Analysis and evaluation for consumer goods containing NORM in Korea.

PubMed

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

2017-08-01

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

A phase I study of LY317615 (enzastaurin) and temozolomide in patients with gliomas (EORTC trial 26054)

PubMed Central

Rampling, Roy; Sanson, Marc; Gorlia, Thiery; Lacombe, Denis; Lai, Christina; Gharib, Myriam; Taal, Walter; Stoffregen, Clemens; Decker, Rodney; van den Bent, Martin J.

2012-01-01

We report a phase 1 study to examine the safety and recommended dose of the oral protein kinase C-beta inhibitor (anti-angiogenic) enzastaurin in combination with single-agent temozolomide. The study was conducted in patients with recurrent glioblastoma or newly diagnosed disease that was not treatable with standard (chemo)radiotherapy. Patients were treated with standard dose temozolomide (200 mg/m2 for 5 days every 4 weeks) together with daily oral enzastaurin. Three dose levels of enzastaurin were investigated: 250 mg daily (OD), 500 mg OD, and 250 mg twice daily (BID). Dose-limiting toxicity was determined in the first 2 cycles, but treatment continued until limiting toxicity or disease progression was identified. Twenty-eight patients were enrolled. No dose-limiting toxicity was noted at 250 mg OD or 500 mg OD. However, at 250 mg BID, 2 dose-limiting episodes of thrombocytopenia were noted. The recommended dose for enzastaurin in combination with standard 4-weekly temozolomide is therefore 500 mg OD. The pharmacokinetics of enzastaurin in combination with temozolomide was evaluated. Temozolomide did not appear to effect enzastaurin exposures at the 250 mg or 500 mg OD dose levels. PMID:22291006

Point-of-use chlorination of turbid water: results from a field study in Tanzania.

PubMed

Mohamed, Hussein; Brown, Joe; Njee, Robert M; Clasen, Thomas; Malebo, Hamisi M; Mbuligwe, Steven

2015-06-01

Household-based chlorine disinfection is widely effective against waterborne bacteria and viruses, and may be among the most inexpensive and accessible options for household water treatment. The microbiological effectiveness of chlorine is limited, however, by turbidity. In Tanzania, there are no guidelines on water chlorination at household level, and limited data on whether dosing guidelines for higher turbidity waters are sufficient to produce potable water. This study was designed to assess the effectiveness of chlorination across a range of turbidities found in rural water sources, following local dosing guidelines that recommend a 'double dose' for water that is visibly turbid. We chlorinated water from 43 sources representing a range of turbidities using two locally available chlorine-based disinfectants: WaterGuard and Aquatabs. We determined free available chlorine at 30 min and 24 h contact time. Our data suggest that water chlorination with WaterGuard or Aquatabs can be effective using both single and double doses up to 20 nephelometric turbidity units (NTU), or using a double dose of Aquatabs up to 100 NTU, but neither was effective at turbidities greater than 100 NTU.

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

Vertical Distribution and Estimated Doses from Artificial Radionuclides in Soil Samples around the Chernobyl Nuclear Power Plant and the Semipalatinsk Nuclear Testing Site

PubMed Central

Taira, Yasuyuki; Hayashida, Naomi; Tsuchiya, Rimi; Yamaguchi, Hitoshi; Takahashi, Jumpei; Kazlovsky, Alexander; Urazalin, Marat; Rakhypbekov, Tolebay; Yamashita, Shunichi; Takamura, Noboru

2013-01-01

For the current on-site evaluation of the environmental contamination and contributory external exposure after the accident at the Chernobyl Nuclear Power Plant (CNPP) and the nuclear tests at the Semipalatinsk Nuclear Testing Site (SNTS), the concentrations of artificial radionuclides in soil samples from each area were analyzed by gamma spectrometry. Four artificial radionuclides (241Am, 134Cs, 137Cs, and 60Co) were detected in surface soil around CNPP, whereas seven artificial radionuclides (241Am, 57Co, 137Cs, 95Zr, 95Nb, 58Co, and 60Co) were detected in surface soil around SNTS. Effective doses around CNPP were over the public dose limit of 1 mSv/y (International Commission on Radiological Protection, 1991). These levels in a contaminated area 12 km from Unit 4 were high, whereas levels in a decontaminated area 12 km from Unit 4 and another contaminated area 15 km from Unit 4 were comparatively low. On the other hand, the effective doses around SNTS were below the public dose limit. These findings suggest that the environmental contamination and effective doses on the ground definitely decrease with decontamination such as removing surface soil, although the effective doses of the sampling points around CNPP in the present study were all over the public dose limit. Thus, the remediation of soil as a countermeasure could be an extremely effective method not only for areas around CNPP and SNTS but also for areas around the Fukushima Dai-ichi Nuclear Power Plant (FNPP), and external exposure levels will be certainly reduced. Long-term follow-up of environmental monitoring around CNPP, SNTS, and FNPP, as well as evaluation of the health effects in the population residing around these areas, could contribute to radiation safety and reduce unnecessary exposure to the public. PMID:23469013

