objects placed directly in the path of the beam.« 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

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose response using different monomers

NASA Astrophysics Data System (ADS)

Senden, R. J.; DeJean, P.; McAuley, K. B.; Schreiner, L. J.

2006-07-01

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.

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.

Preliminary Radiation Analysis of the Total Ionizing Dose for the Resource Prospector Mission

NASA Technical Reports Server (NTRS)

Rojdev, Kristina; Tylka, Allan J.; Atwell, William

2015-01-01

NASA's Resource Prospector (RP) is a collaborative project between multiple centers and institutions to search for volatiles at the polar regions of the Moon as a potential resource for oxygen and propellant production. The mission is rated Class D and will be the first In-Situ Resource Utilization (ISRU) demonstration on the lunar surface and at the lunar poles. Given that this mission is rated Class D, the project is considering using commercial off the shelf (COTS) electronics parts to reduce cost. However, COTS parts can be more susceptible to space radiation than typical aerospace electronic parts and carry some additional risk. Thus, prior to parts selection, having a better understanding of the radiation environment can assist designers in the parts selection process. The focus of this paper is to provide a preliminary analysis of the radiation environment from launch, through landing on the surface, and some surface stay as an initial step in determining worst case mission doses to assist designers in screening out electronic parts that would not meet the potential dose levels experienced on this mission.

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.

Long-term results of high-dose conformal radiotherapy for patients with medically inoperable T1-3N0 non-small-cell lung cancer: is low incidence of regional failure due to incidental nodal irradiation?

PubMed

Chen, Ming; Hayman, James A; Ten Haken, Randall K; Tatro, Daniel; Fernando, Shaneli; Kong, Feng-Ming

2006-01-01

To report the results of high-dose conformal irradiation and examine incidental nodal irradiation and nodal failure in patients with inoperable early-stage non-small-cell lung cancer (NSCLC). This analysis included patients with inoperable CT-staged T1-3N0M0 NSCLC treated on our prospective dose-escalation trial. Patients were treated with radiation alone (total dose, 63-102.9 Gy in 2.1-Gy daily fractions) with a three-dimensional conformal technique without intentional nodal irradiation. Bilateral highest mediastinal and upper/lower paratracheal, prevascular and retrotracheal, sub- and para-aortic, subcarinal, paraesophageal, and ipsilateral hilar regions were delineated individually. Nodal failure and doses of incidental irradiation were studied. The potential median follow-up was 104 months. For patients who completed protocol treatment, median survival was 31 months. The actuarial overall survival rate was 86%, 61%, 43%, and 21% and the cause-specific survival rate was 89%, 70%, 53%, and 35% at 1, 2, 3, and 5 years, respectively. Weight loss (p = 0.008) and radiation dose in Gy (p = 0.013) were significantly associated with overall survival. In only 22% and 13% of patients examined did ipsilateral hilar and paratracheal (and subaortic for left-sided tumor) nodal regions receive a dose of > or = 40 Gy, respectively. Less than 10% of all other nodal regions received a dose of > or = 40 Gy. No patients failed initially at nodal sites. Radiation dose is positively associated with overall survival in patients with medically inoperable T1-3N0 NSCLC, though long-term results remain poor. The nodal failure rate is low and does not seem to be due to high-dose incidental irradiation.

Mitigation Strategies for Acute Radiation Exposure during Space Flight

NASA Technical Reports Server (NTRS)

Hamilton, Douglas R.; Epelman, Slava

2006-01-01

While there are many potential risks in a Moon or Mars mission, one of the most important and unpredictable is that of crew radiation exposure. The two forms of radiation that impact a mission far from the protective environment of low-earth orbit, are solar particle events (SPE) and galactic cosmic radiation (GCR). The effects of GCR occur as a long-term cumulative dose that results increased longer-term medical risks such as malignancy and neurological degeneration. Unfortunately, relatively little has been published on the medical management of an acute SPE that could potentially endanger the mission and harm the crew. Reanalysis of the largest SPE in August 1972 revealed that the dose rate was significantly higher than previously stated in the literature. The peak dose rate was 9 cGy h(sup -1) which exceeds the low dose-rate criteria for 25 hrs (National Council on Radiation Protection) and 16 hrs (United Nations Scientific Committee on the Effects of Atomic Radiation). The bone marrow dose accumulated was 0.8 Gy, which exceeded the 25 and 16 hour criteria and would pose a serious medical risk. Current spacesuits would not provide shielding from the damaging effects for an SPE as large as the 1972 event, as increased shielding from 1-5 grams per square centimeters would do little to shield the bone marrow from exposure. Medical management options for an acute radiation event are discussed based on recommendations from the Department of Homeland Security, Centers for Disease Control and evidence-based scientific literature. The discussion will also consider how to define acute exposure radiation safety limits with respect to exploration-class missions, and to determine the level of care necessary for a crew that may be exposed to an SPE similar to August 1972.

Musculoskeletal imaging with a prototype photon-counting detector.

PubMed

Gruber, M; Homolka, P; Chmeissani, M; Uffmann, M; Pretterklieber, M; Kainberger, F

2012-01-01

To test a digital imaging X-ray device based on the direct capture of X-ray photons with pixel detectors, which are coupled with photon-counting readout electronics. The chip consists of a matrix of 256 × 256 pixels with a pixel pitch of 55 μm. A monolithic image of 11.2 cm × 7 cm was obtained by the consecutive displacement approach. Images of embalmed anatomical specimens of eight human hands were obtained at four different dose levels (skin dose 2.4, 6, 12, 25 μGy) with the new detector, as well as with a flat-panel detector. The overall rating scores for the evaluated anatomical regions ranged from 5.23 at the lowest dose level, 6.32 at approximately 6 μGy, 6.70 at 12 μGy, to 6.99 at the highest dose level with the photon-counting system. The corresponding rating scores for the flat-panel detector were 3.84, 5.39, 6.64, and 7.34. When images obtained at the same dose were compared, the new system outperformed the conventional DR system at the two lowest dose levels. At the higher dose levels, there were no significant differences between the two systems. The photon-counting detector has great potential to obtain musculoskeletal images of excellent quality at very low dose levels.

Radioecological impacts of tin mining.

PubMed

Aliyu, Abubakar Sadiq; Mousseau, Timothy Alexander; Ramli, Ahmad Termizi; Bununu, Yakubu Aliyu

2015-12-01

The tin mining activities in the suburbs of Jos, Plateau State, Nigeria, have resulted in technical enhancement of the natural background radiation as well as higher activity concentrations of primordial radionuclides in the topsoil of mining sites and their environs. Several studies have considered the radiological human health risks of the mining activity; however, to our knowledge no documented study has investigated the radiological impacts on biota. Hence, an attempt is made to assess potential hazards using published data from the literature and the ERICA Tool. This paper considers the effects of mining and milling on terrestrial organisms like shrubs, large mammals, small burrowing mammals, birds (duck), arthropods (earth worm), grasses, and herbs. The dose rates and risk quotients to these organisms are computed using conservative values for activity concentrations of natural radionuclides reported in Bitsichi and Bukuru mining areas. The results suggest that grasses, herbs, lichens, bryophytes and shrubs receive total dose rates that are of potential concern. The effects of dose rates to specific indicator species of interest are highlighted and discussed. We conclude that further investigation and proper regulations should be set in place in order to reduce the risk posed by the tin mining activity on biota. This paper also presents a brief overview of the impact of mineral mining on biota based on documented literature for other countries.

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor.

PubMed

Lin, Yen-Chang; Huang, Jianying; Hileman, Stan; Martin, Karen H; Hull, Robert; Davis, Mary; Yu, Han-Gang

2015-11-15

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 μg/kg) decreased resting heart rate; at high doses (150-300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. Copyright © 2015 the American Physiological Society.

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor

PubMed Central

Lin, Yen-Chang; Huang, Jianying; Hileman, Stan; Martin, Karen H.; Hull, Robert; Davis, Mary

2015-01-01

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1–30 μg/kg) decreased resting heart rate; at high doses (150–300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03–0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. PMID:26408544

Seasonal dynamics of nitrate and ammonium ion concentrations in soil solutions collected using MacroRhizon suction cups.

PubMed

Kabala, Cezary; Karczewska, Anna; Gałka, Bernard; Cuske, Mateusz; Sowiński, Józef

2017-07-01

The aims of the study were to analyse the concentration of nitrate and ammonium ions in soil solutions obtained using MacroRhizon miniaturized composite suction cups under field conditions and to determine potential nitrogen leaching from soil fertilized with three types of fertilizers (standard urea, slow-release urea, and ammonium nitrate) at the doses of 90 and 180 kg ha -1 , applied once or divided into two rates. During a 3-year growing experiment with sugar sorghum, the concentration of nitrate and ammonium ions in soil solutions was the highest with standard urea fertilization and the lowest in variants fertilized with slow-release urea for most of the months of the growing season. Higher concentrations of both nitrogen forms were noted at the fertilizer dose of 180 kg ha -1 . One-time fertilization, at both doses, resulted in higher nitrate concentrations in June and July, while dividing the dose into two rates resulted in higher nitrate concentrations between August and November. The highest potential for nitrate leaching during the growing season was in July. The tests confirmed that the miniaturized suction cups MacroRhizon are highly useful for routine monitoring the concentration of nitrate and ammonium ions in soil solutions under field conditions.

Update to Millstone 3 elevated pH tests

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

Bergmann, C.A.; Perock, J.D.; Hudson, M.J.B.

1995-03-01

In view of the potential radiological benefits of elevated coolant pH operation, Northwest Utilities (NU), in support of an EPRI-Westinghouse program, agreed to operate the Millstone 3 plant at the start of its second fuel cycle as a demonstration of the effect of elevated coolant pH on out-of-core radiation fields. Operating with an elevated pH is defined as operating with an average lithium concentration of 3.35 ppm, until reaching an end of cycle pH of 7.2 or 7.4. The plant operated during its second and third cycles with an elevated coolant pH. The end of cycle pH during the secondmore » cycle was 7.4, and 7.2 during the third cycle. (During the first cycle, operation was with a coordinated pH of 7.0). Evaluation of the dose rate trends in Millstone 3 after two cycles of elevated coolant pH operation concluded that an elevated coolant pH resulted in a 15 percent lower component dose rate compared to other plants that operated with coordinated pH 6.9. However, due to a possible increase in fuel clad corrosion, operation during cycle 4 was restricted to pH 6.9 coordinated chemistry, with the exception of the last two months during which the pH increased to 7.35. At the end of cycle 4 (EOC4), there was a greater increase in component and crud trap dose rates than expected. This paper reviews the radiological trends in the plant and discusses the potential causes for the increase in the dose rates at EOC4.« 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.

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

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Study of variations in structural, optical parameters and bulk etch rate of CR-39 polymer due to electron irradiation

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

Sahoo, G. S.; Joshi, D. S.; Tripathy, S. P., E-mail: sam.tripathy@gmail.com, E-mail: tripathy@barc.gov.in

2016-07-14

In this work, electron induced modifications on the bulk etch rate, structural and optical parameters of CR-39 polymer were studied using gravimetric, FTIR (Fourier Transform Infrared) and UV–vis (Ultraviolet–Visible) techniques, respectively. CR-39 samples were irradiated with 10 MeV electron beam for different durations to have the absorbed doses of 1, 10, 550, 5500, 16 500, and 55 000 kGy. From the FTIR analysis, the peak intensities at different bands were found to be changing with electron dose. A few peaks were observed to shift at high electron doses. From the UV-vis analysis, the optical band gaps for both direct and indirect transitions weremore » found to be decreasing with the increase in electron dose whereas the opacity, number of carbon atoms in conjugation length, and the number of carbon atoms per cluster were found to be increasing. The bulk etch rate was observed to be increasing with the electron dose. The primary objective of this investigation was to study the response of CR-39 to high electron doses and to determine a suitable pre-irradiation condition. The results indicated that, the CR-39 pre-irradiated with electrons can have better sensitivity and thus can be potentially applied for neutron dosimetry.« less

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation.

PubMed

Seed, T M; Fritz, T E; Tolle, D V; Jackson, W E

2002-01-01

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d-1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d-1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (>1 yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d-1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d-1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation. Published by Elsevier Science Ltd on behalf of COSPAR.

Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial.

PubMed

San-Miguel, Jesús F; Hungria, Vania T M; Yoon, Sung-Soo; Beksac, Meral; Dimopoulos, Meletios A; Elghandour, Ashraf; Jedrzejczak, Wieslaw W; Guenther, Andreas; Na Nakorn, Thanyaphong; Siritanaratkul, Noppadol; Schlossman, Robert L; Hou, Jian; Moreau, Philippe; Lonial, Sagar; Lee, Jae-Hoon; Einsele, Hermann; Salwender, Hans; Sopala, Monika; Redhu, Suman; Paul, Sofia; Corrado, Claudia; Richardson, Paul G

2017-10-01

Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key AEs were lower in both arms following the planned reduction of bortezomib dosing frequency in TP2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP1, 56·7%; TP2, 6·0%), diarrhoea (grade 3/4: TP1, 24·1%; TP2, 7·1%), and fatigue (grade 3/4: TP1, 16·3%; TP2, 1·8%) were lower in TP2 compared with TP1. Dose intensity analysis of panobinostat and bortezomib by cycle in the panobinostat arm showed reductions of both agent doses during cycles 1-4 due to dose adjustments for AEs. Exposure-adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes. © 2017 John Wiley & Sons Ltd.

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

NASA Astrophysics Data System (ADS)

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

1995-01-01

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

Radiation of Bactrocera dorsalis (Diptera: Tephritidae) Eggs to Improve the Mass Rearing of Diachasmimorpha longicaudata (Hymenoptera: Braconidae).

PubMed

Cai, Pumo; Hong, Jingfang; Wang, Cong; Yang, Yanchuan; Zhang, Qiwen; Ji, Qinge; Chen, Jiahua

2018-05-28

This study explored the potential for Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) larvae hatched from irradiated eggs as hosts for Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae). B. dorsalis eggs of three different ages (12-, 24-, and 36-h old) were analyzed for hatchability, pupation rate, pupal weight, emergence rate, and sex ratio after exposure to different doses of radiation (5 and 10 Gy) at different dose rates (1 and 6 Gy/min). For the eggs of different ages exposed to radiation, only the hatchability and pupal weight of 36-h-old eggs exposed to the dose rate of 1 Gy/min were not affected; therefore, 6 Gy/min was not suitable for irradiating eggs. The viability of the parents and progenies of D. longicaudata when the parents were reared from 36-h-old eggs irradiated at nine different doses (0, 5, 10, 15, 20, 25, 30, 35, and 40 Gy) under laboratory conditions were investigated. The emergence percentage, sex ratio, and longevity of parasitoids developed from irradiated eggs were similar to those reared from nonirradiated hosts. A significant increase in larva mortality was observed for the eggs irradiated at doses above 25 Gy, and no redundant adult flies emerged at doses above 15 Gy. Hence, for B. dorsalis eggs to be applied in the mass rearing of D. longicaudata, the age of 36 h and a dose of 20-25 Gy are the optimal parameters. The results reveal that hosts and parasitoids need not be separated, enabling a reduction in cost, labor, and time and resulting in an improved mass rearing procedure for D. longicaudata.

Comparison of two neonatal indomethacin protocols: efficacy and outcome for patent ductus arteriosus closure.

PubMed

Rosito, G; Sum, K; Chorne, N

2010-10-01

Indomethacin, a non-selective inhibitor of prostaglandin synthesis, is the gold standard treatment for patent ductus arteriosus (PDA). Indomethacin has been shown to permanently close the ductus and when given prophylactically, it reduces the incidence of PDA (1, 2). This study compares PDA closure and surgical ligation rates between patients using two different indomethacin administration protocols. This is a retrospective comparison analysis of 72 neonates, who received one of two indomethacin administration protocols. Our previous protocol suggested an initial dose of 0·2 mg/kg followed by two 0·1 mg/kg, with doses infused over 4 h and a 24-h dosing interval. A new potentially more useful protocol using the same mg/kg dose regimen but with doses infused over 30 min and a 12-h dosing interval, was evaluated. Each neonate was allowed three courses of treatment before surgical ligation was performed for persistent PDA. There were no statistically significant differences between the two protocol groups when comparing percentages of neonates with gestational age≤28 weeks, birth weight≤1000 g, male gender or receiving indomethacin for the indication of PDA prophylaxis vs. treatment. There was a trend towards a higher PDA closure rate and subsequently a lower PDA ligation rate in the new protocol when compared with the previous protocol. In this small population of premature neonates, there was a trend, but no significant difference, towards increasing PDA closure and lower surgical ligation rates in neonates given indomethacin with more frequent dosing and shorter infusion time. A well-powered randomized controlled trial is now needed. Copyright © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

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

PubMed

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

2018-06-01

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

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

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

DOE PAGES

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

2015-03-25

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

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

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

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

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

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.

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder.

PubMed

van Tilborg, Theodora C; Torrance, Helen L; Oudshoorn, Simone C; Eijkemans, Marinus J C; Koks, Carolien A M; Verhoeve, Harold R; Nap, Annemiek W; Scheffer, Gabrielle J; Manger, A Petra; Schoot, Benedictus C; Sluijmer, Alexander V; Verhoeff, Arie; Groen, Henk; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M

2017-12-01

Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian response (AFC < 11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC < 11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to assess whether an increased dose strategy would increase the cumulative live birth rate from 25 to 40% (two-sided alpha-error 0.05, power 80%). Women with an AFC ≤ 7 were randomized to an FSH dose of 450 IU/day or 150 IU/day, and women with an AFC 8-10 were randomized to 225 IU or 150 IU/day. In the standard group, dose adjustment was allowed in subsequent cycles based on pre-specified criteria. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC < 11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women. This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). T.C.T., H.L.T. and S.C.O. received an unrestricted personal grant from Merck BV. H.R.V. receives monetary compensation as a member on an external advisory board for Ferring pharmaceutical BV. B.W.J.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. F.J.M.B. receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number NTR2657. 20 December 2010. 12 May 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

The behavior of glass fibers in the rat following intraperitoneal injection.

PubMed

Collier, C G; Morris, K J; Launder, K A; Humphreys, J A; Morgan, A; Eastes, W; Townsend, S

1994-12-01

Potential carcinogenicity of fibers is believed to be determined by three factors: the dose, dimensions and durability of the fibers concerned. Currently there is considerable debate on the appropriateness of using results from intraperitoneal (i.p.) injection studies to predict the potential carcinogenicity of airborne fibers following inhalation. For ip results to have any significance to potential inhalation hazards, there should be some relation between the biopersistence, dose, and dose distribution of fibers in the serosal cavity and in the lung. Preliminary results on the durability of one experimental glass fiber in the peritoneal cavity suggest differences in dissolution when compared with durability in the lung. In the lung, the diameters of the long fibers (> 20 microns) were observed to decline at a rate consistent with their exposure to a neutral pH environment. The diameter of shorter fibers declined much more slowly, consistent with exposure to a more acidic environment such as is found in the phagolysosomes of alveolar macrophages. In the peritoneal cavity all fibers, regardless of length, dissolved at the same rate as short fibers in the lung. The effect of dose on the distribution of fibers in the peritoneal cavity was investigated using similar experimental glass fibers and compared with that of a powder made from ground fibers. For both materials at doses up to 1.5 mg, material was taken up by the peritoneal organs roughly in proportion to their surface area. This uptake was complete 1-2 days after injection. At higher doses, the majority of the material in excess of this 1.5 mg formed clumps of fibers (nodules) which were either free in the peritoneal cavity or loosely bound to peritoneal organs. These nodules displayed classic foreign body reactions with an associated granulomatous inflammatory response. The findings on both durability in the peritoneal cavity and the presence of two distinct populations of material following i.p. injection have implications for the justification of the use of i.p. injections to assess potential carcinogenicity of fibers following inhalation.

In vivo thermoluminescence dosimetry dose verification of transperineal 192Ir high-dose-rate brachytherapy using CT-based planning for the treatment of prostate cancer.

PubMed

Anagnostopoulos, G; Baltas, D; Geretschlaeger, A; Martin, T; Papagiannis, P; Tselis, N; Zamboglou, N

2003-11-15

To evaluate the potential of in vivo thermoluminescence dosimetry to estimate the accuracy of dose delivery in conformal high-dose-rate brachytherapy of prostate cancer. A total of 50 LiF, TLD-100 cylindrical rods were calibrated in the dose range of interest and used as a batch for all fractions. Fourteen dosimeters for every treatment fraction were loaded in a plastic 4F catheter that was fixed in either one of the 6F needles implanted for treatment purposes or in an extra needle implanted after consulting with the patient. The 6F needles were placed either close to the urethra or in the vicinity of the median posterior wall of the prostate. Initial results are presented for 18 treatment fractions in 5 patients and compared to corresponding data calculated using the commercial treatment planning system used for the planning of the treatments based on CT images acquired postimplantation. The maximum observed mean difference between planned and delivered dose within a single treatment fraction was 8.57% +/- 2.61% (root mean square [RMS] errors from 4.03% to 9.73%). Corresponding values obtained after averaging results over all fractions of a patient were 6.88% +/- 4.93% (RMS errors from 4.82% to 7.32%). Experimental results of each fraction corresponding to the same patient point were found to agree within experimental uncertainties. Experimental results indicate that the proposed method is feasible for dose verification purposes and suggest that dose delivery in transperineal high-dose-rate brachytherapy after CT-based planning can be of acceptable accuracy.

The influence of dose, dose-rate and particle fragmentation on cataract induction by energetic iron ions

NASA Technical Reports Server (NTRS)

Medvedovsky, C.; Worgul, B. V.; Huang, Y.; Brenner, D. J.; Tao, F.; Miller, J.; Zeitlin, C.; Ainsworth, E. J.

1994-01-01

Because activities in space necessarily involve chronic exposure to a heterogeneous charged particle radiation field it is important to assess the influence of dose-rate and the possible modulating role of heavy particle fragmentation on biological systems. Using the well-studied cataract model, mice were exposed to plateau 600 MeV/amu Fe-56 ions either as acute or fractionated exposures at total doses of 5-504 cGy. Additional groups of mice received 20, 360 and 504 cGy behind 50 mm of polyethylene, which simulates body shielding. The reference radiation consisted of Co-60 gamma radiation. The animals were examined by slit lamp biomicroscopy over their three year life spans. In accordance with our previous observations with heavy particles, the cataractogenic potential of the 600 MeV/amu Fe-56 ions was greater than for low-Linear Energy Transfer (LET) radiation and increased with decreasing dose relative to gamma rays. Fractionation of a given dose of Fe-56 ions did not reduce the cataractogenicity of the radiation compared to the acute regimen. Fragmentation of the beam in the polyethylene did not alter the cataractotoxicity of the ions, either when administered singly or in fractions.

The influence of dose, dose-rate and particle fragmentation on cataract induction by energetic iron ions

NASA Astrophysics Data System (ADS)

Medvedovsky, C.; Worgul, B. V.; Huang, Y.; Brenner, D. J.; Tao, F.; Miller, J.; Zeitlin, C.; Ainsworth, E. J.

1994-10-01

Because activities in space necessarily involve chronic exposure to a heterogeneous charged particle radiation field it is important to assess the influence of dose-rate and the possible modulating role of heavy particle fragmentation on biological systems. Using the well-studied cataract model, mice were exposed to plateau 600 MeV/amu 56Fe ions either as acute or fractionated exposures at total doses of 5 - 504 cGy. Additional groups of mice received 20, 360 and 504 cGy behind 50 mm of polyethylene, which simulates body shielding. The reference radiation consisted of 60Co γ radiation. The animals were examined by slit lamp biomicroscopy over their three year life spans. In accordance with our previous observations with heavy particles, the cataractogenic potential of the 600 MeV/amu 56Fe ions was greater than for low-LET radiation and increased with decreasing dose relative to γ-rays. Fractionation of a given dose of 56Fe ions did not reduce the cataractogenicity of the radiation compared to the acute regimen. Fragmentation of the beam in the polyethylene did not alter the cataractotoxicity of the ions, either when administered singly or in fractions.

A highly infective plant-associated bacterium influences reproductive rates in pea aphids

PubMed Central

Hendry, Tory A.; Clark, Kelley J.; Baltrus, David A.

2016-01-01

Pea aphids, Acyrthosiphon pisum, have the potential to increase reproduction as a defence against pathogens, though how frequently this occurs or how infection with live pathogens influences this response is not well understood. Here we determine the minimum infective dose of an environmentally common bacterium and possible aphid pathogen, Pseudomonas syringae, to determine the likelihood of pathogenic effects to pea aphids. Additionally, we used P. syringae infection to investigate how live pathogens may alter reproductive rates. We found that oral bacterial exposure decreased subsequent survival of aphids in a dose-dependent manner and we estimate that ingestion of less than 10 bacterial cells is sufficient to increase aphid mortality. Pathogen dose was positively related to aphid reproduction. Aphids exposed to low bacterial doses showed decreased, although statistically indistinguishable, fecundity compared to controls. Aphids exposed to high doses reproduced significantly more than low dose treatments and also more, but not significantly so, than controls. These results are consistent with previous studies suggesting that pea aphids may use fecundity compensation as a response to pathogens. Consequently, even low levels of exposure to a common plant-associated bacterium may therefore have significant effects on pea aphid survival and reproduction. PMID:26998321

A highly infective plant-associated bacterium influences reproductive rates in pea aphids.

PubMed

Hendry, Tory A; Clark, Kelley J; Baltrus, David A

2016-02-01

Pea aphids, Acyrthosiphon pisum, have the potential to increase reproduction as a defence against pathogens, though how frequently this occurs or how infection with live pathogens influences this response is not well understood. Here we determine the minimum infective dose of an environmentally common bacterium and possible aphid pathogen, Pseudomonas syringae, to determine the likelihood of pathogenic effects to pea aphids. Additionally, we used P. syringae infection to investigate how live pathogens may alter reproductive rates. We found that oral bacterial exposure decreased subsequent survival of aphids in a dose-dependent manner and we estimate that ingestion of less than 10 bacterial cells is sufficient to increase aphid mortality. Pathogen dose was positively related to aphid reproduction. Aphids exposed to low bacterial doses showed decreased, although statistically indistinguishable, fecundity compared to controls. Aphids exposed to high doses reproduced significantly more than low dose treatments and also more, but not significantly so, than controls. These results are consistent with previous studies suggesting that pea aphids may use fecundity compensation as a response to pathogens. Consequently, even low levels of exposure to a common plant-associated bacterium may therefore have significant effects on pea aphid survival and reproduction.

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

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

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

2016-06-01

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

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

PubMed

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

2018-06-01

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

Neutron-Irradiated Samples as Test Materials for MPEX

DOE PAGES

Ellis, Ronald James; Rapp, Juergen

2015-10-09

Plasma Material Interaction (PMI) is a major concern in fusion reactor design and analysis. The Material-Plasma Exposure eXperiment (MPEX) will explore PMI under fusion reactor plasma conditions. Samples with accumulated displacements per atom (DPA) damage produced by fast neutron irradiations in the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL) will be studied in the MPEX facility. This paper presents assessments of the calculated induced radioactivity and resulting radiation dose rates of a variety of potential fusion reactor plasma-facing materials (such as tungsten). The scientific code packages MCNP and SCALE were used to simulate irradiation of themore » samples in HFIR including the generation and depletion of nuclides in the material and the subsequent composition, activity levels, gamma radiation fields, and resultant dose rates as a function of cooling time. A challenge of the MPEX project is to minimize the radioactive inventory in the preparation of the samples and the sample dose rates for inclusion in the MPEX facility.« less

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

PubMed

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

2017-09-01

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

PM ACTIVITY PATTERN RESEARCH

EPA Science Inventory

Human activity/uptake rate data are necessary to estimate potential human exposure and intake dose to environmental pollutants and to refine human exposure models. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and pre...

HUMAN EXPOSURE ACTIVITY PATTERNS

EPA Science Inventory

Human activity/uptake rate data are necessary to estimate potential human exposure and intake dose to environmental pollutants and to refine human exposure models. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and pre...

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.

Survival, Intestinal Mucosa Adhesion, and Immunomodulatory Potential of Lactobacillus plantarum Strains.

PubMed

Santarmaki, Valentini; Kourkoutas, Yiannis; Zoumpopoulou, Georgia; Mavrogonatou, Eleni; Kiourtzidis, Mikis; Chorianopoulos, Nikos; Tassou, Chrysoula; Tsakalidou, Effie; Simopoulos, Constantinos; Ypsilantis, Petros

2017-09-01

Survival during transit through the gastrointestinal track, intestinal mucosa adhesion, and a potential immunomodulatory effect of Lactobacillus plantarum strains 2035 and ACA-DC 2640 were investigated in a rat model. According to microbiological and multiplex PCR analysis, both strains were detected in feces 24 h after either single-dose or daily administration for 7 days. Intestinal mucosa adhesion of L. plantarum 2035 was noted in the large intestine at 24 h after single-dose administration, while it was not detected at 48 h. Daily dosing, prolonged detection of the strain up to 48 h post-administration, and expanded adhesion to the small intestine. Adhesion of L. plantarum ACA-DC 2640 to the intestinal mucosa after single-dose administration was prolonged and more extended compared to L. plantarum 2035. Daily dosing increased both the levels and the rate of positive cultures of the strains compared to those of the single-dose scheme. In addition, both strains increased total IgG while decreased IgM and IgA serum levels. In conclusion, L. plantarum 2035 and L. plantarum ACA-DC 2640 survived transit through the gastrointestinal track, exhibited transient distinct adhesion to the intestinal mucosa and modulated the systemic immune response.

Childhood intracranial ependymoma: twenty-year experience from a single institution.

PubMed

Shu, Hui-Kuo G; Sall, Walter F; Maity, Amit; Tochner, Zelig A; Janss, Anna J; Belasco, Jean B; Rorke-Adams, Lucy B; Phillips, Peter C; Sutton, Leslie N; Fisher, Michael J

2007-07-15

Because few large studies of pediatric ependymoma treatment are available, the authors believed that a retrospective review of treatment outcomes from a single institution would yield potentially valuable information regarding potential prognostic factors. In this article, they report their 20-year institutional experience with this disease. Medical records were reviews of patients with intracranial ependymoma who received their initial treatment at the Children's Hospital of Philadelphia (CHOP)/Hospital of the University of Pennsylvania (HUP) between January 1980 and December 2000. Of the 61 patients who were identified, 49 patients underwent primary therapy at CHOP/HUP and formed the basis for the study. Actuarial overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and Cox proportional-hazards models. With median follow-up of 110.2 months, the 5-year OS and PFS rates were 66.2% and 40.7%, respectively. Older age and higher radiation dose significantly predicted for improved OS. Anaplastic histology predicted for decreased PFS. Cervical spinal cord extension resulted in decreased OS primarily caused by failures outside the primary site. Patients who had a favorable prognosis (aged >/=3 years, no dissemination or cord extension, complete resection, and radiation dose >/=54 grays [Gy]) had 5-year OS and PFS rates of 83.1% and 60.6%, respectively. In this study of patients with pediatric intracranial ependymoma, OS and PFS rates were concordant with the rates published in other modern series. The finding of a dose response up to 54 Gy supported the current trend toward dose escalation. Tumor extension to the cervical spine was identified as a predictor for failure outside of the primary site. Although the survival rates were encouraging, there is still significant room for improvement in the management of this disease.

Dermatologic radiotherapy and thyroid cancer. Dose measurements and risk quantification.

PubMed

Goldschmidt, H; Gorson, R O; Lassen, M

1983-05-01

Thyroid doses for various dermatologic radiation techniques were measured with thermoluminescent dosimeters and ionization rate meters in an Alderson-Rando anthropomorphic phantom. The effects of changes in radiation quality and of the use or nonuse of treatment cones and thyroid shields were evaluated in detail. The results indicate that the potential risk of radiogenic thyroid cancer is very small when proper radiation protection measures are used. The probability of radiogenic thyroid cancer developing and the potential mortality risk were assessed quantitatively for each measurement. The quantification of radiation risks allows comparisons with risks of other therapeutic modalities and the common hazards of daily life.

Physiologic variability at the verge of systemic inflammation: multi-scale entropy of heart rate variability is affected by very low doses of endotoxin

PubMed Central

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

2014-01-01

Introduction Human injury or infection induces systemic inflammation with characteristic neuro-endocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, we investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and we investigate the size of data sets required for meaningful use of multi-scale entropy (MSE) analysis of HRV. Methods Healthy human volunteers (n=25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 minutes for 6 hours and then at 9, 12, and 24 hours after LPS. Blood samples were drawn at specific time points for cytokine measurements. HRV analysis was performed using EKG epochs of 5 minutes. MSE for HRV was calculated for all dose groups to scale factor 40. Results The lowest significant threshold dose was noted in core temperature at 0.25ng/kg. Endogenous TNF-α and IL-6 were significantly responsive at the next dosage level (0.5ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures ANOVA across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 hours post exposure to LPS. While not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes. Conclusions By usingrANOVA across scale factors, MSE can detect autonomic change after LPS challenge in a group of 25 subjects using EKG epochs of only 5 minutes and entropy analysis to scale factor of only 40, potentially facilitating MSE’s wider use as a research tool or bedside monitor. Traditional markers of inflammation generally exhibit threshold dose behavior. In contrast, MSE’s apparent continuous dose-response pattern, while not statistically verifiable in this study, suggests a potential subclinical harbinger of infectious or other insult. The possible derangement of autonomic complexity prior to or independent of the cytokine surge cannot be ruled out. Future investigation should focus on confirmation of overt inflammation following observed decreases in MSE in a clinical setting. PMID:25526373

Antioxidative potential of Duranta repens (Linn.) fruits against H2O2 induced cell death in vitro.

PubMed

Khan, Md Asaduzzaman; Rahman, Mohammad Mijanur; Tania, Mousumi; Shoshee, Nusrat Fatima; Xu, Ai-hua; Chen, Han-chun

2013-01-01

The effects of Duranta repens fruits were investigated on H2O2 induced oxidative cell death to evaluate its antioxidative potential in vitro. HEK293T cells were treated with different concentrations [0-1000 µg/ ml] of ethanol extract (E-Ex) and methanol extract (M-Ex) of D. repens for 24h, and then treated with 100 µM H2O2 for 24h. Cell viability, antioxidant parameters of cells, and antioxidant constituents of the extracts were determined. Treatment with limited dose of E-Ex or M-Ex increased the survival rate of H2O2-treated HEK293T cells, however the extra-high dose showed growth inhibitory effect. Treatment with E-Ex or M-Ex protected cellular lipid per-oxidation. In vitro analyses showed the 2,2-diphenyl-1-picrylhydrazyl and H2O2 scavenging activities as well as reducing potential of the extracts. We report here that the limited dose of E-Ex and M-Ex possess antioxidative potential, which can protect H2O2-induced oxidative cell damage.

Information profiles on potential occupational hazards: benzoin

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

Not Available

1981-03-01

Information on potential occupational hazards from exposure to benzoin was reviewed. Topics discussed included chemical and physical properties, production, uses, manufacturers and distributors, manufacturing processes, occupational exposure, and biological effects. The annual production of benzoin is approximately 90,000 pounds per year with an historical growth rate of about 6% per year. In carcinogenesis studies, the incidence of lymphomas and leukemia in dosed male rats increased with dose level, but not significantly. Mice demonstrated a significant increase in the incidence of lymphomas and leukemias at low dose levels. Bioassays have indicated that benzoin is not carcinogenic to male or female F344-ratsmore » or B6C3F1-mice. No evidence of mutagenicity, teratogenicity, or reproductive effects was found in animal studies. Allergic contact dermatitis has been reported in humans.« less

Comparison of virtual unenhanced CT images of the abdomen under different iodine flow rates.

PubMed

Li, Yongrui; Li, Ye; Jackson, Alan; Li, Xiaodong; Huang, Ning; Guo, Chunjie; Zhang, Huimao

2017-01-01

To assess the effect of varying iodine flow rate (IFR) and iodine concentration on the quality of virtual unenhanced (VUE) images of the abdomen obtained with dual-energy CT. 94 subjects underwent unenhanced and triphasic contrast-enhanced CT scan of the abdomen, including arterial phase, portal venous phase, and delayed phase using dual-energy CT. Patients were randomized into 4 groups with different IFRs or iodine concentrations. VUE images were generated at 70 keV. The CT values, image noise, SNR and CNR of aorta, portal vein, liver, liver lesion, pancreatic parenchyma, spleen, erector spinae, and retroperitoneal fat were recorded. Dose-length product and effective dose for an examination with and without plain phase scan were calculated to assess the potential dose savings. Two radiologists independently assessed subjective image quality using a five-point scale. The Kolmogorov-Smirnov test was used first to test for normal distribution. Where data conformed to a normal distribution, analysis of variance was used to compare mean HU values, image noise, SNRs and CNRs for the 4 image sets. Where data distribution was not normal, a nonparametric test (Kruskal-Wallis test followed by stepwise step-down comparisons) was used. The significance level for all tests was 0.01 (two-sided) to allow for type 2 errors due to multiple testing. The CT numbers (HU) of VUE images showed no significant differences between the 4 groups (p > 0.05) or between different phases within the same group (p > 0.05). VUE images had equal or higher SNR and CNR than true unenhanced images. VUE images received equal or lower subjective image quality scores than unenhanced images but were of acceptable quality for diagnostic use. Calculated dose-length product and estimated dose showed that the use of VUE images in place of unenhanced images would be associated with a dose saving of 25%. VUE images can replace conventional unenhanced images. VUE images are not affected by varying iodine flow rates and iodine concentrations, and diagnostic examinations could be acquired with a potential dose saving of 25%.

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

NASA Astrophysics Data System (ADS)

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

2014-12-01

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

High resolution digital autoradiographic and dosimetric analysis of heterogeneous radioactivity distribution in xenografted prostate tumors.

PubMed

Timmermand, Oskar V; Nilsson, Jenny; Strand, Sven-Erik; Elgqvist, Jörgen

2016-12-01

The first main aim of this study was to illustrate the absorbed dose rate distribution from 177 Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of 90 Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using 177 Lu-h11B6, directed against the human kallikrein 2 antigen. Male immunodeficient BALB/c nude mice, aged 6-8 w, were inoculated by subcutaneous injection of ∼10 7 LNCaP cells in a 200 μl suspension of a 1:1 mixture of medium and Matrigel. The antibody h11B6 was conjugated with the chelator CHX-A″-DTPA after which conjugated h11B6 was mixed with 177 LuCl 3 . The incubation was performed at room temperature for 2 h, after which the labeling was terminated and the solution was purified on a NAP-5 column. About 20 MBq 177 Lu-h11B6 was injected intravenously in the tail vein. At approximately 10 h postinjection (hpi), the mice were sacrificed and one tumor was collected from each of the five animals and cryosectioned into 10 μm thick slices. The tumor slices were measured and imaged using the DAR MicroImager system and the M3Vision software. Then the absorbed dose rate was calculated using a dose point kernel generated with the Monte Carlo code gate v7.0. The DAR system produced high resolution images of the radioactivity distribution, close to the resolution of single PCa cells. The DAR images revealed a pronounced heterogeneous radioactivity distribution, i.e., count rate per area, in the tumors, indicated by the normalized intensity variations along cross sections as mean ± SD: 0.15 ± 0.15, 0.20 ± 0.18, 0.12 ± 0.17, 0.15 ± 0.16, and 0.23 ± 0.22, for each tumor section, respectively. The absorbed dose rate distribution for 177 Lu at the time of dissection 10 hpi showed a maximum value of 2.9 ± 0.4 Gy/h (mean ± SD), compared to 6.0 ± 0.9 and 159 ± 25 Gy/h for the hypothetical 90 Y and 7 MeV alpha-particle cases assuming the same count rate densities. Mean absorbed dose rate values were 0.13, 0.53, and 6.43 Gy/h for 177 Lu, 90 Y, and alpha-particles, respectively. The initial uptake of 177 Lu-h11B6 produces a high absorbed dose rate, which is important for a successful therapeutic outcome. The hypothetical 90 Y case indicates a less heterogeneous absorbed dose rate distribution and a higher mean absorbed dose rate compared to 177 Lu, although with a potentially increased irradiation of surrounding healthy tissue. The hypothetical alpha-particle case indicates the possibility of a higher maximum absorbed dose rate, although with a more heterogeneous absorbed dose rate distribution.

Adaptive error detection for HDR/PDR brachytherapy: Guidance for decision making during real-time in vivo point dosimetry

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

Kertzscher, Gustavo, E-mail: guke@dtu.dk; Andersen, Claus E., E-mail: clan@dtu.dk; Tanderup, Kari, E-mail: karitand@rm.dk

Purpose: This study presents an adaptive error detection algorithm (AEDA) for real-timein vivo point dosimetry during high dose rate (HDR) or pulsed dose rate (PDR) brachytherapy (BT) where the error identification, in contrast to existing approaches, does not depend on an a priori reconstruction of the dosimeter position. Instead, the treatment is judged based on dose rate comparisons between measurements and calculations of the most viable dosimeter position provided by the AEDA in a data driven approach. As a result, the AEDA compensates for false error cases related to systematic effects of the dosimeter position reconstruction. Given its nearly exclusivemore » dependence on stable dosimeter positioning, the AEDA allows for a substantially simplified and time efficient real-time in vivo BT dosimetry implementation. Methods: In the event of a measured potential treatment error, the AEDA proposes the most viable dosimeter position out of alternatives to the original reconstruction by means of a data driven matching procedure between dose rate distributions. If measured dose rates do not differ significantly from the most viable alternative, the initial error indication may be attributed to a mispositioned or misreconstructed dosimeter (false error). However, if the error declaration persists, no viable dosimeter position can be found to explain the error, hence the discrepancy is more likely to originate from a misplaced or misreconstructed source applicator or from erroneously connected source guide tubes (true error). Results: The AEDA applied on twoin vivo dosimetry implementations for pulsed dose rate BT demonstrated that the AEDA correctly described effects responsible for initial error indications. The AEDA was able to correctly identify the major part of all permutations of simulated guide tube swap errors and simulated shifts of individual needles from the original reconstruction. Unidentified errors corresponded to scenarios where the dosimeter position was sufficiently symmetric with respect to error and no-error source position constellations. The AEDA was able to correctly identify all false errors represented by mispositioned dosimeters contrary to an error detection algorithm relying on the original reconstruction. Conclusions: The study demonstrates that the AEDA error identification during HDR/PDR BT relies on a stable dosimeter position rather than on an accurate dosimeter reconstruction, and the AEDA’s capacity to distinguish between true and false error scenarios. The study further shows that the AEDA can offer guidance in decision making in the event of potential errors detected with real-timein vivo point dosimetry.« less

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

PubMed Central

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

2017-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2013-11-01

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

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.

Milrinone Dosing Issues in Critically Ill Children With Kidney Injury: A Review.

PubMed

Gist, Katja M; Goldstein, Stuart L; Joy, Melanie S; Vinks, Alexander A

2016-02-01

Milrinone is an inotropic drug used in a variety of clinical settings in adults and children. The efficacy of milrinone in pediatric low-cardiac output syndrome after cardiac surgery is reported. Its primary route of removal from the body is through the kidney as unchanged drug in the urine. Milrinone is not known to be efficiently removed by extracorporeal dialytic therapies and thus has the potential to cause serious adverse effects and potentially worsens renal function in patients experiencing acute kidney injury (AKI). AKI is an important public health issue that is associated with increased morbidity, mortality, and cost. It is a known risk factor for the development of chronic kidney disease. There are no specific therapies to mitigate AKI once it has developed, and interventions are focused on supportive care and dose adjustment of medications. Estimating glomerular filtration rate based on height and serum creatinine is the most commonly used clinical method for assessing kidney function and modification of medication doses. The purpose of this review is to discuss our current understanding of milrinone pharmacokinetics and pharmacodynamics in children with AKI and to describe the potential use of urinary biomarkers to guide therapeutic decision making for milrinone dosing.

SU-E-T-105: Development of 3D Dose Verification System for Volumetric Modulated Arc Therapy Using Improved Polyacrylamide-Based Gel Dosimeter

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

Ono, K; Fujimoto, S; Akagi, Y

2014-06-01

Purpose: The aim of this dosimetric study was to develop 3D dose verification system for volumetric modulated arc therapy (VMAT) using polyacrylamide-based gel (PAGAT) dosimeter improved the sensitivity by magnesium chloride (MgCl{sub 2}). Methods: PAGAT gel containing MgCl{sub 2} as a sensitizer was prepared in this study. Methacrylic-acid-based gel (MAGAT) was also prepared to compare the dosimetric characteristics with PAGAT gel. The cylindrical glass vials (4 cm diameter, 12 cm length) filled with each polymer gel were irradiated with 6 MV photon beam using Novalis Tx linear accelerator (Varian/BrainLAB). The irradiated polymer gel dosimeters were scanned with Signa 1.5 Tmore » MRI system (GE), and dose calibration curves were obtained using T{sub 2} relaxation rate (R{sub 2} = 1/T{sub 2}). Dose rate (100-600 MU min{sup −1}) and fractionation (1-8 fractions) were varied. In addition, a cubic acrylic phantom (10 × 10 × 10 cm{sup 3}) filled with improved PAGAT gel inserted into the IMRT phantom (IBA) was irradiated with VMAT (RapidArc). C-shape structure was used for the VMAT planning by the Varian Eclipse treatment planning system (TPS). The dose comparison of TPS and measurements with the polymer gel dosimeter was accomplished by the gamma index analysis, overlaying the dose profiles for a set of data on selected planes using in-house developed software. Results: Dose rate and fractionation dependence of improved PAGAT gel were smaller than MAGAT gel. A high similarity was found by overlaying the dose profiles measured with improved PAGAT gel dosimeter and the TPS dose, and the mean pass rate of the gamma index analysis using 3%/3 mm criteria was achieved 90% on orthogonal planes for VMAT using improved PAGAT gel dosimeter. Conclusion: In-house developed 3D dose verification system using improved polyacrylamide-based gel dosimeter had a potential as an effective tool for VMAT QA.« less

Improving the Accuracy of a Heliocentric Potential (HCP) Prediction Model for the Aviation Radiation Dose

NASA Astrophysics Data System (ADS)

Hwang, Junga; Yoon, Kyoung-Won; Jo, Gyeongbok; Noh, Sung-Jun

2016-12-01

The space radiation dose over air routes including polar routes should be carefully considered, especially when space weather shows sudden disturbances such as coronal mass ejections (CMEs), flares, and accompanying solar energetic particle events. We recently established a heliocentric potential (HCP) prediction model for real-time operation of the CARI-6 and CARI-6M programs. Specifically, the HCP value is used as a critical input value in the CARI-6/6M programs, which estimate the aviation route dose based on the effective dose rate. The CARI-6/6M approach is the most widely used technique, and the programs can be obtained from the U.S. Federal Aviation Administration (FAA). However, HCP values are given at a one month delay on the FAA official webpage, which makes it difficult to obtain real-time information on the aviation route dose. In order to overcome this critical limitation regarding the time delay for space weather customers, we developed a HCP prediction model based on sunspot number variations (Hwang et al. 2015). In this paper, we focus on improvements to our HCP prediction model and update it with neutron monitoring data. We found that the most accurate method to derive the HCP value involves (1) real-time daily sunspot assessments, (2) predictions of the daily HCP by our prediction algorithm, and (3) calculations of the resultant daily effective dose rate. Additionally, we also derived the HCP prediction algorithm in this paper by using ground neutron counts. With the compensation stemming from the use of ground neutron count data, the newly developed HCP prediction model was improved.

Venetoclax: A novel B-cell lymphoma-2 inhibitor for chronic lymphocytic leukemia and other hematologic malignancies.

PubMed

Olin, Jacqueline L; Griffiths, Carrie L; Smith, Morgan B

2017-01-01

Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6) with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis syndrome has been observed during initiation and titration. Assessing risk of tumor lysis syndrome prior to therapy initiation is essential to provide appropriate prophylactic medications. Neutropenia, potentially warranting dose reduction or discontinuation, has been observed. Venetoclax has demonstrated activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has shown response, and is well tolerated in patients with highly resistant chronic lymphocytic leukemia. It has the potential to be part of the treatment armamentarium for other malignancies.

Differential sensitivity of osteoblasts and bacterial pathogens to 405-nm light highlighting potential for decontamination applications in orthopedic surgery

NASA Astrophysics Data System (ADS)

Ramakrishnan, Praveen; Maclean, Michelle; MacGregor, Scott J.; Anderson, John G.; Grant, M. Helen

2014-10-01

Healthcare associated infections pose a major threat to patients admitted to hospitals and infection rates following orthopedic arthroplasty surgery are as high as 4%. A 405-nm high-intensity narrow spectrum light has been proven to reduce environmental contamination in hospital isolation rooms, and there is potential to develop this technology for application in arthroplasty surgery. Cultured rat osteoblasts were exposed to varying light intensities and it was found that exposures of up to a dose of 36 J/cm2 had no significant effect on cell viability [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay], function (alkaline phosphatase activity), and proliferation rate (BrdU cell proliferation assay). High irradiance exposures (54 J/cm2) significantly affected the cell viability indicating that the effects of 405-nm light on osteoblasts are dose dependent. Additionally, exposure of a variety of clinically related bacteria to a dose of 36 J/cm2 resulted in up to 100% kill. These results demonstrating the differential sensitivity of osteoblasts and bacteria to 405-nm light are an essential step toward developing the technique for decontamination in orthopedic surgery.

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

PubMed

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

2010-03-01

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

Minimal and maximal incidence rates of skin cancer in Caucasians estimated by use of sigmoidal UV dose-incidence curves.

PubMed

Juzeniene, Asta; Grigalavicius, Mantas; Baturaite, Zivile; Moan, Johan

2014-11-01

Sigmoidal (S-shaped) dose-cancer incidence relationships are often observed in animal bioassays for carcinogenicity. Ultraviolet (UV) radiation is an established skin carcinogen. The aim of this study is to examine if S-shaped curves describe the relationship between solar UV doses and skin cancer incidences, and if such relationships can be used to estimate threshold levels of non-carcinogenic UV exposure, as well as maximal incidence rates. We studied the incidence rate-annual erythema-effective UV dose relationship for squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and cutaneous melanoma (CM) among different Caucasian populations in Europe, Australia and New Zealand. Our analysis indicates that S-shaped associations describe the data well (P < 0.0001). The age-adjusted incidence rates for cases expected to be due to other causes than solar UV exposure (at zero UV dose) were found to be around 0.6, 9.7 and 4.0 per 100,000 for women in 1997-2007 for SCC, BCC and CM, respectively, and around 1.2, 14.3 and 2.6 per 100,000 for men. The analysis indicates that SCC, BCC and CM have maximal incidence of 361 ± 24, 1544 ± 49 and 36 ± 4 per 100,000 for women, and 592 ± 35, 2204 ± 109 and 50 ± 4 per 100,000 for men. Between 89 and 95% of the annual CM cases, around 99.8% SCC and 99.4% BCC cases are caused by solar UV exposure. The analysis did not identify any "safe" UV dose below which the risk for skin cancer was absent. Avoidance of UV radiation has a potential to reduce the incidence of skin cancer in fair-skinned population. Copyright © 2014 Elsevier GmbH. All rights reserved.

Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

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

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

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

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.

Effects of dose scaling on delivery quality assurance in tomotherapy

PubMed Central

Nalichowski, Adrian; Burmeister, Jay

2012-01-01

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

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

PubMed

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

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

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.

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

PubMed

Hannoun-Lévi, J-M; Peiffert, D

2014-10-01

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

Results From the Imaging and Radiation Oncology Core Houston's Anthropomorphic Phantoms Used for Proton Therapy Clinical Trial Credentialing

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

Taylor, Paige A., E-mail: pataylor@mdanderson.org; Kry, Stephen F.; Alvarez, Paola

Purpose: The purpose of this study was to summarize the findings of anthropomorphic proton phantom irradiations analyzed by the Imaging and Radiation Oncology Core Houston QA Center (IROC Houston). Methods and Materials: A total of 103 phantoms were irradiated by proton therapy centers participating in clinical trials. The anthropomorphic phantoms simulated heterogeneous anatomy of a head, liver, lung, prostate, and spine. Treatment plans included those for scattered, uniform scanning, and pencil beam scanning beam delivery modalities using 5 different treatment planning systems. For every phantom irradiation, point doses and planar doses were measured using thermoluminescent dosimeters (TLD) and film, respectively. Differencesmore » between measured and planned doses were studied as a function of phantom, beam delivery modality, motion, repeat attempt, treatment planning system, and date of irradiation. Results: The phantom pass rate (overall, 79%) was high for simple phantoms and lower for phantoms that introduced higher levels of difficulty, such as motion, multiple targets, or increased heterogeneity. All treatment planning systems overestimated dose to the target, compared to TLD measurements. Errors in range calculation resulted in several failed phantoms. There was no correlation between treatment planning system and pass rate. The pass rates for each individual phantom are not improving over time, but when individual institutions received feedback about failed phantom irradiations, pass rates did improve. Conclusions: The proton phantom pass rates are not as high as desired and emphasize potential deficiencies in proton therapy planning and/or delivery. There are many areas for improvement with the proton phantom irradiations, such as treatment planning system dose agreement, range calculations, accounting for motion, and irradiation of multiple targets.« less

Shielding synchrotron light sources: Advantages of circular shield walls tunnels

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

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

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

Shielding synchrotron light sources: Advantages of circular shield walls tunnels

DOE PAGES

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

2016-04-26

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

The 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

High-pitch computed tomography coronary angiography-a new dose-saving algorithm: estimation of radiation exposure.

PubMed

Ketelsen, Dominik; Buchgeister, Markus; Korn, Andreas; Fenchel, Michael; Schmidt, Bernhard; Flohr, Thomas G; Thomas, Christoph; Schabel, Christoph; Tsiflikas, Ilias; Syha, Roland; Claussen, Claus D; Heuschmid, Martin

2012-01-01

Purpose. To estimate effective dose and organ equivalent doses of prospective ECG-triggered high-pitch CTCA. Materials and Methods. For dose measurements, an Alderson-Rando phantom equipped with thermoluminescent dosimeters was used. The effective dose was calculated according to ICRP 103. Exposure was performed on a second-generation dual-source scanner (SOMATOM Definition Flash, Siemens Medical Solutions, Germany). The following scan parameters were used: 320 mAs per rotation, 100 and 120 kV, pitch 3.4 for prospectively ECG-triggered high-pitch CTCA, scan range of 13.5 cm, collimation 64 × 2 × 0.6 mm with z-flying focal spot, gantry rotation time 280 ms, and simulated heart rate of 60 beats per minute. Results. Depending on the applied tube potential, the effective whole-body dose of the cardiac scan ranged from 1.1 mSv to 1.6 mSv and from 1.2 to 1.8 mSv for males and females, respectively. The radiosensitive breast tissue in the range of the primary beam caused an increased female-specific effective dose of 8.6%±0.3% compared to males. Decreasing the tube potential, a significant reduction of the effective dose of 35.8% and 36.0% can be achieved for males and females, respectively (P < 0.001). Conclusion. The radiologist and the CT technician should be aware of this new dose-saving strategy to keep the radiation exposure as low as reasonablly achievable.

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

Barbee, D; McCarthy, A; Galavis, P

Purpose: Errors found during initial physics plan checks frequently require replanning and reprinting, resulting decreased departmental efficiency. Additionally, errors may be missed during physics checks, resulting in potential treatment errors or interruption. This work presents a process control created using the Eclipse Scripting API (ESAPI) enabling dosimetrists and physicists to detect potential errors in the Eclipse treatment planning system prior to performing any plan approvals or printing. Methods: Potential failure modes for five categories were generated based on available ESAPI (v11) patient object properties: Images, Contours, Plans, Beams, and Dose. An Eclipse script plugin (PlanCheck) was written in C# tomore » check errors most frequently observed clinically in each of the categories. The PlanCheck algorithms were devised to check technical aspects of plans, such as deliverability (e.g. minimum EDW MUs), in addition to ensuring that policy and procedures relating to planning were being followed. The effect on clinical workflow efficiency was measured by tracking the plan document error rate and plan revision/retirement rates in the Aria database over monthly intervals. Results: The number of potential failure modes the PlanCheck script is currently capable of checking for in the following categories: Images (6), Contours (7), Plans (8), Beams (17), and Dose (4). Prior to implementation of the PlanCheck plugin, the observed error rates in errored plan documents and revised/retired plans in the Aria database was 20% and 22%, respectively. Error rates were seen to decrease gradually over time as adoption of the script improved. Conclusion: A process control created using the Eclipse scripting API enabled plan checks to occur within the planning system, resulting in reduction in error rates and improved efficiency. Future work includes: initiating full FMEA for planning workflow, extending categories to include additional checks outside of ESAPI via Aria database queries, and eventual automated plan checks.« less

Assessing dose rate distributions in VMAT plans

NASA Astrophysics Data System (ADS)

Mackeprang, P.-H.; Volken, W.; Terribilini, D.; Frauchiger, D.; Zaugg, K.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2016-04-01

Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within  ±0.4 s and doses  ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min-1 for conventional fractionation. A tool to analyze dose rate distributions in VMAT plans with sub-second accuracy was successfully developed and validated. Dose rates encountered in clinical VMAT test cases show a continuous spectrum with a mean less than or near 100 cGy min-1 for conventional fractionation.

SU-E-J-93: Parametrisation of Dose to the Mucosa of the Anterior Rectal Wall in Transrectal Ultrasound Guided High-Dose-Rate Brachytherapy of the Prostate

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

Aitkenhead, A; Hamlett, L; Wood, D

2014-06-01

Purpose: In high-dose-rate (HDR) brachytherapy of the prostate, radiation is delivered from a number of radioactive sources which are inserted via catheter into the target volume. The rectal mucosa also receives dose during the treatment, which may lead to late toxicity effects. To allow possible links between rectal dose and toxicity to be investigated, suitable methods of parametrising the rectal dose are needed. Methods: During treatment of a series of 95 patients, anatomy and catheter locations were monitored by transrectal ultrasound, and target volume positions were contoured on the ultrasound scan by the therapist. The anterior rectal mucosal wall wasmore » identified by contouring the transrectal ultrasound balloon within the ultrasound scan. Source positions and dwell times, along with the dose delivered to the patient were computed using the Oncentra Prostate treatment planning system (TPS). Data for the series of patients were exported from the TPS in Dicom format, and a series of parametrisation methods were developed in a Matlab environment to assess the rectal dose. Results: Contours of the anterior rectal mucosa were voxelised within Matlab to allow the dose to the rectal mucosa to be analysed directly from the 3D dose grid. Dose parametrisations based on dose-surface (DSH) and dose-line (DLH) histograms were obtained. Both lateral and longitudinal extents of the mucosal dose were parametrised using dose-line histograms in the relevant directions. Conclusion: We have developed a series of dose parametrisations for quantifying the dose to the rectal mucosa during HDR prostate brachytherapy which are suitable for future studies investigating potential associations between mucosal dose and late toxicity effects. The geometry of the transrectal probe standardises the rectal anatomy, making this treatment technique particularly suited to studies of this nature.« less

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.

An Interlaboratory Comparison of Dosimetry for a Multi-institutional Radiobiological

PubMed Central

Seed, TM; Xiao, S; Manley, N; Nikolich-Zugich, J; Pugh, J; van den Brink, M; Hirabayashi, Y; Yasutomo, K; Iwama, A; Koyasu, S; Shterev, I; Sempowski, G; Macchiarini, F; Nakachi, K; Kunugi, KC; Hammer, CG; DeWerd, LA

2016-01-01

Purpose An interlaboratory comparison of radiation dosimetry was conducted to determine the accuracy of doses being used experimentally for animal exposures within a large multi-institutional research project. The background and approach to this effort are described and discussed in terms of basic findings, problems and solutions. Methods Dosimetry tests were carried out utilizing optically stimulated luminescence (OSL) dosimeters embedded midline into mouse carcasses and thermal luminescence dosimeters (TLD) embedded midline into acrylic phantoms. Results The effort demonstrated that the majority (4/7) of the laboratories was able to deliver sufficiently accurate exposures having maximum dosing errors of ≤ 5%. Comparable rates of ‘dosimetric compliance’ were noted between OSL- and TLD-based tests. Data analysis showed a highly linear relationship between ‘measured’ and ‘target’ doses, with errors falling largely between 0–20%. Outliers were most notable for OSL-based tests, while multiple tests by ‘non-compliant’ laboratories using orthovoltage x-rays contributed heavily to the wide variation in dosing errors. Conclusions For the dosimetrically non-compliant laboratories, the relatively high rates of dosing errors were problematic, potentially compromising the quality of ongoing radiobiological research. This dosimetry effort proved to be instructive in establishing rigorous reviews of basic dosimetry protocols ensuring that dosing errors were minimized. PMID:26857121

An interlaboratory comparison of dosimetry for a multi-institutional radiobiological research project: Observations, problems, solutions and lessons learned.

PubMed

Seed, Thomas M; Xiao, Shiyun; Manley, Nancy; Nikolich-Zugich, Janko; Pugh, Jason; Van den Brink, Marcel; Hirabayashi, Yoko; Yasutomo, Koji; Iwama, Atsushi; Koyasu, Shigeo; Shterev, Ivo; Sempowski, Gregory; Macchiarini, Francesca; Nakachi, Kei; Kunugi, Keith C; Hammer, Clifford G; Dewerd, Lawrence A

2016-01-01

An interlaboratory comparison of radiation dosimetry was conducted to determine the accuracy of doses being used experimentally for animal exposures within a large multi-institutional research project. The background and approach to this effort are described and discussed in terms of basic findings, problems and solutions. Dosimetry tests were carried out utilizing optically stimulated luminescence (OSL) dosimeters embedded midline into mouse carcasses and thermal luminescence dosimeters (TLD) embedded midline into acrylic phantoms. The effort demonstrated that the majority (4/7) of the laboratories was able to deliver sufficiently accurate exposures having maximum dosing errors of ≤5%. Comparable rates of 'dosimetric compliance' were noted between OSL- and TLD-based tests. Data analysis showed a highly linear relationship between 'measured' and 'target' doses, with errors falling largely between 0 and 20%. Outliers were most notable for OSL-based tests, while multiple tests by 'non-compliant' laboratories using orthovoltage X-rays contributed heavily to the wide variation in dosing errors. For the dosimetrically non-compliant laboratories, the relatively high rates of dosing errors were problematic, potentially compromising the quality of ongoing radiobiological research. This dosimetry effort proved to be instructive in establishing rigorous reviews of basic dosimetry protocols ensuring that dosing errors were minimized.

Evidence supporting radiation hormesis in atomic bomb survivor cancer mortality data.

PubMed

Doss, Mohan

2012-12-01

A recent update on the atomic bomb survivor cancer mortality data has concluded that excess relative risk (ERR) for solid cancers increases linearly with dose and that zero dose is the best estimate for the threshold, apparently validating the present use of the linear no threshold (LNT) model for estimating the cancer risk from low dose radiation. A major flaw in the standard ERR formalism for estimating cancer risk from radiation (and other carcinogens) is that it ignores the potential for a large systematic bias in the measured baseline cancer mortality rate, which can have a major effect on the ERR values. Cancer rates are highly variable from year to year and between adjacent regions and so the likelihood of such a bias is high. Calculations show that a correction for such a bias can lower the ERRs in the atomic bomb survivor data to negative values for intermediate doses. This is consistent with the phenomenon of radiation hormesis, providing a rational explanation for the decreased risk of cancer observed at intermediate doses for which there is no explanation based on the LNT model. The recent atomic bomb survivor data provides additional evidence for radiation hormesis in humans.

Oxytocin regimen for labor augmentation, labor progression, and perinatal outcomes.

PubMed

Zhang, Jun; Branch, D Ware; Ramirez, Mildred M; Laughon, S Katherine; Reddy, Uma; Hoffman, Mathew; Bailit, Jennifer; Kominiarek, Michelle; Chen, Zhen; Hibbard, Judith U

2011-08-01

To examine the effects and safety of high-dose (compared with low-dose) oxytocin regimen for labor augmentation on perinatal outcomes. Data from the Consortium on Safe Labor were used. A total of 15,054 women from six hospitals were eligible for the analysis. Women were grouped based on their oxytocin starting dose and incremental dosing of 1, 2, and 4 milliunits/min. Duration of labor and a number of maternal and neonatal outcomes were compared among these three groups stratified by parity. Multivariable logistic regression and generalized linear mixed model were used to adjust for potential confounders. Oxytocin regimen did not affect the rate of cesarean delivery or other perinatal outcomes. Compared with 1 milliunit/min, the regimens starting with 2 milliunits/min and 4 milliunits/min reduced the duration of first stage by 0.8 hours (95% confidence interval 0.5-1.1) and 1.3 hours (1.0-1.7), respectively, in nulliparous women. No effect was observed on the second stage of labor. Similar patterns were observed in multiparous women. High-dose regimen was associated with a reduced risk of meconium stain, chorioamnionitis, and newborn fever in multiparous women. High-dose oxytocin regimen (starting dose at 4 milliunits/min and increment of 4 millliunits/min) is associated with a shorter duration of first-stage of labor for all parities without increasing the cesarean delivery rate or adversely affecting perinatal outcomes. II.

Automatic optimisation of gamma dose rate sensor networks: The DETECT Optimisation Tool

NASA Astrophysics Data System (ADS)

Helle, K. B.; Müller, T. O.; Astrup, P.; Dyve, J. E.

2014-05-01

Fast delivery of comprehensive information on the radiological situation is essential for decision-making in nuclear emergencies. Most national radiological agencies in Europe employ gamma dose rate sensor networks to monitor radioactive pollution of the atmosphere. Sensor locations were often chosen using regular grids or according to administrative constraints. Nowadays, however, the choice can be based on more realistic risk assessment, as it is possible to simulate potential radioactive plumes. To support sensor planning, we developed the DETECT Optimisation Tool (DOT) within the scope of the EU FP 7 project DETECT. It evaluates the gamma dose rates that a proposed set of sensors might measure in an emergency and uses this information to optimise the sensor locations. The gamma dose rates are taken from a comprehensive library of simulations of atmospheric radioactive plumes from 64 source locations. These simulations cover the whole European Union, so the DOT allows evaluation and optimisation of sensor networks for all EU countries, as well as evaluation of fencing sensors around possible sources. Users can choose from seven cost functions to evaluate the capability of a given monitoring network for early detection of radioactive plumes or for the creation of dose maps. The DOT is implemented as a stand-alone easy-to-use JAVA-based application with a graphical user interface and an R backend. Users can run evaluations and optimisations, and display, store and download the results. The DOT runs on a server and can be accessed via common web browsers; it can also be installed locally.

ELDRS Characterization for a Very High Dose Mission

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

2010-01-01

Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

Single-hit mechanism of tumour cell killing by radiation.

PubMed

Chapman, J D

2003-02-01

To review the relative importance of the single-hit mechanism of radiation killing for tumour response to 1.8-2.0 Gy day(-1) fractions and to low dose-rate brachytherapy. Tumour cell killing by ionizing radiation is well described by the linear-quadratic equation that contains two independent components distinguished by dose kinetics. Analyses of tumour cell survival curves that contain six or more dose points usually provide good estimates of the alpha- and beta-inactivation coefficients. Superior estimates of tumour cell intrinsic radiosensitivity are obtained when synchronized populations are employed. The characteristics of single-hit inactivation of tumour cells are reviewed and compared with the characteristics of beta-inactivation. Potential molecular targets associated with single-hit inactivation are discussed along with strategies for potentiating cell killing by this mechanism. The single-hit mechanism of tumour cell killing shows no dependence on dose-rate and, consequently, no evidence of sublethal damage repair. It is uniquely potentiated by high linear-energy-transfer radiation, exhibits a smaller oxygen enhancement ratio and exhibits a larger indirect effect by hydroxyl radicals than the beta-mechanism. alpha-inactivation coefficients vary slightly throughout interphase but mitotic cells exhibit extremely high alpha-coefficients in the range of those observed for lymphocytes and some repair-deficient cells. Evidence is accumulating to suggest that chromatin in compacted form could be a radiation-hypersensitive target associated with single-hit radiation killing. Analyses of tumour cell survival curves demonstrate that it is the single-hit mechanism (alpha) that determines the majority of cell killing after doses of 2Gy and that this mechanism is highly variable between tumour cell lines. The characteristics of single-hit inactivation are qualitatively and quantitatively distinct from those of beta-inactivation. Compacted chromatin in tumour cells should be further investigated as a radiation-hypersensitive target that could be modulated for therapeutic advantage.

Silexan, an essential oil from flowers of Lavandula angustifolia, is not recognized as benzodiazepine-like in rats trained to discriminate a diazepam cue.

PubMed

Silenieks, Leo B; Koch, Egon; Higgins, Guy A

2013-01-15

Recently, an essential oil of selected quality produced from the flowering tops of Lavandula angustifolia Mill. by steam distillation (Silexan) has been approved in Germany for the treatment of restlessness in case of anxious mood. Based on the observed clinical effects, it has been speculated that lavender oil may exert benzodiazepine-like action including the known dependence and abuse potential of this class of drugs. Although no evidence for such an activity was generated during the long-standing medicinal use of lavender oil, further preclinical investigations were now conducted to evaluate this potential side effect in more detail. Twelve adult, male, Sprague-Dawley rats were trained to discriminate the benzodiazepine drug diazepam (2 mg/kg i.p.) from saline using a two-lever operant procedure. After approximately 40 training sessions the majority of rats learned the discrimination and pre-treatment with ascending doses of diazepam (0.3-2 mg/kg i.p.) produced a dose related generalization to the diazepam cue. In these same animals Silexan was administered to see if animals recognized the drug as "diazepam-like" i.e. generalized to diazepam or "saline-like". Silexan tested at doses 3-30 mg/kg i.p. produced almost exclusively (>90%) saline-like responding. Also there was no effect of Silexan on response rate, i.e. rate of lever pressing, at any dose suggesting that the test article is well tolerated and does not exert a sedating effect. In sum, Silexan has no diazepam-like interoceptive property in adult, male rats. This suggests that Silexan does not share the potential of benzodiazepines to induce the development of tolerance, dependence and addiction. Copyright © 2012 Elsevier GmbH. All rights reserved.

Obstructive urination problems after high-dose-rate brachytherapy boost treatment for prostate cancer are avoidable.

PubMed

Kragelj, Borut

2016-03-01

Aiming at improving treatment individualization in patients with prostate cancer treated with combination of external beam radiotherapy and high-dose-rate brachytherapy to boost the dose to prostate (HDRB-B), the objective was to evaluate factors that have potential impact on obstructive urination problems (OUP) after HDRB-B. In the follow-up study 88 patients consecutively treated with HDRB-B at the Institute of Oncology Ljubljana in the period 2006-2011 were included. The observed outcome was deterioration of OUP (DOUP) during the follow-up period longer than 1 year. Univariate and multivariate relationship analysis between DOUP and potential risk factors (treatment factors, patients' characteristics) was carried out by using binary logistic regression. ROC curve was constructed on predicted values and the area under the curve (AUC) calculated to assess the performance of the multivariate model. Analysis was carried out on 71 patients who completed 3 years of follow-up. DOUP was noted in 13/71 (18.3%) of them. The results of multivariate analysis showed statistically significant relationship between DOUP and anti-coagulation treatment (OR 4.86, 95% C.I. limits: 1.21-19.61, p = 0.026). Also minimal dose received by 90% of the urethra volume was close to statistical significance (OR = 1.23; 95% C.I. limits: 0.98-1.07, p = 0.099). The value of AUC was 0.755. The study emphasized the relationship between DOUP and anticoagulation treatment, and suggested the multivariate model with fair predictive performance. This model potentially enables a reduction of DOUP after HDRB-B. It supports the belief that further research should be focused on urethral sphincter as a critical structure for OUP.

Interstitial rotating shield brachytherapy for prostate cancer.

PubMed

Adams, Quentin E; Xu, Jinghzu; Breitbach, Elizabeth K; Li, Xing; Enger, Shirin A; Rockey, William R; Kim, Yusung; Wu, Xiaodong; Flynn, Ryan T

2014-05-01

To present a novel needle, catheter, and radiation source system for interstitial rotating shield brachytherapy (I-RSBT) of the prostate. I-RSBT is a promising technique for reducing urethra, rectum, and bladder dose relative to conventional interstitial high-dose-rate brachytherapy (HDR-BT). A wire-mounted 62 GBq(153)Gd source is proposed with an encapsulated diameter of 0.59 mm, active diameter of 0.44 mm, and active length of 10 mm. A concept model I-RSBT needle/catheter pair was constructed using concentric 50 and 75 μm thick nickel-titanium alloy (nitinol) tubes. The needle is 16-gauge (1.651 mm) in outer diameter and the catheter contains a 535 μm thick platinum shield. I-RSBT and conventional HDR-BT treatment plans for a prostate cancer patient were generated based on Monte Carlo dose calculations. In order to minimize urethral dose, urethral dose gradient volumes within 0-5 mm of the urethra surface were allowed to receive doses less than the prescribed dose of 100%. The platinum shield reduced the dose rate on the shielded side of the source at 1 cm off-axis to 6.4% of the dose rate on the unshielded side. For the case considered, for the same minimum dose to the hottest 98% of the clinical target volume (D(98%)), I-RSBT reduced urethral D(0.1cc) below that of conventional HDR-BT by 29%, 33%, 38%, and 44% for urethral dose gradient volumes within 0, 1, 3, and 5 mm of the urethra surface, respectively. Percentages are expressed relative to the prescription dose of 100%. For the case considered, for the same urethral dose gradient volumes, rectum D(1cc) was reduced by 7%, 6%, 6%, and 6%, respectively, and bladder D(1cc) was reduced by 4%, 5%, 5%, and 6%, respectively. Treatment time to deliver 20 Gy with I-RSBT was 154 min with ten 62 GBq (153)Gd sources. For the case considered, the proposed(153)Gd-based I-RSBT system has the potential to lower the urethral dose relative to HDR-BT by 29%-44% if the clinician allows a urethral dose gradient volume of 0-5 mm around the urethra to receive a dose below the prescription. A multisource approach is necessary in order to deliver the proposed (153)Gd-based I-RSBT technique in reasonable treatment times.

Dose rate effects in the radiation damage of the plastic scintillators of the CMS hadron endcap calorimeter

DOE PAGES

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; ...

2016-10-07

We present measurements of the reduction of light output by plastic scintillators irradiated in the CMS detector during the 8 TeV run of the Large Hadron Collider and show that they indicate a strong dose rate effect. The damage for a given dose is larger for lower dose rate exposures. The results agree with previous measurements of dose rate effects, but are stronger due to the very low dose rates probed. Here, we show that the scaling with dose rate is consistent with that expected from diffusion effects.

Radiological survey of the covered and uncovered drilling mud depository.

PubMed

Jónás, Jácint; Somlai, János; Csordás, Anita; Tóth-Bodrogi, Edit; Kovács, Tibor

2018-08-01

In petroleum engineering, the produced drilling mud sometimes contains elevated amounts of natural radioactivity. In this study, a remediated Hungarian drilling mud depository was investigated from a radiological perspective. The depository was monitored before and after a clay layer was applied as covering. In this study, the ambient dose equivalent rate H*(10) of the depository has been measured by a Scintillator Probe (6150AD-b Dose Rate Meter). Outdoor radon concentration, radon concentration in soil gas, and in situ field radon exhalation measurements were carried out using a pulse-type ionization chamber (AlphaGUARD radon monitor). Soil gas permeability (k) measurements were carried out using the permeameter (RADON-JOK) in situ device. Geogenic radon potentials were calculated. The radionuclide content of the drilling mud and cover layer sample has been determined with an HPGe gamma-spectrometer. The gamma dose rate was estimated from the measured radionuclide concentrations and the results were compared with the measured ambient dose equivalent rate. Based on the measured results before and after covering, the ambient dose equivalent rates were 76 (67-85) nSv/h before and 86 (83-89) nSv/h after covering, radon exhalation was 9 (6-12) mBq/m 2 s before and 14 (5-28) mBq/m 2 s after covering, the outdoor radon concentrations were 11 (9-16) before and 13 (10-22) Bq/m 3 after covering and the soil gas radon concentrations were 6 (3-8) before and 24 (14-40) kBq/m 3 after covering. Soil gas permeability measurements were 1E-11 (7E-12-1E-11) and 1E-12 (5E-13-1E-12) m 2 and the calculated geogenic radon potential values were 6 (3-8) and 12 (6-21) before and after the covering. The main radionuclide concentrations of the drilling mud were C U-238 12 (10-15) Bq/kg, C Ra-226 31 (18-40) Bq/kg, C Th-232 35 (33-39) Bq/kg and C K-40 502 (356-673) Bq/kg. The same radionuclide concentrations in the clay were C U-238 31 (29-34) Bq/kg, C Ra-226 45 (40-51) Bq/kg, C Th-232 58 (55-60) Bq/kg and C K-40 651 (620-671) Bq/kg. According to our results, the drilling mud depository exhibits no radiological risk from any radiological aspects (radon, radon exhalation, gamma dose, etc.); therefore, long term monitoring activity is not necessary from the radiological point of view. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity

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

Li, Jun; Sun, Kang; Ni, Lijuan

Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodiummore » selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p < 0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity. -- Highlights: ►Cisplatin resulted in diarrhea in mice by 88%. ►i.p. selenosulfate at 9.5 μmol/kg daily for 11 days reduced diarrhea to 6%. ►i.p. selenosulfate at 19 μmol/kg daily for 55 days was not toxic. ►i.p. selenite at 19 μmol/kg daily for 55 days was lethal. ►Innocuous dose of selenosulfate greatly prevents cisplatin-induced diarrhea.« less

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

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

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

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

Linear response theory for annealing of radiation damage in semiconductor devices

NASA Technical Reports Server (NTRS)

Litovchenko, Vitaly

1988-01-01

A theoretical study of the radiation/annealing response of MOS ICs is described. Although many experiments have been performed in this field, no comprehensive theory dealing with radiation/annealing response has been proposed. Many attempts have been made to apply linear response theory, but no theoretical foundation has been presented. The linear response theory outlined here is capable of describing a broad area of radiation/annealing response phenomena in MOS ICs, in particular, both simultaneous irradiation and annealing, as well as short- and long-term annealing, including the case when annealing is nearing completion. For the first time, a simple procedure is devised to determine the response function from experimental radiation/annealing data. In addition, this procedure enables us to study the effect of variable temperature and dose rate, effects which are of interest in spaceflight. In the past, the shift in threshold potential due to radiation/annealing has usually been assumed to depend on one variable: the time lapse between an impulse dose and the time of observation. While such a suggestion of uniformity in time is certainly true for a broad range of radiation annealing phenomena, it may not hold for some ranges of the variables of interest (temperature, dose rate, etc.). A response function is projected which is dependent on two variables: the time of observation and the time of the impulse dose. This dependence on two variables allows us to extend the theory to the treatment of a variable dose rate. Finally, the linear theory is generalized to the case in which the response is nonlinear with impulse dose, but is proportional to some impulse function of dose. A method to determine both the impulse and response functions is presented.

Pharmacokinetic Correlates of the Effects of a Heroin Vaccine on Heroin Self-Administration in Rats

PubMed Central

Raleigh, Michael D.; Pentel, Paul R.; LeSage, Mark G.

2014-01-01

The purpose of this study was to evaluate the effects of a morphine-conjugate vaccine (M-KLH) on the acquisition, maintenance, and reinstatement of heroin self-administration (HSA) in rats, and on heroin and metabolite distribution during heroin administration that approximated the self-administered dosing rate. Vaccination with M-KLH blocked heroin-primed reinstatement of heroin responding. Vaccination also decreased HSA at low heroin unit doses but produced a compensatory increase in heroin self-administration at high unit doses. Vaccination shifted the heroin dose-response curve to the right, indicating reduced heroin potency, and behavioral economic demand curve analysis further confirmed this effect. In a separate experiment heroin was administered at rates simulating heroin exposure during HSA. Heroin and its active metabolites, 6-acetylmorphine (6-AM) and morphine, were retained in plasma and metabolite concentrations were reduced in brain in vaccinated rats compared to controls. Reductions in 6-AM concentrations in brain after vaccination were consistent with the changes in HSA rates accompanying vaccination. These data provide evidence that 6-AM is the principal mediator of heroin reinforcement, and the principal target of the M-KLH vaccine, in this model. While heroin vaccines may have potential as therapies for heroin addiction, high antibody to drug ratios appear to be important for obtaining maximal efficacy. PMID:25536404

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

PubMed

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

2017-06-01

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

Can a Compact Pre-Filled Auto-Disable Injection System (cPAD) Save Costs for DTP-HepB-Hib Vaccine as Compared with Single-Dose (SDV) and Multi-Dose Vials (MDV)? Evidence from Cambodia, Ghana, and Peru.

PubMed

Nogier, Cyril; Hanlon, Patrick; Wiedenmayer, Karin; Maire, Nicolas

2015-03-01

A compact pre-filled auto-disable injection (cPAD) presentation is being developed for the fully liquid pentavalent DTP-HepB-Hib vaccine. A cost analysis (CA) to compare this presentation with the presently used single-dose vial (SDV) and multi-dose vial (MDV) was conducted in Cambodia, Ghana, and Peru. The CA included the development of an excel-based costing model and considered the costs of vaccine, safe injection equipment, procurement, storage, transport and distribution, vaccine administration by health staff, medical waste management, start-up activities, as well as coverage, birth cohort, vaccine, and safe injection equipment wastage rates. The outcome was the change in cost per pentavalent fully immunized child (PFIC) for a switch to cPAD. Field visits to health facilities, and interviews with key informants from immunization services and regulatory authorities, were conducted to collect data and to test the costing model in country context. Cost data were also obtained from manufacturers, published price lists, and author estimates. A sensitivity analysis (SA) was conducted to explore possible variations in values of data collected. Based on vaccine price trends estimated for 2016, cPAD is less costly in Ghana [incremental cost per PFIC: $US-0.59 (-6.46 %)] than the current presentation (ten-dose MDV) and in Peru (SDV): $US-0.89 (-7.14 %). In Cambodia, cPAD is more costly than SDV: $US+0.33 (+3.90 %). The most significant cost item per PFIC is the vaccine (reflecting wastage rates) in all presentations. The dominance of the vaccine price per dose and, to a lesser extent, the wastage rates in the incremental cost per PFIC show potential to simplify future analyses. Other relevant considerations at country level for a change of presentation include the potential for improved safety with cPAD, planned introduction of other vaccines, environmental and safety issues, and financial sustainability.

Novel high dose rate lip brachytherapy technique to improve dose homogeneity and reduce toxicity by customized mold.

PubMed

Feldman, Jon; Appelbaum, Limor; Sela, Mordechay; Voskoboinik, Ninel; Kadouri, Sarit; Weinberger, Jeffrey; Orion, Itzhak; Meirovitz, Amichay

2014-12-23

The purpose of this study is to describe a novel brachytherapy technique for lip Squamous Cell Carcinoma, utilizing a customized mold with embedded brachytherapy sleeves, which separates the lip from the mandible, and improves dose homogeneity. Seven patients with T2 lip cancer treated with a "sandwich" technique of High Dose Rate (HDR) brachytherapy to the lip, consisting of interstitial catheters and a customized mold with embedded catheters, were reviewed for dosimetry and outcome using 3D planning. Dosimetric comparison was made between the "sandwich" technique to "classic" - interstitial catheters only plan. We compared dose volume histograms for Clinical Tumor Volume (CTV), normal tissue "hot spots" and mandible dose. We are reporting according to the ICRU 58 and calculated the Conformal Index (COIN) to show the advantage of our technique. The seven patients (ages 36-81 years, male) had median follow-up of 47 months. Four patients received Brachytherapy and External Beam Radiation Therapy, 3 patients received brachytherapy alone. All achieved local control, with excellent esthetic and functional results. All patients are disease free. The Customized Mold Sandwich technique (CMS) reduced the high dose region receiving 150% (V150) by an average of 20% (range 1-47%), The low dose region (les then 90% of the prescribed dose) improved by 73% in average by using the CMS technique. The COIN value for the CMS was in average 0.92 as opposed to 0.88 for the interstitial catheter only. All differences (excluding the low dose region) were statistically significant. The CMS technique significantly reduces the high dose volume and increases treatment homogeneity. This may reduce the potential toxicity to the lip and adjacent mandible, and results in excellent tumor control, cosmetic and functionality.

The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation

PubMed Central

Brooks, Antone L.; Hoel, David G.; Preston, R. Julian

2016-01-01

Abstract Purpose: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Conclusions: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2–30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP (2007) and BEIR VII (NRC/NAS 2006). PMID:27266588

Fractal kinetics of radiation-induced point-defect formation and decay in amorphous insulators: Application to color centers in silica-based optical fibers

NASA Astrophysics Data System (ADS)

Griscom, David L.