Vertical distribution and estimated doses from artificial radionuclides in soil samples around the Chernobyl nuclear power plant and the Semipalatinsk nuclear testing site.

PubMed

Taira, Yasuyuki; Hayashida, Naomi; Tsuchiya, Rimi; Yamaguchi, Hitoshi; Takahashi, Jumpei; Kazlovsky, Alexander; Urazalin, Marat; Rakhypbekov, Tolebay; Yamashita, Shunichi; Takamura, Noboru

2013-01-01

For the current on-site evaluation of the environmental contamination and contributory external exposure after the accident at the Chernobyl Nuclear Power Plant (CNPP) and the nuclear tests at the Semipalatinsk Nuclear Testing Site (SNTS), the concentrations of artificial radionuclides in soil samples from each area were analyzed by gamma spectrometry. Four artificial radionuclides ((241)Am, (134)Cs, (137)Cs, and (60)Co) were detected in surface soil around CNPP, whereas seven artificial radionuclides ((241)Am, (57)Co, (137)Cs, (95)Zr, (95)Nb, (58)Co, and (60)Co) were detected in surface soil around SNTS. Effective doses around CNPP were over the public dose limit of 1 mSv/y (International Commission on Radiological Protection, 1991). These levels in a contaminated area 12 km from Unit 4 were high, whereas levels in a decontaminated area 12 km from Unit 4 and another contaminated area 15 km from Unit 4 were comparatively low. On the other hand, the effective doses around SNTS were below the public dose limit. These findings suggest that the environmental contamination and effective doses on the ground definitely decrease with decontamination such as removing surface soil, although the effective doses of the sampling points around CNPP in the present study were all over the public dose limit. Thus, the remediation of soil as a countermeasure could be an extremely effective method not only for areas around CNPP and SNTS but also for areas around the Fukushima Dai-ichi Nuclear Power Plant (FNPP), and external exposure levels will be certainly reduced. Long-term follow-up of environmental monitoring around CNPP, SNTS, and FNPP, as well as evaluation of the health effects in the population residing around these areas, could contribute to radiation safety and reduce unnecessary exposure to the public.

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2010 CFR

2010-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2011 CFR

2011-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2013 CFR

2013-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2012 CFR

2012-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2014 CFR

2014-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

Vocal Dose Measures: Quantifying Accumulated Vibration Exposure in Vocal Fold Tissues

PubMed Central

Titze, Ingo R.; Švec, Jan G.; Popolo, Peter S.

2011-01-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses. PMID:12959470

Vocal dose measures: quantifying accumulated vibration exposure in vocal fold tissues.

PubMed

Titze, Ingo R; Svec, Jan G; Popolo, Peter S

2003-08-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses.

Committed effective dose determination in southern Brazilian cereal flours.

PubMed

Scheibel, V; Appoloni, C R

2013-01-01

The health impact of radionuclide ingestion from foodstuffs was evaluated by the committed effective doses determined in eight commercial samples of South-Brazilian cereal flours (soy, wheat, cornmeal, cassava, rye, oat, barley and rice flours). The radioactivity traces of (228)Th, (228)Ra, (226)Ra, (40)K, (7)Be and (137)Cs were measured by gamma-ray spectrometry employing an HPGe detector of 66 % relative efficiency. The efficiency curve has taken into account the differences in densities and chemical composition between the matrix and the certified sample. The highest concentration levels of (228)Th and (40)K were 3.5±0.4 and 1469±17 Bq kg(-1) for soy flour, respectively, within the 95 % confidence level. The lower limit of detection for (137)Cs ranged from 0.04 to 0.4 Bq kg(-1). The highest committed effective dose was 0.36 μSv.y(-1) for (228)Ra in cassava flour (adults). All committed effective doses determined at the present work were lower than the International Atomic Energy Agency dose limit of 1 mSv.y(-1), to the public exposure.

Introduction to benchmark dose methods and U.S. EPA's benchmark dose software (BMDS) version 2.1.1

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

Davis, J. Allen, E-mail: davis.allen@epa.gov; Gift, Jeffrey S.; Zhao, Q. Jay

2011-07-15

Traditionally, the No-Observed-Adverse-Effect-Level (NOAEL) approach has been used to determine the point of departure (POD) from animal toxicology data for use in human health risk assessments. However, this approach is subject to substantial limitations that have been well defined, such as strict dependence on the dose selection, dose spacing, and sample size of the study from which the critical effect has been identified. Also, the NOAEL approach fails to take into consideration the shape of the dose-response curve and other related information. The benchmark dose (BMD) method, originally proposed as an alternative to the NOAEL methodology in the 1980s, addressesmore » many of the limitations of the NOAEL method. It is less dependent on dose selection and spacing, and it takes into account the shape of the dose-response curve. In addition, the estimation of a BMD 95% lower bound confidence limit (BMDL) results in a POD that appropriately accounts for study quality (i.e., sample size). With the recent advent of user-friendly BMD software programs, including the U.S. Environmental Protection Agency's (U.S. EPA) Benchmark Dose Software (BMDS), BMD has become the method of choice for many health organizations world-wide. This paper discusses the BMD methods and corresponding software (i.e., BMDS version 2.1.1) that have been developed by the U.S. EPA, and includes a comparison with recently released European Food Safety Authority (EFSA) BMD guidance.« less

Radiological protection and medical dosimetry for the Skylab crewmen

NASA Technical Reports Server (NTRS)

Bailey, J. V.; Hoffman, R. A.; English, R. A.

1977-01-01

Dosimetry results for Skylab crewmembers show that the Skylab 4 crewmen received the highest dose equivalents but remained well within the established limits for Skylab missions below the threshold of significant clinical effects. These dose equivalents apply specificially to long term effects such as general life shortening, increased neoplasm incidence, and cataract production. A Skylab crewman could fly a mission comparable to one 84-day Skylab 4 mission per year for 50 years before exceeding these career limits.

Acute effects of THC on time perception in frequent and infrequent cannabis users.

PubMed

Sewell, R Andrew; Schnakenberg, Ashley; Elander, Jacqueline; Radhakrishnan, Rajiv; Williams, Ashley; Skosnik, Patrick D; Pittman, Brian; Ranganathan, Mohini; D'Souza, D Cyril

2013-03-01

Cannabinoids have been shown to alter time perception, but existing literature has several limitations. Few studies have included both time estimation and production tasks, few control for subvocal counting, most had small sample sizes, some did not record subjects' cannabis use, many tested only one dose, and used either oral or inhaled administration of Δ⁹-tetrahydrocannabinol (THC), leading to variable pharmacokinetics, and some used whole-plant cannabis containing cannabinoids other than THC. Our study attempted to address these limitations. This study aims to characterize the acute effects of THC and frequent cannabis use on seconds-range time perception. THC was hypothesized to produce transient, dose-related time overestimation and underproduction. Frequent cannabis smokers were hypothesized to show blunted responses to these alterations. IV THC was administered at doses from 0.015 to 0.05 mg/kg to 44 subjects who participated in several double-blind, randomized, counterbalanced, crossover, placebo-controlled studies. Visual time estimation and production tasks in the seconds range were presented to subjects three times on each test day. All doses induced time overestimation and underproduction. Chronic cannabis use had no effect on baseline time perception. While infrequent/nonsmokers showed temporal overestimation at medium and high doses and temporal underproduction at all doses, frequent cannabis users showed no differences. THC effects on time perception were not dose related. A psychoactive dose of THC increases internal clock speed as indicated by time overestimation and underproduction. This effect is not dose related and is blunted in chronic cannabis smokers who did not otherwise have altered baseline time perception.

Severe neuropathy after high dose carboplatin in three patients receiving multidrug chemotherapy

PubMed Central

Heinzlef, O.; Lotz, J.; Roullet, E.

1998-01-01

Three patients are described who developed a severe neuropathy after chemotherapy with high dose cis-diamine-(1,1-cyclobutane dicarboxylato) platinum (carboplatin). This toxic side effect, which is unusual at conventional doses, might become more frequent as increasing doses are administered to overcome drug resistance in cancer treatment, and might limit its use at very high doses before haematopoietic stem cell transplantation. 