2001-11-01

Formalisms have been developed to express the time evolution of bimolecular processes taking place in fractal spaces. These ``stretched-second-order'' solutions are specifically applicable to radiation-induced electron-hole pairs and/or vacancy-interstitial pairs in insulating glasses. Like the analogous Kohlrausch-type (stretched-first-order) expressions, the present solutions are functions of (kt)β, where 0<β<1, k is an effective rate coefficient, and t is time. Both the new second-order formalism and the familiar Kohlrausch approach have been used to fit experimental data (induced optical absorptions in silica-based glasses monitored at selected wavelengths) that serve as proxies for the numbers of color centers created by γ irradiation and/or destroyed by processes involving thermal, optical, or γ-ray activation. Two material systems were investigated: (1) optical fibers with Ge-doped-silica cores and (2) fibers with low-OH/low-chloride pure-silica cores. Successful fits of the growth curves for the Ge-doped-silica-core fibers at four widely separated dose rates were accomplished using solutions for color-center concentrations, N[(kt)β], which approach steady-state values, Nsat, as t-->∞. The parametrization of these fits reveals some unexpected, and potentially useful, empirical rules regarding the dose-rate dependences of β, k, and Nsat in the fractal regime (0<β<1). Similar, though possibly not identical, rules evidently apply to color centers in the pure-silica-core fibers as well. In both material systems, there appear to be fractal<==> classical phase transitions at certain threshold values of dose rate, below which the dose-rate dependencies of k and Nsat revert to those specified by classical (β=1) first- or second-order kinetics. For kt<<1, both the first- and second-order fractal kinetic growth curves become identical, i.e., N((kt)β)~Atβ, where the coefficient A depends on dose rate but not kinetic order. It is found empirically that A depends on the 3β/2 power of dose rate in both first- and second-order kinetics, thus ``accidentally'' becoming linearly proportional to dose rate in cases where β~2/3 (characteristic of random fractals and many disordered materials). If interfering dose-rate-independent components are absent, it is possible to distinguish the order of the kinetics from the shapes of the growth and decay curves in both fractal and classical regimes. However, for reasons that are discussed, the parameters that successfully fit the experimental growth curves could not be used as bases for closed-form predictions of the shapes of the decay curves recorded when the irradiation is interrupted.

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

Marsh, I; Otto, M; Weichert, J

Purpose: The focus of this work is to perform Monte Carlo-based dosimetry for several pediatric cancer xenografts in mice treated with a novel radiopharmaceutical {sup 131}I-CLR1404. Methods: Four mice for each tumor cell line were injected with 8–13 µCi/g of the {sup 124}124I-CLR1404. PET/CT images of each individual mouse were acquired at 5–6 time points over the span of 96–170 hours post-injection. Following acquisition, the images were co-registered, resampled, rescaled, corrected for partial volume effects (PVE), and masked. For this work the pre-treatment PET images of {sup 124}I-CLR1404 were used to predict therapeutic doses from {sup 131}I-CLR1404 at each timemore » point by assuming the same injection activity and accounting for the difference in physical decay rates. Tumors and normal tissues were manually contoured using anatomical and functional images. The CT and the PET images were used in the Geant4 (v9.6) Monte Carlo simulation to define the geometry and source distribution, respectively. The total cumulated absorbed dose was calculated by numerically integrating the dose-rate at each time point over all time on a voxel-by-voxel basis. Results: Spatial distributions of the absorbed dose rates and dose volume histograms as well as mean, minimum, maximum, and total dose values for each ROI were generated for each time point. Conclusion: This work demonstrates how mouse-specific MC-based dosimetry could potentially provide more accurate characterization of efficacy of novel radiopharmaceuticals in radionuclide therapy. This work is partially funded by NIH grant CA198392.« less

Radiation dose-rate meter using an energy-sensitive counter

DOEpatents

Kopp, Manfred K.

1988-01-01

A radiation dose-rate meter is provided which uses an energy-sensitive detector and combines charge quantization and pulse-rate measurement to monitor radiation dose rates. The charge from each detected photon is quantized by level-sensitive comparators so that the resulting total output pulse rate is proportional to the dose-rate.

Medication dosing errors and associated factors in hospitalized pediatric patients from the South Area of the West Bank - Palestine.

PubMed

Al-Ramahi, Rowa'; Hmedat, Bayan; Alnjajrah, Eman; Manasrah, Israa; Radwan, Iqbal; Alkhatib, Maram

2017-09-01

Medication dosing errors are a significant global concern and can cause serious medical consequences for patients. Pediatric patients are at increased risk of dosing errors due to differences in medication pharmacodynamics and pharmacokinetics. The aims of this study were to find the rate of medication dosing errors in hospitalized pediatric patients and possible associated factors. The study was an observational cohort study including pediatric inpatients less than 16 years from three governmental hospitals from the West Bank/Palestine during one month in 2014, and sample size was 400 pediatric inpatients from these three hospitals. Pediatric patients' medical records were reviewed. Patients' weight, age, medical conditions, all prescribed medications, their doses and frequency were documented. Then the doses of medications were evaluated. Among 400 patients, the medications prescribed were 949 medications, 213 of them (22.4%) were out of the recommended range, and 160 patients (40.0%) were prescribed one or more potentially inappropriate doses. The most common cause of hospital admission was sepsis which presented 14.3% of cases, followed by fever (13.5%) and meningitis (10.0%). The most commonly used medications were ampicillin in 194 cases (20.4%), ceftriaxone in 182 cases (19.2%), and cefotaxime in 144 cases (12.0%). No significant association was found between potentially inappropriate doses and gender or hospital (chi-square test p -value > 0.05).The results showed that patients with lower body weight, who had a higher number of medications and stayed in hospital for a longer time, were more likely to have inappropriate doses. Potential medication dosing errors were high among pediatric hospitalized patients in Palestine. Younger patients, patients with lower body weight, who were prescribed higher number of medications and stayed in hospital for a longer time were more likely to have inappropriate doses, so these populations require special care. Many children were hospitalized for infectious causes and antibiotics were widely used. Strategies to reduce pediatric medication dosing errors are recommended.

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

[Brachytherapy for head and neck cancers].

PubMed

Peiffert, D; Coche-Dequéant, B; Lapeyre, M; Renard, S

2018-05-29

The main indications of the brachytherapy of head and neck cancers are the limited tumours of the lip, the nose, the oral cavity and the oropharynx. Nasopharynx tumours are nowadays treated by intensity-modulated radiotherapy. This technique can be exclusive, associated with external radiotherapy or postoperative. It can also be a salvage treatment for the second primaries in previously irradiated areas. If the low dose rate brachytherapy rules remain the reference, the pulse dose rate technique allows the prescription of the dose rate and the optimisation of the dose distribution. Results of high dose rate brachytherapy are now published. This paper reports the recommendations of the Gec-ESTRO, published in 2017, and takes into account the data of the historical low dose rate series, and is upgraded with the pulsed-dose rate and high dose rate series. Copyright © 2018. Published by Elsevier SAS.

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

PubMed

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

1999-10-01

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

Dose/Exposure‐Response Modeling to Support Dosing Recommendation for Phase III Development of Baricitinib in Patients with Rheumatoid Arthritis

PubMed Central

Chua, Laiyi; Ernest, Charles; Macias, William; Rooney, Terence; Tham, Lai San

2017-01-01

Baricitinib is an oral inhibitor of Janus kinases (JAKs), selective for JAK1 and 2. It demonstrated dose‐dependent efficacy in patients with moderate‐to‐severe rheumatoid arthritis (RA) in a phase IIb study up to 24 weeks. Population pharmacokinetic/pharmacodynamic (PopPK/PD) models were developed to characterize concentration‐time profiles and dose/exposure‐response (D/E‐R) relationships for the key efficacy (proportion of patients achieving American College of Rheumatology 20%, 50%, or 70% response rate) and safety endpoints (incidence of anemia) for the phase IIb study. The modeling suggested that 4 mg q.d. was likely to offer the optimum risk/benefit balance, whereas 2 mg q.d. had the potential for adequate efficacy. In addition, at the same total daily dose, a twice‐daily regimen is not expected to provide an advantage over q.d. dosing for the efficacy or safety endpoints. The model‐based simulations formed the rationale for key aspects of dosing, such as dose levels and dosing frequency for phase III development. PMID:28891251

Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization

NASA Astrophysics Data System (ADS)

Gay, H. A.; Allison, R. R.; Downie, G. H.; Mota, H. C.; Austerlitz, C.; Jenkins, T.; Sibata, C. H.

2007-06-01

A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed.

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.

Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes.

PubMed

Mergenthal, Michelle C; Senapati, Suneeta; Zee, Jarcy; Allen-Taylor, Lynne; Whittaker, Paul G; Takacs, Peter; Sammel, Mary D; Barnhart, Kurt T

2016-11-01

Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P < .001, P = .011, P < .001, and P = .035, respectively). Women had similar initial human chorionic gonadotropin levels in either protocol but the mean rate of decline of human chorionic gonadotropin from day 0 (day of administration of first dose of methotrexate) to day 7 was significantly more rapid in women who received the single-dose protocol compared to those treated with the 2-dose protocol (mean change -31.3% vs -10.4%, P = .037, adjusted for propensity score and site). The 2 protocols had no significant differences in success rate or time to resolution. In a racially and geographically diverse group of women, the single- and double-dose methotrexate protocols had comparable outcomes. The more rapid human chorionic gonadotropin initial decline in the single-dose group suggested these patients were probably at lower risk for ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication. Copyright © 2016 Elsevier Inc. All rights reserved.

Leuco-crystal-violet micelle gel dosimeters: Component effects on dose-rate dependence

NASA Astrophysics Data System (ADS)

Xie, J. C.; Katz, E. A. B.; Alexander, K. M.; Schreiner, L. J.; McAuley, K. B.

2017-05-01

Designed experiments were performed to produce empirical models for the dose sensitivity, initial absorbance, and dose-rate dependence respectively for leucocrystal violet (LCV) micelle gel dosimeters containing cetyltrimethylammonium bromide (CTAB) and 2,2,2-trichloroethanol (TCE). Previous gels of this type showed dose-rate dependent behaviour, producing an ˜18% increase in dose sensitivity between dose rates of 100 and 600 cGy min-1. Our models predict that the dose rate dependence can be reduced by increasing the concentration of TCE, CTAB and LCV. Increasing concentrations of LCV and CTAB produces a significant increase in dose sensitivity with a corresponding increase in initial absorbance. An optimization procedure was used to determine a nearly dose-rate independent gel which maintained high sensitivity and low initial absorbance. This gel which contains 33 mM CTAB, 1.25 mM LCV, and 96 mM TCE in 25 mM trichloroacetic acid and 4 wt% gelatin showed an increase in dose sensitivity of only 4% between dose rates of 100 and 600 cGy min-1, and provides an 80% greater dose sensitivity compared to Jordan’s standard gels with similar initial absorbance.

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

NASA Technical Reports Server (NTRS)

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

2001-01-01

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

Estimation of the Dose and Dose Rate Effectiveness Factor

NASA Technical Reports Server (NTRS)

Chappell, L.; Cucinotta, F. A.

2013-01-01

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

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

Dose Rate Effects in Linear Bipolar Transistors

NASA Technical Reports Server (NTRS)

Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis

2011-01-01

Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

Subjective, cognitive, and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers

PubMed Central

Bedi, Gillinder; Cooper, Ziva D.; Haney, Margaret

2011-01-01

Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 (CB1) agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal, but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers, and compare these with dronabinol's effects. Participants (4F; 10M) smoking marijuana 6.6 (SD = 0.7) days/week completed this outpatient, within-subjects, double-blind, randomized protocol. Over 7 sessions, the time-dependent subjective, cognitive, and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect, and/or `high' relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose-dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose-related increases in positive mood, few cognitive decrements, and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol and effects were more dose-related, suggesting improved bioavailability. Nabilone was well-tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence. PMID:22260337

Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers.

PubMed

Bedi, Gillinder; Cooper, Ziva D; Haney, Margaret

2013-09-01

Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol's effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within-subjects, double-blind, randomized protocol. Over seven sessions, the time-dependent subjective, cognitive and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect and/or 'high' relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose-dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose-related increases in positive mood, few cognitive decrements and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol, and effects were more dose-related, suggesting improved bioavailability. Nabilone was well tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

[Allergology and clinical immunology].

PubMed

Coattrenec, Yann; Harr, Thomas; Chizzolini, Carlo; Jandus, Peter

2018-01-10

Hereditary angioedema (HA) is a disabling and potentially fatal condition. The management of HA includes treatment of acute attacks, short-term prophylaxis to prevent an attack, and long-term prophylaxis to minimize the frequency and severity of recurrent attacks. In this article, we will present new therapeutic alternatives for long term prophylaxis. Glucocorticoids (GC) usage leads to a number of severe side-effects. In giant cell arteritis, the use of tocilizumab in conjunction with low doses of GC reduces the number of relapses. In ANCA-associated vasculitis the use of an anti-C5R (avacopan) alone or in conjunction with low doses of GC results in similar remission rates to those induced by high dose GC.

LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

PubMed

Leonard, B E; Lucas, A C

2009-02-01

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to <10 cGy h(-1) and involve multiple patients to detect patient variability. Results may suggest a preference for high dose rate brachytherapy or LDR brachytherapy without permanent retention of the implant seeds (hence the dose rates in peripheral tissues and organs remain above IDRE thresholds).

TU-H-BRC-06: Temperature Simulation of Tungsten and W25Re Targets to Deliver High Dose Rate 10 MV Photons

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

Wang, J; Trovati, S; Loo, B

Purpose: To study the impact of electron beam size, target thickness, and target temperature on the ability of the flattening filter-free mode (FFF) treatment head to deliver high-dose-rate irradiations. Methods: The dose distribution and transient temperature of the X-ray target under 10 MeV electron beam with pulse length of 5 microseconds, and repetition rate of 1000 Hz was studied. A MCNP model was built to calculate the percentage depth dose (PPD) distribution in a water phantom at a distance of 100 cm. ANSYS software was used to run heat transfer simulations. The PPD and temperature for both tungsten and W25Remore » targets for different electron beam sizes (FHWM 0.2, 0.5, 1 and 2 mm) and target thickness (0.2 to 2 mm) were studied. Results: Decreasing the target thickness from 1 mm to 0.5 mm, caused a surface dose increase about 10 percent. For both target materials, the peak temperature was about 1.6 times higher for 0.5 mm electron beam compared to the 1 mm beam after reaching their equilibrium. For increasing target thicknesses, the temperature rise caused by the first pulse is similar for all thicknesses, however the temperature difference for subsequent pulses becomes larger until a constant ratio is reached. The target peak temperature after reaching equilibrium can be calculated by adding the steady state temperature and the amplitude of the temperature oscillation. Conclusion: This work indicates the potential to obtain high dose rate irradiation by selecting target material, geometry and electron beam parameters. W25Re may not outperformed tungsten when the target is thick due to its relatively low thermal conductivity. The electron beam size only affects the target temperature but not the PPD. Thin target is preferred to obtain high dose rate and low target temperature, however, the resulting high surface dose is a major concern. NIH funding:R21 EB015957-01; DOD funding:W81XWH-13-1-0165 BL, PM, PB, and RF are founders of TibaRay, Inc. BL is also a borad member. BL and PM have received research grants from Varian Medical System, Inc. and RaySearch Laboratory. RF is an employee of Siemens Healthcare GmbH.« less

Effect of Bar-code Technology on the Incidence of Medication Dispensing Errors and Potential Adverse Drug Events in a Hospital Pharmacy

PubMed Central

Poon, Eric G; Cina, Jennifer L; Churchill, William W; Mitton, Patricia; McCrea, Michelle L; Featherstone, Erica; Keohane, Carol A; Rothschild, Jeffrey M; Bates, David W; Gandhi, Tejal K

2005-01-01

We performed a direct observation pre-post study to evaluate the impact of barcode technology on medication dispensing errors and potential adverse drug events in the pharmacy of a tertiary-academic medical center. We found that barcode technology significantly reduced the rate of target dispensing errors leaving the pharmacy by 85%, from 0.37% to 0.06%. The rate of potential adverse drug events (ADEs) due to dispensing errors was also significantly reduced by 63%, from 0.19% to 0.069%. In a 735-bed hospital where 6 million doses of medications are dispensed per year, this technology is expected to prevent about 13,000 dispensing errors and 6,000 potential ADEs per year. PMID:16779372

Potential third-party radiation exposure from outpatients treated with {sup 131}I for hyperthyroidism

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

Matheoud, Roberta; Reschini, Eugenio; Canzi, Cristina

2004-12-01

Thirty-three hyperthyroid patients treated with radioiodine (mean administered activity 414 MBq, range 163-555) were studied to determine if pretreatment dosimetry could be used to give radiation protection advice that could assure compliance with the effective dose constraints suggested by the European Commission. Effective doses to travelers, co-workers, and sleeping partners were estimated by integrating the effective dose rate-versus-time curve obtained by fitting the dose rates measured several times after radioiodine administration to a biexponential function. The mean estimated effective doses to travelers, co-workers, and sleeping partners were 0.11 mSv (0.05-0.24), 0.24 mSv (0.07-0.52), and 1.8 mSv (0.6-4.1), respectively. The bestmore » correlation was found between effective dose (D) in mSv and maximum activity (AU{sub max}) in MBq taken up in the thyroid: D{sub traveler}=0.0005*(AU{sub max})+0.04 (r=0.88,p<0.01); D{sub co-worker}=0.0013*(AU{sub max})+0.03(r=0.89,p<0.01); D{sub sleepingpartners}=0.0105*(AU{sub max})+0.16 (r=0.93,p<0.01). Private/public transports are always allowed. For the co-workers the effective dose constraint of 0.3 mSv is met without restrictions and with 3 days off work if AU{sub max} is lower or higher than 185 MBq, respectively. For the sleeping partners the effective dose constraint of 3 mSv is met without restriction and with 4 nights separate sleeping arrangements if AU{sub max} is lower or higher than 185 MBq, respectively. The potential for contamination by the patients was determined from perspiration samples taken from the patient's hands, forehead, and neck and in saliva at 4, 24, and 48 h after radioiodine treatment. The mean highest {sup 131}I activity levels for hands, forehead, neck, and saliva were 4.1 Bq/cm{sup 2}, 1.9 Bq/cm{sup 2}, 0.9 Bq/cm{sup 2}, and 796 kBq/g, respectively. The results indicate that there is minimal risk of contamination from these patients.« less

AREA RADIATION MONITOR

DOEpatents

Manning, F.W.; Groothuis, S.E.; Lykins, J.H.; Papke, D.M.

1962-06-12

S>An improved area radiation dose monitor is designed which is adapted to compensate continuously for background radiation below a threshold dose rate and to give warning when the dose integral of the dose rate of an above-threshold radiation excursion exceeds a selected value. This is accomplished by providing means for continuously charging an ionization chamber. The chamber provides a first current proportional to the incident radiation dose rate. Means are provided for generating a second current including means for nulling out the first current with the second current at all values of the first current corresponding to dose rates below a selected threshold dose rate value. The second current has a maximum value corresponding to that of the first current at the threshold dose rate. The excess of the first current over the second current, which occurs above the threshold, is integrated and an alarm is given at a selected integrated value of the excess corresponding to a selected radiation dose. (AEC)

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.

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

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

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

2011-02-15

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

Long-term bradycardia caused by atrioventricular block can remodel the canine heart to detect the histamine H1 blocker terfenadine-induced torsades de pointes arrhythmias.

PubMed

Takahara, Akira; Sugiyama, Atsushi; Ishida, Yuko; Satoh, Yoshioki; Wang, Kai; Nakamura, Yuji; Hashimoto, Keitaro

2006-03-01

Although a second-generation histamine H(1) blocker terfenadine induced torsades de pointes (TdP) arrhythmias in patients via the blockade of a rapid component of delayed rectifier K(+) current (I(Kr)), such action of terfenadine has not been detected in previous animal models. We analysed the potential of the canine persistent atrioventricular block heart, a new in vivo proarrhythmia model, to detect a torsadogenic effect of terfenadine of an oral dose of 3 or 30 mg kg(-1). The doses can provide therapeutic to supra-therapeutic plasma concentrations as an anti-histamine. In 2 weeks of bradycardiac heart model, there were no significant changes in any of the electrocardiogram parameters after the administration of both doses of terfenadine. In 4-6 weeks of bradycardiac heart model, the low dose of terfenadine hardly affected any of the electrocardiogram parameters except that it induced TdP in one out of six animals. The high dose significantly decreased the atrial rate and ventricular rate, prolonged the QT interval, and induced TdP in five out of six animals. Moreover, temporal variability of repolarization increased after the high-dose administration. These results suggest that long-term bradycardia caused by atrioventricular block can remodel the canine heart to detect terfenadine-induced TdP.

Small-Field Measurements of 3D Polymer Gel Dosimeters through Optical Computed Tomography.

PubMed

Shih, Tian-Yu; Wu, Jay; Shih, Cheng-Ting; Lee, Yao-Ting; Wu, Shin-Hua; Yao, Chun-Hsu; Hsieh, Bor-Tsung

2016-01-01

With advances in therapeutic instruments and techniques, three-dimensional dose delivery has been widely used in radiotherapy. The verification of dose distribution in a small field becomes critical because of the obvious dose gradient within the field. The study investigates the dose distributions of various field sizes by using NIPAM polymer gel dosimeter. The dosimeter consists of 5% gelatin, 5% monomers, 3% cross linkers, and 5 mM THPC. After irradiation, a 24 to 96 hour delay was applied, and the gel dosimeters were read by a cone beam optical computed tomography (optical CT) scanner. The dose distributions measured by the NIPAM gel dosimeter were compared to the outputs of the treatment planning system using gamma evaluation. For the criteria of 3%/3 mm, the pass rates for 5 × 5, 3 × 3, 2 × 2, 1 × 1, and 0.5 × 0.5 cm2 were as high as 91.7%, 90.7%, 88.2%, 74.8%, and 37.3%, respectively. For the criteria of 5%/5 mm, the gamma pass rates of the 5 × 5, 3 × 3, and 2 × 2 cm2 fields were over 99%. The NIPAM gel dosimeter provides high chemical stability. With cone-beam optical CT readouts, the NIPAM polymer gel dosimeter has potential for clinical dose verification of small-field irradiation.

The potential radiological impact from a Brazilian phosphate facility.

PubMed

Glória dos Reis, Rócio; da Costa Lauria, Dejanira

2014-10-01

In the semiarid region of Brazil, a facility for the production of phosphoric acid for fertilizer is in the last stages of the planning phase. The raw feedstock of Santa Quiteria has a very high level of uranium associated with the phosphate in form of apatite. The reaction by which phosphoric acid is produced generates phosphogypsum (PG) as a by-product. The ratio of phosphogypsum to phosphoric acid is approximately 5 to 1. After all of the phosphate has been extracted and processed, it is expected that some 37 million tons of phosphogypsum will be produced, containing 13 Bq/g of (226)Ra and 11 Bq/g of (210)Pb. To assess the potential impact of this PG stack on the surrounding inhabitants, a generic impact assessment was performed using a modeling approach. We estimated the amount and shape of the residue stack and used computational codes for assessing the radiological impact in a prospective risk assessment. A hypothetical farmer scenario was used to calculate two potential doses, one near the site boundary and another directly over the stack piles after the project is shut down. Using a conservative approach, the potential public dose was estimated to be 2.8 mSv/y. This study identified the rainfall erosion index, dissolution rate of PG, radionuclide distribution coefficients and fish consumption rate as parameters where improved information could enhance the quality of the dose assessment. The disposal and shape of the stack is of major concern, since the PG erosion might be the main pathway for the environmental contamination; therefore, studies should be carried out to determine a suitable shape and disposal of the stack. Furthermore, containment barriers should be evaluated for their potential to reduce or avoid environmental contamination by runoff. In addition, the onsite public dose underscores the importance of a planning for remediation of the area after the plant is shut down to assure that neither the public nor the environmental health will be affected by the presence of the PG stack. Copyright © 2014 Elsevier Ltd. All rights reserved.

An in-beam PET system for monitoring ion-beam therapy: test on phantoms using clinical 62 MeV protons

NASA Astrophysics Data System (ADS)

Camarlinghi, N.; Sportelli, G.; Battistoni, G.; Belcari, N.; Cecchetti, M.; Cirrone, G. A. P.; Cuttone, G.; Ferretti, S.; Kraan, A.; Retico, A.; Romano, F.; Sala, P.; Straub, K.; Tramontana, A.; Del Guerra, A.; Rosso, V.

2014-04-01

Ion therapy allows the delivery of highly conformal dose taking advantage of the sharp depth-dose distribution at the Bragg-peak. However, patient positioning errors and anatomical uncertainties can cause dose distortions. To exploit the full potential of ion therapy, an accurate monitoring system of the ion range is needed. Among the proposed methods to monitor the ion range, Positron Emission Tomography (PET) has proven to be the most mature technique, allowing to reconstruct the β+ activity generated in the patient by the nuclear interaction of the ions, that can be acquired during or after the treatment. Taking advantages of the spatial correlation between positron emitters created along the ions path and the dose distribution, it is possible to reconstruct the ion range. Due to the high single rates generated during the beam extraction, the acquisition of the β+ activity is typically performed after the irradiation (cyclotron) or in between the synchrotron spills. Indeed the single photon rate can be one or more orders of magnitude higher than normal for cyclotron. Therefore, acquiring the activity during the beam irradiation requires a detector with a very short dead time. In this work, the DoPET detector, capable of sustaining the high event rate generated during the cyclotron irradiation, is presented. The capability of the system to acquire data during and after the irradiation will be demonstrated by showing the reconstructed activity for different PMMA irradiations performed using clinical dose rates and the 62 MeV proton beam at the CATANA-LNS-INFN. The reconstructed activity widths will be compared with the results obtained by simulating the proton beam interaction with the FLUKA Monte Carlo. The presented data are in good agreement with the FLUKA Monte Carlo.

Method to determine the position-dependant metal correction factor for dose-rate equivalent laser testing of semiconductor devices

DOEpatents

Horn, Kevin M.

2013-07-09

A method reconstructs the charge collection from regions beneath opaque metallization of a semiconductor device, as determined from focused laser charge collection response images, and thereby derives a dose-rate dependent correction factor for subsequent broad-area, dose-rate equivalent, laser measurements. The position- and dose-rate dependencies of the charge-collection magnitude of the device are determined empirically and can be combined with a digital reconstruction methodology to derive an accurate metal-correction factor that permits subsequent absolute dose-rate response measurements to be derived from laser measurements alone. Broad-area laser dose-rate testing can thereby be used to accurately determine the peak transient current, dose-rate response of semiconductor devices to penetrating electron, gamma- and x-ray irradiation.

Impact of the Amount of Liquid Intake on the Dose Rate of Patients Treated with Radioiodine.

PubMed

Haghighatafshar, Mahdi; Banani, Aida; Zeinali-Rafsanjani, Banafsheh; Etemadi, Zahra; Ghaedian, Tahereh

2018-01-01

Despite therapeutic effects of radioiodine in patients with differentiated thyroid cancer, there are some disadvantages due to harmful radiation to other tissues. According to the current guidelines, patients are recommended to drink lots of water and frequent voiding to reduce the amount of 131 I in the body. This study was designed to assess the impact of the amount of liquid intake on reduction of the measured dose rate of radioiodine-treated patients. A total of 42 patients with differentiated thyroid cancer without metastasis who had undergone total thyroidectomy and had been treated with radioiodine were selected. The patients were divided into two groups according to the amount of their fluid intake which was measured during the first 48 h after 131 I administration. In all patients, the dose rate was measured immediately and 48 h after iodine administration. Each group included 21 patients. Dose rate ratio (the ratio of the second dose rate to the first dose rate) and dose rate difference ratio (the ratio of the difference between the two measured dose rates to the first dose rate) were calculated for each patient. Despite the significant difference in the amount of the liquid drunk, no statistically significant difference was seen between the different groups in parameters of dose-rate ratio and dose-rate difference ratio. Higher fluid intake (>60 ml/h in our study) alone would not effectively reduce the patient's radiation dose rate at least not more than a well-hydrated state. It seems that other interfering factors in the thyroidectomized patients may also have some impacts on this physiologic process.

The benefit of individualized low-dose hCG support for high responders in GnRHa-triggered IVF/ICSI cycles.

PubMed

Huang, Chen-Yu; Shieh, Miawh-Lirng; Li, Hsin-Yang

2016-07-01

To assess the pregnancy outcome and ovarian hyperstimulation syndrome (OHSS) incidence in high responders receiving gonadotropin-releasing hormone agonist (GnRHa) trigger plus individualized support of low-dose human chorionic gonadotropin (hCG). Such support includes 500-1000 IU hCG given at trigger and, if serum estradiol (E2) dropped to below 800 pg/mL before the 6(th) day after oocyte retrieval, an additional rescue dose of 300 IU hCG. This was a retrospective study of potential high responders aged from 28 years to 40 years at a tertiary fertility center in Taiwan. By means of chart review, we assessed the pregnancy outcome and OHSS incidence in high responders receiving GnRHa trigger plus individualized low-dose hCG support. The main outcomes were measured by ongoing pregnancy rate and OHSS incidence (SPSS), in which statistical significance was determined by Chi-square test. Moderate to severe OHSS did not develop in any patient receiving GnRHa trigger plus individualized low-dose hCG support. In fact, a satisfactory ongoing pregnancy rate (46.9%) was noted in patients receiving GnRHa trigger plus individualized low-dose hCG support. Our study suggested that GnRHa trigger combined with individualized low-dose hCG support appears to be a safe approach with a satisfactory pregnancy outcome. Copyright © 2016. Published by Elsevier Taiwan LLC.

Responses to simulated nitrogen deposition by the neotropical epiphytic orchid Laelia speciosa

PubMed Central

Díaz-Álvarez, Edison A.; Lindig-Cisneros, Roberto

2015-01-01

Potential ecophysiological responses to nitrogen deposition, which is considered to be one of the leading causes for global biodiversity loss, were studied for the endangered endemic Mexican epiphytic orchid, Laelia speciosa, via a shadehouse dose-response experiment (doses were 2.5, 5, 10, 20, 40, and 80 kg N ha−1 yr−1) in order to assess the potential risk facing this orchid given impending scenarios of nitrogen deposition. Lower doses of nitrogen of up to 20 kg N ha yr−1, the dose that led to optimal plant performance, acted as fertilizer. For instance, the production of leaves and pseudobulbs were respectively 35% and 36% greater for plants receiving 20 kg N ha yr−1 than under any other dose. Also, the chlorophyll content and quantum yield peaked at 0.66 ± 0.03 g m−2 and 0.85 ± 0.01, respectively, for plants growing under the optimum dose. In contrast, toxic effects were observed at the higher doses of 40 and 80 kg N ha yr−1. The δ13C for leaves averaged −14.7 ± 0.2‰ regardless of the nitrogen dose. In turn, δ15N decreased as the nitrogen dose increased from 0.9 ± 0.1‰ under 2.5 kg N ha−1yr−1 to −3.1 ± 0.2‰ under 80 kg N ha−1yr−1, indicating that orchids preferentially assimilate NH4+ rather than NO3− of the solution under higher doses of nitrogen. Laelia speciosa showed a clear response to inputs of nitrogen, thus, increasing rates of atmospheric nitrogen deposition can pose an important threat for this species. PMID:26131375

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.

An evaluation of the various aspects of the progress in clinical applications of laser driven ionizing radiation

NASA Astrophysics Data System (ADS)

Hideghéty, K.; Szabó, E. R.; Polanek, R.; Szabó, Z.; Ughy, B.; Brunner, S.; Tőkés, T.

2017-03-01

There has been a vast development of laser-driven particle acceleration (LDPA) using high power lasers. This has initiated by the radiation oncology community to use the dose distribution and biological advantages of proton/heavy ion therapy in cancer treatment with a much greater accessibility than currently possible with cyclotron/synchrotron acceleration. Up to now, preclinical experiments have only been performed at a few LDPA facilities; technical solutions for clinical LDPA have been theoretically developed but there is still a long way to go for the clinical introduction of LDPA. Therefore, to explore the further potential bio-medical advantages of LDPA has pronounced importance. The main characteristics of LDPA are the ultra-high beam intensity, the flexibility in beam size reduction and the potential particle and energy selection whilst conventional accelerators generate single particle, quasi mono-energetic beams. There is a growing number of studies on the potential advantages and applications of Energy Modulated X-ray Radiotherapy, Modulated Electron Radiotherapy and Very High Energy Electron (VHEE) delivery system. Furthermore, the ultra-high space and/or time resolution of super-intense beams are under intensive investigation at synchrotrons (microbeam radiation and very high dose rate (> 40 Gy/s) electron accelerator flash irradiation) with growing evidence of significant improvement of the therapeutic index. Boron Neutron Capture Therapy (BNCT) is an advanced cell targeted binary treatment modality. Because of the high linear energy transfer (LET) of the two particles (7Li and 4He) released by 10BNC reaction, all of the energy is deposited inside the tumour cells, killing them with high probability, while the neighbouring cells are not damaged. The limited availability of appropriate neutron sources, prevent the more extensive exploration of clinical benefit of BNCT. Another boron-based novel binary approach is the 11B-Proton Fusion, which result in the release of three high LET alpha particles. These promising, innovative approaches for cancer therapy present huge challenges for dose calculation, dosimetry and for investigation of the biological effects. The planned LDPA (photons, VHEE, protons, carbon ions) at ELI facilities has the unique property of ultra-high dose rate (> Gy/s-10), short pulses, and at ELI-ALPS high repetition rate, have the potential to develop and establish encouraging novel methods working towards compact hospital-based clinical applications.

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.

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

PubMed

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

2009-01-01

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

Prospective Measurement of Patient Exposure to Radiation During Pediatric Ureteroscopy

PubMed Central

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

2013-01-01

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

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.

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.

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

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

Monte Carlo simulations of radioactive waste encapsulated by bisphenol-A polycarbonate and effect of bismuth-III oxide filler material

NASA Astrophysics Data System (ADS)

Özdemir, Tonguç

2017-06-01

Radioactive waste generated from the nuclear industry and non-power applications should carefully be treated, conditioned and disposed according to the regulations set by the competent authority(ies). Bisphenol-a polycarbonate (BPA-PC), a very widely used polymer, might be considered as a potential candidate material for low level radioactive waste encapsulation. In this work, the dose rate distribution in the radioactive waste drum (containing radioactive waste and the BPA-PC polymer matrix) was determined using Monte Carlo simulations. Moreover, the change of mechanical properties of BPA-PC was estimated and their variation within the waste drum was determined for the periods of 15, 30 and 300 years after disposal to the final disposal site. The change of the dose rate within the waste drum with different contents of bismuth-III oxide were also simulated. It was concluded that addition of bismuth-III oxide filler decreases the dose delivered to the polymeric matrix due to photoelectric effect.

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

NASA Astrophysics Data System (ADS)

Arno, Matthew Gordon

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

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

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

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

2010-08-06

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

From dust to dose: Effects of forest disturbance on increased inhalation exposure.

PubMed

Whicker, Jeffrey J; Pinder, John E; Breshears, David D; Eberhart, Craig F

2006-09-15

Ecosystem disturbances that remove vegetation and disturb surface soils are major causes of excessive soil erosion and can result in accelerated transport of soils contaminated with hazardous materials. Accelerated wind erosion in disturbed lands that are contaminated is of particular concern because of potential increased inhalation exposure, yet measurements regarding these relationships are lacking. The importance of this was highlighted when, in May of 2000, the Cerro Grande fire burned over roughly 30% of Los Alamos National Laboratory (LANL), mostly in ponderosa pine (Pinus ponderosa) forest, and through areas with soils containing contaminants, particularly excess depleted and natural uranium. Additionally, post-fire thinning was performed in burned and unburned forests on about 25% of LANL land. The first goal of this study was to assess the potential for increased inhalation dose from uranium contaminated soils via wind-driven resuspension of soil following the Cerro Grande Fire and subsequent forest thinning. This was done through analysis of post-disturbance measurements of uranium air concentrations and their relationships with wind velocity and seasonal vegetation cover. We found a 14% average increase in uranium air concentrations at LANL perimeter locations after the fire, and the greatest air concentrations occurred during the months of April-June when wind velocities are highest, no snow cover, and low vegetation cover. The second goal was to develop a methodology to assess the relative contribution of each disturbance type towards increasing public and worker exposure to these resuspended soils. Measurements of wind-driven dust flux in severely burned, moderately burned, thinned, and unburned/unthinned forest areas were used to assess horizontal dust flux (HDF) in these areas. Using empirically derived relationships between measurements of HDF and respirible dust, coupled with onsite uranium soil concentrations, we estimate relative increases in inhalation doses for workers ranging from 15% to 38%. Despite the potential for increased doses resulting from these forest disturbances, the estimated annual dose rate for the public was <1 microSv yr(-1), which is far below the dose limits for public exposures, and the upper-bound dose rate for a LANL worker was estimated to be 140 microSv yr(-1), far below the 5 x 10(4) microSv yr(-1) occupational dose limit. These results show the importance of ecosystem disturbance in increasing mobility of soil-bound contaminants, which can ultimately increase exposure. However, it is important to investigate the magnitude of the increases when deciding appropriate strategies for management and long-term stewardship of contaminated lands.

Fruit Flies Provide New Insights in Low-Radiation Background Biology at the INFN Underground Gran Sasso National Laboratory (LNGS).

PubMed

Morciano, Patrizia; Cipressa, Francesca; Porrazzo, Antonella; Esposito, Giuseppe; Tabocchini, Maria Antonella; Cenci, Giovanni

2018-06-04

Deep underground laboratories (DULs) were originally created to host particle, astroparticle or nuclear physics experiments requiring a low-background environment with vastly reduced levels of cosmic-ray particle interference. More recently, the range of science projects requiring an underground experiment site has greatly expanded, thus leading to the recognition of DULs as truly multidisciplinary science sites that host important studies in several fields, including geology, geophysics, climate and environmental sciences, technology/instrumentation development and biology. So far, underground biology experiments are ongoing or planned in a few of the currently operating DULs. Among these DULs is the Gran Sasso National Laboratory (LNGS), where the majority of radiobiological data have been collected. Here we provide a summary of the current scenario of DULs around the world, as well as the specific features of the LNGS and a summary of the results we obtained so far, together with other findings collected in different underground laboratories. In particular, we focus on the recent results from our studies of Drosophila melanogaster, which provide the first evidence of the influence of the radiation environment on life span, fertility and response to genotoxic stress at the organism level. Given the increasing interest in this field and the establishment of new projects, it is possible that in the near future more DULs will serve as sites of radiobiology experiments, thus providing further relevant biological information at extremely low-dose-rate radiation. Underground experiments can be nicely complemented with above-ground studies at increasing dose rate. A systematic study performed in different exposure scenarios provides a potential opportunity to address important radiation protection questions, such as the dose/dose-rate relationship for cancer and non-cancer risk, the possible existence of dose/dose-rate threshold(s) for different biological systems and/or end points and the possible role of radiation quality in triggering the biological response.

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

Interstitial rotating shield brachytherapy for prostate cancer

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

Adams, Quentin E., E-mail: quentin-adams@uiowa.edu; Xu, Jinghzu; Breitbach, Elizabeth K.

Purpose: To present a novel needle, catheter, and radiation source system for interstitial rotating shield brachytherapy (I-RSBT) of the prostate. I-RSBT is a promising technique for reducing urethra, rectum, and bladder dose relative to conventional interstitial high-dose-rate brachytherapy (HDR-BT). Methods: A wire-mounted 62 GBq{sup 153}Gd source is proposed with an encapsulated diameter of 0.59 mm, active diameter of 0.44 mm, and active length of 10 mm. A concept model I-RSBT needle/catheter pair was constructed using concentric 50 and 75 μm thick nickel-titanium alloy (nitinol) tubes. The needle is 16-gauge (1.651 mm) in outer diameter and the catheter contains a 535more » μm thick platinum shield. I-RSBT and conventional HDR-BT treatment plans for a prostate cancer patient were generated based on Monte Carlo dose calculations. In order to minimize urethral dose, urethral dose gradient volumes within 0–5 mm of the urethra surface were allowed to receive doses less than the prescribed dose of 100%. Results: The platinum shield reduced the dose rate on the shielded side of the source at 1 cm off-axis to 6.4% of the dose rate on the unshielded side. For the case considered, for the same minimum dose to the hottest 98% of the clinical target volume (D{sub 98%}), I-RSBT reduced urethral D{sub 0.1cc} below that of conventional HDR-BT by 29%, 33%, 38%, and 44% for urethral dose gradient volumes within 0, 1, 3, and 5 mm of the urethra surface, respectively. Percentages are expressed relative to the prescription dose of 100%. For the case considered, for the same urethral dose gradient volumes, rectum D{sub 1cc} was reduced by 7%, 6%, 6%, and 6%, respectively, and bladder D{sub 1cc} was reduced by 4%, 5%, 5%, and 6%, respectively. Treatment time to deliver 20 Gy with I-RSBT was 154 min with ten 62 GBq {sup 153}Gd sources. Conclusions: For the case considered, the proposed{sup 153}Gd-based I-RSBT system has the potential to lower the urethral dose relative to HDR-BT by 29%–44% if the clinician allows a urethral dose gradient volume of 0–5 mm around the urethra to receive a dose below the prescription. A multisource approach is necessary in order to deliver the proposed {sup 153}Gd-based I-RSBT technique in reasonable treatment times.« less

Dose to heart substructures is associated with non-cancer death after SBRT in stage I-II NSCLC patients.

PubMed

Stam, Barbara; Peulen, Heike; Guckenberger, Matthias; Mantel, Frederick; Hope, Andrew; Werner-Wasik, Maria; Belderbos, Jose; Grills, Inga; O'Connell, Nicolette; Sonke, Jan-Jakob

2017-06-01

To investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). 803 patients with early stage NSCLC received SBRT with predominant schedules of 3×18Gy (59%) or 4×12Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively. Median follow-up was 34.8months. Two year Kaplan-Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5Gy EQD2, range=0.009-197, HR=1.005, p-value=0.035), and the dose to 90% of the superior vena cava (median 0.59Gy EQD2, range=0.003-70, HR=1.025, p-value=0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria+vessels) to be significantly associated with non-cancer death. Doses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2003-02-21

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

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

NASA Astrophysics Data System (ADS)

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

2003-02-01

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

Low-Dose Curcumin Stimulates Proliferation, Migration and Phagocytic Activity of Olfactory Ensheathing Cells

PubMed Central

Tello Velasquez, Johana; Watts, Michelle E.; Todorovic, Michael; Nazareth, Lynnmaria; Pastrana, Erika; Diaz-Nido, Javier; Lim, Filip; Ekberg, Jenny A. K.; Quinn, Ronald J.; John, James A. St

2014-01-01

One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies. PMID:25360677

Intermittent blood pressure control: potential consequences for outcome.