 PMID:9598687

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

Unkelbach, J; Perko, Z; Wolfgang, J

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

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2012 CFR

2012-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2014 CFR

2014-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2011 CFR

2011-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2013 CFR

2013-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2010 CFR

2010-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

A novel method for the evaluation of uncertainty in dose-volume histogram computation.

PubMed

Henríquez, Francisco Cutanda; Castrillón, Silvia Vargas

2008-03-15

Dose-volume histograms (DVHs) are a useful tool in state-of-the-art radiotherapy treatment planning, and it is essential to recognize their limitations. Even after a specific dose-calculation model is optimized, dose distributions computed by using treatment-planning systems are affected by several sources of uncertainty, such as algorithm limitations, measurement uncertainty in the data used to model the beam, and residual differences between measured and computed dose. This report presents a novel method to take them into account. To take into account the effect of associated uncertainties, a probabilistic approach using a new kind of histogram, a dose-expected volume histogram, is introduced. The expected value of the volume in the region of interest receiving an absorbed dose equal to or greater than a certain value is found by using the probability distribution of the dose at each point. A rectangular probability distribution is assumed for this point dose, and a formulation that accounts for uncertainties associated with point dose is presented for practical computations. This method is applied to a set of DVHs for different regions of interest, including 6 brain patients, 8 lung patients, 8 pelvis patients, and 6 prostate patients planned for intensity-modulated radiation therapy. Results show a greater effect on planning target volume coverage than in organs at risk. In cases of steep DVH gradients, such as planning target volumes, this new method shows the largest differences with the corresponding DVH; thus, the effect of the uncertainty is larger.

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

PubMed

Koivisto, Juha H; Wolff, Jan E; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-07-08

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

A chromogranin A ELISA absent of an apparent high-dose hook effect observed in other chromogranin A ELISAs.

PubMed

Erickson, J Alan; Grenache, David G

2016-01-15

Routine testing for chromogranin A (CgA) using an established commercial ELISA revealed an apparent high-dose hook effect in approximately 15% of specimens. Investigations found the same effect in two additional ELISAs. We hypothesized that a CgA derived peptide(s) at high concentrations was responsible but experiments were inconclusive. Here we describe the analytical performance characteristics of the Chromoa™ CgA ELISA that did not display the apparent high-dose hook effect. Performance characteristics of the Chromoa ELISA were assessed. The reference interval was established utilizing healthy volunteers. Specimens producing the apparent high-dose hook effect in other assays were evaluated using the Chromoa ELISA. The limit of detection was 8ng/ml. Linearity was acceptable (slope=1.04, intercept=18.1 and r(2)=0.997). CVs were ≤4.6 and ≤9.3% for repeatability and within-laboratory imprecision, respectively. CgA was stable at ambient and refrigerated temperatures for a minimum of two and 14days, respectively. An upper reference interval limit of 95ng/ml was established. Specimens demonstrating the apparent high-dose hook effect in other ELISAs did not exhibit the phenomenon using the Chromoa ELISA. The Chromoa ELISA demonstrates acceptable performance for quantifying serum CgA. The apparent high-dose hook effect exhibited in other ELISAs was absent using the Chromoa assay. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis of the track- and dose-averaged LET and LET spectra in proton therapy using the geant4 Monte Carlo code

PubMed Central

Guan, Fada; Peeler, Christopher; Bronk, Lawrence; Geng, Changran; Taleei, Reza; Randeniya, Sharmalee; Ge, Shuaiping; Mirkovic, Dragan; Grosshans, David; Mohan, Radhe; Titt, Uwe

2015-01-01

Purpose: The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the geant 4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from geant 4 simulations to correlate with biological effectiveness of therapeutic protons. Methods: The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LETt and dose-averaged LET, LETd) using geant 4 for different tracking step size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LETt and LETd of protons with six different step limits ranging from 1 to 500 μm in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Results: Simulation results showed that the step limit effect was small for LETt but significant for LETd. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in geant 4 can result in incorrect LETd calculation results in the dose plateau region for small step limits. The erroneous LETd results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in geant 4. The incorrect LETd values lead to substantial differences in the calculated RBE. Conclusions: When the geant 4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 μm, the authors recommend the use of LETt in the dose plateau region and LETd around the Bragg peak. For a large step limit, i.e., 500 μm, LETd is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LETd and LETt becomes positive. PMID:26520716