PubMed

Leenen, F H

1999-05-01

Although both blood pressure (BP) and left ventricular (LV) mass at initial evaluation predict future cardiovascular risk, the actual BP and LV mass achieved over years of treatment more clearly relate to cardiovascular event rates. Intermittent compliance or noncompliance is the major reason for uncontrolled hypertension and presumably persistent LV hypertrophy. In general, drugs with rapid onset and short duration of action are not desirable because this profile may lead to large variations in BP lowering effect during actual drug intake and rapid disappearance of the antihypertensive effect with missed doses. In addition, intermittent compliance per se introduces the potential for adverse events. For drugs requiring several dose-titrations (e.g., alpha1-blockers), restarting at full doses may lead to excessive drug action and symptomatic hypotension. For other drugs (e.g., short acting beta-blockers or clonidine-like drugs), sudden discontinuation with intermittent compliance may lead to rebound-enhanced sympathetic responsiveness after one to two days, resulting not only in side effects, but also in adverse events, particularly in patients with (silent) coronary artery disease. The rapid onset, short acting dihydropyridines cause intermittent BP control at each dosing, particularly at higher doses. This intermittent control of BP is even more apparent at dosing intervals that are long relative to the duration of action. Thus, sympathetic activation and potential for adverse events can be anticipated at each dosing unless these drugs are being taken frequently at relatively low doses. For diuretics, angiotensin-converting enzyme inhibitors and angiotensin I receptor blockers, no adverse effects have been identified with intermittent compliance. Intermittent BP control is, in general, not an appropriate approach to the management of hypertension and introduces additional risks depending on the type of antihypertensive drug. In contrast, drugs with slow onset and long duration of action provide a more consistent effect during actual drug intake and a more persistent effect during short periods of noncompliance.

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

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

Dose-response relation between physical activity and cognitive function: guangzhou biobank cohort study.

PubMed

Xu, Lin; Jiang, Chao Qiang; Lam, Tai Hing; Zhang, Wei Sen; Thomas, G Neil; Cheng, Kar Keung

2011-11-01

To examine, via cross-sectional analysis, the dose-response association between physical activity and cognitive function in Chinese subjects. A total of 27,651 participants aged 50 to 85 years were recruited from 2003 to 2008. Information on potential confounders, including demographic and anthropometric characteristics, socioeconomic position, lifestyle, and disease history, was collected by standardized interview and procedures. Cognitive function was assessed by the delayed 10-word recall test (DWRT). When the International Physical Activity Questionnaire was used, we found that most of the participants were classified as physically active (53.1%), with 42.4% moderately active and 4.5% physically inactive. Significant dose-response relations across quintiles of metabolic equivalent value (METs) with DWRT score in participants with or without good self-rated health were found (all p for trend <.001). In participants with poor self-rated heath, compared with the first quintile of METs, those in the fifth quintile (highest METs) had a significantly reduced risk for mild cognitive impairment by 28% (adjusted odds ratio, 0.72; 95% confidence interval, 0.58-0.89, p < .01; p for trend = .006). After additional adjustment for depression, we found that the association between physical activity and DWRT score remained significant. A significant dose-response relationship between physical activity and cognitive function was found, and the association was more pronounced in participants with poor self-rated health. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of betel nut chewing on the otolithic reflex system.

PubMed

Lin, Chuan-Yi; Young, Yi-Ho

2017-01-01

This study investigated the effect of betel nut chewing on the otolithic reflex system. Seventeen healthy volunteers without any experience of chewing betel nut (fresh chewers) and 17 habitual chewers underwent vital sign measurements, ocular vestibular-evoked myogenic potential (oVEMP), and cervical VEMP (cVEMP) tests prior to the study. Each subject then chewed two pieces of betel nut for 2min (dosing). The same paradigm was repeated immediately, 10min, and 20min after chewing. On a different day, 10 fresh chewers masticated chewing gum as control. Fresh chewers exhibited significantly decreased response rates of oVEMP (53%) and cVEMP (71%) after dosing compared with those from the predosing period. These abnormal VEMPs returned to normal 20min after dosing. In contrast, 100% response rates of oVEMP and cVEMP were observed before and after masticating chewing gum. In habitual chewers, the response rates of oVEMP and cVEMP were 32% and 29%, respectively, 20min after dosing. Chewing betel nuts induced a transient loss of the otolithic reflexes in fresh chewers but may cause permanent loss in habitual chewers. Chewing betel nuts can cause a loss of otholitic reflex function. This creates a risk for disturbed balance and malfunction, for instance, during driving. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2013-01-01

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

Association of malignancy with rapid growth in early lesions induced by irradiation of rat skin

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

McGregor, J.F.

1979-04-01

Epithelial lesions induced by irradiation of rat skin were studied to determine (a) the relationship of malignancy to dose, (b) the types of lesions and circumstances leading to overt malignancy, and (c) the growth rates of lesions progressing to malignancy versus those of lesions remaining benign. High doses of radiation were shown to be associated with the production of epidermal cancers, the maximum yield being obtained at 6,400 rads. Conversely, a peak yield of noncancerous lesions was obtained at 1,600 rads. This association between malignancy and high dose was consistent for cancers evolving from warts, cysts, and chronic ulcers. Althoughmore » the proportion of warts among the induced lesions was much higher than that of the cysts or chronic ulcers (76, 14, and 10%, respectively), the likelihood of warts becoming cancerous was substantially lower (14, 23, and 21%). The combined data for all doses showed that the latency period of the epidermal cancers was significantly (P = 0.015) shorter than that of the benign tumors. Rapid growth rates were observed for warts, cysts, and chronic ulcers progressing to overt cancer, and these did not overlap at any point on the growth scale with rates for benign tumors. This finding suggested that the potential for malignant development had been established early in the carcinogenic process, very likely at induction.« less

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

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

Radev, R

2009-01-13

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

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

The estimation of galactic cosmic ray penetration and dose rates

NASA Technical Reports Server (NTRS)

Burrell, M. O.; Wright, J. J.

1972-01-01

This study is concerned with approximation methods that can be readily applied to estimate the absorbed dose rate from cosmic rays in rads - tissue or rems inside simple geometries of aluminum. The present work is limited to finding the dose rate at the center of spherical shells or behind plane slabs. The dose rate is calculated at tissue-point detectors or for thin layers of tissue. This study considers cosmic-rays dose rates for both free-space and earth-orbiting missions.

Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management

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

Kopelson, G.; Linggood, R.M.; Kleinman, G.M.

1983-01-15

For 43 medulloblatoma patients who had five-and ten-year actuarial survival rates of 56%, prognostic factors of statistical significance included: T-stage, M-stage and histopathologic tumor score. Posterior fossa local control rates were also function of T-stage and TS. Combining TS with T-stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS less than or equal to 5) histology had a 92% ten-year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group, increasing the irradiation dose alone maymore » improve survival because these tumors exhibited an irradiation dose-response relationship. However, it is the poor prognosis group which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.« less

Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study.

PubMed

Alda, Martin; McKinnon, Margaret; Blagdon, Ryan; Garnham, Julie; MacLellan, Susan; O'Donovan, Claire; Hajek, Tomas; Nair, Cynthia; Dursun, Serdar; MacQueen, Glenda

2017-01-01

Residual symptoms and cognitive impairment are among important sources of disability in patients with bipolar disorder. Methylene blue could improve such symptoms because of its potential neuroprotective effects. We conducted a double-blind crossover study of a low dose (15 mg, 'placebo') and an active dose (195 mg) of methylene blue in patients with bipolar disorder treated with lamotrigine. Thirty-seven participants were enrolled in a 6-month trial (trial registration: NCT00214877). The outcome measures included severity of depression, mania and anxiety, and cognitive functioning. The active dose of methylene blue significantly improved symptoms of depression both on the Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression (P = 0.02 and 0.05 in last-observation-carried-forward analysis). It also reduced the symptoms of anxiety measured by the Hamilton Rating Scale for Anxiety (P = 0.02). The symptoms of mania remained low and stable throughout the study. The effects of methylene blue on cognitive symptoms were not significant. The medication was well tolerated with transient and mild side-effects. Methylene blue used as an adjunctive medication improved residual symptoms of depression and anxiety in patients with bipolar disorder. © The Royal College of Psychiatrists 2017.

Estimation of ambient dose equivalent distribution in the 18F-FDG administration room using Monte Carlo simulation.

PubMed

Nagamine, Shuji; Fujibuchi, Toshioh; Umezu, Yoshiyuki; Himuro, Kazuhiko; Awamoto, Shinichi; Tsutsui, Yuji; Nakamura, Yasuhiko

2017-03-01

In this study, we estimated the ambient dose equivalent rate (hereafter "dose rate") in the fluoro-2-deoxy-D-glucose (FDG) administration room in our hospital using Monte Carlo simulations, and examined the appropriate medical-personnel locations and a shielding method to reduce the dose rate during FDG injection using a lead glass shield. The line source was assumed to be the FDG feed tube and the patient a cube source. The dose rate distribution was calculated with a composite source that combines the line and cube sources. The dose rate distribution was also calculated when a lead glass shield was placed in the rear section of the lead-acrylic shield. The dose rate behind the automatic administration device decreased by 87 % with respect to that behind the lead-acrylic shield. Upon positioning a 2.8-cm-thick lead glass shield, the dose rate behind the lead-acrylic shield decreased by 67 %.

Comparison of Monoenergetic Photon Organ Dose Rate Coefficients for the Female Stylized and Voxel Phantoms Submerged in Air

DOE PAGES

Hiller, Mauritius; Dewji, Shaheen Azim

2017-02-16

Dose rate coefficients computed using the International Commission on Radiological Protection (ICRP) reference adult female voxel phantom were compared with values computed using the Oak Ridge National Laboratory (ORNL) adult female stylized phantom in an air submersion exposure geometry. This is a continuation of previous work comparing monoenergetic organ dose rate coefficients for the male adult phantoms. With both the male and female data computed, effective dose rate as defined by ICRP Publication 103 was compared for both phantoms. Organ dose rate coefficients for the female phantom and ratios of organ dose rates for the voxel and stylized phantoms aremore » provided in the energy range from 30 to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Lastly, comparison of effective dose rates between the voxel and stylized phantoms was within 8% at 100 keV and is <5% between 200 and 5000 keV.« less

Comparison of Monoenergetic Photon Organ Dose Rate Coefficients for the Female Stylized and Voxel Phantoms Submerged in Air

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

Hiller, Mauritius; Dewji, Shaheen Azim

Dose rate coefficients computed using the International Commission on Radiological Protection (ICRP) reference adult female voxel phantom were compared with values computed using the Oak Ridge National Laboratory (ORNL) adult female stylized phantom in an air submersion exposure geometry. This is a continuation of previous work comparing monoenergetic organ dose rate coefficients for the male adult phantoms. With both the male and female data computed, effective dose rate as defined by ICRP Publication 103 was compared for both phantoms. Organ dose rate coefficients for the female phantom and ratios of organ dose rates for the voxel and stylized phantoms aremore » provided in the energy range from 30 to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Lastly, comparison of effective dose rates between the voxel and stylized phantoms was within 8% at 100 keV and is <5% between 200 and 5000 keV.« less

Starting Dose of Sorafenib for the Treatment of Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study.

PubMed

Reiss, Kim A; Yu, Shun; Mamtani, Ronac; Mehta, Rajni; D'Addeo, Kathryn; Wileyto, E Paul; Taddei, Tamar H; Kaplan, David E

2017-11-01

Purpose Sorafenib is currently the only Food and Drug Administration-approved first-line therapy for patients with advanced hepatocellular carcinoma. There are few data examining how sorafenib starting dose may influence patient outcomes and costs. Patients and Methods We retrospectively evaluated 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. After 1:1 propensity score matching to account for potential treatment bias, hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. A matched multivariate logistic regression was performed to adjust for potential confounders. The primary end point was overall survival (OS) of patients who were prescribed standard starting dosage sorafenib (800 mg/d per os) versus that of patients who were prescribed reduced starting dose sorafenib (< 800 mg/d per os). Results There were 3,094 standard dose sorafenib patients (63%) and 1,809 reduced starting dose sorafenib patients (37%). Reduced starting dose sorafenib patients had more Barcelona Clinic Liver Cancer stage D ( P < .001), higher Model for End-Stage Liver Disease Sodium scores ( P < .001), higher Child-Turcotte-Pugh scores ( P < .001), and higher Cirrhosis Comorbidity Index scores ( P = .01). Consequently, reduced starting dose sorafenib patients had lower OS (median, 200 v 233 days, HR = 1.10). After propensity score matching and adjusting for potential confounders, there was no longer a significant OS difference (adjusted hazard ratio [HR adj ], 0.92; 95% CI, 0.83 to 1.01), and this fell significantly below the noninferiority margin ( P < .001). Reduced starting dose sorafenib patients experienced significantly lower total cumulative sorafenib cost and were less likely to discontinue sorafenib because of gastrointestinal adverse effects (8.7% v 10.8%; P = .047). Conclusion The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior OS relative to standard dosing.

Controlled release systems containing solid dispersions: strategies and mechanisms.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

2011-10-01

In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

Evaluating exposure and potential effects on honeybee brood (Apis mellifera) development using glyphosate as an example.

PubMed

Thompson, Helen M; Levine, Steven L; Doering, Janine; Norman, Steve; Manson, Philip; Sutton, Peter; von Mérey, Georg

2014-07-01

This study aimed to develop an approach to evaluate potential effects of plant protection products on honeybee brood with colonies at realistic worst-case exposure rates. The approach comprised 2 stages. In the first stage, honeybee colonies were exposed to a commercial formulation of glyphosate applied to flowering Phacelia tanacetifolia with glyphosate residues quantified in relevant matrices (pollen and nectar) collected by foraging bees on days 1, 2, 3, 4, and 7 postapplication and glyphosate levels in larvae were measured on days 4 and 7. Glyphosate levels in pollen were approximately 10 times higher than in nectar and glyphosate demonstrated rapid decline in both matrices. Residue data along with foraging rates and food requirements of the colony were then used to set dose rates in the effects study. In the second stage, the toxicity of technical glyphosate to developing honeybee larvae and pupae, and residues in larvae, were then determined by feeding treated sucrose directly to honeybee colonies at dose rates that reflect worst-case exposure scenarios. There were no significant effects from glyphosate observed in brood survival, development, and mean pupal weight. Additionally, there were no biologically significant levels of adult mortality observed in any glyphosate treatment group. Significant effects were observed only in the fenoxycarb toxic reference group and included increased brood mortality and a decline in the numbers of bees and brood. Mean glyphosate residues in larvae were comparable at 4 days after spray application in the exposure study and also following dosing at a level calculated from the mean measured levels in pollen and nectar, showing the applicability and robustness of the approach for dose setting with honeybee brood studies. This study has developed a versatile and predictive approach for use in higher tier honeybee toxicity studies. It can be used to realistically quantify exposure of colonies to pesticides to allow the appropriate dose rates to be determined, based on realistic worst-case residues in pollen and nectar and estimated intake by the colony, as shown by the residue analysis. Previous studies have used the standard methodology developed primarily to identify pesticides with insect-growth disrupting properties of pesticide formulations, which are less reliant on identifying realistic exposure scenarios. However, this adaptation of the method can be used to determine dose-response effects of colony level exposure to pesticides with a wide range of properties. This approach would limit the number of replicated tunnel or field-scale studies that need to be undertaken to assess effects on honeybee brood and may be of particular benefit where residues in pollen and nectar are crop- and/or formulation-specific, such as systemic seed treatments and granular applications. © 2014 The Authors. Integrated Environmental Assessment and Management Published by SETAC.

Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response

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

Viel, Francis; Duzenli, Cheryl; British Columbia Cancer Agency, Department of Medical Physics, Vancouver Centre

2014-08-15

Introduction: Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA. Materials and Methods: Linac log file data andmore » a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate. Results: Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range. Conclusions: QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.« less

Acute changes in the central nervous system of monkeys exposed to protons.

NASA Technical Reports Server (NTRS)

Haymaker, W.; Ibrahim, M. Z. M.; Miquel, J.; Call, N.; Noden, P.; Ashley, W.; Ballinger, E. R.; Ghidoni, J.; Lindsay, I. R.; Behar, A. J.

1972-01-01

Study of the changes occurring in simian brain exposed to protons of varied energy, given in wide dose and dose-rate ranges. Results show that inflammatory reaction and glycogen accumulation in astrocytes occurred practically in all animals. Cerebral cortical necrosis, granule cell pyknosis, and inflammatory reaction occurred at doses far lower than effective for high-energy gamma radiation given other series of monkeys at comparable dose rates. Metallic impregnation, carried out in virtually all the animals tested, revealed a wide variation in glial response even at equal doses and dose rates in the same proton energy series. Proton energy effect, dose effect, dose-time effect, and dose-rate effect were evident in the various morphological categories investigated, but inconsistencies were encountered.

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

NASA Technical Reports Server (NTRS)

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

1989-01-01

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

Geographical diffusion of prazosin across Veterans Health Administration: Examination of regional variation in daily dosing and quality indicators among veterans with posttraumatic stress disorder.

PubMed

Abrams, Thad E; Lund, Brian C; Alexander, Bruce; Bernardy, Nancy C; Friedman, Matthew J

2015-01-01

Posttraumatic stress disorder (PTSD) is a high-priority treatment area for the Veterans Health Administration (VHA), and dissemination patterns of innovative, efficacious therapies can inform areas for potential improvement of diffusion efforts and quality prescribing. In this study, we replicated a prior examination of the period prevalence of prazosin use as a function of distance from Puget Sound, Washington, where prazosin was first tested as an effective treatment for PTSD and where prazosin use was previously shown to be much greater than in other parts of the United States. We tested the following three hypotheses related to prazosin geographic diffusion: (1) a positive geographical correlation exists between the distance from Puget Sound and the proportion of users treated according to a guideline recommended minimum therapeutic target dose (>/=6 mg/d), (2) an inverse geographic correlation exists between prazosin and benzodiazepine use, and (3) no geographical correlation exists between prazosin use and serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) use. Among a national sample of veterans with PTSD, overall prazosin utilization increased from 5.5 to 14.8% from 2006 to 2012. During this time period, rates at the Puget Sound VHA location declined from 34.4 to 29.9%, whereas utilization rates at locations a minimum of 2,500 miles away increased from 3.0 to 12.8%. Rates of minimum target dosing fell from 42.6 to 34.6% at the Puget Sound location. In contrast, at distances of at least 2,500 miles from Puget Sound, minimum threshold dosing rates remained stable (range, 18.6 to 17.7%). No discernible association was demonstrated between SSRI/SNRI or benzodiazepine utilization and the geographic distance from Puget Sound. Minimal threshold dosing of prazosin correlated positively with increased diffusion of prazosin use, but there was still a distance diffusion gradient. Although prazosin adoption has improved, geographic differences persist in both prescribing rates and minimum target dosing. Importantly, these regional disparities appear to be limited to prazosin prescribing and are not meaningfully correlated with SSRI/SNRI and benzodiazepine use as indicators of PTSD prescribing quality.

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

PubMed

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

2014-02-01

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

Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

PubMed

Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

2011-05-01

The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

Comparative performance analysis for computer aided lung nodule detection and segmentation on ultra-low-dose vs. standard-dose CT

NASA Astrophysics Data System (ADS)

Wiemker, Rafael; Rogalla, Patrik; Opfer, Roland; Ekin, Ahmet; Romano, Valentina; Bülow, Thomas

2006-03-01

The performance of computer aided lung nodule detection (CAD) and computer aided nodule volumetry is compared between standard-dose (70-100 mAs) and ultra-low-dose CT images (5-10 mAs). A direct quantitative performance comparison was possible, since for each patient both an ultra-low-dose and a standard-dose CT scan were acquired within the same examination session. The data sets were recorded with a multi-slice CT scanner at the Charite university hospital Berlin with 1 mm slice thickness. Our computer aided nodule detection and segmentation algorithms were deployed on both ultra-low-dose and standard-dose CT data without any dose-specific fine-tuning or preprocessing. As a reference standard 292 nodules from 20 patients were visually identified, each nodule both in ultra-low-dose and standard-dose data sets. The CAD performance was analyzed by virtue of multiple FROC curves for different lower thresholds of the nodule diameter. For nodules with a volume-equivalent diameter equal or larger than 4 mm (149 nodules pairs), we observed a detection rate of 88% at a median false positive rate of 2 per patient in standard-dose images, and 86% detection rate in ultra-low-dose images, also at 2 FPs per patient. Including even smaller nodules equal or larger than 2 mm (272 nodules pairs), we observed a detection rate of 86% in standard-dose images, and 84% detection rate in ultra-low-dose images, both at a rate of 5 FPs per patient. Moreover, we observed a correlation of 94% between the volume-equivalent nodule diameter as automatically measured on ultra-low-dose versus on standard-dose images, indicating that ultra-low-dose CT is also feasible for growth-rate assessment in follow-up examinations. The comparable performance of lung nodule CAD in ultra-low-dose and standard-dose images is of particular interest with respect to lung cancer screening of asymptomatic patients.

Intensity-Modulated Radiation Therapy for the Treatment of Squamous Cell Anal Cancer With Para-aortic Nodal Involvement

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

Hodges, Joseph C.; Das, Prajnan, E-mail: PrajDas@mdanderson.or; Eng, Cathy

2009-11-01

Purpose: To determine the rates of toxicity, locoregional control, distant control, and survival in anal cancer patients with para-aortic nodal involvement, treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy at a single institution. Methods and Materials: Between 2001 and 2007, 6 patients with squamous cell anal cancer and para-aortic nodal involvement were treated with IMRT and concurrent infusional 5-fluorouracil and cisplatin. The primary tumor was treated with a median dose of 57.5 Gy (range, 54-60 Gy), involved para-aortic, pelvic, and inguinal lymph nodes were treated with a median dose of 55 Gy (range, 50.5-55 Gy), and noninvolved nodal regions weremore » treated with a median dose of 45 Gy (range, 43.5-45 Gy). Results: After a median follow-up of 25 months, none of the patients had a recurrence at the primary tumor, pelvic/inguinal nodes, or para-aortic nodes, whereas 2 patients developed distant metastases to the liver. Four of the 6 patients are alive. The 3-year actuarial locoregional control, distant control, and overall survival rates were 100%, 56%, and 63%, respectively. Four of the 6 patients developed Grade 3 acute gastrointestinal toxicity during chemoradiation. Conclusions: Intensity-modulated radiotherapy and concurrent chemotherapy could potentially serve as definitive therapy in anal cancer patients with para-aortic nodal involvement. Adjuvant chemotherapy may be indicated in these patients, as demonstrated by the distant failure rates. These patients need to be followed carefully because of the potential for treatment-related toxicities.« less

Mechanisms of Autonomic Dysfunction Associated with Extreme Exertional Heat Stroke and Potential Efficacy of Novel Pharmacological Treatments

DTIC Science & Technology

2014-12-01

cardiovascular diseases. At higher doses, these medications have been prescribed to treat high blood pressure in humans and both may have relevance as...HR, and Tc. § Low frequency (LF) systolic blood pressure variability as an index of sympathetic modulation of vascular tone. § LF and high ... blood pressure variability (LFSYS), LF heart rate variability (LFHR), and high frequency heart rate variability (HFHR) in placebo-, clonidine-, and

Computational Model Prediction and Biological Validation Using Simplified Mixed Field Exposures for the Development of a GCR Reference Field

NASA Technical Reports Server (NTRS)

Hada, M.; Rhone, J.; Beitman, A.; Saganti, P.; Plante, I.; Ponomarev, A.; Slaba, T.; Patel, Z.

2018-01-01

The yield of chromosomal aberrations has been shown to increase in the lymphocytes of astronauts after long-duration missions of several months in space. Chromosome exchanges, especially translocations, are positively correlated with many cancers and are therefore a potential biomarker of cancer risk associated with radiation exposure. Although extensive studies have been carried out on the induction of chromosomal aberrations by low- and high-LET radiation in human lymphocytes, fibroblasts, and epithelial cells exposed in vitro, there is a lack of data on chromosome aberrations induced by low dose-rate chronic exposure and mixed field beams such as those expected in space. Chromosome aberration studies at NSRL will provide the biological validation needed to extend the computational models over a broader range of experimental conditions (more complicated mixed fields leading up to the galactic cosmic rays (GCR) simulator), helping to reduce uncertainties in radiation quality effects and dose-rate dependence in cancer risk models. These models can then be used to answer some of the open questions regarding requirements for a full GCR reference field, including particle type and number, energy, dose rate, and delivery order. In this study, we designed a simplified mixed field beam with a combination of proton, helium, oxygen, and iron ions with shielding or proton, helium, oxygen, and titanium without shielding. Human fibroblasts cells were irradiated with these mixed field beam as well as each single beam with acute and chronic dose rate, and chromosome aberrations (CA) were measured with 3-color fluorescent in situ hybridization (FISH) chromosome painting methods. Frequency and type of CA induced with acute dose rate and chronic dose rates with single and mixed field beam will be discussed. A computational chromosome and radiation-induced DNA damage model, BDSTRACKS (Biological Damage by Stochastic Tracks), was updated to simulate various types of CA induced by acute exposures of the mixed field beams used for the experiments. The chromosomes were simulated by a polymer random walk algorithm with restrictions to their respective domains in the nucleus [1]. The stochastic dose to the nucleus was calculated with the code RITRACKS [2]. Irradiation of a target volume by a mixed field of ions was implemented within RITRACKs, and the fields of ions can be delivered over specific periods of time, allowing the simulation of dose-rate effects. Similarly, particles of various types and energies extracted from a pre-calculated spectra of galactic cosmic rays (GCR) can be used in RITRACKS. The number and spatial location of DSBs (DNA double-strand breaks) were calculated in BDSTRACKS using the simulated chromosomes and local (voxel) dose. Assuming that DSBs led to chromosome breaks, and simulating the rejoining of damaged chromosomes occurring during repair, BDSTRACKS produces the yield of various types of chromosome aberrations as a function of time (only final yields are presented). A comparison between experimental and simulation results will be shown.

Comparison of proposed alternative methods for rescaling dialysis dose: resting energy expenditure, high metabolic rate organ mass, liver size, and body surface area.

PubMed

Daugirdas, John T; Levin, Nathan W; Kotanko, Peter; Depner, Thomas A; Kuhlmann, Martin K; Chertow, Glenn M; Rocco, Michael V

2008-01-01

A number of denominators for scaling the dose of dialysis have been proposed as alternatives to the urea distribution volume (V). These include resting energy expenditure (REE), mass of high metabolic rate organs (HMRO), visceral mass, and body surface area. Metabolic rate is an unlikely denominator as it varies enormously among humans with different levels of activity and correlates poorly with the glomerular filtration rate. Similarly, scaling based on HMRO may not be optimal, as many organs with high metabolic rates such as spleen, brain, and heart are unlikely to generate unusually large amounts of uremic toxins. Visceral mass, in particular the liver and gut, has potential merit as a denominator for scaling; liver size is related to protein intake and the liver, along with the gut, is known to be responsible for the generation of suspected uremic toxins. Surface area is time-honored as a scaling method for glomerular filtration rate and scales similarly to liver size. How currently recommended dialysis doses might be affected by these alternative rescaling methods was modeled by applying anthropometric equations to a large group of dialysis patients who participated in the HEMO study. The data suggested that rescaling to REE would not be much different from scaling to V. Scaling to HMRO mass would mandate substantially higher dialysis doses for smaller patients of either gender. Rescaling to liver mass would require substantially more dialysis for women compared with men at all levels of body size. Rescaling to body surface area would require more dialysis for smaller patients of either gender and also more dialysis for women of any size. Of these proposed alternative rescaling measures, body surface area may be the best, because it reflects gender-based scaling of liver size and thereby the rate of generation of uremic toxins.

Total dose bias dependency and ELDRS effects in bipolar linear devices

NASA Technical Reports Server (NTRS)

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

2002-01-01

Total dose tests of several bipolar linear devices show sensitivity to both dose rate and bias during exposure. All devices exhibited Enhanced Low Dose Rate Sensitivity (ELDRS). An accelerated ELDRS test method for three different devices demonstrate results similar to tests at low dose rate. Behavior and critical parameters from these tests are compared and discussed.

The Impact of Dose Rate on the Accuracy of Step-and-Shoot Intensity-modulated Radiation Therapy Quality Assurance Using Varian 2300CD.

PubMed

Njeh, Christopher F; Salmon, Howard W; Schiller, Claire

2017-01-01

Intensity-modulated radiation therapy (IMRT) delivery using "step-and-shoot" technique on Varian C-Series linear accelerator (linac) is influenced by the communication frequency between the multileaf collimator and linac controllers. Hence, the dose delivery accuracy is affected by the dose rate. Our aim was to quantify the impact of using two dose rates on plan quality assurance (QA). Twenty IMRT patients were selected for this study. The plan QA was measured at two different dose rates. A gamma analysis was performed, and the degree of plan modulation on the QA pass rate was also evaluated in terms of average monitor unit per segment (MU/segment) and the total number of segments. The mean percentage gamma pass rate of 94.9% and 93.5% for 300 MU/min and 600 MU/min dose rate, respectively, was observed. There was a significant ( P = 0.001) decrease in percentage gamma pass rate when the dose rate was increased from 300 MU/min to 600 MU/min. There was a weak, but significant association between the percentage pass rate at both dose rate and total number of segments. The total number of MU was significantly correlated to the total number of segments ( r = 0.59). We found a positive correlation between the percentage pass rate and mean MU/segment, r = 0.52 and r = 0.57 for 300 MU/min and 600 MU/min, respectively. IMRT delivery using step-and-shoot technique on Varian 2300CD is impacted by the dose rate and the total amount of segments.

Enhanced Low Dose Rate Effects in Bipolar Circuits: A New Hardness Assurance Problem for NASA

NASA Technical Reports Server (NTRS)

Johnston, A.; Barnes, C.

1995-01-01

Many bipolar integrated circuits are much more susceptible to ionizing radiation at low dose rates than they are at high dose rates typically used for radiation parts testing. Since the low dose rate is equivalent to that seen in space, the standard lab test no longer can be considered conservative and has caused the Air Force to issue an alert. Although a reliable radiation hardness assurance test has not yet been designed, possible mechanisms for low dose rate enhancement and hardness assurance tests are discussed.

Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

PubMed

Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

2012-06-01

Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

Acute effect of ivabradine on heart rate and myocardial oxygen consumption in dogs with asymptomatic mitral valve degeneration.

PubMed

Pirintr, Prapawadee; Limprasutr, Vudhiporn; Saengklub, Nakkawee; Pavinadol, Parnpradub; Yapao, Napat; Limvanicharat, Natthakarn; Kuecharoen, Hathaisiri; Kijtawornrat, Anusak

2018-05-14

Degenerative mitral valve disease (DMVD) is a common cardiac disease in geriatric dogs characterized by the degeneration of the mitral valve, leading to decreased cardiac output and activation of the sympathetic and renin-angiotensin-aldosterone system. This disease results in an increased resting heart rate (HR) and myocardial oxygen consumption (MVO 2 ). A recent publication demonstrated that dogs with asymptomatic DMVD had a significantly higher HR and systemic blood pressure (BP) than age-matched control dogs. This higher HR will eventually contribute to increased MVO 2 . This study aimed to determine the effects of a single oral dose of ivabradine on the HR, MVO 2 as assessed by the rate-pressure product, and BP in dogs with asymptomatic DMVD. Seven beagles with naturally occurring DMVD were instrumented by the Holter recorder and an oscillometric device to measure electrocardiogram and BP for 24 and 12 h, respectively. Each dog was randomly subjected to receive either placebo or ivabradine (0.5, 1.0 and 2.0 mg/kg). The results revealed that oral administration of ivabradine significantly decreased the HR and rate-pressure product in a dose-dependent manner without adverse effects. The highest dose of 2.0 mg/kg significantly reduced systolic and mean BP. Therefore, the findings imply that a single oral ivabradine administration at a dose of 1.0 mg/kg is suitable for dogs with asymptomatic DMVD to reduce the HR and MVO 2 without marked effects on BP. This may potentially make ivabradine promising for management of an elevated HR in DMVD dogs.

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.

Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators.

PubMed

Eichmann, Marion; Flühs, Dirk; Spaan, Bernhard

2009-10-01

The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. In order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate distribution, which then can be used as input for a refined clinical treatment planning system. The improved dose rate measurements will facilitate a clinical study, which could correlate the therapeutic outcome of a brachytherapy treatment with an applicator and its individual dose rate distribution.

Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators

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

Eichmann, Marion; Fluehs, Dirk; Spaan, Bernhard

2009-10-15

Purpose: The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. Methods: Inmore » order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. Results: The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. Conclusions: The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate distribution, which then can be used as input for a refined clinical treatment planning system. The improved dose rate measurements will facilitate a clinical study, which could correlate the therapeutic outcome of a brachytherapy treatment with an applicator and its individual dose rate distribution.« less

Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

PubMed

Lundy, P M

1978-04-01

Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

Seasonal influenza vaccine dose distribution in 195 countries (2004-2013): Little progress in estimated global vaccination coverage.

PubMed

Palache, Abraham; Oriol-Mathieu, Valerie; Fino, Mireli; Xydia-Charmanta, Margarita

2015-10-13

Seasonal influenza is an important disease which results in 250,000-500,000 annual deaths worldwide. Global targets for vaccination coverage rates (VCRs) in high-risk groups are at least 75% in adults ≥65 years and increased coverage in other risk groups. The International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply (IFPMA IVS) International Task Force developed a survey methodology in 2008, to assess the global distribution of influenza vaccine doses as a proxy for VCRs. This paper updates the previous survey results on absolute numbers of influenza vaccine doses distributed between 2004 and 2013 inclusive, and dose distribution rates per 1000 population, and provides a qualitative assessment of the principal enablers and barriers to seasonal influenza vaccination. The two main findings from the quantitative portion of the survey are the continued negative trend for dose distribution in the EURO region and the perpetuation of appreciable differences in scale of dose distribution between WHO regions, with no observed convergence in the rates of doses distributed per 1000 population over time. The main findings from the qualitative portion of the survey were that actively managing the vaccination program in real-time and ensuring political commitment to vaccination are important enablers of vaccination, whereas insufficient access to vaccination and lack of political commitment to seasonal influenza vaccination programs are likely contributing to vaccination target failures. In all regions of the world, seasonal influenza vaccination is underutilized as a public health tool. The survey provides evidence of lost opportunity to protect populations against potentially serious influenza-associated disease. We call on the national and international public health communities to re-evaluate their political commitment to the prevention of the annual influenza disease burden and to develop a systematic approach to improve vaccine distribution equitably. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Daily radionuclide ingestion and internal radiation doses in Aomori prefecture, Japan.

PubMed

Ohtsuka, Yoshihito; Kakiuchi, Hideki; Akata, Naofumi; Takaku, Yuichi; Hisamatsu, Shun'ichi

2013-10-01

To assess internal annual dose in the general public in Aomori Prefecture, Japan, 80 duplicate cooked diet samples, equivalent to the food consumed over a 400-d period by one person, were collected from 100 volunteers in Aomori City and the village of Rokkasho during 2006–2010 and were analyzed for 11 radionuclides. To obtain average rates of ingestion of radionuclides, the volunteers were selected from among office, fisheries, agricultural, and livestock farm workers. Committed effective doses from ingestion of the diet over a 1-y period were calculated from the analytical results and from International Commission on Radiological Protection dose coefficients; for 40K, an internal effective dose rate from the literature was used. Fisheries workers had significantly higher combined internal annual dose than the other workers, possibly because of high rates of ingestion of marine products known to have high 210Po concentrations. The average internal dose rate, weighted by the numbers of households in each worker group in Aomori Prefecture, was estimated at 0.47 mSv y-1. Polonium-210 contributed 49% of this value. The sum of committed effective dose rates for 210Po, 210Pb, 228Ra, and 14C and the effective dose rate of 40K accounted for approximately 99% of the average internal dose rate.

Rate-dependent activation failure in isolated cardiac cells and tissue due to Na+ channel block.

PubMed

Varghese, Anthony; Spindler, Anthony J; Paterson, David; Noble, Denis

2015-11-15

While it is well established that class-I antiarrhythmics block cardiac sodium channels, the mechanism of action of therapeutic levels of these drugs is not well understood. Using a combination of mathematical modeling and in vitro experiments, we studied the failure of activation of action potentials in single ventricular cells and in tissue caused by Na(+) channel block. Our computations of block and unblock of sodium channels by a theoretical class-Ib antiarrhythmic agent predict differences in the concentrations required to cause activation failure in single cells as opposed to multicellular preparations. We tested and confirmed these in silico predictions with in vitro experiments on isolated guinea-pig ventricular cells and papillary muscles stimulated at various rates (2-6.67 Hz) and exposed to various concentrations (5 × 10(-6) to 500 × 10(-6) mol/l) of lidocaine. The most salient result was that whereas large doses (5 × 10(-4) mol/l or higher) of lidocaine were required to inhibit action potentials temporarily in single cells, much lower doses (5 × 10(-6) mol/l), i.e., therapeutic levels, were sufficient to have the same effect in papillary muscles: a hundredfold difference. Our experimental results and mathematical analysis indicate that the syncytial nature of cardiac tissue explains the effects of clinically relevant doses of Na(+) channel blockers. Copyright © 2015 the American Physiological Society.

Rate-dependent activation failure in isolated cardiac cells and tissue due to Na+ channel block

PubMed Central

Spindler, Anthony J.; Paterson, David; Noble, Denis

2015-01-01

While it is well established that class-I antiarrhythmics block cardiac sodium channels, the mechanism of action of therapeutic levels of these drugs is not well understood. Using a combination of mathematical modeling and in vitro experiments, we studied the failure of activation of action potentials in single ventricular cells and in tissue caused by Na+ channel block. Our computations of block and unblock of sodium channels by a theoretical class-Ib antiarrhythmic agent predict differences in the concentrations required to cause activation failure in single cells as opposed to multicellular preparations. We tested and confirmed these in silico predictions with in vitro experiments on isolated guinea-pig ventricular cells and papillary muscles stimulated at various rates (2–6.67 Hz) and exposed to various concentrations (5 × 10−6 to 500 × 10−6 mol/l) of lidocaine. The most salient result was that whereas large doses (5 × 10−4 mol/l or higher) of lidocaine were required to inhibit action potentials temporarily in single cells, much lower doses (5 × 10−6 mol/l), i.e., therapeutic levels, were sufficient to have the same effect in papillary muscles: a hundredfold difference. Our experimental results and mathematical analysis indicate that the syncytial nature of cardiac tissue explains the effects of clinically relevant doses of Na+ channel blockers. PMID:26342072

D-cycloserine adjuvant therapy to molindone in the treatment of schizophrenia.

PubMed

Rosse, R B; Fay-McCarthy, M; Kendrick, K; Davis, R E; Deutsch, S I

1996-10-01

This preliminary investigation examined the therapeutic efficacy of two doses of oral D-cycloserine (5 and 15 mg p.o. b.i.d.) administered as an adjuvant to molindone (150 mg p.o. q.d.) in the treatment of schizophrenia. D-Cycloserine is an agonist at the N-methyl-D-aspartate (NMDA) subclass of glutamate receptor complex. An NMDA agonist intervention was studied because of the schizophreniform psychosis precipitated by phencyclidine (PCP), which is a noncompetitive antagonist at the NMDA glutamate receptor. The PCP model of schizophrenia is regarded as the most comprehensive pharmacological model of this disorder. In this preliminary, placebo-controlled, double-blind, parallel-group study, the measures of treatment efficacy were the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms, and Clinical Global Impression Scale. The final scores for each item of the outcome measures employed were based on the consensus of at least two trained raters who were present during each rating interview. In the 13 subjects evaluated, although the D-cycloserine was well tolerated, neither dose seemed to possess adjuvant therapeutic efficacy. However, since another recent report of nine patients with schizophrenia treated for 2 weeks with a slightly higher dose of D-cycloserine (50 mg/day) described significant clinical and neuropsychological improvement, further study of the adjuvant potential of slightly higher doses of D-cycloserine seems warranted. Additionally, there might be a therapeutic window for D-cycloserine dosing, as daily doses of 250 mg have been associated with symptom worsening.

Dose rate effects on array CCDs exposed by Co-60 γ rays induce saturation output degradation and annealing tests

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

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Chen, Wei; He, Baoping

The experimental tests of dose rate and annealing effects on array charge-coupled devices (CCDs) are presented. The saturation output voltage (V{sub S}) versus the total dose at the dose rates of 0.01, 0.1, 1.0, 10.0 and 50 rad(Si)/s are compared. Annealing tests are performed to eliminate the time-dependent effects. The V{sub S} degradation levels depend on the dose rates. The V{sub S} degradation mechanism induced by dose rate and annealing effects is analyzed. The V{sub S} at 20 krad(Si) with the dose rate of 0.03 rad(Si)/s are supplemented to assure the degradation curves between the dose rates of 0.1 andmore » 0.01 rad(Si)/s. The CCDs are divided into two groups, with one group biased and the other unbiased during {sup 60}Co γ radiation. The V{sub S} degradation levels of the biased CCDs during radiation are more severe than that of the unbiased CCDs.« less

Measurement of ambient dose equivalent rates by walk survey around Fukushima Dai-ichi Nuclear Power Plant using KURAMA-II until 2016.

PubMed

Andoh, Masaki; Yamamoto, Hideaki; Kanno, Takashi; Saito, Kimiaki

2018-05-17

Ambient dose equivalent rates in various environments related to human lives were measured by walk surveys using the KURAMA-II systems from 2013 to 2016 within an 80-km radius of the Fukushima Dai-ichi Nuclear Power Plant. The dose rate of the locations where the walk survey was performed decreased to about 38% of its initial value in the 42 months from June 2013 to the December 2016, which was beyond that attributable to the physical decay of radiocaesium. The ecological half-life of the slow decreasing component was evaluated to be 4.1 ± 0.2 y. The air dose rates decreased depending on the level of the evacuation areas, and the decrease in the dose rates was slightly larger in populated areas where humans are active. The dose rates as measured by walk surveys exhibited a good correlation with those by car-borne surveys, suggesting that car-borne survey data are reflecting the air dose rates in living environments surrounding roads. The comparison of walk survey data with car-borne survey data indicated that the air dose rate varies largely even within a 100 m square area, and the variation is enhanced by human activities. The dose rates measured by the walk surveys were estimated to be medial of those along roads and those of undisturbed flat ground, and they were found to be decreasing quickly compared with the air dose rate from the flat ground fixed-point measurements. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acute methanol toxicity in minipigs

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

Dorman, D.C.; Dye, J.A.; Nassise, M.P.

1993-01-01

The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Methanol- andmore » formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuroocular toxicosis.« less

Fricke-gel dosimetry in epithermal or thermal neutron beams of a research reactor

NASA Astrophysics Data System (ADS)

Gambarini, G.; Artuso, E.; Giove, D.; Volpe, L.; Agosteo, S.; Barcaglioni, L.; Campi, F.; Garlati, L.; Pola, A.; Durisi, E.; Borroni, M.; Carrara, M.; Klupak, V.; Marek, M.; Viererbl, L.; Vins, M.; d'Errico, F.

2015-11-01

Fricke-xylenol-orange gel has shown noticeable potentiality for in-phantom dosimetry in epithermal or thermal neutron fields with very high fluence rate, as those characteristic of nuclear research reactors. Fricke gels in form of layers give the possibility of achieving spatial distribution of gamma dose, fast neutron dose and dose due to charged particles generated by thermal neutron reactions. The thermal neutron fluence has been deduced from the dose coming from the charge particles emitted by neutron reactions with the isotope 10B. Some measurements have been performed for improving the information on the relative sensitivity of Fricke gel dosimeters to the particles produced by 10B reactions, because at present the precision of dose evaluations is limited by the scanty knowledge about the dependence of the dosimeter sensitivity on the radiation LET. For in-air measurements, the dosimeter material can produce an enhancement of thermal neutron fluence. Measurements and Monte Carlo calculations have been developed to investigate the importance of this effect.

Characteristics and verification of a car-borne survey system for dose rates in air: KURAMA-II.

PubMed

Tsuda, S; Yoshida, T; Tsutsumi, M; Saito, K

2015-01-01

The car-borne survey system KURAMA-II, developed by the Kyoto University Research Reactor Institute, has been used for air dose rate mapping after the Fukushima Dai-ichi Nuclear Power Plant accident. KURAMA-II consists of a CsI(Tl) scintillation detector, a GPS device, and a control device for data processing. The dose rates monitored by KURAMA-II are based on the G(E) function (spectrum-dose conversion operator), which can precisely calculate dose rates from measured pulse-height distribution even if the energy spectrum changes significantly. The characteristics of KURAMA-II have been investigated with particular consideration to the reliability of the calculated G(E) function, dose rate dependence, statistical fluctuation, angular dependence, and energy dependence. The results indicate that 100 units of KURAMA-II systems have acceptable quality for mass monitoring of dose rates in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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

Bruner, A.

1976-09-01

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

Acute Biological Effects of Simulating the Whole-Body Radiation Dose Distribution from a Solar Particle Event Using a Porcine Model

PubMed Central

Wilson, Jolaine M.; Sanzari, Jenine K.; Diffenderfer, Eric S.; Yee, Stephanie S.; Seykora, John T.; Maks, Casey; Ware, Jeffrey H.; Litt, Harold I.; Reetz, Jennifer A.; McDonough, James; Weissman, Drew; Kennedy, Ann R.; Cengel, Keith A.

2011-01-01

In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses. PMID:21859326

High-dose ascorbate with low-dose amphotericin B attenuates severity of disease in a model of the reappearance of candidemia during sepsis in the mouse

PubMed Central

Somparn, Poorichaya; Bootprapan, Tanabodee; Tu, Hongbin; Tangtanatakul, Pattarin; Nuengjumnong, Ratchanok; Worasilchai, Navaporn; Tiranathanagul, Khajohn; Eiam-ong, Somchai; Levine, Mark; Chinampon, Ariya; Srisawat, Nattachai

2015-01-01

Amphotericin B (Ampho B) is a fungicidal drug that causes cell wall injury. Pharmacological ascorbate induces the extracellular prooxidants, which might enter the Ampho B-induced cell wall porosity and act synergistically. We tested low-dose Ampho B with a short course of pharmacological ascorbate using a mouse model of sepsis preconditioned with an injection of Candida albicans 6 h prior to cecal ligation and puncture (CLP). In this model, candidemia reappeared as early as 6 h after CLP with a predictably high mortality rate. This characteristic mimics sepsis in the phase of immunosuppression in patients. Using the model, at 12- and 18-h post-CLP, we administered isotonic (pH neutralized) pharmacological ascorbate intravenously with low-dose Ampho B or sodium deoxycholate, vehicle-controlled, administered IP. The survival rate of low-dose Ampho B plus ascorbate was 53%, compared with <11% for low-dose Ampho B or high-dose Ampho B alone. In addition, a beneficial effect was demonstrated in terms of kidney damage, liver injury, spleen histopathology, and serum markers at 24 h after CLP. Kidney injury was less severe in low-dose Ampho B plus ascorbate combination therapy due to less severe sepsis. Moreover, ascorbate enhanced the effectiveness of phagocytosis against C. albicans in human phagocytic cells. Taken together, the data indicate that the new mouse model simulates sepsis-induced immunosuppression and that the combination of pharmacological ascorbate with an antifungal drug is a potentially effective treatment that may reduce nephrotoxicity, and perhaps also increase fungicidal activity in patients with systemic candidiasis caused by Candida albicans. PMID:25994956

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PubMed

Eisbruch, A; Dawson, L A; Kim, H M; Bradford, C R; Terrell, J E; Chepeha, D B; Teknos, T N; Anzai, Y; Marsh, L H; Martel, M K; Ten Haken, R K; Wolf, G T; Ship, J A

1999-01-01

To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Influenza vaccine strategies for solid organ transplant recipients.

PubMed

Hirzel, Cédric; Kumar, Deepali

2018-05-15

The aim of this study was to highlight recent evidence on important aspects of influenza vaccination in solid organ transplant recipients. Influenza vaccine is the most evaluated vaccine in transplant recipients. The immunogenicity of the vaccine is suboptimal after transplantation. Newer formulations such as inactivated unadjuvanted high-dose influenza vaccine and the administration of a booster dose within the same season have shown to increase response rates. Intradermal vaccination and adjuvanted vaccines did not show clear benefit over standard influenza vaccines. Recent studies in transplant recipients do not suggest a higher risk for allograft rejection, neither after vaccination with a standard influenza vaccine nor after the administration of nonstandard formulation (high-dose, adjuvanted vaccines), routes (intradermally) or a booster dose. Nevertheless, influenza vaccine coverage in transplant recipients is still unsatisfactory low, potentially due to misinterpretation of risks and benefits. Annual influenza vaccination is well tolerated and is an important part of long-term care of solid organ transplant recipients.

Brachytherapy devices and methods employing americium-241

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

Gray, L. A.

1985-04-16

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

Variation of indoor radon concentration and ambient dose equivalent rate in different outdoor and indoor environments.

PubMed

Stojanovska, Zdenka; Boev, Blazo; Zunic, Zora S; Ivanova, Kremena; Ristova, Mimoza; Tsenova, Martina; Ajka, Sorsa; Janevik, Emilija; Taleski, Vaso; Bossew, Peter

2016-05-01

Subject of this study is an investigation of the variations of indoor radon concentration and ambient dose equivalent rate in outdoor and indoor environments of 40 dwellings, 31 elementary schools and five kindergartens. The buildings are located in three municipalities of two, geologically different, areas of the Republic of Macedonia. Indoor radon concentrations were measured by nuclear track detectors, deployed in the most occupied room of the building, between June 2013 and May 2014. During the deploying campaign, indoor and outdoor ambient dose equivalent rates were measured simultaneously at the same location. It appeared that the measured values varied from 22 to 990 Bq/m(3) for indoor radon concentrations, from 50 to 195 nSv/h for outdoor ambient dose equivalent rates, and from 38 to 184 nSv/h for indoor ambient dose equivalent rates. The geometric mean value of indoor to outdoor ambient dose equivalent rates was found to be 0.88, i.e. the outdoor ambient dose equivalent rates were on average higher than the indoor ambient dose equivalent rates. All measured can reasonably well be described by log-normal distributions. A detailed statistical analysis of factors which influence the measured quantities is reported.

Development and Process Evaluation of a Primary Care Internet-Based Intervention to Prevent Depression in Emerging Adults

PubMed Central

Van Voorhees, Benjamin W.; Ellis, Justin M.; Gollan, Jackie K.; Bell, Carl C.; Stuart, Scott S.; Fogel, Joshua; Corrigan, Patrick W.; Ford, Daniel E.

2007-01-01

Background: Primary care is a potential setting for implementation of depression prevention interventions using cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT). The purpose of this study was to develop and conduct a process evaluation of a primary care/ Internet-based intervention that addresses key dissemination barriers in a community setting. Method: We used an interdisciplinary team of investigators in a multistep intervention development process among a sample of primary care patients (aged 18 to 24 years). The intervention included an initial primary care motivational interview to engage the participant, 11 Internet-based modules based on CBT (to counter pessimistic thinking) and IPT (to activate social networks and strengthen relationship skills), and a follow-up motivational interview in primary care to enhance behavior change. Each component of the intervention was rated with regard to dissemination barriers of (1) fidelity, (2) motivation, (3) dose, (4) perceived helpfulness (rated on a Likert scale), and (5) potential costs. The study was conducted from April through June of 2004. Results: Fidelity checklist and serial reviews were satisfactory (100% core concepts translated into intervention). Key motivations for participation included (1) risk reduction, (2) intervention effectiveness, (3) “resiliency,” and (4) altruism. In terms of dose, 13 of 14 participants engaged the Internet-based components, completing a mean of 7.2 modules (SD = 3.9). The 2 primary care interviews and the self-assessment and resiliency modules received the highest helpfulness ratings. The duration of the 2 motivational interviews was approximately 17–18 minutes, which is similar to a typical primary care visit. Conclusions: By using multidisciplinary teams and incorporating the opinions of potential users, complex preventive mental health interventions can be translated into primary care settings with adequate fidelity, motivation, dose, and perceived helpfulness, and at a reasonably low cost. PMID:17998953

Radiotherapy.

PubMed

Krause, Sonja; Debus, Jürgen; Neuhof, Dirk

2011-01-01

Solitary plasmocytoma occurring in bone (solitary plasmocytoma of the bone, SBP) or in soft tissue (extramedullary plasmocytoma, EP) can be treated effectively and with little toxicity by local radiotherapy. Ten-year local control rates of up to 90% can be achieved. Patients with multiple myeloma often suffer from symptoms such as pain or neurological impairments that are amenable to palliative radiotherapy. In a palliative setting, short treatment schedules and lower radiation doses are used to reduce toxicity and duration of hospitalization. In future, low-dose total body irradiation (TBI) may play a role in a potentially curative regimen with nonmyeloablative conditioning followed by allogenic peripheral blood stem cell transplantation.

Micronucleus induction in Vicia faba roots. Part 1. Absence of dose-rate, fractionation, and oxygen effect at low doses of low LET radiations.

PubMed

Marshall, I; Bianchi, M

1983-08-01

Micronucleus indication in Vicia faba roots has been evaluated after irradiation with 60Co gamma-rays. The dependence of the damage on dose, dose rate, fractionation, and oxygen has been studied. The best fit to the experimental data in the dose region between 7 and 190 cGy is represented, for single-dose exposures, by a linear + quadratic relationship. In the low-dose region, between 7 and 20 cGy, where the linear dose dependence is dominant, no dose-rate, fractionation, or oxygen effect could be observed. These effects were, however, present in the high-dose region, where the quadratic dependence is dominant.

In Vivo Absorption and Disposition of Cefadroxil after Escalating Oral Doses in Wild-Type and PepT1 Knockout Mice

PubMed Central

Posada, Maria M.; Smith, David E.

2013-01-01

Purpose To determine the effect of PepT1 on the absorption and disposition of cefadroxil, including the potential for saturable intestinal uptake, after escalating oral doses of drug. Methods The absorption and disposition kinetics of [3H]cefadroxil was determined in wild-type and PepT1 knockout mice after 44.5, 89.1, 178, and 356 nmol/g oral doses of drug. The pharmacokinetics of [3H]cefadroxil was also determined in both genotypes after 44.5 nmol/g intravenous bolus doses. Results PepT1 deletion reduced the area under the plasma concentration-time profile (AUC0-120) of cefadroxil by 10-fold, the maximum plasma concentration (Cmax) by 17.5-fold, and increased the time to reach a maximum plasma concentration (Tmax) by 3-fold. There was no evidence of nonlinear intestinal absorption since AUC0-120 and Cmax values changed in a dose-proportional manner. Moreover, the pharmacokinetics of cefadroxil was not different between genotypes after intravenous bolus doses, indicating that PepT1 did not affect drug disposition. Finally, no differences were observed in the peripheral tissue distribution of cefadroxil (i.e., outside gastrointestinal tract) once these tissues were corrected for differences in perfusing blood concentrations. Conclusions The findings demonstrate convincingly the critical role of intestinal PepT1 in both the rate and extent of oral administration for cefadroxil and potentially other aminocephalosporin drugs. PMID:23959853

Investigation of Natural Radioactivity in a Monazite Processing Plant in Japan.

PubMed

Iwaoka, Kazuki; Yajima, Kazuaki; Suzuki, Toshikazu; Yonehara, Hidenori; Hosoda, Masahiro; Tokonami, Shinji; Kanda, Reiko

2017-09-01

Monazite is a naturally occurring radioactive material that is processed for use in a variety of domestic applications. At present, there is little information available on potential radiation doses experienced by people working with monazite. The ambient dose rate and activity concentration of natural radionuclides in raw materials, products, and dust in work sites as well as the Rn and Rn concentrations in work sites were measured in a monazite processing plant in Japan. Dose estimations for plant workers were also conducted. The activity concentration of the U series in raw materials and products for the monazite processing plant was found to be higher than the relevant values described in the International Atomic Energy Agency Safety Standards. The ambient dose rates in the raw material yard were higher than those in other work sites. Moreover, the activity concentrations of dust in the milling site were higher than those in other work sites. The Rn concentrations in all work sites were almost the same as those in regular indoor environments in Japan. The Rn concentrations in all work sites were much higher than those in regular indoor environments in Japan. The maximum value of the effective dose for workers was 0.62 mSv y, which is lower than the reference level range (1-20 mSv y) for abnormally high levels of natural background radiation published in the International Commission of Radiological Protection Publication 103.

Response to varying the nicotine content of cigarettes in vulnerable populations: an initial experimental examination of acute effects.

PubMed

Higgins, Stephen T; Heil, Sarah H; Sigmon, Stacey C; Tidey, Jennifer W; Gaalema, Diann E; Stitzer, Maxine L; Durand, Hanna; Bunn, Janice Y; Priest, Jeff S; Arger, Christopher A; Miller, Mollie E; Bergeria, Cecilia L; Davis, Danielle R; Streck, Joanna M; Zvorsky, Ivori; Redner, Ryan; Vandrey, Ryan; Pacek, Lauren R

2017-01-01

The purpose of this study was to begin researching the effects of very low nicotine content cigarettes in smokers especially vulnerable to dependence to assess their potential as a less dependence-producing alternative to current commercial cigarettes. Participants were 26 adult, daily cigarette smokers from one of three populations: economically disadvantaged women of reproductive age (n = 9), opioid-dependent individuals (n = 11), and individuals with affective disorders (n = 6). Participants completed fourteen 2-4-h experimental sessions in a within-subjects research design. Sessions were conducted following brief smoking abstinence. Four research cigarettes varying in nicotine content (0.4, 2.4, 5.2, and 15.8 mg/g) were studied under double-blind conditions, assessing smoking topography, subjective effects, and relative reinforcing effects of varying doses in concurrent choice tests. Results were collapsed across vulnerable populations and analyzed using repeated measures ANOVA. No significant differences between doses were discernible in smoking topography. All doses were equi-effective at reducing nicotine withdrawal. Ratings of satisfaction from smoking were lower at the 0.4 compared to 15.8 mg/g dose. Participants preferred the 15.8 mg/g dose over the 0.4 and 2.4 but not the 5.2 mg/g doses in concurrent choice testing; no differences between the two lowest doses were noted. All cigarettes effectively reduced nicotine withdrawal with no differences in smoking topography, suggesting minimal compensatory smoking. Dependence potential was lowest at the 0.4 mg/g dose. These initial results are promising regarding the feasibility of lowering nicotine content in cigarettes to very low levels in vulnerable populations without untoward effects.

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.

Acute fluoxetine modulates emotional processing in young adult volunteers.

PubMed

Capitão, L P; Murphy, S E; Browning, M; Cowen, P J; Harmer, C J

2015-08-01

Fluoxetine is generally regarded as the first-line pharmacological treatment for young people, as it is believed to show a more favourable benefit:risk ratio than other antidepressants. However, the mechanisms through which fluoxetine influences symptoms in youth have been little investigated. This study examined whether acute administration of fluoxetine in a sample of young healthy adults altered the processing of affective information, including positive, sad and anger cues. A total of 35 male and female volunteers aged between 18 and 21 years old were randomized to receive a single 20 mg dose of fluoxetine or placebo. At 6 h after administration, participants completed a facial expression recognition task, an emotion-potentiated startle task, an attentional dot-probe task and the Rapid Serial Visual Presentation. Subjective ratings of mood, anxiety and side effects were also taken pre- and post-fluoxetine/placebo administration. Relative to placebo-treated participants, participants receiving fluoxetine were less accurate at identifying anger and sadness and did not show the emotion-potentiated startle effect. There were no overall significant effects of fluoxetine on subjective ratings of mood. Fluoxetine can modulate emotional processing after a single dose in young adults. This pattern of effects suggests a potential cognitive mechanism for the greater benefit:risk ratio of fluoxetine in adolescent patients.

Thin film organic photodetectors for indirect X-ray detection demonstrating low dose rate sensitivity at low voltage operation

NASA Astrophysics Data System (ADS)

Starkenburg, Daken J.; Johns, Paul M.; Baciak, James E.; Nino, Juan C.; Xue, Jiangeng

2017-12-01

Developments in the field of organic semiconductors have generated organic photodetectors with high quantum efficiency, wide spectral sensitivity, low power consumption, and unique form factors that are flexible and conformable to their substrate shape. In this work, organic photodetectors coupled with inorganic CsI(Tl) scintillators are used to showcase the low dose rate sensitivity that is enabled when high performance organic photodetectors and scintillator crystals are integrated. The detection capability of these organic-inorganic coupled systems to high energy radiation highlights their potential as an alternative to traditional photomultiplier tubes for nuclear spectroscopy applications. When exposed to Bremsstrahlung radiation produced from an X-ray generator, SubPc:C60, AlPcCl:C70, and P3HT:PC61BM thin film photodetectors with active layer thicknesses less than 100 nm show detection of incident radiation at low and no applied bias. Remarkably low dose rates, down to at least 0.18 μGy/s, were detectable with a characteristic linear relationship between exposure rate and photodetector current output. These devices also demonstrate sensitivities as high as 5.37 mC Gy-1 cm-2 when coupled to CsI(Tl). Additionally, as the tube voltage across the X-ray generator was varied, these organic-inorganic systems showed their ability to detect a range of continuous radiation spectra spanning several hundred keV.

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

Hobbs, R; Le, Y; Armour, E

Purpose: Dose-response studies in radiation therapy are typically using single response values for tumors across ensembles of tumors. Using the high dose rate (HDR) treatment plan dose grid and pre- and post-therapy FDG-PET images, we look for correlations between voxelized dose and FDG uptake response in individual tumors. Methods: Fifteen patients were treated for localized rectal cancer using 192Ir HDR brachytherapy in conjunction with surgery. FDG-PET images were acquired before HDR therapy and 6–8 weeks after treatment (prior to surgery). Treatment planning was done on a commercial workstation and the dose grid was calculated. The two PETs and the treatmentmore » dose grid were registered to each other using non-rigid registration. The difference in PET SUV values before and after HDR was plotted versus absorbed radiation dose for each voxel. The voxels were then separated into bins for every 400 cGy of absorbed dose and the bin average values plotted similarly. Results: Individual voxel doses did not correlate with PET response; however, when group into tumor subregions corresponding to dose bins, eighty percent of the patients showed a significant positive correlation (R2 > 0) between PET uptake difference in the targeted region and the absorbed dose. Conclusion: By considering larger ensembles of voxels, such as organ average absorbed dose or the dose bins considered here, valuable information may be obtained. The dose-response correlations as measured by FDG-PET difference potentially underlines the importance of FDG-PET as a measure of response, as well as the value of voxelized information.« less

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.

Object Kinetic Monte Carlo Simulations of Radiation Damage In Bulk Tungsten

NASA Astrophysics Data System (ADS)

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard; Roche, Kenneth; Kurtz, Richard; Wirth, Brian

2015-11-01

Results are presented for the evolution of radiation damage in bulk tungsten investigated using the object KMC simulation tool, KSOME, as a function of dose, dose rate and primary knock-on atom (PKA) energies in the range of 10 to 100 keV, at temperatures of 300, 1025 and 2050 K. At 300 K, the number density of vacancies changes minimally with dose rate while the number density of vacancy clusters slightly decreases with dose rate indicating that larger clusters are formed at higher dose rates. Although the average vacancy cluster size increases slightly, the vast majority exists as mono-vacancies. At 1025 K void lattice formation was observed at all dose rates for cascades below 60 keV and at lower dose rates for higher PKA energies. After the appearance of initial features of the void lattice, vacancy cluster density increased minimally while the average vacancy cluster size increases rapidly with dose. At 2050 K, no accumulation of defects was observed over a broad range of dose rates for all PKA energies studied in this work. Further comparisons of results of irradiation simulations at various dose rates and PKA spectra, representative of the High Flux Isotope Reactor and future fusion relevant irradiation facilities will be discussed. The U.S. Department of Energy, Office of Fusion Energy Sciences (FES) and Office of Advanced Scientific Computing Research (ASCR) has supported this study through the SciDAC-3 program.

Electron trapping in rad-hard RCA IC's irradiated with electrons and gamma rays

NASA Technical Reports Server (NTRS)

Danchenko, V.; Brashears, S. S.; Fang, P. H.

1984-01-01

Enhanced electron trapping has been observed in n-channels of rad-hard CMOS devices due to electron and gamma-ray irradiation. Room-temperature annealing results in a positive shift in the threshold potential far beyond its initial value. The slope of the annealing curve immediately after irradiation was found to depend strongly on the gate bias applied during irradiation. Some dependence was also observed on the electron dose rate. No clear dependence on energy and shielding over a delidded device was observed. The threshold shift is probably due to electron trapping at the radiation-induced interface states and tunneling of electrons through the oxide-silicon energy barrier to fill the radiation-induced electron traps. A mathematical analysis, based on two parallel annealing kinetics, hole annealing and electron trapping, is applied to the data for various electron dose rates.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors.

PubMed

Karsch, L; Beyreuther, E; Burris-Mog, T; Kraft, S; Richter, C; Zeil, K; Pawelke, J

2012-05-01

The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10(11) Gy∕s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. The dosimeters are dose rate independent up to 4●10(9) Gy∕s within 2% (OSL and TLD) and up to 15●10(9) Gy∕s within 5% (EBT films). The diamond detectors show strong dose rate dependence. TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors

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

Karsch, L.; Beyreuther, E.; Burris-Mog, T.

Purpose: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10{sup 11} Gy/s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. Methods: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the numbermore » of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. Results: The dosimeters are dose rate independent up to 410{sup 9} Gy/s within 2% (OSL and TLD) and up to 1510{sup 9} Gy/s within 5% (EBT films). The diamond detectors show strong dose rate dependence. Conclusions: TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.« less

Clinical treatment outcomes of tuberculosis treated with the basic regimen recommended by the Brazilian National Ministry of Health using fixed-dose combination tablets in the greater metropolitan area of Goiânia, Brazil *

PubMed Central

Ferreira, Anna Carolina Galvão; da Silva, José Laerte Rodrigues; Conde, Marcus Barreto; Rabahi, Marcelo Fouad

2013-01-01

OBJECTIVE: To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health-rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months-involving the use of fixed-dose combination tablets (self-administered treatment), as well as to describe adverse events and their potential impact on treatment outcomes. METHODS: This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (≥ 18 years of age) treated with the basic regimen at either of two primary health care facilities in the greater metropolitan area of Goiânia, Brazil. RESULTS: The study sample comprised 40 tuberculosis patients. The rate of cure was 67.5%, the rate of treatment abandonment was 17.5%, and there were no cases of treatment failure. Of the 40 patients in the sample, 19 (47%) reported adverse reactions, which were mild and moderate, respectively, in 87% and 13% of the cases. It was not necessary to alter the regimen or discontinue the treatment in any of the cases evaluated. CONCLUSIONS: The rate of cure obtained with the self-administered, fixed-dose combination tablet form of the new basic regimen was similar to the historical rates of cure obtained with the previous basic regimen. The rate of treatment abandonment in our sample was much higher than that considered appropriate (up to 5%). PMID:23503489

Clinical treatment outcomes of tuberculosis treated with the basic regimen recommended by the Brazilian National Ministry of Health using fixed-dose combination tablets in the greater metropolitan area of Goiânia, Brazil.

PubMed

Ferreira, Anna Carolina Galvão; Silva Júnior, José Laerte Rodrigues da; Conde, Marcus Barreto; Rabahi, Marcelo Fouad

2013-01-01

To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health (rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months) involving the use of fixed-dose combination tablets (self-administered treatment), as well as to describe adverse events and their potential impact on treatment outcomes. This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (> 18 years of age) treated with the basic regimen at either of two primary health care facilities in the greater metropolitan area of Goiânia, Brazil. The study sample comprised 40 tuberculosis patients. The rate of cure was 67.5%, the rate of treatment abandonment was 17.5%, and there were no cases of treatment failure. Of the 40 patients in the sample, 19 (47%) reported adverse reactions, which were mild and moderate, respectively, in 87% and 13% of the cases. It was not necessary to alter the regimen or discontinue the treatment in any of the cases evaluated. The rate of cure obtained with the self-administered, fixed-dose combination tablet form of the new basic regimen was similar to the historical rates of cure obtained with the previous regimen. The rate of treatment abandonment in our sample was much higher than that considered appropriate (up to 5%).

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.

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

PubMed Central

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

2016-01-01

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

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…

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.

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.

Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

PubMed

Dionet, Claude; Müller-Barthélémy, Melanie; Marceau, Geoffroy; Denis, Jean-Marc; Averbeck, Dietrich; Gueulette, John; Sapin, Vincent; Pereira, Bruno; Tchirkov, Andrei; Chautard, Emmanuel; Verrelle, Pierre

2016-09-01

To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts. We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS. HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS. Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

A nanotube based electron microbeam cellular irradiator for radiobiology research

PubMed Central

Bordelon, David E.; Zhang, Jian; Graboski, Sarah; Cox, Adrienne; Schreiber, Eric; Zhou, Otto Z.; Chang, Sha

2008-01-01

A prototype cellular irradiator utilizing a carbon nanotube (CNT) based field emission electron source has been developed for microscopic image-guided cellular region irradiation. The CNT cellular irradiation system has shown great potential to be a high temporal and spatial resolution research tool to enable researchers to gain a better understanding of the intricate cellular and intercellular microprocesses occurring following radiation deposition, which is essential to improving radiotherapy cancer treatment outcomes. In this paper, initial results of the system development are reported. The relationship between field emission current, the dose rate, and the dose distribution has been investigated. A beam size of 23 μm has been achieved with variable dose rates of 1–100 Gy∕s, and the system dosimetry has been measured using a radiochromic film. Cell irradiation has been demonstrated by the visualization of H2AX phosphorylation at DNA double-strand break sites following irradiation in a rat fibroblast cell monolayer. The prototype single beam cellular irradiator is a preliminary step to a multipixel cell irradiator that is under development. PMID:19123587

Sci-Thur PM – Brachytherapy 04: Commissioning and Implementation of a Cobalt-60 High Dose Rate Brachytherapy Source

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

Dysart, Jonathan

An Eckert & Ziegler Bebig Co0.A86 cobalt 60 high dose rate (HDR) brachytherapy source was commissioned for clinical use. Long-lived Co-60 HDR sources offer potential logistical and economic advantages over Ir-192 sources, and should be considered for low to medium workload brachytherapy departments where modest increases in treatment times are not a factor. In optimized plans, the Co-60 source provides a similar dose distribution to Ir-192 despite the difference in radiation energy. By switching to Co-60, source exchange frequency can be reduced by a factor of 20, resulting in overall financial savings of more than 50% compared to Ir-192 sources.more » In addition, a reduction in Physicist QA workload of roughly 200 hours over the 5 year life of the Co-60 source is also expected. These benefits should be considered against the modest increases in average treatment time compared to those of Ir-192 sources, as well as the centre-specific needs for operating room shielding modification.« less

Vaccine hypersensitivity--update and overview.

PubMed

Fritsche, Philipp J; Helbling, Arthur; Ballmer-Weber, Barbara K

2010-05-01

Concerns about possible reactions to vaccines or vaccinations are frequently raised. However, the rate of reported vaccine-induced adverse events is low and ranges between 4.8-83.0 per 100,000 doses of the most frequently used vaccines. The number of true allergic reactions to routine vaccines is not known; estimations range from 1 per 500,000 to 1 per 1,000,000 doses for most vaccines. When allergens such as gelatine or egg proteins are components of the formulation, the rate for serious allergic reactions may be higher. Nevertheless, anaphylactic, potentially life-threatening reactions to vaccines are still a rare event (approximately 1 per 1,500,000 doses). The variety of reported vaccine-related adverse events is broad. Most frequently, reactions to vaccines are limited to the injection site and result from a non specific activation of the inflammatory system by, for example, aluminium salts or the active microbial components. If allergy is suspected, an accurate examination followed by algorithms is the key for correct diagnosis, treatment and the decision regarding revaccination in patients with immediate-type reactions to vaccines.

Cosmic-ray interaction data for designing biological experiments in space

NASA Astrophysics Data System (ADS)

Straume, T.; Slaba, T. C.; Bhattacharya, S.; Braby, L. A.

2017-05-01

There is growing interest in flying biological experiments beyond low-Earth orbit (LEO) to measure biological responses potentially relevant to those expected during a human mission to Mars. Such experiments could be payloads onboard precursor missions, including unmanned private-public partnerships, as well as small low-cost spacecraft (satellites) designed specifically for biosentinel-type missions. It is the purpose of this paper to provide physical cosmic-ray interaction data and related information useful to biologists who may be planning such experiments. It is not the objective here to actually design such experiments or provide radiobiological response functions, which would be specific for each experiment and biological endpoint. Nuclide-specific flux and dose rates were calculated using OLTARIS and these results were used to determine particle traversal rates and doses in hypothetical biological targets. Comparisons are provided between GCR in interplanetary space and inside the ISS. Calculated probabilistic estimates of dose from solar particle events are also presented. Although the focus here is on biological experiments, the information provided may be useful for designing other payloads as well if the space radiation environment is a factor to be considered.

DOSE-RATE DEPENDENCE OF INSTANTANEOUS PHYSIOLOGICAL RADIATION EFFECTS

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

Hug, O.

Nastic movements in Mimosa pudica were induced by x radiation. Using short radiation impulses of 10 to 30 sec and doses up to 120 kr/min, the leaflets were observed to close and the stem to bend in the main joint during the first minute. After irradiation of parts of the leaflet, the reaction spreads along the physiological pathways as in any other stimulus. When the action potential is completed, slow depolarization continues and reaches a maximum, finally returning to the initial value in about two hr. The effect was found to be dose- dependent. It is hypothesized that either amore » direct physicochemical change of the cell membrane or a damage of substances which influence the function of the cell membrane is induced by the irradiation. (H.M.G.)« less

An investigation of flat panel equipment variables on image quality with a dedicated cardiac phantom

NASA Astrophysics Data System (ADS)

Dragusin, O.; Bosmans, H.; Pappas, C.; Desmet, W.

2008-09-01

Image quality (IQ) evaluation plays a key role in the process of optimization of new x-ray systems. Ideally, this process should be supported by real clinical images, but ethical issues and differences in anatomy and pathology of patients make it impossible. Phantom studies might overcome these issues. This paper presents the IQ evaluation of 30 cineangiographic films acquired with a cardiac flat panel system. The phantom used simulates the anatomy of the heart and allows the circulation of contrast agent boluses through coronary arteries. Variables investigated with influence on IQ and radiation dose are: tube potential, detector dose, added Copper filters, dynamic density optimization (DDO) and viewing angle. The IQ evaluation consisted of scoring 4 simulated calcified lesions located on different coronary artery segments in terms of degree of visualization. Eight cardiologists rated the lesions using a five-point scale ((1) lesion not visible to (5) very good visibility). Radiation doses associated to the angiograms are expressed in terms of incident air kerma (IAK) and effective dose that has been calculated with PCXMX software (STUK, Finland) from the exposure settings assuming a standard sized patient of 70 Kg. Mean IQ scores ranged from 1.68 to 4.88. The highest IQ scores were obtained for the angiograms acquired with tube potential 80 kVp, no added Cu filters, DDO 60%, RAO and LAO views and the highest entrance detector dose that has been used in the present study, namely 0.17 μGy/im. Radiation doses (IAK ~40 mGy and effective dose of 1 mSv) were estimated for angiograms acquired at 15 frames s-1, detector field-of-view 20 cm, and a length of 5 s. The following parameters improved the IQ factor significantly: a change in tube potential from 96 to 80 kVp, detector dose from 0.10 μGy/im to 0.17 μGy/im, the absence of Copper filtration. DDO variable which is a post-processing parameter should be carefully evaluated because it alters the quality of the images independently of radiation exposure settings. The SAM anthropomorphic phantom has the advantage of visualization of stenotic lesions during the injection of a contrast agent and using an anatomical background. In the future, this phantom could potentially bridge the gap between physics tests and the clinical reality in the catheterization laboratory.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-01-01

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

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

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

PubMed

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

1983-07-01

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

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.

Acrosin activity is a suitable indicator of boar semen preservation at 17 °C when increasing environmental temperature and radiation.

PubMed

Pinart, E; Yeste, M; Puigmulé, M; Barrera, X; Bonet, S

2013-08-01

The effect of increasing environmental temperature and radiation on the sperm quality and the field fertility of refrigerated seminal doses from AI boars (N = 30) was analyzed throughout four experimental months (from March through June). In each experimental month, analyses of sperm quality were performed at days 0, 1, 3, 5, 7, and 9 of refrigeration of seminal doses; pregnancy rate and litter size were evaluated using double monospermic inseminations of multiparous female animals using seminal doses at Days 1 to 2 and Days 3 to 4 of refrigeration. Sperm quality was assessed from the evaluation of conventional parameters of sperm concentration, sperm motility, sperm morphology, and sperm viability, and capacitation parameters of membrane lipid disorder, intracellular calcium content, and acrosin activity. Results showed that sperm quality of boar seminal doses was negatively affected by increasing temperature and radiation, which resulted in significantly decreased sperm motility and viability, acrosin activity, pregnancy rate, and litter size, and significantly increased intracellular calcium levels in the trials performed in June. In any experimental month, aging of refrigerated doses was associated with the progressive increase of intracellular calcium levels and inactivation of acrosin, that began from Day 5 of storage in the trials performed in March and April, from Day 3 in those of May, and from Day 0 in those of June. Among the sperm parameters analyzed, only acrosin activity exhibited a clearly differentiated pattern in association with increasing temperature and radiation, and a significant correlation with pregnancy rate and litter size. These results highlighted the potential role of acrosin activity as an indicator of boar sperm preservation at 17 °C in boars. Copyright © 2013 Elsevier Inc. All rights reserved.

[Safety and immunogenicity of combined hepatitis A and hepatitis B vaccine according to 0 and 6 months schedule in healthy children].

PubMed

Wang, Ya-Long; Chen, Wen-Yu; Xu, Wen-Guo; Wang, Xu; Liu, Yan; Wu, Jian-Fang; Chen, Jiang-Ting

2010-02-01

To evaluate the safety and immunogenicity of the Bilive(TM) combined hepatitis A and hepatitis B vaccine in healthy children. A total of 116 healthy children aged 1 - 10 years, who, without history of hepatitis A vaccine vaccination and anti-HAV negative, had completed the full immunization of hepatitis B vaccine were recruited in city of Changzhou in Jiangsu province. The Bilive(TM) combined hepatitis A and hepatitis B vaccine was administered according to a two-dose schedule (0, 6 months). The dosage was 250 U for hepatitis A antigen and 5 microg for hepatitis B surface antigen. The potential adverse effects were observed within 72 hours after vaccination. The serum samples were collected for the testing of anti-HAV and anti-HBs at month 1, 6 and 7 after initial dose. The local and systemic adverse reactions after immunization were slight and temporary. The rates of local and systemic adverse reactions were 12.1% (14/116) and 6.0% (7/116). The sero-conversion rates of HAV were from 92.9% (92/99) to 100.0% (101/101) and the geometric mean titers (GMT) ranged from 47.0 mIU/ml to 2762.3 mIU/ml 1, 6, 7 months after initial dose. The sero-protection rate of HBV was 86.1% (87/101) before vaccination and came up to 100.0% (101/101) one month after initial dose, and the GMTs of HBV were from 894.3 mIU/ml to 3314.3 mIU/ml 1, 6, 7 months after initial dose. The Bilive(TM) combined hepatitis A and hepatitis B vaccine has good safety and immunogenicity in healthy children who had preexisting immunity to hepatitis B virus.

Feasibility and radiation dose of high-pitch acquisition protocols in patients undergoing dual-source cardiac CT.

PubMed

Sommer, Wieland H; Albrecht, Edda; Bamberg, Fabian; Schenzle, Jan C; Johnson, Thorsten R; Neumaier, Klement; Reiser, Maximilian F; Nikolaou, Konstatin

2010-12-01

The objective of this study was to compare image quality and radiation dose between high-pitch and established retrospectively and prospectively gated cardiac CT protocols using an Alderson-Rando phantom and a set of patients. An anthropomorphic Alderson-Rando phantom equipped with thermoluminiscent detectors and a set of clinical patients underwent the following cardiac CT protocols: high-pitch acquisition (pitch 3.4), prospectively triggered acquisition, and retrospectively gated acquisition (pitch 0.2). For patients with sinus rhythm below 65 beats per minute (bpm), high-pitch protocol was used, whereas for patients in sinus rhythm between 65 and 100 bpm, prospective triggering was used. Patients with irregular heart rates or heart rates of ≥ 100 bpm, were examined using retrospectively gated acquisition. Evaluability of coronary artery segments was determined, and effective radiation dose was derived from the phantom study. In the phantom study, the effective radiation dose as determined with thermoluminescent detector (TLD) measurements was lowest in the high-pitch acquisition (1.21, 3.12, and 11.81 mSv, for the high-pitch, the prospectively triggered, and the retrospectively gated acquisition, respectively). There was a significant difference with respect to the percentage of motion-free coronary artery segments (99%, 87%, and 92% for high-pitch, prospectively triggered, and retrospectively gated, respectively (p < 0.001), whereas image noise was lowest for the high-pitch protocol (p < 0.05). High-pitch scans have the potential to reduce radiation dose up to 61.2% and 89.8% compared with prospectively triggered and retrospectively gated scans. High-pitch protocols lead to excellent image quality when used in patients with stable heart rates below 65 bpm.

Seizure threshold increases can be predicted by EEG quality in right unilateral ultrabrief ECT.

PubMed

Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Waite, Susan; Loo, Colleen K

2017-12-01

Increases in seizure threshold (ST) over a course of brief pulse ECT can be predicted by decreases in EEG quality, informing ECT dose adjustment to maintain adequate supra-threshold dosing. ST increases also occur over a course of right unilateral ultrabrief (RUL UB) ECT, but no data exist on the relationship between ST increases and EEG indices. This study (n = 35) investigated if increases in ST over RUL UB ECT treatments could be predicted by a decline in seizure quality. ST titration was performed at ECT session one and seven, with treatment dosing maintained stable (at 6-8 times ST) in intervening sessions. Seizure quality indices (slow-wave onset, mid-ictal amplitude, regularity, stereotypy, and post-ictal suppression) were manually rated at the first supra-threshold treatment, and last supra-threshold treatment before re-titration, using a structured rating scale, by a single trained rater blinded to the ECT session being rated. Twenty-one subjects (60%) had a ST increase. The association between ST changes and EEG quality indices was analysed by logistic regression, yielding a significant model (p < 0.001). Initial ST (p < 0.05) and percentage change in mid-ictal amplitude (p < 0.05) were significant predictors of change in ST. Percentage change in post-ictal suppression reached trend level significance (p = 0.065). Increases in ST over a RUL UB ECT course may be predicted by decreases in seizure quality, specifically decline in mid-ictal amplitude and potentially in post-ictal suppression. Such EEG indices may be able to inform when dose adjustments are necessary to maintain adequate supra-threshold dosing in RUL UB ECT.

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

NASA Technical Reports Server (NTRS)

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

1992-01-01

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

Medication Errors in Vietnamese Hospitals: Prevalence, Potential Outcome and Associated Factors

PubMed Central

Nguyen, Huong-Thao; Nguyen, Tuan-Dung; van den Heuvel, Edwin R.; Haaijer-Ruskamp, Flora M.; Taxis, Katja

2015-01-01

Background Evidence from developed countries showed that medication errors are common and harmful. Little is known about medication errors in resource-restricted settings, including Vietnam. Objectives To determine the prevalence and potential clinical outcome of medication preparation and administration errors, and to identify factors associated with errors. Methods This was a prospective study conducted on six wards in two urban public hospitals in Vietnam. Data of preparation and administration errors of oral and intravenous medications was collected by direct observation, 12 hours per day on 7 consecutive days, on each ward. Multivariable logistic regression was applied to identify factors contributing to errors. Results In total, 2060 out of 5271 doses had at least one error. The error rate was 39.1% (95% confidence interval 37.8%- 40.4%). Experts judged potential clinical outcomes as minor, moderate, and severe in 72 (1.4%), 1806 (34.2%) and 182 (3.5%) doses. Factors associated with errors were drug characteristics (administration route, complexity of preparation, drug class; all p values < 0.001), and administration time (drug round, p = 0.023; day of the week, p = 0.024). Several interactions between these factors were also significant. Nurse experience was not significant. Higher error rates were observed for intravenous medications involving complex preparation procedures and for anti-infective drugs. Slightly lower medication error rates were observed during afternoon rounds compared to other rounds. Conclusions Potentially clinically relevant errors occurred in more than a third of all medications in this large study conducted in a resource-restricted setting. Educational interventions, focusing on intravenous medications with complex preparation procedure, particularly antibiotics, are likely to improve patient safety. PMID:26383873

Antimicrobial prescribing practice in UK equine veterinary practice.

PubMed

Hughes, L A; Pinchbeck, G; Callaby, R; Dawson, S; Clegg, P; Williams, N

2013-03-01

Antimicrobial use is known to select for the emergence of resistant strains of bacteria; therefore prudent use in both human and veterinary medicine is essential to preserve their efficacy. To characterise antimicrobial prescribing patterns in UK equine practice and evaluate factors associated with prescribing. A postal questionnaire including 4 clinical scenarios was sent to 740 veterinary surgeons that treat horses. Data were collected on the clinician, their practice and sources of information regarding antimicrobials and their use. Multivariable logistic regression analysis was used to ascertain factors associated with 5 outcomes; prescribing off-licence drugs; prescribing at incorrect doses; prescribing 3rd or 4th generation cephalosporins; prescribing fluoroquinolones and prescribing potentiated sulphonamides. Questionnaires were completed by 38% of veterinary surgeons who were sent questionnaires. Less than 1% of practices had antimicrobial use guidelines. Trimethoprim-sulphonamides were most commonly prescribed in each clinical scenario. Eleven percent of prescriptions were for antimicrobial drugs not licensed for use in horses in the UK. Five percent of prescriptions for licensed antimicrobials were under the recommended dose rate and 56% over the recommended dose rate. Fluoroquinolones and 3rd and 4th generation cephalosporins accounted for 1 and 3% of prescriptions, respectively. Veterinary surgeons working at referral practices were more likely to prescribe 3rd and 4th generation cephalosporins and fluoroquinolones and off-licence antimicrobials whereas those working in first-opinion practices were more likely to prescribe potentiated sulphonamides. Sources of information regarding antimicrobials also had an effect on prescribing. Prescription of antimicrobials at inappropriate doses was common even when provided with the weight of the animal. It is uncommon for UK equine veterinary practices to have guidelines for antimicrobial use. The introduction of such guidelines could lead to more prudent use of antimicrobials. © 2012 EVJ Ltd.