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

PubMed

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

2017-06-15

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

Adult Lead Exposure: Time for Change

PubMed Central

Schwartz, Brian S.; Hu, Howard

2007-01-01

We have assembled this mini-monograph on adult lead exposure to provide guidance to clinicians and public health professionals, to summarize recent thinking on lead biomarkers and their relevance to epidemiologic research, and to review two key lead-related outcomes, namely, cardiovascular and cognitive. The lead standards of the U.S. Occupational Safety and Health Administration are woefully out of date given the growing evidence of the health effects of lead at levels of exposure previously thought to be safe, particularly newly recognized persistent or progressive effects of cumulative dose. The growing body of scientific evidence suggests that occupational standards should limit recent dose to prevent the acute effects of lead and separately limit cumulative dose to prevent the chronic effects of lead. We hope this mini-monograph will motivate renewed discussion of ways to protect lead-exposed adults in the United States and around the world. PMID:17431498

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer

NASA Astrophysics Data System (ADS)

González, S. J.; Pozzi, E. C. C.; Monti Hughes, A.; Provenzano, L.; Koivunoro, H.; Carando, D. G.; Thorp, S. I.; Casal, M. R.; Bortolussi, S.; Trivillin, V. A.; Garabalino, M. A.; Curotto, P.; Heber, E. M.; Santa Cruz, G. A.; Kankaanranta, L.; Joensuu, H.; Schwint, A. E.

2017-10-01

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson’s correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer.

PubMed

González, S J; Pozzi, E C C; Monti Hughes, A; Provenzano, L; Koivunoro, H; Carando, D G; Thorp, S I; Casal, M R; Bortolussi, S; Trivillin, V A; Garabalino, M A; Curotto, P; Heber, E M; Santa Cruz, G A; Kankaanranta, L; Joensuu, H; Schwint, A E

2017-10-03

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson's correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method

PubMed Central

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Patel, Maxine X.; Furukawa, Toshi; Cipriani, Andrea; Geddes, John; Davis, John M.

2015-01-01

Background: The concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics. Methods: We searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents. Results: We included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available. Conclusions: The classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of “minimum effective dose methods” and “dose-response curve methods.” In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods. PMID:25841041

Guidance on radiation dose limits for the lens of the eye: overview of the recommendations in NCRP Commentary No. 26.

PubMed

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

2017-10-01

This review summarizes the conclusions and recommendations of the new National Council on Radiation Protection and Measurements (NCRP) Commentary No. 26 guidance on radiation dose limits for the lens of the eye. The NCRP addressed radiation protection principles in respect to the lens of the eye, discussed the current understanding of eye biology and lens effects, reviewed and evaluated epidemiology, and assessed exposed populations with the potential for significant radiation exposures to the lens while suggesting monitoring and protection practices. Radiation-induced damage to the lens of the eye can include the loss of clarity resulting in opacification or clouding several years after exposure. The impact is highly dependent on the type of radiation, how the exposure of the lens was delivered, the genetic susceptibilities of the individual exposed, and the location of the opacity relative to the visual axis of the individual. The preponderance of epidemiological evidence suggests that lens damage could occur at lower doses than previously considered and the NCRP has determined that it is prudent to reduce the recommended annual lens of the eye occupational dose limit from an equivalent dose of 150 mSv to an absorbed dose of 50 mGy. Significant additional research is still needed in the following areas: comprehensive evaluation of the overall effects of ionizing radiation on the eye, dosimetry methodology and dose-sparing optimization techniques, additional high quality epidemiology studies, and a basic understanding of the mechanisms of cataract development.

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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.

Safety of stavudine in the treatment of HIV infection with a special focus on resource-limited settings.

PubMed

Makinson, Alain; Moing, Vincent Le; Kouanfack, Charles; Laurent, Christian; Delaporte, Eric

2008-05-01

Western randomized trials and prospective cohorts in resource-limited settings have proven virological success with stavudine-based highly active antiretroviral therapy. However, stavudine is no longer recommended in first-line treatments in these two settings due to its intrinsic toxicities and side effects. Yet it remains a cornerstone of treatment in resource-limited settings, due to lack of alternatives and its availability in generic fixed-dose combinations. To review the toxic effects of stavudine and their prevention and management strategies, especially in resource-limited settings. Data from clinical and pharmacological trials in Western countries, as well as prospective cohorts in resource-limited settings, were reviewed. Initiating or switching to less toxic nucleoside analogues whenever possible, or lowering stavudine doses to 30 mg b.i.d., is strongly recommended.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

PubMed

Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

2016-11-01

To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2011-05-01

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

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

PubMed Central

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

2011-01-01

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

[Optimizing staff radiation protection in radiology by minimizing the effective dose].