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.

Shielding NSLS-II light source: Importance of geometry for calculating radiation levels from beam losses

NASA Astrophysics Data System (ADS)

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

2016-11-01

Third generation high brightness light sources are designed to have low emittance and high current beams, which contribute to higher beam loss rates that will be compensated by Top-Off injection. Shielding for these higher loss rates will be critical to protect the projected higher occupancy factors for the users. Top-Off injection requires a full energy injector, which will demand greater consideration of the potential abnormal beam miss-steering and localized losses that could occur. The high energy electron injection beam produces significantly higher neutron component dose to the experimental floor than a lower energy beam injection and ramped operations. Minimizing this dose will require adequate knowledge of where the miss-steered beam can occur and sufficient EM shielding close to the loss point, in order to attenuate the energy of the particles in the EM shower below the neutron production threshold (<10 MeV), which will spread the incident energy on the bulk shield walls and thereby the dose penetrating the shield walls. Designing supplemental shielding near the loss point using the analytic shielding model is shown to be inadequate because of its lack of geometry specification for the EM shower process. To predict the dose rates outside the tunnel requires detailed description of the geometry and materials that the beam losses will encounter inside the tunnel. Modern radiation shielding Monte-Carlo codes, like FLUKA, can handle this geometric description of the radiation transport process in sufficient detail, allowing accurate predictions of the dose rates expected and the ability to show weaknesses in the design before a high radiation incident occurs. The effort required to adequately define the accelerator geometry for these codes has been greatly reduced with the implementation of the graphical interface of FLAIR to FLUKA. This made the effective shielding process for NSLS-II quite accurate and reliable. The principles used to provide supplemental shielding to the NSLS-II accelerators and the lessons learned from this process are presented.

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.

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.

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.

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.

Detailed Distribution Map of Absorbed Dose Rate in Air in Tokatsu Area of Chiba Prefecture, Japan, Constructed by Car-Borne Survey 4 Years after the Fukushima Daiichi Nuclear Power Plant Accident.

PubMed

Inoue, Kazumasa; Arai, Moeko; Fujisawa, Makoto; Saito, Kyouko; Fukushi, Masahiro

2017-01-01

A car-borne survey was carried out in the northwestern, or Tokatsu, area of Chiba Prefecture, Japan, to make a detailed distribution map of absorbed dose rate in air four years after the Fukushima Daiichi Nuclear Power Plant accident. This area was chosen because it was the most heavily radionuclide contaminated part of Chiba Prefecture and it neighbors metropolitan Tokyo. Measurements were performed using a 3-in × 3-in NaI(Tl) scintillation spectrometer in June 2015. The survey route covered the whole Tokatsu area which includes six cities. A heterogeneous distribution of absorbed dose rate in air was observed on the dose distribution map. Especially, higher absorbed dose rates in air exceeding 80 nGy h-1 were observed along national roads constructed using high porosity asphalt, whereas lower absorbed dose rates in air were observed along local roads constructed using low porosity asphalt. The difference between these asphalt types resulted in a heterogeneous dose distribution in the Tokatsu area. The mean of the contribution ratio of artificial radionuclides to absorbed dose rate in air measured 4 years after the accident was 29% (9-50%) in the Tokatsu area. The maximum absorbed dose rate in air, 201 nGy h-1 was observed at Kashiwa City. Radiocesium was deposited in the upper 1 cm surface layer of the high porosity asphalt which was collected in Kashiwa City and the environmental half-life of the absorbed dose rate in air was estimated to be 1.7 years.

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;

Assessment of ambient gamma dose rate around a prospective uranium mining area of South India - A comparative study of dose by direct methods and soil radioactivity measurements

NASA Astrophysics Data System (ADS)

Karunakara, N.; Yashodhara, I.; Sudeep Kumara, K.; Tripathi, R. M.; Menon, S. N.; Kadam, S.; Chougaonkar, M. P.

Indoor and outdoor gamma dose rates were evaluated around a prospective uranium mining region - Gogi, South India through (i) direct measurements using a GM based gamma dose survey meter, (ii) integrated measurement days using CaSO4:Dy based thermo luminescent dosimeters (TLDs), and (iii) analyses of 273 soil samples for 226Ra, 232Th, and 40K activity concentration using HPGe gamma spectrometry. The geometric mean values of indoor and outdoor gamma dose rates were 104 nGy h-1 and 97 nGy h-1, respectively with an indoor to outdoor dose ratio of 1.09. The gamma dose rates and activity concentrations of 226Ra, 232Th, and 40K varied significantly within a small area due to the highly localized mineralization of the elements. Correlation study showed that the dose estimated from the soil radioactivity is better correlated with that measured directly using the portable survey meter, when compared to that obtained from TLDs. This study showed that in a region having localized mineralization in situ measurements using dose survey meter provide better representative values of gamma dose rates.

Low radiation dose in computed tomography: the role of iodine

PubMed Central

Aschoff, Andrik J; Catalano, Carlo; Krix, Martin; Albrecht, Thomas

2017-01-01

Recent approaches to reducing radiation exposure during CT examinations typically utilize automated dose modulation strategies on the basis of lower tube voltage combined with iterative reconstruction and other dose-saving techniques. Less clearly appreciated is the potentially substantial role that iodinated contrast media (CM) can play in low-radiation-dose CT examinations. Herein we discuss the role of iodinated CM in low-radiation-dose examinations and describe approaches for the optimization of CM administration protocols to further reduce radiation dose and/or CM dose while maintaining image quality for accurate diagnosis. Similar to the higher iodine attenuation obtained at low-tube-voltage settings, high-iodine-signal protocols may permit radiation dose reduction by permitting a lowering of mAs while maintaining the signal-to-noise ratio. This is particularly feasible in first pass examinations where high iodine signal can be achieved by injecting iodine more rapidly. The combination of low kV and IR can also be used to reduce the iodine dose. Here, in optimum contrast injection protocols, the volume of CM administered rather than the iodine concentration should be reduced, since with high-iodine-concentration CM further reductions of iodine dose are achievable for modern first pass examinations. Moreover, higher concentrations of CM more readily allow reductions of both flow rate and volume, thereby improving the tolerability of contrast administration. PMID:28471242

Risk assessment of human exposure to Ra-226 in oil produced water from the Bakken Shale.

PubMed

Torres, Luisa; Yadav, Om Prakash; Khan, Eakalak

2018-06-01

Unconventional oil production in North Dakota (ND) and other states in the United States uses large amounts of water for hydraulic fracturing to stimulate oil flow. Most of the water used returns to the surface as produced water (PW) containing different constituents. Some of these contents are total dissolved solids and radionuclides. The most predominant radionuclide in PW is radium-226 (Ra-226) of which level depends on several factors including the content of certain cations. A multivariate regression model was developed to predict Ra-226 in PW from the Bakken Shale based on the levels of barium, strontium, and calcium. The simulated Ra-226 activity concentration in PW was 535 pCi/L supporting extremely limited actual data based on three PW samples from the Bakken (527, 816, and 1210 pCi/L). The simulated activity concentration was further analyzed by studying its impact in the event of a PW spill reaching a surface water body that provides drinking water, irrigation water for crops, and recreational fishing. Using food transfer factors found in the literature, the final annual effective dose rate for an adult in ND was estimated. The global average annual effective dose rate via food and drinking water is 0.30 mSv, while the predicted dose rate in this study was 0.49 mSv indicating that there is potential risk to human health in ND due to Ra-226 in PW spills. This predicted dose rate is considered the best case scenario as it is based on the simulated Ra-226 activity concentration in PW of 535 pCi/L which is close to the low end actual activity concentration of 527 pCi/L. Copyright © 2018 Elsevier B.V. All rights reserved.

For Single Dosing, Levofloxacin Is Superior to Ciprofloxacin When Combined With an Aminoglycoside in Preventing Severe Infections After Prostate Biopsy.

PubMed

Unnikrishnan, Raman; El-Shafei, Ahmed; Klein, Eric A; Jones, J Stephen; Kartha, Ganesh; Goldman, Howard B

2015-06-01

To investigate whether there is benefit with a longer acting oral fluoroquinolone, we compared the rate of infection after transrectal ultrasound-guided prostate biopsy between 2 prophylactic antibiotic regimens: ciprofloxacin vs levofloxacin, each combined with an aminoglycoside (AG). A retrospective review was performed of all transrectal ultrasound-guided prostate biopsies from September 2011 to January 2013. Initially our regimen entailed 1 dose of 500-mg ciprofloxacin and an AG. In June 2012, we switched to 1 dose of 750-mg levofloxacin and an AG. Infections were categorized as severe if requiring hospital admission, overnight observation, or emergency room treatment for fever or chills. Those treated as an outpatient were defined as mild. Of 1189 total biopsies, the total infection rate was 3.18% (17 of 535) in the ciprofloxacin group and 2.14% (14 of 654) in the levofloxacin group (P = .26). The rate of mild infection was 0.75% (4 of 535) in the ciprofloxacin group and 1.22% (8 of 654) in the levofloxacin group (P = .56). The rate of severe infection was significantly higher in the ciprofloxacin group at 2.43% (13 of 535) compared with that of 0.92% (6 of 654) in the levofloxacin group (P = .04). On multivariate analysis, use of ciprofloxacin rather than levofloxacin was associated with an increased risk of severe infection (odds ratio, 4.59; P = .04). Empiric prophylaxis for prostate biopsies with a single-dose fluoroquinolone augmented with an AG is optimal to reduce infectious complications. We found 750-mg levofloxacin resulted in significantly fewer severe infections compared with 500-mg ciprofloxacin potentially because of its longer half-life. Copyright © 2015 Elsevier Inc. All rights reserved.

Are radiosensitivity data derived from natural field conditions consistent with data from controlled exposures? A case study of Chernobyl wildlife chronically exposed to low dose rates.

PubMed

Garnier-Laplace, J; Geras'kin, S; Della-Vedova, C; Beaugelin-Seiller, K; Hinton, T G; Real, A; Oudalova, A

2013-07-01

The discrepancy between laboratory or controlled conditions ecotoxicity tests and field data on wildlife chronically exposed to ionising radiation is presented for the first time. We reviewed the available chronic radiotoxicity data acquired in contaminated fields and used a statistical methodology to support the comparison with knowledge on inter-species variation of sensitivity to controlled external γ irradiation. We focus on the Chernobyl Exclusion Zone and effects data on terrestrial wildlife reported in the literature corresponding to chronic dose rate exposure situations (from background ~100 nGy/h up to ~10 mGy/h). When needed, we reconstructed the dose rate to organisms and obtained consistent unbiased data sets necessary to establish the dose rate-effect relationship for a number of different species and endpoints. Then, we compared the range of variation of radiosensitivity of species from the Chernobyl-Exclusion Zone with the statistical distribution established for terrestrial species chronically exposed to purely gamma external irradiation (or chronic Species radioSensitivity Distribution - SSD). We found that the best estimate of the median value (HDR50) of the distribution established for field conditions at Chernobyl (about 100 μGy/h) was eight times lower than the one from controlled experiments (about 850 μGy/h), suggesting that organisms in their natural environmental were more sensitive to radiation. This first comparison highlights the lack of mechanistic understanding and the potential confusion coming from sampling strategies in the field. To confirm the apparent higher sensitive of wildlife in the Chernobyl Exclusion Zone, we call for more a robust strategy in field, with adequate design to deal with confounding factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Phase II Study of Fixed-Dose Rate Gemcitabine Plus Low-Dose Cisplatin Followed by Consolidative Chemoradiation for Locally Advanced Pancreatic Cancer

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

Ko, Andrew H.; Quivey, Jeanne M.; Venook, Alan P.

Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m{sup 2} at 10 mg/m{sup 2}/min) plus cisplatin 20 mg/m{sup 2} on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800more » mg/m{sup 2} orally twice daily on the day of radiation) as a radiosensitizer. Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.« less

High LET radiation shows no major cellular and functional effects on primary cardiomyocytes in vitro

NASA Astrophysics Data System (ADS)

Heselich, Anja; Frieß, Johannes L.; Ritter, Sylvia; Benz, Naja P.; Layer, Paul G.; Thielemann, Christiane

2018-02-01

It is well known that ionizing radiation causes adverse effects on various mammalian tissues. However, there is little information on the biological effects of heavy ion radiation on the heart. In order to fill this gap, we systematically examined DNA-damage induction and repair, as well as proliferation and apoptosis in avian cardiomyocyte cultures irradiated with heavy ions such as titanium and iron, relevant for manned space-flight, and carbon ions, as used for radiotherapy. Further, and to our knowledge for the first time, we analyzed the effect of heavy ion radiation on the electrophysiology of primary cardiomyocytes derived from chicken embryos using the non-invasive microelectrode array (MEA) technology. As electrophysiological endpoints beat rate and field action potential duration were analyzed. The cultures clearly exhibited the capacity to repair induced DNA damage almost completely within 24 h, even at doses of 7 Gy, and almost completely recovered from radiation-induced changes in proliferative behavior. Interestingly, no significant effects on apoptosis could be detected. Especially the functionality of primary cardiac cells exhibited a surprisingly high robustness against heavy ion radiation, even at doses of up to 7 Gy. In contrast to our previous study with X-rays the beat rate remained more or less unaffected after heavy ion radiation, independently of beam quality. The only change we could observe was an increase of the field action potential duration of up to 30% after titanium irradiation, diminishing within the following three days. This potentially pathological observation may be an indication that heavy ion irradiation at high doses could bear a long-term risk for cardiovascular disease induction.

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.

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.

Radiation dose rates now and in the future for residents neighboring restricted areas of the Fukushima Daiichi Nuclear Power Plant

PubMed Central

Harada, Kouji H.; Niisoe, Tamon; Imanaka, Mie; Takahashi, Tomoyuki; Amako, Katsumi; Fujii, Yukiko; Kanameishi, Masatoshi; Ohse, Kenji; Nakai, Yasumichi; Nishikawa, Tamami; Saito, Yuuichi; Sakamoto, Hiroko; Ueyama, Keiko; Hisaki, Kumiko; Ohara, Eiji; Inoue, Tokiko; Yamamoto, Kanako; Matsuoka, Yukiyo; Ohata, Hitomi; Toshima, Kazue; Okada, Ayumi; Sato, Hitomi; Kuwamori, Toyomi; Tani, Hiroko; Suzuki, Reiko; Kashikura, Mai; Nezu, Michiko; Miyachi, Yoko; Arai, Fusako; Kuwamori, Masanori; Harada, Sumiko; Ohmori, Akira; Ishikawa, Hirohiko; Koizumi, Akio

2014-01-01

Radiation dose rates were evaluated in three areas neighboring a restricted area within a 20- to 50-km radius of the Fukushima Daiichi Nuclear Power Plant in August–September 2012 and projected to 2022 and 2062. Study participants wore personal dosimeters measuring external dose equivalents, almost entirely from deposited radionuclides (groundshine). External dose rate equivalents owing to the accident averaged 1.03, 2.75, and 1.66 mSv/y in the village of Kawauchi, the Tamano area of Soma, and the Haramachi area of Minamisoma, respectively. Internal dose rates estimated from dietary intake of radiocesium averaged 0.0058, 0.019, and 0.0088 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. Dose rates from inhalation of resuspended radiocesium were lower than 0.001 mSv/y. In 2012, the average annual doses from radiocesium were close to the average background radiation exposure (2 mSv/y) in Japan. Accounting only for the physical decay of radiocesium, mean annual dose rates in 2022 were estimated as 0.31, 0.87, and 0.53 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. The simple and conservative estimates are comparable with variations in the background dose, and unlikely to exceed the ordinary permissible dose rate (1 mSv/y) for the majority of the Fukushima population. Health risk assessment indicates that post-2012 doses will increase lifetime solid cancer, leukemia, and breast cancer incidences by 1.06%, 0.03% and 0.28% respectively, in Tamano. This assessment was derived from short-term observation with uncertainties and did not evaluate the first-year dose and radioiodine exposure. Nevertheless, this estimate provides perspective on the long-term radiation exposure levels in the three regions. PMID:24567380

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.

Antitrypanosomal Activity of Fexinidazole Metabolites, Potential New Drug Candidates for Chagas Disease

PubMed Central

Nascimento, Alvaro F. S.; Mazzeti, Ana Lia; Marques, Luiz F.; Gonçalves, Karolina R.; Mota, Ludmilla W. R.; Diniz, Lívia de F.; Caldas, Ivo S.; Talvani, André; Shackleford, David M.; Koltun, Maria; Saunders, Jessica; White, Karen L.; Scandale, Ivan; Charman, Susan A.; Chatelain, Eric

2014-01-01

This study was designed to verify the in vivo efficacy of sulfoxide and sulfone fexinidazole metabolites following oral administration in a murine model of Chagas disease. Female Swiss mice infected with the Y strain of Trypanosoma cruzi were treated orally once per day with each metabolite at doses of 10 to 100 mg/kg of body weight for a period of 20 days. Parasitemia was monitored throughout, and cures were detected by parasitological and PCR assays. The results were compared with those achieved with benznidazole treatment at the same doses. Fexinidazole metabolites were effective in reducing the numbers of circulating parasites and protecting mice against death, compared with untreated mice, but without providing cures at daily doses of 10 and 25 mg/kg. Both metabolites were effective in curing mice at 50 mg/kg/day (30% to 40%) and 100 mg/kg/day (100%). In the benznidazole-treated group, parasitological cure was detected only in animals treated with the higher dose of 100 mg/kg/day (80%). Single-dose pharmacokinetic parameters for each metabolite were obtained from a parallel group of uninfected mice and were used to estimate the profiles following repeated doses. Pharmacokinetic data suggested that biological efficacy most likely resides with the sulfone metabolite (or subsequent reactive metabolites formed following reduction of the nitro group) following administration of either the sulfoxide or the sulfone and that prolonged plasma exposure over the 24-h dosing window is required to achieve high cure rates. Fexinidazole metabolites were effective in treating T. cruzi in a mouse model of acute infection, with cure rates superior to those achieved with either fexinidazole itself or benznidazole. PMID:24841257

Evaluation of sedative R51703 in cattle: effects on cardiorespiratory functions and rumen contraction rate.

PubMed Central

Doherty, T J; Valverde, A; Valliant, A E

1988-01-01

R51703, a substance with 5-hydroxytryptamine type 2 receptor antagonist properties, was studied to assess its potential as a sedative in cattle. Six cattle in the study group were given R51703 intramuscularly at a dose rate of 0.15 mg/kg. Sedation became obvious between 10 and 15 minutes postinjection in five of these animals and lasted for approximately 120 minutes. No significant changes (P less than or equal to 0.05) were observed in respiratory rate, arterial blood gas, acid-base values or systemic arterial blood pressure. Heart rate was significantly elevated at 40, 60, 90 and 120 minutes posttreatment, but dysrhythmias were not detected. Rumen motility, as judged by the contraction rate, was decreased but not to significant levels. All animals ate normally at the end of the study period. The results indicated that R51703 may have a role in the management of domestic cattle and that further work is indicated to assess its potential in this area. PMID:3196977

Reduced Sodium Transport With Nasal Administration of the Prostasin Inhibitor Camostat in Subjects With Cystic Fibrosis

PubMed Central

Reeves, Ginger; Hathorne, Heather; Solomon, G. Martin; Abbi, Smita; Renard, Didier; Lock, Ruth; Zhou, Ping; Danahay, Henry; Clancy, John P.; Waltz, David A.

2013-01-01

Background: Prostasin, a trypsin-like serine protease, is a channel-activating protease and major regulator of epithelial sodium channel-mediated sodium absorption. Its direct inhibition by camostat represents a potential approach to inhibiting sodium transport in cystic fibrosis (CF). Methods: To determine whether a topical formulation of camostat represents an efficacious and tolerable approach to reducing Na+ transport in the CF airway, we conducted a two-part randomized, double-blind, placebo-controlled, crossover, ascending single-dose study to evaluate the pharmacodynamics, safety, and pharmacokinetics of camostat administered through a nasal spray pump in subjects with CF. Nasal potential difference (PD) was measured before and after treatment, and safety and pharmacokinetics were assessed by a standardized approach. Results: In part 1, nine subjects were enrolled, and six completed crossover dosing at the maximally tolerated dose. The change in maximal (most polarizing) basal PD 2 h following administration of camostat was +13.1 mV (1.6-mg dose group) compared with −8.6 mV following placebo (P < .005). Intrasubject change in Ringer and amiloride-sensitive PDs exhibited similar and consistent responses. Bayesian analysis in an additional six subjects in part 2 estimated a dose of 18 μg/mL to provide 50% of the maximum effect. There was no significant change in chloride transport or total nasal symptom score, nasal examination rating, and laboratory parameters. Conclusions: This study establishes the proof of concept that a reduction in sodium transport in the human CF airway can be achieved through inhibition of prostasin activity, identifying a potential therapeutic target in the disease. Trial registration: ClinicalTrials.gov; No.: NCT00506792; URL: www.clinicaltrials.gov PMID:23412700

Identifying Risk for Acute Kidney Injury in Infants and Children Following Cardiac Arrest.

PubMed

Neumayr, Tara M; Gill, Jeff; Fitzgerald, Julie C; Gazit, Avihu Z; Pineda, Jose A; Berg, Robert A; Dean, J Michael; Moler, Frank W; Doctor, Allan

2017-10-01

Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. Retrospective analysis of a public access dataset. Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. None. Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Stability analysis of a deterministic dose calculation for MRI-guided radiotherapy.

PubMed

Zelyak, O; Fallone, B G; St-Aubin, J

2017-12-14

Modern effort in radiotherapy to address the challenges of tumor localization and motion has led to the development of MRI guided radiotherapy technologies. Accurate dose calculations must properly account for the effects of the MRI magnetic fields. Previous work has investigated the accuracy of a deterministic linear Boltzmann transport equation (LBTE) solver that includes magnetic field, but not the stability of the iterative solution method. In this work, we perform a stability analysis of this deterministic algorithm including an investigation of the convergence rate dependencies on the magnetic field, material density, energy, and anisotropy expansion. The iterative convergence rate of the continuous and discretized LBTE including magnetic fields is determined by analyzing the spectral radius using Fourier analysis for the stationary source iteration (SI) scheme. The spectral radius is calculated when the magnetic field is included (1) as a part of the iteration source, and (2) inside the streaming-collision operator. The non-stationary Krylov subspace solver GMRES is also investigated as a potential method to accelerate the iterative convergence, and an angular parallel computing methodology is investigated as a method to enhance the efficiency of the calculation. SI is found to be unstable when the magnetic field is part of the iteration source, but unconditionally stable when the magnetic field is included in the streaming-collision operator. The discretized LBTE with magnetic fields using a space-angle upwind stabilized discontinuous finite element method (DFEM) was also found to be unconditionally stable, but the spectral radius rapidly reaches unity for very low-density media and increasing magnetic field strengths indicating arbitrarily slow convergence rates. However, GMRES is shown to significantly accelerate the DFEM convergence rate showing only a weak dependence on the magnetic field. In addition, the use of an angular parallel computing strategy is shown to potentially increase the efficiency of the dose calculation.

Stability analysis of a deterministic dose calculation for MRI-guided radiotherapy

NASA Astrophysics Data System (ADS)

Zelyak, O.; Fallone, B. G.; St-Aubin, J.

2018-01-01

Modern effort in radiotherapy to address the challenges of tumor localization and motion has led to the development of MRI guided radiotherapy technologies. Accurate dose calculations must properly account for the effects of the MRI magnetic fields. Previous work has investigated the accuracy of a deterministic linear Boltzmann transport equation (LBTE) solver that includes magnetic field, but not the stability of the iterative solution method. In this work, we perform a stability analysis of this deterministic algorithm including an investigation of the convergence rate dependencies on the magnetic field, material density, energy, and anisotropy expansion. The iterative convergence rate of the continuous and discretized LBTE including magnetic fields is determined by analyzing the spectral radius using Fourier analysis for the stationary source iteration (SI) scheme. The spectral radius is calculated when the magnetic field is included (1) as a part of the iteration source, and (2) inside the streaming-collision operator. The non-stationary Krylov subspace solver GMRES is also investigated as a potential method to accelerate the iterative convergence, and an angular parallel computing methodology is investigated as a method to enhance the efficiency of the calculation. SI is found to be unstable when the magnetic field is part of the iteration source, but unconditionally stable when the magnetic field is included in the streaming-collision operator. The discretized LBTE with magnetic fields using a space-angle upwind stabilized discontinuous finite element method (DFEM) was also found to be unconditionally stable, but the spectral radius rapidly reaches unity for very low-density media and increasing magnetic field strengths indicating arbitrarily slow convergence rates. However, GMRES is shown to significantly accelerate the DFEM convergence rate showing only a weak dependence on the magnetic field. In addition, the use of an angular parallel computing strategy is shown to potentially increase the efficiency of the dose calculation.

Corrigendum to "Stability analysis of a deterministic dose calculation for MRI-guided radiotherapy".

PubMed

Zelyak, Oleksandr; Fallone, B Gino; St-Aubin, Joel

2018-03-12

Modern effort in radiotherapy to address the challenges of tumor localization and motion has led to the development of MRI guided radiotherapy technologies. Accurate dose calculations must properly account for the effects of the MRI magnetic fields. Previous work has investigated the accuracy of a deterministic linear Boltzmann transport equation (LBTE) solver that includes magnetic field, but not the stability of the iterative solution method. In this work, we perform a stability analysis of this deterministic algorithm including an investigation of the convergence rate dependencies on the magnetic field, material density, energy, and anisotropy expansion. The iterative convergence rate of the continuous and discretized LBTE including magnetic fields is determined by analyzing the spectral radius using Fourier analysis for the stationary source iteration (SI) scheme. The spectral radius is calculated when the magnetic field is included (1) as a part of the iteration source, and (2) inside the streaming-collision operator. The non-stationary Krylov subspace solver GMRES is also investigated as a potential method to accelerate the iterative convergence, and an angular parallel computing methodology is investigated as a method to enhance the efficiency of the calculation. SI is found to be unstable when the magnetic field is part of the iteration source, but unconditionally stable when the magnetic field is included in the streaming-collision operator. The discretized LBTE with magnetic fields using a space-angle upwind stabilized discontinuous finite element method (DFEM) was also found to be unconditionally stable, but the spectral radius rapidly reaches unity for very low density media and increasing magnetic field strengths indicating arbitrarily slow convergence rates. However, GMRES is shown to significantly accelerate the DFEM convergence rate showing only a weak dependence on the magnetic field. In addition, the use of an angular parallel computing strategy is shown to potentially increase the efficiency of the dose calculation. © 2018 Institute of Physics and Engineering in Medicine.

Effects of Acute Administration of Ketorolac on Mammalian Vestibular Sensory Evoked Potentials

PubMed Central

Gaines, G Christopher; Jones, Timothy A

2013-01-01

The nonsteroidal antiinflammatory drug (NSAID) ketorolac is a candidate for use as a supplemental analgesic during major surgery in anesthetized rodents. The use of ketorolac during surgery is believed to reduce the anesthetic dose required to achieve and maintain an adequate surgical plane, thus improving the physiologic condition and survival of animals during long experimental procedures. Ketorolac has reported side effects that include dizziness, ear pain, hearing loss, tinnitus, and vertigo in humans, but ketorolac has not been reported to affect the vestibular system in animals. To investigate this possibility, we evaluated the acute effects of ketorolac on vestibular compound action potentials in C57BL/6 mice. Linear vestibular sensory-evoked potentials (VsEP) were recorded during the administration of ketorolac at doses 3 to 14 times the effective analgesic dose. VsEP results for ketorolac were compared with those from a control group maintained under anesthesia for the same period. Ketorolac did not significantly affect the temporal profiles of response latencies and amplitudes or the rate of change in response measures over time between controls and ketorolac-treated mice. These findings demonstrate that ketorolac can be used as an analgesic to supplement anesthesia in mice without concerns of modifying the amplitudes and latencies of the linear VsEP. PMID:23562034

MO-E-17A-09: Has Cancer Risk for Pediatric CT Increased Or Decreased? An Analysis of Cohort Data From 2004-2013

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

Brady, S; Kaufman, R

Purpose: To analyze CT radiation dosimetry trends in a pediatric population imaged with modern (2004-2013) CT technology Methods: The institutional review board approved this retrospective review. Two cohorts of pediatric patients that received CT scans for treatment or surveillance for Wilms tumor (n=73) or Neuroblastoma (n=74) from 2004–2013 were included in this study. Patients were scanned during this time period on a GE Ultra (8 slice; 2004–2007), a GE VCT (2008–2011), or a GE VCT-XTe (2011–2013). Each patient's individual or combined chest, abdomen, and pelvic CT exams (n=4138) were loaded onto a PACS workstation (Intelerad, Canada) and measured to calculatemore » their effective diameter and SSDE. Patient SSDE was used to estimate patient organ dosimetry based on previously published data. Patient's organ dosimetry were sorted by gender, weight, age, scan protocol (i.e., chest, abdomen, or pelvis), and CT scanner technology and averaged accordingly to calculate population averaged absolute and effective dose values. Results: Patient radiation dose burden calculated for all genders, weights, and ages decreased at a rate of 0.2 mSv/year (4.2 mGy/year; average organ dose) from 2004–2013; overall levels decreased by 50% from 3.0 mSv (60.0 mGy) to 1.5 mSv (25.9 mGy). Patient dose decreased at equal rates for both male and female, and for individual scan protocols. The greatest dose savings was found for patients between 0–4 years old (65%) followed by 5-9 years old (45%), 10–14 years old (30%), and > 14 years old (21%). Conclusion: Assuming a linear-nothreshold model, there always will be potential risk of cancer induction from CT. However, as demonstrated among these patient populations, effective and organ dose has decreased over the last decade; thus, potential risk of long-term side effects from pediatric CT examinations has also been reduced.« less

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-C-16A-04: Dosimetric Validation of a Partially-Shielded Gd-153 Brachytherapy Concept

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

Li, X; Adams, Q; Flynn, R

Purpose: To demonstrate by measurement that using partially shielded Gd-153 sources for rotating-shield brachytherapy (RSBT) is feasible. RSBT is a potentially superior alternative to conventional high-dose-rate brachytherapy and provides the opportunity to dramatically improve tumor dose conformity for the treatment of, for example, prostate cancer. Methods: A custom-built, stainless steel encapsulated 150 mCi Gd-153 capsule with an outer length of 12.8 mm, outer diameter of 2.10 mm, active length of 9.98 mm, and active diameter of 1.53 mm was used. A partially shielded catheter was constructed with a 500 μm platinum shield and a 500 μm aluminum emission window, bothmore » with 180° azimuthal coverage. An acrylic phantom was constructed to measure the dose distributions from the shielded catheter in the transverse plane using Gafchromic EBT3 films. Film calibration curves were generated from 50, 70, and 100 kVp x-ray beams with NIST-traceable air kerma values to account for energy variation. Results: The transmission ratios of platinum to aluminum shielding at 1 cm off-axis are 7.5% and 7.6% for Monte Carlo (MCNP5) predicted and experimental results, respectively. The predicted/measured relative dose rates at 1 cm, 2 cm and 3 cm off-axis through the Al window were 100%/92.9%, 28.6%/27.0% and 13.8%/12.7%, respectively. Through the Pt shield, the predicted/measured relative dose rates were 7.5%/7.1%, 3.8%/3.0% and 2.4%/1.7%, respectively. Conclusion: Using partially-shielded Gd-153 sources for RSBT is a promising approach to improving brachytherapy dose distributions. The next step in making Gd-153 based RSBT a reality is developing a Gd-153 source that is small enough such that the source, shield, and catheter all fit within a 16 gauge needle, which has a 1.65 mm diameter. University of Iowa Research Foundation.« less

Characterization of a synthetic single crystal diamond detector for dosimetry in spatially fractionated synchrotron x-ray fields.

PubMed

Livingstone, Jayde; Stevenson, Andrew W; Butler, Duncan J; Häusermann, Daniel; Adam, Jean-François

2016-07-01

Modern radiotherapy modalities often use small or nonstandard fields to ensure highly localized and precise dose delivery, challenging conventional clinical dosimetry protocols. The emergence of preclinical spatially fractionated synchrotron radiotherapies with high dose-rate, sub-millimetric parallel kilovoltage x-ray beams, has pushed clinical dosimetry to its limit. A commercially available synthetic single crystal diamond detector designed for small field dosimetry has been characterized to assess its potential as a dosimeter for synchrotron microbeam and minibeam radiotherapy. Experiments were carried out using a synthetic diamond detector on the imaging and medical beamline (IMBL) at the Australian Synchrotron. The energy dependence of the detector was characterized by cross-referencing with a calibrated ionization chamber in monoenergetic beams in the energy range 30-120 keV. The dose-rate dependence was measured in the range 1-700 Gy/s. Dosimetric quantities were measured in filtered white beams, with a weighted mean energy of 95 keV, in broadbeam and spatially fractionated geometries, and compared to reference dosimeters. The detector exhibits an energy dependence; however, beam quality correction factors (kQ) have been measured for energies in the range 30-120 keV. The kQ factor for the weighted mean energy of the IMBL radiotherapy spectrum, 95 keV, is 1.05 ± 0.09. The detector response is independent of dose-rate in the range 1-700 Gy/s. The percentage depth dose curves measured by the diamond detector were compared to ionization chambers and agreed to within 2%. Profile measurements of microbeam and minibeam arrays were performed. The beams are well resolved and the full width at halfmaximum agrees with the nominal width of the beams. The peak to valley dose ratio (PVDR) calculated from the profiles at various depths in water agrees within experimental error with PVDR calculations from Gafchromic film data. The synthetic diamond detector is now well characterized and will be used to develop an experimental dosimetry protocol for spatially fractionated synchrotron radiotherapy.

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.

Comparative analysis of dose rates in bricks determined by neutron activation analysis, alpha counting and X-ray fluorescence analysis for the thermoluminescence fine grain dating method

NASA Astrophysics Data System (ADS)

Bártová, H.; Kučera, J.; Musílek, L.; Trojek, T.

2014-11-01

In order to evaluate the age from the equivalent dose and to obtain an optimized and efficient procedure for thermoluminescence (TL) dating, it is necessary to obtain the values of both the internal and the external dose rates from dated samples and from their environment. The measurements described and compared in this paper refer to bricks from historic buildings and a fine-grain dating method. The external doses are therefore negligible, if the samples are taken from a sufficient depth in the wall. However, both the alpha dose rate and the beta and gamma dose rates must be taken into account in the internal dose. The internal dose rate to fine-grain samples is caused by the concentrations of natural radionuclides 238U, 235U, 232Th and members of their decay chains, and by 40K concentrations. Various methods can be used for determining trace concentrations of these natural radionuclides and their contributions to the dose rate. The dose rate fraction from 238U and 232Th can be calculated, e.g., from the alpha count rate, or from the concentrations of 238U and 232Th, measured by neutron activation analysis (NAA). The dose rate fraction from 40K can be calculated from the concentration of potassium measured, e.g., by X-ray fluorescence analysis (XRF) or by NAA. Alpha counting and XRF are relatively simple and are accessible for an ordinary laboratory. NAA can be considered as a more accurate method, but it is more demanding regarding time and costs, since it needs a nuclear reactor as a neutron source. A comparison of these methods allows us to decide whether the time- and cost-saving simpler techniques introduce uncertainty that is still acceptable.

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.

Comparative effects of pulmonary and parenteral Δ⁹-tetrahydrocannabinol exposure on extinction of opiate-induced conditioned aversion in rats.

PubMed

Manwell, Laurie A; Mallet, Paul E

2015-05-01

Evidence suggesting that the endogenous cannabinoid (eCB) system can be manipulated to facilitate or impair extinction of learned behaviours has important consequences for opiate withdrawal and abstinence. We demonstrated that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases eCB levels, facilitates extinction of a naloxone-precipitated morphine withdrawal-induced conditioned place aversion (CPA). The potential of the exogenous CB1 ligand, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), to facilitate extinction of this CPA was tested. Effects of both pulmonary and parenteral Δ(9)-THC exposure were evaluated using comparable doses previously determined. Rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered Δ(9)-THC-pulmonary (1, 5, 10 mg vapour inhalation) or parenteral (0.5, 1.0, 1.5 mg/kg intraperitoneal injection)-prior to each of 20 to 28 extinction/testing trials. Vapourized Δ(9)-THC facilitated extinction of the CPA in a dose- and time-dependent manner: 5 and 10 mg facilitated extinction compared to vehicle and 1 mg Δ(9)-THC. Injected Δ(9)-THC significantly impaired extinction only for the 1.0-mg/kg dose: it prolonged the CPA fourfold longer than the vehicle and 0.5- and 1.5-mg/kg doses. These data suggest that both dose and route of Δ(9)-THC administration have important consequences for its pharmacokinetic and behavioural effects; specifically, pulmonary exposure at higher doses facilitates, whereas pulmonary and parenteral exposure at lower doses impairs, rates of extinction learning for CPA. Pulmonary-administered Δ(9)-THC may prove beneficial for potentiation of extinction learning for aversive memories, such as those supporting drug-craving/seeking in opiate withdrawal syndrome, and other causes of conditioned aversions, such as illness and stress.

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

NASA Astrophysics Data System (ADS)

Dolan, David J.

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

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder.

PubMed

Oudshoorn, Simone C; van Tilborg, Theodora C; Eijkemans, Marinus J C; Oosterhuis, G Jur E; Friederich, Jaap; van Hooff, Marcel H A; van Santbrink, Evert J P; Brinkhuis, Egbert A; Smeenk, Jesper M J; Kwee, Janet; de Koning, Corry H; Groen, Henk; Lambalk, Cornelis B; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed. Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS. No consensus has been reached on whether ORT-based FSH dosing improves effectiveness and safety in women with a predicted hyper response. Between May 2011 and May 2014, we performed an open-label, multicentre RCT in women with regular menstrual cycles and an AFC > 15. Women with polycystic ovary syndrome (Rotterdam criteria) were excluded. The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. Secondary outcomes included the occurrence of OHSS and cost-effectiveness. Since this RCT was embedded in a cohort study assessing over 1500 women, we expected to randomize 300 predicted hyper responders. Women with an AFC > 15 were randomized to an FSH dose of 100 IU or 150 IU/day. In both groups, dose adjustment was allowed in subsequent cycles (maximum 25 IU in the reduced and 50 IU in the standard group) based on pre-specified criteria. Both effectiveness and cost-effectiveness were evaluated from an intention-to-treat perspective. We randomized 255 women to a daily FSH dose of 100 IU and 266 women to a daily FSH dose of 150 IU. The cumulative live birth rate was 66.3% (169/255) in the reduced versus 69.5% (185/266) in the standard group (relative risk (RR) 0.95 [95%CI, 0.85-1.07], P = 0.423). The occurrence of any grade of OHSS was lower after a lower FSH dose (5.2% versus 11.8%, RR 0.44 [95%CI, 0.28-0.71], P = 0.001), but the occurrence of severe OHSS did not differ (1.3% versus 1.1%, RR 1.25 [95%CI, 0.38-4.07], P = 0.728). As dose reduction was not less expensive (€4.622 versus €4.714, delta costs/woman €92 [95%CI, -479-325]), there was no dominant strategy in the economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. Although strict cancellation criteria were provided, selective cancelling in the reduced dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as first cycle live birth rates did not differ from the cumulative results, the open design probably did not mask a potential benefit for the reduced dosing group. As this RCT was embedded in a larger cohort study, the power in this study was unavoidably lower than it should be. Participants had a relatively low BMI from an international perspective, which may limit generalization of the findings. In women with a predicted hyper response scheduled for IVF/ICSI, a reduced FSH dose does not affect live birth rates. A lower FSH dose did reduce the incidence of mild and moderate OHSS, but had no impact on severe OHSS. Future research into ORT-based dosing in women with a predicted hyper response should compare various safety management strategies and should be powered on a clinically relevant safety outcome while assessing non-inferiority towards live birth rates. This trial was funded by The Netherlands Organization for Health Research and Development (ZonMW, Project Number 171102020). SCO, TCvT and HLT received an unrestricted research grant from Merck Serono (the Netherlands). CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV and Merck Serono for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657. 20 December 2010. 12 May 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

In vivo dose verification method in catheter based high dose rate brachytherapy.

PubMed

Jaselskė, Evelina; Adlienė, Diana; Rudžianskas, Viktoras; Urbonavičius, Benas Gabrielis; Inčiūra, Arturas

2017-12-01

In vivo dosimetry is a powerful tool for dose verification in radiotherapy. Its application in high dose rate (HDR) brachytherapy is usually limited to the estimation of gross errors, due to inability of the dosimetry system/ method to record non-uniform dose distribution in steep dose gradient fields close to the radioactive source. In vivo dose verification in interstitial catheter based HDR brachytherapy is crucial since the treatment is performed inserting radioactive source at the certain positions within the catheters that are pre-implanted into the tumour. We propose in vivo dose verification method for this type of brachytherapy treatment which is based on the comparison between experimentally measured and theoretical dose values calculated at well-defined locations corresponding dosemeter positions in the catheter. Dose measurements were performed using TLD 100-H rods (6 mm long, 1 mm diameter) inserted in a certain sequences into additionally pre-implanted dosimetry catheter. The adjustment of dosemeter positioning in the catheter was performed using reconstructed CT scans of patient with pre-implanted catheters. Doses to three Head&Neck and one Breast cancer patient have been measured during several randomly selected treatment fractions. It was found that the average experimental dose error varied from 4.02% to 12.93% during independent in vivo dosimetry control measurements for selected Head&Neck cancer patients and from 7.17% to 8.63% - for Breast cancer patient. Average experimental dose error was below the AAPM recommended margin of 20% and did not exceed the measurement uncertainty of 17.87% estimated for this type of dosemeters. Tendency of slightly increasing average dose error was observed in every following treatment fraction of the same patient. It was linked to the changes of theoretically estimated dosemeter positions due to the possible patient's organ movement between different treatment fractions, since catheter reconstruction was performed for the first treatment fraction only. These findings indicate potential for further average dose error reduction in catheter based brachytherapy by at least 2-3% in the case that catheter locations will be adjusted before each following treatment fraction, however it requires more detailed investigation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Research design strategies to evaluate the impact of formulations on abuse liability.

PubMed

McColl, Shelley; Sellers, Edward M

2006-06-01

Scheduling of a chemical drug substance under the Controlled Substances Act (CSA) includes an evaluation of preclinical and clinical safety, and experimental abuse liability studies, as well as information on diversion and overdose. Formulations that mitigate abuse liability, dependence potential and public health risks (e.g., altered absorption rate and tamperability, long half-life, pro-drugs and combination products) are amenable to preclinical and clinical studies to compare their abuse potential to reference compounds. For new formulations (NF) as marketed agents, direct comparison to the immediate release (IR) formulation of the reference compound is typically needed across the full range of potential studies. While the public health advantage of formulation changes in the marketplace can be conceptualized in behavioral economic terms, generating persuasive data is challenging. Study complexity increases because of additional conditions (e.g., placebo, 2-3 doses of the IR formulation, 2-3 doses of the new formulation, and 2-3 doses of the unscheduled or negative control drug), larger sample sizes (study power driven by the comparison of the new formulation versus the IR or placebo), and associated increases in study duration. However, the use of single maximal doses of well-characterized controls can reduce the number of study arms, and using incomplete block designs can reduce study duration. Less typical experimental approaches may also be useful, such as human choice or discrimination procedures, or pre-marketing consumer studies among experienced drug tamperers. New formulations that demonstrate a substantial difference from marketed or reference products have a potential marketing advantage and should require less onerous risk management. Post-marketing epidemiological data demonstrating the lack of abuse will carry the most weight from a public health and physician perspective.

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.

Evaluating exposure and potential effects on honeybee brood (Apis mellifera) development using glyphosate as an example

PubMed Central

Thompson, Helen M; Levine, Steven L; Doering, Janine; Norman, Steve; Manson, Philip; Sutton, Peter; von Mérey, Georg

2014-01-01

This study aimed to develop an approach to evaluate potential effects of plant protection products on honeybee brood with colonies at realistic worst-case exposure rates. The approach comprised 2 stages. In the first stage, honeybee colonies were exposed to a commercial formulation of glyphosate applied to flowering Phacelia tanacetifolia with glyphosate residues quantified in relevant matrices (pollen and nectar) collected by foraging bees on days 1, 2, 3, 4, and 7 postapplication and glyphosate levels in larvae were measured on days 4 and 7. Glyphosate levels in pollen were approximately 10 times higher than in nectar and glyphosate demonstrated rapid decline in both matrices. Residue data along with foraging rates and food requirements of the colony were then used to set dose rates in the effects study. In the second stage, the toxicity of technical glyphosate to developing honeybee larvae and pupae, and residues in larvae, were then determined by feeding treated sucrose directly to honeybee colonies at dose rates that reflect worst-case exposure scenarios. There were no significant effects from glyphosate observed in brood survival, development, and mean pupal weight. Additionally, there were no biologically significant levels of adult mortality observed in any glyphosate treatment group. Significant effects were observed only in the fenoxycarb toxic reference group and included increased brood mortality and a decline in the numbers of bees and brood. Mean glyphosate residues in larvae were comparable at 4 days after spray application in the exposure study and also following dosing at a level calculated from the mean measured levels in pollen and nectar, showing the applicability and robustness of the approach for dose setting with honeybee brood studies. This study has developed a versatile and predictive approach for use in higher tier honeybee toxicity studies. It can be used to realistically quantify exposure of colonies to pesticides to allow the appropriate dose rates to be determined, based on realistic worst-case residues in pollen and nectar and estimated intake by the colony, as shown by the residue analysis. Previous studies have used the standard methodology developed primarily to identify pesticides with insect-growth disrupting properties of pesticide formulations, which are less reliant on identifying realistic exposure scenarios. However, this adaptation of the method can be used to determine dose–response effects of colony level exposure to pesticides with a wide range of properties. This approach would limit the number of replicated tunnel or field-scale studies that need to be undertaken to assess effects on honeybee brood and may be of particular benefit where residues in pollen and nectar are crop- and/or formulation-specific, such as systemic seed treatments and granular applications. Integr Environ Assess Manag 2014;10:463–470. PMID:24616275

Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Motov, Sergey; Yasavolian, Matthew; Likourezos, Antonios; Pushkar, Illya; Hossain, Rukhsana; Drapkin, Jefferson; Cohen, Victor; Filk, Nicholas; Smith, Andrew; Huang, Felix; Rockoff, Bradley; Homel, Peter; Fromm, Christian

2017-08-01

Nonsteroidal anti-inflammatory drugs are used extensively for the management of acute and chronic pain, with ketorolac tromethamine being one of the most frequently used parenteral analgesics in the emergency department (ED). The drugs may commonly be used at doses above their analgesic ceiling, offering no incremental analgesic advantage while potentially adding risk of harm. We evaluate the analgesic efficacy of 3 doses of intravenous ketorolac in ED patients with acute pain. We conducted a randomized, double-blind trial to assess the analgesic efficacy of 3 doses of intravenous ketorolac (10, 15, and 30 mg) in patients aged 18 to 65 years and presenting to the ED with moderate to severe acute pain, defined by a numeric rating scale score greater than or equal to 5. We excluded patients with peptic ulcer disease, gastrointestinal hemorrhage, renal or hepatic insufficiency, allergies to nonsteroidal anti-inflammatory drugs, pregnancy or breastfeeding, systolic blood pressure less than 90 or greater than 180 mm Hg, and pulse rate less than 50 or greater than 150 beats/min. Primary outcome was pain reduction at 30 minutes. We recorded pain scores at baseline and up to 120 minutes. Intravenous morphine 0.1 mg/kg was administered as a rescue analgesic if subjects still desired additional pain medication at 30 minutes after the study drug was administered. Data analyses included mixed-model regression and ANOVA. We enrolled 240 subjects (80 in each dose group). At 30 minutes, substantial pain reduction was demonstrated without any differences between the groups (95% confidence intervals 4.5 to 5.7 for the 10-mg group, 4.5 to 5.6 for the 15-mg group, and 4.2 to 5.4 for the 30-mg group). The mean numeric rating scale pain scores at baseline were 7.7, 7.5, and 7.8 and improved to 5.1, 5.0, and 4.8, respectively, at 30 minutes. Rates of rescue analgesia were similar, and there were no serious adverse events. Secondary outcomes showed similar rates of adverse effects per group, of which the most common were dizziness, nausea, and headache. Ketorolac has similar analgesic efficacy at intravenous doses of 10, 15, and 30 mg, showing that intravenous ketorolac administered at the analgesic ceiling dose (10 mg) provided effective pain relief to ED patients with moderate to severe pain without increased adverse effects. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

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

Detailed Distribution Map of Absorbed Dose Rate in Air in Tokatsu Area of Chiba Prefecture, Japan, Constructed by Car-Borne Survey 4 Years after the Fukushima Daiichi Nuclear Power Plant Accident

PubMed Central

Inoue, Kazumasa; Arai, Moeko; Fujisawa, Makoto; Saito, Kyouko; Fukushi, Masahiro

2017-01-01

A car-borne survey was carried out in the northwestern, or Tokatsu, area of Chiba Prefecture, Japan, to make a detailed distribution map of absorbed dose rate in air four years after the Fukushima Daiichi Nuclear Power Plant accident. This area was chosen because it was the most heavily radionuclide contaminated part of Chiba Prefecture and it neighbors metropolitan Tokyo. Measurements were performed using a 3-in × 3-in NaI(Tl) scintillation spectrometer in June 2015. The survey route covered the whole Tokatsu area which includes six cities. A heterogeneous distribution of absorbed dose rate in air was observed on the dose distribution map. Especially, higher absorbed dose rates in air exceeding 80 nGy h-1 were observed along national roads constructed using high porosity asphalt, whereas lower absorbed dose rates in air were observed along local roads constructed using low porosity asphalt. The difference between these asphalt types resulted in a heterogeneous dose distribution in the Tokatsu area. The mean of the contribution ratio of artificial radionuclides to absorbed dose rate in air measured 4 years after the accident was 29% (9–50%) in the Tokatsu area. The maximum absorbed dose rate in air, 201 nGy h-1 was observed at Kashiwa City. Radiocesium was deposited in the upper 1 cm surface layer of the high porosity asphalt which was collected in Kashiwa City and the environmental half-life of the absorbed dose rate in air was estimated to be 1.7 years. PMID:28129382

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.

Changes in ambient dose equivalent rates around roads at Kawamata town after the Fukushima accident.

PubMed

Kinase, Sakae; Sato, Satoshi; Sakamoto, Ryuichi; Yamamoto, Hideaki; Saito, Kimiaki

2015-11-01

Changes in ambient dose equivalent rates noted through vehicle-borne surveys have elucidated ecological half-lives of radioactive caesium in the environment. To confirm that the ecological half-lives are appropriate for predicting ambient dose equivalent rates within living areas, it is important to ascertain ambient dose equivalent rates on/around roads. In this study, radiation monitoring on/around roads at Kawamata town, located about 37 km northwest of the Fukushima Daiichi Nuclear Power Plant, was performed using monitoring vehicles and survey meters. It was found that the ambient dose equivalent rates around roads were higher than those on roads as of October 2012. And withal the ecological half-lives on roads were essentially consistent with those around roads. With dose predictions using ecological half-lives on roads, it is necessary to make corrections to ambient dose equivalent rates through the vehicle-borne surveys against those within living areas. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Incidental renal tumours on low-dose CT lung cancer screening exams.

PubMed

Pinsky, Paul F; Dunn, Barbara; Gierada, David; Nath, P Hrudaya; Munden, Reginald; Berland, Lincoln; Kramer, Barnett S

2017-06-01

Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55-74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9-1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P < 0.001). Cases with abnormalities below the diaphragms had shorter median time to diagnosis than those without (71 vs. 160 days, P = 0.004). In the reader study, 64% of renal cancer cases versus 13% of non-cases had abnormalities below the diaphragms; 55% of cases and 0.8% of non-cases had a finding suspicious for renal cancer (P < 0.001). Conclusion Low-dose computed tomography screens can potentially detect renal cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown.

Correlation between measles vaccine doses: implications for the maintenance of elimination.

PubMed

McKee, A; Ferrari, M J; Shea, K

2018-03-01

Measles eradication efforts have been successful at achieving elimination in many countries worldwide. Such countries actively work to maintain this elimination by continuing to improve coverage of two routine doses of measles vaccine following measles elimination. While improving measles vaccine coverage is always beneficial, we show, using a steady-state analysis of a dynamical model, that the correlation between populations receiving the first and second routine dose also has a significant impact on the population immunity achieved by a specified combination of first and second dose coverage. If the second dose is administered to people independently of whether they had the first dose, high second-dose coverage improves the proportion of the population receiving at least one dose, and will have a large effect on population immunity. If the second dose is administered only to people who have had the first dose, high second-dose coverage reduces the rate of primary vaccine failure, but does not reach people who missed the first dose; this will therefore have a relatively small effect on population immunity. When doses are administered dependently, and assuming the first dose has higher coverage, increasing the coverage of the first dose has a larger impact on population immunity than does increasing the coverage of the second. Correlation between vaccine doses has a significant impact on the level of population immunity maintained by current vaccination coverage, potentially outweighing the effects of age structure and, in some cases, recent improvements in vaccine coverage. It is therefore important to understand the correlation between vaccine doses as such correlation may have a large impact on the effectiveness of measles vaccination strategies.

Modeling potential responses to smallpox as a bioterrorist weapon.

PubMed

Meltzer, M I; Damon, I; LeDuc, J W; Millar, J D

2001-01-01

We constructed a mathematical model to describe the spread of smallpox after a deliberate release of the virus. Assuming 100 persons initially infected and 3 persons infected per infectious person, quarantine alone could stop disease transmission but would require a minimum daily removal rate of 50% of those with overt symptoms. Vaccination would stop the outbreak within 365 days after release only if disease transmission were reduced to <0.85 persons infected per infectious person. A combined vaccination and quarantine campaign could stop an outbreak if a daily quarantine rate of 25% were achieved and vaccination reduced smallpox transmission by > or = 33%. In such a scenario, approximately 4,200 cases would occur and 365 days would be needed to stop the outbreak. Historical data indicate that a median of 2,155 smallpox vaccine doses per case were given to stop outbreaks, implying that a stockpile of 40 million doses should be adequate.

Radiation biology of HZE particles

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.

1990-01-01

The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets which may be related to charge, velocity, or rate of energy loss. There are many consequences of this feature to biological endpoints when compared to effects of ionizing photons. Dose vs response and dose rate kinetics are modified, DNA and cellular repair systems are altered in their abilities to cope with damage and, the qualitative features of damage are unique for different ions. These features must be incorporated into any risk assessment system for radiation health management. HZE induced mutation, cell inactivation and altered organogenesis will be discussed emphasizing studies with the nematode Caenorhabditis elegans and cultured cells. Observations from radiobiology experiments in space will also be reviewed along with plans for future space-based studies.

Radiation synthesis and characterization of hyaluronan capped gold nanoparticles.

PubMed

Hien, Nguyen Quoc; Van Phu, Dang; Duy, Nguyen Ngoc; Quoc, Le Anh

2012-06-20

Gold nanoparticles (AuNPs) with diameter from 4 to 10nm, capping by hyaluronan (HA) were synthesized using a γ-irradiation method. The maximum absorption wavelengths at 517-525 nm of colloidal AuNPs/HA solutions were measured by UV-vis spectroscopy. The size and size distribution of AuNPs were determined from TEM images. The influence of various factors on the size of AuNPs particularly the concentration of Au3+ and HA, and dose rate were also investigated. Results indicated that higher dose rate and HA concentration favor smaller sizes of AuNPs whereas the size increases with Au3+ concentration. The colloidal AuNPs/HA solution was fairly stable more than 6 months under storage at ambient condition. The AuNPs stabilized by biocompatible HA with the size less than 10nm as prepared can potentially be applied in biomedicines and cosmetics. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

MAGIC with formaldehyde applied to dosimetry of HDR brachytherapy source

NASA Astrophysics Data System (ADS)

Marques; T; Fernandes; J; Barbi; G; Nicolucci; P; Baffa; O

2009-05-01

The use of polymer gel dosimeters in brachytherapy can allow the determination of three-dimensional dose distributions in large volumes and with high spatial resolution if an adequate calibration process is performed. One of the major issues in these experiments is the polymer gel response dependence on dose rate when high dose rate sources are used and the doses in the vicinity of the sources are to be determinated. In this study, the response of a modified MAGIC polymer gel with formaldehyde around an Iridium-192 HDR brachytherapy source is presented. Experimental results obtained with this polymer gel were compared with ionization chamber measurements and with Monte Carlo simulation with PENELOPE. A maximum difference of 3.10% was found between gel dose measurements and Monte Carlo simulation at a radial distance of 18 mm from the source. The results obtained show that the gel's response is strongly influenced by dose rate and that a different calibration should be used for the vicinity of the source and for regions of lower dose rates. The results obtained in this study show that, provided the proper calibration is performed, MAGIC with formaldehyde can be successfully used to accurate determinate dose distributions form high dose rate brachytherapy sources.

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.

Sperm Oxidative Stress Is Detrimental to Embryo Development: A Dose-Dependent Study Model and a New and More Sensitive Oxidative Status Evaluation

PubMed Central

de Castro, Letícia S.; de Assis, Patrícia M.; Siqueira, Adriano F. P.; Hamilton, Thais R. S.; Mendes, Camilla M.; Losano, João D. A.; Nichi, Marcílio; Visintin, José A.; Assumpção, Mayra E. O. A.

2016-01-01

Our study aimed to assess the impact of sperm oxidative stress on embryo development by means of a dose-dependent model. In experiment 1, straws from five bulls were subjected to incubation with increasing H2O2 doses (0, 12.5, 25, and 50 μM). Motility parameters were evaluated by Computed Assisted System Analysis (CASA). Experiment 2 was designed to study a high (50 μM) and low dose (12.5 μM) of H2O2 compared to a control (0 μM). Samples were incubated and further used for in vitro fertilization. Analyses of motility (CASA), oxidative status (CellROX green and 2'-7' dichlorofluorescein diacetate), mitochondrial potential (JC-1), chromatin integrity (AO), and sperm capacitation status (chlortetracycline) were performed. Embryos were evaluated based on fast cleavage (30 h.p.i.), cleavage (D = 3), development (D = 5), and blastocyst rates (D = 8). We observed a dose-dependent deleterious effect of H2O2 on motility and increase on the percentages of positive cells for CellROX green, capacitated sperm, and AO. A decrease on cleavage and blastocyst rates was observed as H2O2 increased. Also, we detected a blockage on embryo development. We concluded that sperm when exposed to oxidative environment presents impaired motility traits, prooxidative status, and premature capacitation; such alterations resulting in embryo development fail. PMID:26770658

Lead accumulation in feathers of nestling black-crowned night herons (Nycticorax nycticorax) experimentally treated in the field.

PubMed

Golden, Nancy H; Rattner, Barnett A; Cohen, Jonathan B; Hoffman, David J; Russek-Cohen, Estelle; Ottinger, Mary Ann

2003-07-01

Although lead can attain high concentrations in feathers, interpretation of the biological significance of this phenomenon is difficult. As part of an effort to develop and validate noninvasive methods to monitor contaminant exposure in free-ranging birds, lead uptake by feathers of nestling black-crowned night herons (Nycticorax nycticorax) was evaluated in a controlled exposure study. Four- to 6-d-old heron nestlings (one/nest) at Chincoteague Bay, Virginia (USA), received a single intraperitoneal injection of dosing vehicle (control, n = 7) or a dose of lead nitrate in water (0.01, 0.05, or 0.25 mg Pb/g body wt of nestling; n = 6 or 7/dose) chosen to yield feather lead concentrations found at low- to moderately polluted sites. Nestlings were euthanized at 15 d of age. Lead accumulation in feathers was associated with concentrations in bone, kidney, and liver (r = 0.32-0.74, p < 0.02) but exhibited only modest dose dependence. Blood delta-aminolevulinic acid dehydratase activity was inhibited by lead, although effects on other biochemical endpoints were marginal. Tarsus growth rate was inversely related to feather lead concentration. Culmen growth rate was depressed in nestlings treated with the highest dose of lead but not correlated with feather lead concentration. These findings provide evidence that feathers of nestling herons are a sensitive indicator of lead exposure and have potential application for the extrapolation of lead concentrations in other tissues and the estimation of environmental lead exposure in birds.

Lead accumulation in feathers of nestling black-crowned night-herons (Nycticorax nycticorax) experimentally treated in the field

USGS Publications Warehouse

Golden, N.H.; Rattner, B.A.; Cohen, J.B.; Hoffman, D.J.; Russek-Cohen, E.; Ottinger, M.A.

2003-01-01

Although lead can attain high concentrations in feathers, interpretation of the biological significance of this phenomenon is difficult. As part of an effort to develop and validate non-invasive methods to monitor contaminant exposure in free-ranging birds, lead uptake by feathers of nestling black-crowned night-herons (Nycticorax nycticorax) was evaluated in a controlled exposure study. Four to six day-old heron nestlings (one/nest) at Chincoteague Bay, Virginia, received a single intraperitoneal injection of dosing vehicle (control; n=7) or a dose of lead nitrate in water (0.01, 0.05, or 0.25 mg Pb/g body weight of nestling; n=6 or 7/dose) chosen to yield feather lead concentrations found at low to moderately polluted sites. Nestlings were euthanized at 15 days of age. Lead accumulation in feathers was associated with concentrations in bone, kidney, and liver (r = 0.32 - 0.74, p < 0.02), but exhibited only modest dose-dependence. Blood delta-aminolevulinic acid dehydratase activity was inhibited by lead, although effects on other biochemical endpoints were marginal. Tarsus growth rate was inversely related to feather lead concentration. Culmen growth rate was depressed in nestlings treated with the highest dose of lead, but not correlated with feather lead concentration. These findings provide evidence that feathers of nestling herons are a sensitive indicator of lead exposure and have potential application for the extrapolation of lead concentrations in other tissues and the estimation of environmental lead exposure in birds.

Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

PubMed Central

Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John

2018-01-01

Introduction Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED). Methods We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a period over six years (2010–2016). Primary data analyses included dosing and duration of infusion, rates of pre- and post-infusion analgesic administration, and final diagnoses. Secondary data included pre- and post-infusion pain scores and rates of side effects. Results A total of 104 patients were enrolled in the study. Average dosing of SDK infusion was 11.26 mg/hr, and the mean duration of infusion was 135.87 minutes. There was a 38% increase in patients not requiring post-infusion analgesia. The average decrease in pain score was 5.04. There were 12 reported adverse effects, with nausea being the most prevalent. Conclusion Continuous intravenous SDK infusion has a role in controlling pain of various etiologies in the ED with a potential to reduce the need for co-analgesics or rescue analgesic administration. There is a need for more robust, prospective, randomized trials that will further evaluate the analgesic efficacy and safety of this modality across a wide range of pain syndromes and different age groups in the ED. PMID:29760856

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

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.

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

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

NASA Astrophysics Data System (ADS)

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

2010-07-01

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

Thin film organic photodetectors for indirect X-ray detection demonstrating low dose rate sensitivity at low voltage operation

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

Starkenburg, Daken J.; Johns, Paul M.; Baciak, James E.

Here, developments in the field of organic semiconductors have generated organic photodetectors with high quantum efficiency, wide spectral sensitivity, low power consumption, and unique form factors that are flexible and conformable to their substrate shape. In this work, organic photodetectors coupled with inorganic CsI(Tl) scintillators are used to showcase the low dose rate sensitivity that is enabled when high performance organic photodetectors and scintillator crystals are integrated. The detection capability of these organic-inorganic coupled systems to high energy radiation highlights their potential as an alternative to traditional photomultiplier tubes for nuclear spectroscopy applications. When exposed to Bremsstrahlung radiation produced frommore » an X-ray generator, SubPc:C 60, AlPcCl:C 70, and P3HT:PC 61BM thin film photodetectors with active layer thicknesses less than 100 nm show detection of incident radiation at low and no applied bias. Remarkably low dose rates, down to at least 0.28 µGy/s, were detectable with a characteristic linear relationship between exposure rate and photodetector current output. These devices also demonstrate sensitivities as high as 5.37 mC Gy -1 cm -2 when coupled to CsI(Tl). Additionally, as the tube voltage across the X-ray generator was varied, these organic-inorganic systems showed their ability to detect a range of continuous radiation spectra spanning several hundred keV.« less

Thin film organic photodetectors for indirect X-ray detection demonstrating low dose rate sensitivity at low voltage operation

DOE PAGES

Starkenburg, Daken J.; Johns, Paul M.; Baciak, James E.; ...

2017-12-14

Developments in the field of organic semiconductors have generated organic photodetectors with high quantum efficiency, wide spectral sensitivity, low power consumption, and unique form factors that are flexible and conformable to their substrate shape. In this work, organic photodetectors coupled with inorganic CsI(Tl) scintillators are used to showcase the low dose rate sensitivity that is enabled when high performance organic photodetectors and scintillator crystals are integrated. The detection capability of these organic-inorganic coupled systems to high energy radiation highlights their potential as an alternative to traditional photomultiplier tubes for nuclear spectroscopy applications. When exposed to Bremsstrahlung radiation produced from anmore » X-ray generator, SubPc:C60, AlPcCl:C70, and P3HT:PC61BM thin film photodetectors with active layer thicknesses less than 100 nm show detection of incident radiation at low and no applied bias. Remarkably low dose rates, down to at least 0.28 µGy/s, were detectable with a characteristic linear relationship between exposure rate and photodetector current output. These devices also demonstrate sensitivities as high as 5.37 mC Gy-1 cm-2 when coupled to CsI(Tl). Additionally, as the tube voltage across the X-ray generator was varied, these organic-inorganic systems showed their ability to detect a range of continuous radiation spectra spanning several hundred keV.« less

Focal application of low-dose-rate brachytherapy for prostate cancer: a pilot study

PubMed Central

Spadinger, Ingrid T.; Salcudean, Septimiu E.; Kozlowski, Piotr; Chang, Silvia D.; Ng, Tony; Lobo, Julio; Nir, Guy; Moradi, Hamid; Peacock, Michael; Morris, W. James

2017-01-01

Purpose To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low-dose-rate brachytherapy (LDR-PB). Material and methods Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Focal LDR-PB was performed on five eligible patients using dual air kerma strength treatment plans based on planning target volumes derived from cancer locations and determined by TTMB. Patient follow-up includes prostate specific antigen (PSA) measurements, urinary and sexual function questionnaires, repeated imaging and TTMB at specific intervals post-treatment. Results Feasibility of focal LDR-PB was shown and short-term outcomes are promising. While the detection rate of tumors, a majority of which were low grade GS 3 + 3, was found to be low on mpMRI (sensitivity of 37.5%), our results suggest the potential of mpMRI in detecting the presence of higher grade (GS ≥ 3 + 4), and bilateral disease indicating its usefulness as a screening tool for focal LDR-PB. Conclusions Low-dose-rate brachytherapy is a favorable ablation option for focal treatment of prostate cancer, requiring minimal modification to the standard (whole gland) LDR-PB treatment, and appears to have a more favorable side effect profile. Further investigation, in the form of a larger study, is needed to assess the methods used and the long-term outcomes of focal LDR-PB. PMID:28725242

Bundled-rate legislation for Medicare reimbursement for dialysis services: implications for anemia management with ESAs.

PubMed

Charytan, Chaim

2010-12-01

With the incidence of ESRD on the rise, there is a continuing need to control anemia-related treatment costs in dialysis patients receiving reimbursement through Medicare. Currently, erythropoiesis-stimulating agents (ESAs) are billed separately from dialysis services, potentially creating little financial incentive for more efficient use. The Medicare Improvement for Patients and Providers Act, passed by the U.S. Congress in July 2008, includes provisions intended to address this concern. Under this act, dialysis services will be reimbursed using a fully bundled, comprehensive payment system that includes all services currently covered in the basic composite rate, as well as certain separately billable items, including ESAs. A base rate of $229.63 per treatment has been assigned, to be individualized using case-mix adjusters. The implications of this new system for anemia management with ESAs continue to be elucidated. With fixed compensation for ESAs, management strategies that maximize efficiencies and, thereby, optimize cost savings will be favored. Select strategies may include switching from intravenous (IV) to subcutaneous routes, lowering Hb targets and ESA doses in hyporesponsive patients, increasing administration of IV iron, increasing use of home dialysis, and optimizing ESA dosing intervals. Once-monthly ESA therapy has potential advantages under this new system as an alternative to more frequently administered ESAs and may help achieve quality metrics in a cost-efficient manner.

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.

The Schwarzschild effect of the dosimetry film Kodak EDR 2.

PubMed

Djouguela, A; Kollhoff, R; Rubach, A; Harder, D; Poppe, B

2005-11-07

The magnitude of the Schwarzschild effect or failure of the reciprocity law has been experimentally investigated for the dosimetry film EDR 2 from Kodak. When the dose rate applied to achieve a given dose was reduced by a factor of 12, the net optical density was reduced by up to 5%. The clinical importance of this effect is negligible as long as the films are calibrated at a value of the dose rate approximately representative of the dose rates occurring in the target volume, but in target regions of strongly reduced dose rate the Schwarzschild effect should be allowed for by a correction of the net optical density.

SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial.

PubMed

Crabb, Simon; Danson, Sarah J; Catto, James W F; McDowell, Cathy; Lowder, James N; Caddy, Joshua; Dunkley, Denise; Rajaram, Jessica; Ellis, Deborah; Hill, Stephanie; Hathorn, David; Whitehead, Amy; Kalevras, Mihalis; Huddart, Robert; Griffiths, Gareth

2018-04-03

Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers. The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1-5 for combination with GC at conventional doses (cisplatin 70 mg/m 2 , IV infusion, day 8; gemcitabine 1000 mg/m 2 , IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm. SPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC. EudraCT Number: 2015-004062-29 (entered Dec 7, 2015) ISRCTN registry number: 16332228 (registered on Feb 3, 2016).

The role of intraoperative radiation therapy in patients with pancreatic cancer.

PubMed

Palta, Manisha; Willett, Christopher; Czito, Brian

2014-04-01

Intraoperative radiation therapy (IORT) techniques allow for the delivery of high doses of radiation therapy while excluding part or all of the nearby dose-limiting sensitive structures. Therefore, the effective radiation dose is increased and local tumor control potentially improved. This is pertinent in the case of pancreatic cancer because local failure rates are as high as 50%-80% in patients with resected and locally advanced disease. Available data in patients receiving IORT after pancreaticoduodenectomy reveal an improvement in local control, though overall survival benefit is unclear. Series of patients with locally advanced pancreatic cancer also suggest pain relief, and in select studies, improved survival associated with the inclusion of IORT. At present, no phase III data clearly supports the use of IORT in the management of pancreatic cancer. © 2013 Published by Elsevier Inc.

Assessment of Intervention by a Palliative Care Team Working in a Japanese General Hospital: A Retrospective Study.

PubMed

Amano, Koji; Morita, Tatsuya; Tatara, Ryohei; Katayama, Hirofumi; Aiki, Sayo; Kitada, Namiki; Fumimoto, Hiromi; Sato, Emi

2015-09-01

Our objective was to explore the effectiveness of a palliative care team (PCT) by investigating potential differences in opioid prescription between patients who had had PCT involvement before admission to an inpatient hospice and those who had not. A total of 221 patients met the criteria; they were divided into an intervention group (n = 140) and a control group (n = 81). The daily dose of opioid before admission to the hospice was significantly higher in the intervention group (P < .001). The difference between the maximum opioid dose and the initial dose, the rate of increase in opioids until death, and the length of stay in the hospice were not significantly different between the groups. A PCT contributes to more appropriate use of opioids before admission to a hospice. © The Author(s) 2014.

Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

PubMed Central

Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

2012-01-01

Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

Stroke prevention in atrial fibrillation: pooled analysis of SPORTIF III and V trials.

PubMed

Albers, Gregory W

2004-12-01

This article will review 2 clinical trials that recently compared the safety and efficacy of the oral direct thrombin inhibitor ximelagatran (fixed dose, 36 mg twice daily) with warfarin (adjusted dose, target international normalized ratio [INR] 2.0-3.0) in patients with nonvalvular atrial fibrillation and at least 1 risk factor for stroke. These noninferiority trials involved 7329 patients and a mean exposure to study drug of 18.5 months. The Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III (open-label, N = 3407) and V trials (double-blind, N = 3922) were designed for pooled analysis, and the data showed the efficacy of ximelagatran therapy was comparable (noninferior) with extremely well-controlled warfarin therapy in preventing stroke and systemic embolic events; the primary event rates were 1.65% per year and 1.62% per year in the warfarin and ximelagatran groups, respectively (P = .941). In patients with a history of stroke or transient ischemic attack (about 20% of the SPORTIF population), the event rates were 3.27% per year and 2.83% per year in the warfarin and ximelagatran groups, respectively (P = .625). The distribution of stroke subtypes was similar in the 2 treatment groups. Intracranial hemorrhage occurred at a rate of 0.20% per year with warfarin and 0.11% per year with ximelagatran. Combined rates of minor and major bleeding were significantly lower with ximelagatran than with warfarin (32% per year vs 39% per year; P < .0001). The myocardial infarction rates were the same in the pooled database (no difference between agents). The aspirin data will be the subject of two substudy papers. Oral ximelagatran administered without coagulation monitoring or dose adjustment was as effective as well-controlled, adjusted-dose warfarin for prevention of stroke and systemic embolic events and was associated with significantly less total bleeding. This oral direct thrombin inhibitor is a potentially promising treatment option for the prevention of thromboembolism.

Prescription errors before and after introduction of electronic medication alert system in a pediatric emergency department.

PubMed

Sethuraman, Usha; Kannikeswaran, Nirupama; Murray, Kyle P; Zidan, Marwan A; Chamberlain, James M

2015-06-01

Prescription errors occur frequently in pediatric emergency departments (PEDs).The effect of computerized physician order entry (CPOE) with electronic medication alert system (EMAS) on these is unknown. The objective was to compare prescription errors rates before and after introduction of CPOE with EMAS in a PED. The hypothesis was that CPOE with EMAS would significantly reduce the rate and severity of prescription errors in the PED. A prospective comparison of a sample of outpatient, medication prescriptions 5 months before and after CPOE with EMAS implementation (7,268 before and 7,292 after) was performed. Error types and rates, alert types and significance, and physician response were noted. Medication errors were deemed significant if there was a potential to cause life-threatening injury, failure of therapy, or an adverse drug effect. There was a significant reduction in the errors per 100 prescriptions (10.4 before vs. 7.3 after; absolute risk reduction = 3.1, 95% confidence interval [CI] = 2.2 to 4.0). Drug dosing error rates decreased from 8 to 5.4 per 100 (absolute risk reduction = 2.6, 95% CI = 1.8 to 3.4). Alerts were generated for 29.6% of prescriptions, with 45% involving drug dose range checking. The sensitivity of CPOE with EMAS in identifying errors in prescriptions was 45.1% (95% CI = 40.8% to 49.6%), and the specificity was 57% (95% CI = 55.6% to 58.5%). Prescribers modified 20% of the dosing alerts, resulting in the error not reaching the patient. Conversely, 11% of true dosing alerts for medication errors were overridden by the prescribers: 88 (11.3%) resulted in medication errors, and 684 (88.6%) were false-positive alerts. A CPOE with EMAS was associated with a decrease in overall prescription errors in our PED. Further system refinements are required to reduce the high false-positive alert rates. © 2015 by the Society for Academic Emergency Medicine.

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

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.

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

PubMed

Brugger, M; Roesler, S

2005-01-01

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

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.

Dose Response of Endotoxin on Hepatocyte and Muscle Mitochondrial Respiration In Vitro

PubMed Central

Brandt, Sebastian; Porta, Francesca; Jakob, Stephan M.; Takala, Jukka; Djafarzadeh, Siamak

2015-01-01

Introduction. Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria. Methods. Human hepatocellular carcinoma cells (HepG2) were exposed to placebo or LPS (0.1, 1, and 10 μg/mL) for 4, 8, 16, and 24 hours and primary human hepatocytes to 1 μg/mL LPS or placebo (4, 8, and 16 hours). Mitochondria from porcine skeletal muscle samples were exposed to increasing doses of LPS (0.1–100 μg/mg) for 2 and 4 hours. Respiration rates of intact and permeabilized cells and isolated mitochondria were measured by high-resolution respirometry. Results. In HepG2 cells, LPS reduced mitochondrial membrane potential and cellular ATP content but did not modify basal respiration. Stimulated complex II respiration was reduced time-dependently using 1 μg/mL LPS. In primary human hepatocytes, stimulated mitochondrial complex II respiration was reduced time-dependently using 1 μg/mL LPS. In isolated porcine skeletal muscle mitochondria, stimulated respiration decreased at high doses (50 and 100 μg/mL LPS). Conclusion. LPS reduced cellular ATP content of HepG2 cells, most likely as a result of the induced decrease in membrane potential. LPS decreased cellular and isolated mitochondrial respiration in a time-dependent, dose-dependent and complex-dependent manner. PMID:25649304

Radiation Risks From A Weak Field in the Coming Years

NASA Astrophysics Data System (ADS)

Rahmanifard, F.; Schwadron, N.; Smith, C. W.; Joyce, C. J.; Townsend, L.

2017-12-01

Recent solar conditions, including a prolonged solar minimum (2005-2009) and the recent small solar maximum, indicate that we are entering an era of lower solar activity than observed at other times during the space age- possibly similar to the past solar grand minima. During such periods of extremely low activity, the fluxes of galactic cosmic rays (GCRs) increase dramatically and limit the allowable days for human space missions. We use data from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter (LRO) to examine the correlation between the heliospheric magnetic field at 1AU and the modulation potential of the GCRs. We apply past grand solar minima conditions, including the Maunder minimum (1645-1715) and the Dalton minimum (1790-1830), to predict the modulation potential and the dose rates of the GCRs throughout the next solar cycle. The heliospheric magnetic field can drop to 4.21 (3.72) nT, leading to a modulation potential of 448.51 (235.96) MV and dose rates as high as 11.72 (16.68) cGy/yr for the case of conditions similar to the Dalton minimum (Maunder minimum). We use these results to predict the most conservative estimations of the time to 3% risk of exposure-induced death (REID) and the allowable mission durations in interplanetary space.

A Single Dose of Intraoperative Antibiotics Is Sufficient to Prevent Urinary Tract Infection During Ureteroscopy.

PubMed

Chew, Ben H; Flannigan, Ryan; Kurtz, Michael; Gershman, Boris; Arsovska, Olga; Paterson, Ryan F; Eisner, Brian H; Lange, Dirk

2016-01-01

American Urology Association (AUA) Best Practice Guidelines for ureteroscopic stone treatment recommend antibiotic coverage for <24 hours following the procedure. The purpose of this study was to evaluate if the addition of postoperative antibiotics reduces urinary tract infections (UTIs) following ureteroscopic stone treatment beyond the recommended preoperative dose. A retrospective review was performed of consecutive patients at two institutions, University of British Columbia and Massachusetts General Hospital, Harvard. All patients received a single dose of antibiotics before ureteroscopic stone treatment. A subset of patients was also given postoperative antibiotics. The rate of UTI was compared in patients receiving only preoperative antibiotics (group 1) vs those who received pre- and postoperative antibiotics (group 2). Eighty-one patients underwent ureteroscopy for renal calculi. Mean time to follow up was 42 ± 88 days. Eight (9.9%) patients in total (two from group 1 and six from group 2, p = 0.1457) developed UTIs postoperatively. In group 1, both patients presented with pyelonephritis (n = 2); those patients with infections in group 2 presented with urosepsis (n = 2) and cystitis (n = 2) and two patients had asymptomatic bacteriuria. Risk factors such as preoperative stenting, nephrostomy tubes, and foley catheters neither differed between groups nor did they predispose patients to postoperative infections. The postoperative UTI rate in this study (9.9%) is consistent with previous reports. Our data suggest that a single preoperative dose of antibiotics is sufficient, and additional postoperative antibiotics do not decrease infection rates after ureteroscopic stone treatment. Risk for selection bias is a potential limitation.

Differences in rates of decrease of environmental radiation dose rates by ground surface property in Fukushima City after the Fukushima Daiichi nuclear power plant accident.

PubMed

Kakamu, Takeyasu; Kanda, Hideyuki; Tsuji, Masayoshi; Kobayashi, Daisuke; Miyake, Masao; Hayakawa, Takehito; Katsuda, Shin-ichiro; Mori, Yayoi; Okouchi, Toshiyasu; Hazama, Akihiro; Fukushima, Tetsuhito

2013-01-01

After the Great East Japan Earthquake on 11 March 2011, the environmental radiation dose in Fukushima City increased. On 11 April, 1 mo after the earthquake, the environmental radiation dose rate at various surfaces in the same area differed greatly by surface property. Environmental radiation measurements continue in order to determine the estimated time to 50% reduction in environmental radiation dose rates by surface property in order to make suggestions for decontamination in Fukushima. The measurements were carried out from 11 April to 11 November 2011. Forty-eight (48) measurement points were selected, including four kinds of ground surface properties: grass (13), soil (5), artificial turf (7), and asphalt (23). Environmental radiation dose rate was measured at heights of 100 cm above the ground surface. Time to 50% reduction of environmental radiation dose rates was estimated for each ground surface property. Radiation dose rates on 11 November had decreased significantly compared with those on 11 April for all surface properties. Artificial turf showed the longest time to 50% reduction (544.32 d, standard error: 96.86), and soil showed the shortest (213.20 d, standard error: 35.88). The authors found the environmental radiation dose rate on artificial materials to have a longer 50% reduction time than that on natural materials. These results contribute to determining an order of priority for decontamination after nuclear disasters.

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

Characterizing regional-scale temporal evolution of air dose rates after the Fukushima Daiichi Nuclear Power Plant accident.

PubMed

Wainwright, Haruko M; Seki, Akiyuki; Mikami, Satoshi; Saito, Kimiaki

2018-09-01

In this study, we quantify the temporal changes of air dose rates in the regional scale around the Fukushima Dai-ichi Nuclear Power Plant in Japan, and predict the spatial distribution of air dose rates in the future. We first apply the Bayesian geostatistical method developed by Wainwright et al. (2017) to integrate multiscale datasets including ground-based walk and car surveys, and airborne surveys, all of which have different scales, resolutions, spatial coverage, and accuracy. This method is based on geostatistics to represent spatial heterogeneous structures, and also on Bayesian hierarchical models to integrate multiscale, multi-type datasets in a consistent manner. We apply this method to the datasets from three years: 2014 to 2016. The temporal changes among the three integrated maps enables us to characterize the spatiotemporal dynamics of radiation air dose rates. The data-driven ecological decay model is then coupled with the integrated map to predict future dose rates. Results show that the air dose rates are decreasing consistently across the region. While slower in the forested region, the decrease is particularly significant in the town area. The decontamination has contributed to significant reduction of air dose rates. By 2026, the air dose rates will continue to decrease, and the area above 3.8 μSv/h will be almost fully contained within the non-residential forested zone. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Sublethal doses of imidacloprid disrupt sexual communication and host finding in a parasitoid wasp

NASA Astrophysics Data System (ADS)

Tappert, Lars; Pokorny, Tamara; Hofferberth, John; Ruther, Joachim

2017-02-01

Neonicotinoids are widely used insecticides, but their use is subject of debate because of their detrimental effects on pollinators. Little is known about the effect of neonicotinoids on other beneficial insects such as parasitoid wasps, which serve as natural enemies and are crucial for ecosystem functioning. Here we show that sublethal doses of the neonicotinoid imidacloprid impair sexual communication and host finding in the parasitoid wasp Nasonia vitripennis. Depending on the dose, treated females were less responsive to the male sex pheromone or unable to use it as a cue at all. Courtship behaviour of treated couples was also impeded resulting in a reduction of mating rates by up to 80%. Moreover, treated females were no longer able to locate hosts by using olfactory cues. Olfaction is crucial for the reproductive success of parasitoid wasps. Hence, sublethal doses of neonicotinoids might compromise the function of parasitoid wasps as natural enemies with potentially dire consequences for ecosystem services.

Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man.

PubMed

Bukara, Katarina; Schueller, Laurent; Rosier, Jan; Martens, Mark A; Daems, Tinne; Verheyden, Loes; Eelen, Siemon; Van Speybroeck, Michiel; Libanati, Cristian; Martens, Johan A; Van Den Mooter, Guy; Frérart, Françoise; Jolling, Koen; De Gieter, Marjan; Bugarski, Branko; Kiekens, Filip

2016-11-01

Formulating poorly water soluble drugs using ordered mesoporous silica materials is an emerging approach to tackle solubility-related bioavailability problems. The current study was conducted to assess the bioavailability-enhancing potential of ordered mesoporous silica in man. In this open-label, randomized, two-way cross-over study, 12 overnight fasted healthy volunteers received a single dose of fenofibrate formulated with ordered mesoporous silica or a marketed product based on micronized fenofibrate. Plasma concentrations of fenofibric acid, the pharmacologically active metabolite of fenofibrate, were monitored up to 96h post-dose. The rate (C max /dose increased by 77%; t max reduced by 0.75h) and extent of absorption (AUC 0-24h /dose increased by 54%) of fenofibrate were significantly enhanced following administration of the ordered mesoporous silica based formulation. The results of this study serve as a proof of concept in man for this novel formulation approach. Copyright © 2016 Elsevier B.V. All rights reserved.