PubMed

von Boetticher, H; Lachmund, J; Hoffmann, W; Luska, G

2006-03-01

In the present study the optimization of radiation protection devices is achieved by minimizing the effective dose of the staff members since the stochastic radiation effects correlate to the effective dose. Radiation exposure dosimetry was performed with TLD measurements using one Alderson Phantom in the patient position and a second phantom in the typical position of the personnel. Various types of protective clothing as well as fixed shields were considered in the calculations. It was shown that the doses of the unshielded organs (thyroid, parts of the active bone marrow) contribute significantly to the effective dose of the staff. Therefore, there is no linear relationship between the shielding factors for protective garments and the effective dose. An additional thyroid protection collar reduces the effective dose by a factor of 1.7 - 3.0. X-ray protective clothing with a 0.35 mm lead equivalent and an additional thyroid protection collar provides better protection against radiation than an apron with a 0.5 mm lead equivalent but no collar. The use of thyroid protection collars is an effective preventive measure against exceeding occupational organ dose limits, and a thyroid shield also considerably reduces the effective dose. Therefore, thyroid protection collars should be a required component of anti-X protection.

Radiation safety standards: space hazards vs. terrestrial hazards.

PubMed

Sinclair, W K

1983-01-01

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

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior

PubMed Central

Thanos, Panayotis K.; Robison, Lisa S.; Steier, Jessica; Hwang, Yu Fen; Cooper, Thomas; Swanson, James M.; Komatsu, David E.; Hadjiargyrou, Michael; Volkow, Nora D.

2015-01-01

Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (i.e. quicker and higher peak concentrations). Here, we evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic the clinical drug delivery profile. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60 mg/kg/day; as well as dual-dosages of 4 and 10 mg/kg/day, 20 and 30 mg/kg/day, or 30 and 60 mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Blood was sampled and plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60 mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30 ng/mL), while the 4/10 mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8 ng/mL). Treatment with the higher dual-dosage (HD: 30/60 mg/kg) resulted in hyperactivity, while the lower (LD: 4/10 mg/kg) had no effect. Next, chronic effects of these dual-dosages were assessed on behavior throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle; decreased exploratory behavior; and increased anxiolytic behavior. These findings suggest that this dual-dosage-drinking-paradigm can be used to examine the effects of clinically relevant pharmacokinetic doses of MP, and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes. PMID:25641666

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior.

PubMed

Thanos, Panayotis K; Robison, Lisa S; Steier, Jessica; Hwang, Yu Fen; Cooper, Thomas; Swanson, James M; Komatsu, David E; Hadjiargyrou, Michael; Volkow, Nora D

2015-04-01

Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (quicker and higher peak concentrations). We evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic clinical drug delivery. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60mg/kg/day; as well as dual-dosages of 4 and 10mg/kg/day, 20 and 30mg/kg/day, or 30 and 60mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30ng/mL), while the 4/10mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8ng/mL). Treatment with the higher dual-dosage (HD: 30/60mg/kg) resulted in hyperactivity, while the lower (LD: 4/10mg/kg) had no effect. Chronic effects of these dual-dosages were assessed throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle, decreased exploratory behavior, and increased anxiolytic behavior. Findings suggest that these dual-dosage-drinking-paradigms can be used to examine the effects of clinically relevant pharmacokinetic doses of MP and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Beta-carotene conversion to vitamin A decreases as the dietary dose increases in humans

USDA-ARS?s Scientific Manuscript database

It has been suggested that high doses of B-carotene limit its conversion to vitamin A, yet this effect has not been well established in humans. A feeding study was conducted in which volunteers consumed two doses of deuterium labeled B-carotene on two occasions, with B-carotene and vitamin A respon...

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2016-02-01

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

Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation.