Antibiotic dosing in critically ill patients receiving CRRT: underdosing is overprevalent.

PubMed

Lewis, Susan J; Mueller, Bruce A

2014-01-01

Published CRRT drug dosing algorithms and other dosing guidelines appear to result in underdosed antibiotics, leading to failure to attain pharmacodynamic targets. High mortality rates persist with inadequate antibiotic therapy as the most important risk factor for death. Reasons for unintended antibiotic underdosing in patients receiving CRRT are many. Underdosing may result from lack of the recognition that better hepatic function in AKI patients yields higher nonrenal antibiotic clearance compared to ESRD patients. Other factors include the variability in body size and fluid composition of patients, the serious consequence of delayed achievement of antibiotic pharmacodynamic targets in septic patients, potential subtherapeutic antibiotic concentrations at the infection site, and the influence of RRT intensity on antibiotic concentrations. Too often, clinicians weigh the benefits of overcautious antibiotic dosing to avoid antibiotic toxicity too heavily against the benefits of rapid attainment of therapeutic antibiotic concentrations in critically ill patients receiving CRRT. We urge clinicians to prescribe antibiotics aggressively for these vulnerable patients. © 2014 Wiley Periodicals, Inc.

Trivalent influenza vaccine-induced antibody response to circulating influenza a (H3N2) viruses in 2010/11 and 2011/12 seasons.

PubMed

Hiroi, Satoshi; Morikawa, Saeko; Nakata, Keiko; Maeda, Akiko; Kanno, Tsuneji; Irie, Shin; Ohfuji, Satoko; Hirota, Yoshio; Kase, Tetsuo

2015-01-01

To evaluate antibody response induced by trivalent inactivated influenza vaccine (TIV) against circulating influenza A (H3N2) strains in healthy adults during the 2010/11 and 2011/12 seasons, a hemagglutination-inhibition (HI) assay was utilized to calculate geometric mean antibody titer (GMT), seroprotection rate (post vaccination HI titers of ≥1 :40), and seroresponse rate (4-fold increase in antibody level). In the 2010/11 season, GMT increased 1.8- to 2.0-fold following the first dose of TIV against 3 circulating strains and 2.2-fold following the second compared to before vaccination. The seroresponse rate ranged from 22% to 26% following the first dose of TIV and from 31% to 33% following the second (n = 54 ). The seroprotection rate increased from a range of 6% to 13% to a range of 26% to 33% following the first dose of TIV and to a range of 37% to 42% following the second (n = 54 ). In the 2011/12 season, GMT increased 1.4-fold against A/Osaka/110/2011 and 1.8-fold against A/Osaka/5/2012. For A/Osaka/110/2011, the seroresponse rate was 29%, and the seroprotection rate increased from 26% to 55% following vaccination (n = 31 ). For A/Osaka/5/2012, the seroresponse rate was 26%, and the seroprotection rate increased from 68% to 84% following vaccination (n = 31 ). HI assays with reference antisera demonstrated that the strains in the 2011/12 season were antigenically distinct from vaccine strain (A/Victoria/210/2009). In conclusion, the vaccination increased the seroprotection rate against circulating H3N2 strains in the 2010/11 and 2011/12 seasons. Vaccination of TIV might have potential to induce reactive antibodies against antigenically distinct circulating H3N2 viruses.

TH-C-19A-05: Evaluation of a New Reusable 3D Dosimeter

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

Juang, T; Adamovics, J; Oldham, M

Purpose: PRESAGE is a radiochromic plastic which has demonstrated strong potential for high resolution single-use 3D dosimetry. This study evaluates a new PRESAGE formulation (Presage-RU) in which the radiochromic response is reversible (the dosimeter optically clears after irradiation), enabling the potential for reusability. Methods: Presage-RU dose response and optical-clearing rates were evaluated in both small volume dosimeters (1×1×4.5cm) and a larger cylindrical dosimeter (8cm diameter, 4.5cm length). All dosimeters were allowed to fully optically clear in dark, room temperature conditions between irradiations. Dose response was determined by irradiating small volume samples from 0–8.0Gy and measuring change in optical density. Themore » cylindrical dosimeter was irradiated with a simple 4-field box plan (parallel opposed pairs of 4cm×4cm AP-PA beams and 2cm×4cm lateral beams) to 20Gy. High resolution 3D dosimetry was achieved utilizing optical-CT readout. Readings were tracked up to 14 days to characterize optical clearing. Results: Initial irradiation yielded a response of 0.0119△OD/(Gy*cm) while two subsequent reirradiations yielded a lower but consistent response of 0.0087△OD/(Gy*cm). Strong linearity of dose response was observed for all irradiations. In the large cylindrical dosimeter, the integral dose within the high dose region exhibited an exponential decay in signal over time (halflife= 23.9 hours), with the dosimeter effectively cleared (0.04% of the initial signal) after 10 days. Subsequent irradiation resulted in 19.5% lower initial signal but demonstrated that the exponential clearing rate remained consistent. Results of additional subsequent irradiations will also be presented. Conclusion: This work introduces a new re-usable radiochromic dosimeter (Presage-RU) compatible with high resolution (sub-millimeter) 3D dosimetry. Sensitivity of the initial radiation was observed to be slightly higher than subsequent irradiations, but the clearing time remained constant, indicating the dosimeter can be re-used after 10 days. Presage-RU has potential to dramatically improve cost-effectiveness and thereby lower the barrier for implementing comprehensive, high resolution 3D dosimetry. John Adamovics is the president of Heuris Inc., which commercializes PRESAGE.« less

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.

Determination of spatial dose distribution in UCC treatments with LDR brachytherapy using Monte Carlo methods.

PubMed

Benites-Rengifo, Jorge Luis; Vega-Carrillo, Hector Rene

2018-05-19

Using Monte Carlos methods, with the MCNP5 code, a gynecological phantom and a vaginal cylinder were modeled. The spatial distribution of absorbed dose rates in Uterine Cervical Cancer treatment through low dose rate brachytherapy was determined. A liquid water gynecology computational phantom, including a vaginal cylinder applicator made of Lucite, was designed. The applicator has a linear array of four radioactive sources of Cesium 137. Around the vaginal cylinder, 13 water spherical cells of 0.5 cm-diameter were modeled to calculate absorbed dose emulating the procedure made by the treatment planning system. The gamma-ray fluence distribution was estimated, as well as the absorbed doses resulting approximately symmetrical for cells located at upper and lower of vaginal cylinder. Obtained results allow the use of the radioactive decay law to determine dose rate for Uterine Cervical Cancer using low dose rate brachytherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

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.

Concentration dependence of biotransformation in fish liver S9: Optimizing substrate concentrations to estimate hepatic clearance for bioaccumulation assessment.

PubMed

Lo, Justin C; Allard, Gayatri N; Otton, S Victoria; Campbell, David A; Gobas, Frank A P C

2015-12-01

In vitro bioassays to estimate biotransformation rate constants of contaminants in fish are currently being investigated to improve bioaccumulation assessments of hydrophobic contaminants. The present study investigates the relationship between chemical substrate concentration and in vitro biotransformation rate of 4 environmental contaminants (9-methylanthracene, pyrene, chrysene, and benzo[a]pyrene) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions and methods to determine maximum first-order biotransformation rate constants. Substrate depletion experiments using a series of initial substrate concentrations showed that in vitro biotransformation rates exhibit strong concentration dependence, consistent with a Michaelis-Menten kinetic model. The results indicate that depletion rate constants measured at initial substrate concentrations of 1 μM (a current convention) could underestimate the in vitro biotransformation potential and may cause bioconcentration factors to be overestimated if in vitro biotransformation rates are used to assess bioconcentration factors in fish. Depletion rate constants measured using thin-film sorbent dosing experiments were not statistically different from the maximum depletion rate constants derived using a series of solvent delivery-based depletion experiments for 3 of the 4 test chemicals. Multiple solvent delivery-based depletion experiments at a range of initial concentrations are recommended for determining the concentration dependence of in vitro biotransformation rates in fish liver fractions, whereas a single sorbent phase dosing experiment may be able to provide reasonable approximations of maximum depletion rates of very hydrophobic substances. © 2015 SETAC.

The Effect of Ingested Glucose Dose on the Suppression of Endogenous Glucose Production in Humans.

PubMed

Kowalski, Greg M; Moore, Samantha M; Hamley, Steven; Selathurai, Ahrathy; Bruce, Clinton R

2017-09-01

Insulin clamp studies have shown that the suppressive actions of insulin on endogenous glucose production (EGP) are markedly more sensitive than for stimulating glucose disposal ( R d ). However, clamp conditions do not adequately mimic postprandial physiological responses. Here, using the variable infusion dual-tracer approach, we used a threefold range of ingested glucose doses (25, 50, and 75 g) to investigate how physiological changes in plasma insulin influence EGP in healthy subjects. Remarkably, the glucose responses were similar for all doses tested, yet there was a dose-dependent increase in insulin secretion and plasma insulin levels. Nonetheless, EGP was suppressed with the same rapidity and magnitude (∼55%) across all doses. The progressive hyperinsulinemia, however, caused a dose-dependent increase in the estimated rates of R d , which likely accounts for the lack of a dose effect on plasma glucose excursions. This suggests that after glucose ingestion, the body preferentially permits a transient and optimal degree of postprandial hyperglycemia to efficiently enhance insulin-induced changes in glucose fluxes, thereby minimizing the demand for insulin secretion. This may represent an evolutionarily conserved mechanism that not only reduces the secretory burden on β-cells but also avoids the potential negative consequences of excessive insulin release into the systemic arterial circulation. © 2017 by the American Diabetes Association.

Sub-second pencil beam dose calculation on GPU for adaptive proton therapy.

PubMed

da Silva, Joakim; Ansorge, Richard; Jena, Rajesh

2015-06-21

Although proton therapy delivered using scanned pencil beams has the potential to produce better dose conformity than conventional radiotherapy, the created dose distributions are more sensitive to anatomical changes and patient motion. Therefore, the introduction of adaptive treatment techniques where the dose can be monitored as it is being delivered is highly desirable. We present a GPU-based dose calculation engine relying on the widely used pencil beam algorithm, developed for on-line dose calculation. The calculation engine was implemented from scratch, with each step of the algorithm parallelized and adapted to run efficiently on the GPU architecture. To ensure fast calculation, it employs several application-specific modifications and simplifications, and a fast scatter-based implementation of the computationally expensive kernel superposition step. The calculation time for a skull base treatment plan using two beam directions was 0.22 s on an Nvidia Tesla K40 GPU, whereas a test case of a cubic target in water from the literature took 0.14 s to calculate. The accuracy of the patient dose distributions was assessed by calculating the γ-index with respect to a gold standard Monte Carlo simulation. The passing rates were 99.2% and 96.7%, respectively, for the 3%/3 mm and 2%/2 mm criteria, matching those produced by a clinical treatment planning system.

Dose-related difference in progression rates of cytomegalovirus retinopathy during foscarnet maintenance therapy. AIDS Clinical Trials Group Protocol 915 Team.

PubMed

Holland, G N; Levinson, R D; Jacobson, M A

1995-05-01

A previous dose-ranging study of foscarnet maintenance therapy for cytomegalovirus retinopathy showed a positive relationship between dose and survival but could not confirm a relationship between dose and time to first progression. This retrospective analysis of data from that study was undertaken to determine whether there was a relationship between dose and progression rates, which reflects the amount of retina destroyed when progression occurs. Patients were randomly given one of two foscarnet maintenance therapy doses (90 mg/kg of body weight/day [FOS-90 group] or 120 mg/kg of body weight/day [FOS-120 group] after induction therapy. Using baseline and follow-up photographs and pre-established definitions and methodology in a masked analysis, posterior progression rates and foveal proximity rates for individual lesions, selected by prospectively defined criteria, were calculated in each patient. Rates were compared between groups. The following median rates were greater for the FOS-90 group (N = 8) than for the FOS-120 group (N = 10): greatest maximum rate at which lesions enlarged in a posterior direction (43.5 vs 12.5 microns/day; P = .002); posterior progression rate for lesions closest to the fovea (42.8 vs 5.5 microns/day; P = .010); and maximum foveal proximity rate for either eye (32.3 vs 3.4 microns/day; P = .031). Patients receiving higher doses of foscarnet have slower rates of progression and therefore less retinal tissue damage during maintenance therapy. A foscarnet maintenance therapy dose of 120 mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to preserve vision in patients with cytomegalovirus retinopathy.

Guidance on the Use of Hand-Held Survey Meters for Radiological Triage: Time-Dependent Detector Count Rates Corresponding to 50, 250, and 500 mSv Effective Dose for Adult Males and Adult Females

PubMed Central

Bolch, Wesley E.; Hurtado, Jorge L.; Lee, Choonsik; Manger, Ryan; Hertel, Nolan; Dickerson, William

2013-01-01

In June of 2006, the Radiation Studies Branch of the Centers for Disease Control and Prevention held a workshop to explore rapid methods of facilitating radiological triage of large numbers of potentially contaminated individuals following detonation of a radiological dispersal device. Two options were discussed. The first was the use of traditional gamma-cameras in nuclear medicine departments operated as make-shift whole-body counters. Guidance on this approach is currently available from the CDC. This approach is feasible if a manageable number of individuals were involved, transportation to the relevant hospitals was quickly provided, and the medical staff at each facility had been previously trained in this non-traditional use of their radiopharmaceutical imaging devices. If, however, substantially large numbers of individuals (100s to 1000s) needed radiological screening, other options must be given to first responders, first receivers, and health physicists providing medical management. In this study, the second option of the workshop was investigated – the use of commercially available portable survey meters (either NaI or GM based) for assessing potential ranges of effective dose (<50, 50–250, 250–500, and >500 mSv). Two hybrid computational phantoms were used to model an adult male and an adult female subject internally contaminated with either 241Am, 60Cs, 137Cs, 131I, and 192Ir following an acute inhalation or ingestion intake. As a function of time following the exposure, the net count rates corresponding to committed effective doses of 50, 250, and 500 mSv were estimated via Monte Carlo radiation transport simulation for each of four different detectors types, positions, and screening distances. Measured count rates can be compared to these values and an assignment of one of four possible effective dose ranges could be made. The method implicitly assumes that all external contamination has been removed prior to screening, and that the measurements be conducted in a low-background, and possibly mobile, facility positioned at the triage location. Net count rate data are provided in both tabular and graphical format within a series of eight handbooks available at the CDC website http://emergency.cdc.gov/radiation. PMID:22420020

Guidance on the Use of Hand-Held Survey Meters for radiological Triage: Time-Dependent Detector Count Rates Corresponding to 50, 250, and 500 mSv Effective Dose for Adult Males and Adult Females

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

Bolch, W.E.; Hurtado, J.L.; Lee, C.

2012-01-01

In June 2006, the Radiation Studies Branch of the Centers for Disease Control and Prevention held a workshop to explore rapid methods of facilitating radiological triage of large numbers of potentially contaminated individuals following detonation of a radiological dispersal device. Two options were discussed. The first was the use of traditional gamma cameras in nuclear medicine departments operated as makeshift wholebody counters. Guidance on this approach is currently available from the CDC. This approach would be feasible if a manageable number of individuals were involved, transportation to the relevant hospitals was quickly provided, and the medical staff at each facilitymore » had been previously trained in this non-traditional use of their radiopharmaceutical imaging devices. If, however, substantially larger numbers of individuals (100 s to 1,000 s) needed radiological screening, other options must be given to first responders, first receivers, and health physicists providing medical management. In this study, the second option of the workshop was investigated by the use of commercially available portable survey meters (either NaI or GM based) for assessing potential ranges of effective dose (G50, 50Y250, 250Y500, and 9500 mSv). Two hybrid computational phantoms were used to model an adult male and an adult female subject internally contaminated with 241Am, 60Cs, 137Cs, 131I, or 192Ir following an acute inhalation or ingestion intake. As a function of time following the exposure, the net count rates corresponding to committed effective doses of 50, 250, and 500 mSv were estimated via Monte Carlo radiation transport simulation for each of four different detector types, positions, and screening distances. Measured net count rates can be compared to these values, and an assignment of one of four possible effective dose ranges could be made. The method implicitly assumes that all external contamination has been removed prior to screening and that the measurements be conducted in a low background, and possibly mobile, facility positioned at the triage location. Net count rate data are provided in both tabular and graphical format within a series of eight handbooks available at the CDC website (http://www.bt.cdc.gov/radiation/clinicians/evaluation).« less

Proton radiography and proton computed tomography based on time-resolved dose measurements

NASA Astrophysics Data System (ADS)

Testa, Mauro; Verburg, Joost M.; Rose, Mark; Min, Chul Hee; Tang, Shikui; Hassane Bentefour, El; Paganetti, Harald; Lu, Hsiao-Ming

2013-11-01

We present a proof of principle study of proton radiography and proton computed tomography (pCT) based on time-resolved dose measurements. We used a prototype, two-dimensional, diode-array detector capable of fast dose rate measurements, to acquire proton radiographic images expressed directly in water equivalent path length (WEPL). The technique is based on the time dependence of the dose distribution delivered by a proton beam traversing a range modulator wheel in passive scattering proton therapy systems. The dose rate produced in the medium by such a system is periodic and has a unique pattern in time at each point along the beam path and thus encodes the WEPL. By measuring the time dose pattern at the point of interest, the WEPL to this point can be decoded. If one measures the time-dose patterns at points on a plane behind the patient for a beam with sufficient energy to penetrate the patient, the obtained 2D distribution of the WEPL forms an image. The technique requires only a 2D dosimeter array and it uses only the clinical beam for a fraction of second with negligible dose to patient. We first evaluated the accuracy of the technique in determining the WEPL for static phantoms aiming at beam range verification of the brain fields of medulloblastoma patients. Accurate beam ranges for these fields can significantly reduce the dose to the cranial skin of the patient and thus the risk of permanent alopecia. Second, we investigated the potential features of the technique for real-time imaging of a moving phantom. Real-time tumor tracking by proton radiography could provide more accurate validations of tumor motion models due to the more sensitive dependence of proton beam on tissue density compared to x-rays. Our radiographic technique is rapid (˜100 ms) and simultaneous over the whole field, it can image mobile tumors without the problem of interplay effect inherently challenging for methods based on pencil beams. Third, we present the reconstructed pCT images of a cylindrical phantom containing inserts of different materials. As for all conventional pCT systems, the method illustrated in this work produces tomographic images that are potentially more accurate than x-ray CT in providing maps of proton relative stopping power (RSP) in the patient without the need for converting x-ray Hounsfield units to proton RSP. All phantom tests produced reasonable results, given the currently limited spatial and time resolution of the prototype detector. The dose required to produce one radiographic image, with the current settings, is ˜0.7 cGy. Finally, we discuss a series of techniques to improve the resolution and accuracy of radiographic and tomographic images for the future development of a full-scale detector.

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

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

Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts; Leonard, Kara Lynne

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients permore » cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.« less

A survival model for fractionated radiotherapy with an application to prostate cancer

NASA Astrophysics Data System (ADS)

Zaider, Marco; Zelefsky, Michael J.; Hanin, Leonid G.; Tsodikov, Alexander D.; Yakovlev, Andrei Y.; Leibel, Steven A.

2001-10-01

This paper explores the applicability of a mechanistic survival model, based on the distribution of clonogens surviving a course of fractionated radiation therapy, to clinical data on patients with prostate cancer. The study was carried out using data on 1100 patients with clinically localized prostate cancer who were treated with three-dimensional conformal radiation therapy. The patients were stratified by radiation dose (group 1: <67.5 Gy; group 2: 67.5-72.5 Gy; group 3: 72.5-77.5 Gy; group 4: 77.5-87.5 Gy) and prognosis category (favourable, intermediate and unfavourable as defined by pre-treatment PSA and Gleason score). A relapse was recorded when tumour recurrence was diagnosed or when three successive prostate specific antigen (PSA) elevations were observed from a post-treatment nadir PSA level. PSA relapse-free survival was used as the primary end point. The model, which is based on an iterated Yule process, is specified in terms of three parameters: the mean number of tumour clonogens that survive the treatment, the mean of the progression time of post-treatment tumour development and its standard deviation. The model parameters were estimated by the maximum likelihood method. The fact that the proposed model provides an excellent description both of the survivor function and of the hazard rate is prima facie evidence of the validity of the model because closeness of the two survivor functions (empirical and model-based) does not generally imply closeness of the corresponding hazard rates. The estimated cure probabilities for the favourable group are 0.80, 0.74 and 0.87 (for dose groups 1-3, respectively); for the intermediate group: 0.25, 0.51, 0.58 and 0.78 (for dose groups 1-4, respectively) and for the unfavourable group: 0.0, 0.27, 0.33 and 0.64 (for dose groups 1-4, respectively). The distribution of progression time to tumour relapse was found to be independent of prognosis group but dependent on dose. As the dose increases the mean progression time decreases (41, 28.5, 26.2 and 14.7 months for dose groups 1-4, respectively). This analysis confirms that, in terms of cure rate, dose escalation has a significant positive effect only in the intermediate and unfavourable groups. It was found that progression time is inversely proportional to dose, which means that patients recurring in higher dose groups have shorter recurrence times, yet these groups have better survival, particularly long-term. The explanation for this seemingly illogical observation lies in the fact that less aggressive tumours, potentially recurring after a long period of time, are cured by higher doses and do not contribute to the recurrence pattern. As a result, patients in higher dose groups are less likely to recur; however, if they do, they tend to recur earlier. The estimated hazard rates for prostate cancer pass through a clear-cut maximum, thus revealing a time period with especially high values of instantaneous cancer-specific risk; the estimates appear to be nonproportional across dose strata.

Absorbed doses of lungs from radon retained in airway lumens of mice and rats.

PubMed

Sakoda, Akihiro; Ishimori, Yuu; Yamaoka, Kiyonori; Kataoka, Takahiro; Mitsunobu, Fumihiro

2013-08-01

This paper provides absorbed doses arising from radon gas in air retained in lung airway lumens. Because radon gas exposure experiments often use small animals, the calculation was performed for mice and rats. For reference, the corresponding computations were also done for humans. Assuming that radon concentration in airway lumens is the same as that in the environment, its progeny's production in and clearance from airways were simulated. Absorbed dose rates were obtained for three lung regions and the whole lung, considering that secretory and basal cells are sensitive to radiation. The results showed that absorbed dose rates for all lung regions and whole lung generally increase from mice to rats to humans. For example, the dose rates for the whole lung were 25.4 in mice, 41.7 in rats, and 59.9 pGy (Bq m⁻³)⁻¹ h⁻¹ in humans. Furthermore, these values were also compared with lung dose rates from two other types of exposures, that is, due to inhalation of radon or its progeny, which were already reported. It was confirmed that the direct inhalation of radon progeny in the natural environment, which is known as a cause of lung cancer, results in the highest dose rates for all species. Based on the present calculations, absorbed dose rates of the whole lung from radon gas were lower by a factor of about 550 (mice), 200 (rats), or 70 (humans) than those from radon progeny inhalation. The calculated dose rate values are comparatively small. Nevertheless, the present study is considered to contribute to our understanding of doses from inhalation of radon and its progeny.

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

Pediatric 131I-MIBG Therapy for Neuroblastoma: Whole-Body 131I-MIBG Clearance, Radiation Doses to Patients, Family Caregivers, Medical Staff, and Radiation Safety Measures.

PubMed

Willegaignon, José; Crema, Karin Paola; Oliveira, Nathaliê Canhameiro; Pelissoni, Rogério Alexandre; Coura-Filho, George Barberio; Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto

2018-06-19

I-metaiodobenzylguanidine (I-MIBG) has been used in the diagnosis and therapy of neuroblastoma in adult and pediatric patients for many years. In this study, we evaluated whole-body I-MIBG clearance and radiation doses received by patients, family caregivers, and medical staff to establish appropriate radiation safety measures to be used in therapy applications. Research was focused on 23 children and adolescents with metastatic neuroblastoma, with ages ranging from 1.8 to 13 years, being treated with I-MIBG. Based on measured external dose rates from patients, dosimetric data to patients, family members, and others were calculated. The mean ± SD I-MIBG activity administered was 8.55 ± 1.69 GBq. Percent whole-body retention rates of I-MIBG at 24, 48, and 72 hours after administration were 48% ± 7%, 23% ± 7%, and 12% ± 6%, with a whole-body I-MIBG effective half-life of 23 ± 5 hours for all patients. The mean doses for patients were 0.234 ± 0.096 mGy·MBq to red-marrow and 0.251 ± 0.101 mGy·MBq to whole body. The maximum potential radiation doses transmitted by patients to others at 1.0 m was estimated to be 11.9 ± 3.4 mSv, with 97% of this dose occurring over 120 hours after therapy administration. Measured mean dose received by the 22 family caregivers was 1.88 ± 1.85 mSv, and that received by the 19 pediatric physicians was 43 ± 51 μSv. In this study, we evaluated the whole-body clearance of I-MIBG in 23 pediatric patients, and the radiation doses received by family caregivers and medical staff during these therapy procedures, thus facilitating the establishment of radiation safety measures to be applied in pediatric therapy.

Estimating Effective Dose of Radiation From Pediatric Cardiac CT Angiography Using a 64-MDCT Scanner: New Conversion Factors Relating Dose-Length Product to Effective Dose.

PubMed

Trattner, Sigal; Chelliah, Anjali; Prinsen, Peter; Ruzal-Shapiro, Carrie B; Xu, Yanping; Jambawalikar, Sachin; Amurao, Maxwell; Einstein, Andrew J

2017-03-01

The purpose of this study is to determine the conversion factors that enable accurate estimation of the effective dose (ED) used for cardiac 64-MDCT angiography performed for children. Anthropomorphic phantoms representative of 1- and 10-year-old children, with 50 metal oxide semiconductor field-effect transistor dosimeters placed in organs, underwent scanning performed using a 64-MDCT scanner with different routine clinical cardiac scan modes and x-ray tube potentials. Organ doses were used to calculate the ED on the basis of weighting factors published in 1991 in International Commission on Radiological Protection (ICRP) publication 60 and in 2007 in ICRP publication 103. The EDs and the scanner-reported dose-length products were used to determine conversion factors for each scan mode. The effect of infant heart rate on the ED and the conversion factors was also assessed. The mean conversion factors calculated using the current definition of ED that appeared in ICRP publication 103 were as follows: 0.099 mSv · mGy -1 · cm -1 , for the 1-year-old phantom, and 0.049 mSv · mGy -1 · cm -1 , for the 10-year-old phantom. These conversion factors were a mean of 37% higher than the corresponding conversion factors calculated using the older definition of ED that appeared in ICRP publication 60. Varying the heart rate did not influence the ED or the conversion factors. Conversion factors determined using the definition of ED in ICRP publication 103 and cardiac, rather than chest, scan coverage suggest that the radiation doses that children receive from cardiac CT performed using a contemporary 64-MDCT scanner are higher than the radiation doses previously reported when older chest conversion factors were used. Additional up-to-date pediatric cardiac CT conversion factors are required for use with other contemporary CT scanners and patients of different age ranges.

Dose rate evaluation of workers on the operation floor in Fukushima-Daiichi Unit 3

NASA Astrophysics Data System (ADS)

Matsushita, Kaoru; Kurosawa, Masahiko; Shirai, Keisuke; Matsuoka, Ippei; Mukaida, Naoki

2017-09-01

At Fukushima Daiichi Nuclear Power Plant Unit 3, installation of a fuel handling machine is planned to support the removal of spent fuel. The dose rates at the workplace were calculated based on the source distribution measured using a collimator in order to confirm that the dose rates on the operation floor were within a manageable range. It was confirmed that the accuracy of the source distribution was C/M = 1.0-2.4. These dose rates were then used to plan the work on the operation floor.

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

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

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.

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

PubMed

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

2017-10-01

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

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.

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.

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.

Evaluating biomarkers to model cancer risk post cosmic ray exposure

PubMed Central

Sridhara, Deepa M.; Asaithamby, Aroumougame; Blattnig, Steve R.; Costes, Sylvain V.; Doetsch, Paul W.; Dynan, William S.; Hahnfeldt, Philip; Hlatky, Lynn; Kidane, Yared; Kronenberg, Amy; Naidu, Mamta D.; Peterson, Leif E.; Plante, Ianik; Ponomarev, Artem L.; Saha, Janapriya; Snijders, Antoine M.; Srinivasan, Kalayarasan; Tang, Jonathan; Werner, Erica; Pluth, Janice M.

2017-01-01

Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing biomarkers and to evaluate the potential for biomarkers to inform models of post exposure cancer risk. Because cellular stress response pathways to space radiation and environmental carcinogens share common nodes, biomarker-driven risk models may be broadly applicable for estimating risks for other carcinogens. PMID:27345199

(-)-Norpseudoephedrine, a metabolite of cathinone with amphetamine-like stimulus properties, enhances the analgesic and rate decreasing effects of morphine, but inhibits its discriminative properties.

PubMed

Nencini, P; Fraioli, S; Pascucci, T; Nucerito, C V

1998-04-01

Like psychomotor stimulants, a weak amphetamine-like agent, such as phenylpropanolamine, enhances the analgesic effects of morphine (MOR). Thus, it is possible that full psychomotor stimulant potency is not required to increase the analgesic action of opiates. The validity of this assumption is here tested by studying the ability of (-)-norpseudoephedrine (NPE), an enantiomer of phenylpropanolamine and a metabolite of cathinone, to influence both the analgesic effects of MOR and its discriminative stimulus properties. In mice NPE (5.6-10.0-17.0 mg/kg i.p.) did not prolong the latency to lick or to remove paws from a plate warmed at 54 degrees C. However, it significantly potentiated the analgesic effect of 3.2 mg/kg of MOR. These results were replicated in rats by use of the formalin test, which measures the numbers of hind paw flinches produced by injecting 50 microl of formalin into the dorsal surface of the paw. The higher dose of NPE (17 mg/kg) increased the effect of sub-analgesic doses of MOR (0.56 and 1.0 mg/kg). In rats trained to discriminate between 0.5 mg/kg of amphetamine and solvent in a two-lever operant behavior reinforced by water access. NPE induced a dose-dependent increment of drug lever responding from 0% at 1.0 mg/kg to 100% at 32.0 mg/kg. In contrast, NPE did not generalize for the MOR cue up to the dose of 56.0 mg/kg, which produced a substantial reduction of the response rate. However, when given in combination, NPE attenuated the discriminative effects of MOR and potentiated its inhibitory action on the response rate. These results exclude a direct action of NPE on the mu opiate system. In conclusion, NPE preserves amphetamine-like properties and these properties are probably responsible for the interaction of the drug with the analgesic and discriminative effects of MOR. Therefore, this study contradicts the assumption that the analgesic effects of MOR can be enhanced by a sympathomimetic drug that lacks significant psychostimulant actions.

Evaluating biomarkers to model cancer risk post cosmic ray exposure

NASA Astrophysics Data System (ADS)

Sridharan, Deepa M.; Asaithamby, Aroumougame; Blattnig, Steve R.; Costes, Sylvain V.; Doetsch, Paul W.; Dynan, William S.; Hahnfeldt, Philip; Hlatky, Lynn; Kidane, Yared; Kronenberg, Amy; Naidu, Mamta D.; Peterson, Leif E.; Plante, Ianik; Ponomarev, Artem L.; Saha, Janapriya; Snijders, Antoine M.; Srinivasan, Kalayarasan; Tang, Jonathan; Werner, Erica; Pluth, Janice M.

2016-06-01

Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing biomarkers and to evaluate the potential for biomarkers to inform models of post exposure cancer risk. Because cellular stress response pathways to space radiation and environmental carcinogens share common nodes, biomarker-driven risk models may be broadly applicable for estimating risks for other carcinogens.

Evaluating biomarkers to model cancer risk post cosmic ray exposure.

PubMed

Sridharan, Deepa M; Asaithamby, Aroumougame; Blattnig, Steve R; Costes, Sylvain V; Doetsch, Paul W; Dynan, William S; Hahnfeldt, Philip; Hlatky, Lynn; Kidane, Yared; Kronenberg, Amy; Naidu, Mamta D; Peterson, Leif E; Plante, Ianik; Ponomarev, Artem L; Saha, Janapriya; Snijders, Antoine M; Srinivasan, Kalayarasan; Tang, Jonathan; Werner, Erica; Pluth, Janice M

2016-06-01

Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing biomarkers and to evaluate the potential for biomarkers to inform models of post exposure cancer risk. Because cellular stress response pathways to space radiation and environmental carcinogens share common nodes, biomarker-driven risk models may be broadly applicable for estimating risks for other carcinogens. Copyright © 2016 The Committee on Space Research (COSPAR). All rights reserved.

Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture

PubMed Central

Malik, Deepika; Tarek, Mohamed; Caceres del Carpio, Javier; Ramirez, Claudio; Boyer, David; Kenney, M Cristina; Kuppermann, Baruch D

2014-01-01

Purpose To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. Methods Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. Results Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. Conclusions At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses. PMID:24836865

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.

Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with high-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response.

PubMed

Ridolfi, Laura; de Rosa, Francesco; Ridolfi, Ruggero; Gentili, Giorgia; Valmorri, Linda; Scarpi, Emanuela; Parisi, Elisabetta; Romeo, Antonino; Guidoboni, Massimo

2014-09-23

Tumor cells killed by radiation therapy (RT) are a potentially good source of antigens for dendritic cell (DC) uptake and presentation to T-cells. RT upregulates cell death receptors such as Fas/CD95 and MHC-I, induces the expression of co-stimulatory molecules on tumor cells, and promotes production of pro-inflammatory cytokines. High-dose interleukin-2 (HD-IL-2) bolus has been shown to obtain objective response rates ranging from 15% to 17% in patients with metastatic melanoma or renal cell carcinoma (RCC), with 6% to 8% of cases experiencing a durable complete response. However, HD-IL-2 is also associated with severe side-effects; if it is to remain a component of the curative treatment strategy in patients with metastatic melanoma or RCC, its therapeutic efficacy must be improved and patients who are most likely to benefit from treatment must be identified a priori. We designed a clinical study combining immunomodulating RT and HD-IL-2 to evaluate their clinical and immunological efficacy and to explore the predictive and prognostic value of 1) tumor-specific immune response and 2) serum levels of proangiogenic cytokines. The primary endpoint of this proof-of-principle phase II study is immune response. Secondary endpoints are the identification of biomarkers potentially predictive of response, toxicity, response rate and overall survival. Three daily doses of booster radiotherapy (XRT) at 6-12 Gy will be administered to at least one metastatic field on days -3 to -1 before the first and third cycle. Treatment with IL-2 (dose 18 MIU/m2/day by continuous IV infusion for 72 hours) will start on day +1 and will be repeated every 3 weeks for up to 4 cycles and then every 4 weeks for a further 2 cycles. Immune response against tumor antigens expressed by melanoma and/or RCC will be evaluated during treatment. Circulating immune effectors and regulators, e.g. cytotoxic T lymphocytes and regulatory T cells, as well as serum levels of proangiogenic/proinflammatory cytokines will also be quantified. This study aims to evaluate the potential immunological synergism between HD-IL-2 and XRT, and to identify biomarkers that are predictive of response to IL-2 in order to spare potentially non responding patients from toxicity. EudraCT no. 2012-001786-32.

Trends in opioid use and dosing among socio-economically disadvantaged patients

PubMed Central

Gomes, Tara; Juurlink, David N; Dhalla, Irfan A; Mailis-Gagnon, Angela; Paterson, J Michael; Mamdani, Muhammad M

2011-01-01

Background Opioid therapy for patients with chronic nonmalignant pain remains controversial, primarily because of safety concerns and the potential for abuse. The objective of this study was to examine trends in opioid utilization for nonmalignant pain among recipients of social assistance and to explore the relation between dose of analgesic and mortality. Methods Using a cross-sectional study design, we characterized annual trends in prescriptions for and daily dose of opioid analgesics between 2003 and 2008 for beneficiaries (aged 15 to 64 years) of Ontario’s public drug plan. We defined moderate, high and very high dose thresholds as daily doses of up to 200, 201 to 400, and more than 400 mg oral morphine (or equivalent), respectively. In an exploratory cohort study, we followed, over a 2-year period, patients who received at least one prescription for an opioid in 2004 to investigate the relation between opioid dose and opioid-related mortality. Results Over the study period, opioid prescribing rates rose by 16.2%, and 180 974 individuals received nearly 1.5 million opioid prescriptions in 2008. Also by 2008, the daily dose dispensed exceeded 200 mg morphine equivalent for almost a third (32.6%) of recipients of long-acting oxycodone but only 20.3% of those treated with fentanyl or other long-acting opioids. Among patients for whom high or very high doses of opioids were dispensed in 2004, 19.3% of deaths during the subsequent 2 years were opioid-related, occurring at a median age of 46 years. Two-year opioid-related mortality rates were 1.63 per 1000 population (95% confidence interval [CI] 1.42–1.85) among people with moderate-dose prescriptions, 7.92 per 1000 population (95% CI 5.25–11.49) among those with high-dose prescriptions, and 9.94 per 1000 population (95% CI 2.78–25.12) among those with very-high-dose prescriptions. Interpretation Among socio-economically disadvantaged patients in Ontario, the use and dose of opioids for nonmalignant pain has increased substantially, driven primarily by the use of long-acting oxycodone and, to a lesser extent, fentanyl. The findings of our exploratory study suggested a strong association between opioid-related mortality and the dose of opioid dispensed. PMID:22046214

β-blocker dosage and outcomes after acute coronary syndrome.

PubMed

Allen, Jason E; Knight, Stacey; McCubrey, Raymond O; Bair, Tami; Muhlestein, Joseph Brent; Goldberger, Jeffrey J; Anderson, Jeffrey L

2017-02-01

Although β-blockers increase survival in acute coronary syndrome (ACS) patients, the doses used in trials were higher than doses used in practice, and recent data do not support an advantage of higher doses. We hypothesized that rates of major adverse cardiac events (MACE), all-cause death, myocardial infarction, and stroke are equivalent for patients on low-dose and high-dose β-blocker. Patients admitted to Intermountain Healthcare with ACS and diagnosed with ≥70% coronary stenosis between 1994 and 2013 were studied (N = 7,834). We classified low dose as ≤25% and high dose as ≥50% of an equivalent daily dose of 200 mg of metoprolol. Multivariate analyses were used to test association between low-dose versus high-dose β-blocker dosage and MACE at 0-6 months and 6-24 months. A total of 5,287 ACS subjects were discharged on β-blockers (87% low dose, 12% high dose, and 1% intermediate dose). The 6-month MACE outcomes rates for the β-blocker dosage (low versus high) were not equivalent (P = .18) (hazard ratio [HR] = 0.76; 95% CI, 0.52-1.10). However, subjects on low-dose β-blocker therapy did have a significantly decreased risk of myocardial infarction for 0-6 months (HR = 0.53; 95% CI, 0.33-0.86). The rates of MACE events during the 6-24 months after presentation with ACS were equivalent for the 2 doses (P = .009; HR = 1.03 [95% CI, 0.70-1.50]). In ACS patients, rates of MACE for high-dose and low-dose β-blocker doses are similar. These findings question the importance of achieving a high dose of β-blocker in ACS patients and highlight the need for further investigation of this clinical question. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

The effect of the eye's surface topography on the total irradiance of ultraviolet radiation on the inner canthus.

PubMed

Birt, Benjamin; Cowling, Ian; Coyne, Steve; Michael, Greg

2007-04-02

Basal cell carcinoma is the most commonly occurring skin cancer in sub tropical climates. The link between ultraviolet radiation (UVR) and basal cell carcinomas (BCC) is strong. Numerous studies have investigated the spatial distribution of BCCs over the head and neck region and the relative UVR dose, with little or no correlation found between the UVR dose and occurrence rates. This is particularly noted in the inner canthus region. The inner canthus' field of view is restricted by the eye brow ridge, eye orbit and the cheek bone. Yet, the occurrence rate here of BCC's when compared to other regions that are more directly exposed to the environment is significantly higher. A possible causal effect for the increase in occurrence rate in this region is the focussed reflection of UVR from the tear film surface associated with the eye not previously considered in earlier studies. This paper investigates the potential for the surface topography of the eye to reflect focussed radiation towards the inner canthus using a ray tracing programme where the analysis is conducted at a cellular level. Defined hot spots, or striations, of increased irradiation were evidenced across the surface of the inner canthus. This increase in irradiation was not observed with macroscopic detectors which also possibly explain why this increased dose has not previously been detected during environmental measurements with large detectors on manikins or humans.

Human stem cell-derived cardiomyocytes detect drug-mediated changes in action potentials and ion currents.

PubMed

Gibson, John K; Yue, Yimei; Bronson, Jared; Palmer, Cassie; Numann, Randy

2014-01-01

It has been proposed that proarrhythmia assessment for safety pharmacology testing includes the use of human pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to detect drug-induced changes in cardiac electrophysiology. This study measured the actions of diverse agents on action potentials (AP) and ion currents recorded from hiPSC-CM. During AP experiments, the hiPSC-CM were paced at 1Hz during a baseline period, and when increasing concentrations of test compound were administered at 4-minute intervals. AP parameters, including duration (APD60 and APD90), resting membrane potential, rate of rise, and amplitude, were measured throughout the entire experiment. Voltage clamp experiments with E-4031 and nifedipine were similarly conducted. E-4031 produced a dose-dependent prolongation of cardiac action potential and blocked the hERG/IKr current with an IC50 of 17nM. At 3nM, dofetilide significantly increased APD90. Astemizole significantly increased APD60 and APD90 at 30nM. Terfenadine significantly increased APD90 at concentrations greater than 10nM. Fexofenadine, a metabolite of terfenadine, did not produce any electrophysiologic changes in cardiac action potentials. Flecainide produced a dose-dependent prolongation of the cardiac action potential at 1 and 3μM. Acute exposure to nifedipine significantly decreased APD60 and APD90 and produced a dose-dependent block of calcium current with an IC50 of 0.039μM. Verapamil first shortened APD60 and APD90 in a dose-dependent manner, until a compensating increase in APD90, presumably via hERG blockade, was observed at 1 and 3μM. Following a chronic exposure (20-24h) to clinically relevant levels of pentamidine, a significant increase in action potential duration was accompanied by early afterdepolarizations (EADs). These experiments show the ability of AP measured from hiPSC-CM to record the interactions of various ion channels via AP recording and avoid the limitations of using several single ion channel assays in a noncardiac tissue. Copyright © 2014 Elsevier Inc. All rights reserved.

Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer

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

Yamada, Shigeru, E-mail: s_yamada@nirs.go.jp; Kamada, Tadashi; Ebner, Daniel K.

Purpose: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. Methods and Materials: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. Results: Duringmore » phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. Conclusion: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.« less