PubMed

Loveman, E; Cooper, K; Bryant, J; Colquitt, J L; Frampton, G K; Clegg, A

2012-01-01

The present report was commissioned as a supplement to an existing technology assessment report produced by the Peninsula Technology Assessment Group (PenTAG), which evaluated the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in patients who are either resistant or intolerant to standard-dose imatinib. This report evaluates the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and high-dose imatinib within their licensed indications for the treatment of people with chronic myeloid leukaemia (CML) who are resistant to standard-dose imatinib. Bibliographic databases were searched from inception to January 2011, including The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences were searched, and experts were contacted to identify additional published and unpublished references. This report includes systematic reviews of clinical effectiveness and cost-effectiveness studies, an independent appraisal of information submitted by drug manufacturers to the National Institute for Health and Clinical Excellence (NICE), an independent appraisal of the PenTAG economic evaluation, and new economic analyses adapting the PenTAG economic model. Standard systematic procedures involving two reviewers to maintain impartiality and transparency, and to minimise bias, were conducted. Eleven studies met the inclusion criteria. Four of these studies included new data published since the PenTAG report; all of these were in chronic-phase CML. No relevant studies on the clinical effectiveness of nilotinib were found. The clinical effectiveness studies on dasatinib [one arm of a randomised controlled trial (RCT)] and high-dose imatinib (one arm of a RCT and three single-arm cohort studies) had major methodological limitations. These limitations precluded a comparison of the different arms within the RCT. Data from the studies are summarised in this report, but caution in interpretation is required. One economic evaluation was identified that compared dasatinib with high-dose imatinib in patients with chronic-phase CML who were CML resistant to standard-dose imatinib. Two industry submissions and the PenTAG economic evaluation were critiqued and differences in the assumptions and results were identified. The PenTAG economic model was adapted and new analyses conducted for the interventions dasatinib, nilotinib and high-dose imatinib and the comparators interferon alfa, standard-dose imatinib, stem cell transplantation and hydroxycarbamide. The results suggest that the three interventions, dasatinib, nilotinib and high-dose imatinib, have similar costs and cost-effectiveness compared with hydroxycarbamide, with a cost-effectiveness of around £30,000 per quality-adjusted life-year gained. However, it is not possible to derive firm conclusions about the relative cost-effectiveness of the three interventions owing to great uncertainty around data inputs. Uncertainty was explored using deterministic sensitivity analyses, threshold analyses and probabilistic sensitivity analyses. The paucity of good-quality evidence should be considered when interpreting this report. This review has identified very limited new information on clinical effectiveness of the interventions over that already shown in the PenTAG report. Limitations in the data exist; however, the results of single-arm studies suggest that the interventions can lead to improvements in haematological and cytogenetic responses in people with imatinib-resistant CML. The economic analyses do not highlight any one of the interventions as being the most cost-effective; however, the analysis results are highly uncertain owing to lack of agreement on appropriate assumptions. Recommendations for future research made by PenTAG, for a good-quality RCT comparing the three treatments remain.

[Clinical pharmacist influence at hospital to prevent overdosed prescription of acetaminophen].

PubMed

Viguier, F; Roessle, C; Zerhouni, L; Rouleau, A; Benmelouka, C; Chevallier, A; Chast, F; Conort, O

2016-11-01

The recommended daily dose of acetaminophen is limited to 60mg/kg/day with a maximum of 3g daily dose in adults weighing less than 50kg or in patients undergoing certain risk factors. This study aimed at assessing the fulfillment of those recommendations and the possible impact on the liver dysfunction at supra-therapeutic doses of acetaminophen. This study was performed one day in 9 services. Patients characteristics, acetaminophen dose, daily dose administered, physiopathological aspects, markers of liver damage were collected. Among 542 prescriptions analyzed, 343 of them contained acetaminophen. The median age of patients studied was 81 years and one third weighed less than 50kg. The main risk factor of supra-therapeutic prescriptions was the lack of dose acetaminophen based on weight with 14% patients concerned and this risk raised at 17% when the pathophysiological conditions were included. The presence of pharmacists in medicals departments was more effective than the use of informatics programs limiting the dose systematically to 3g/day, or a distant pharmaceutical validation from care services to reduce the risk of acetaminophen overdose. According to the statement of administrations, only 4 of 49 patients received doses above 60mg/kg/day with a low impact on liver function tests. The continuous presence in pharmaceutical care services was the most effective measure to ensure effective implementation of acetaminophen recommendations. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

PubMed Central

Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

2015-01-01

Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect surveillance data and uncertainty about the transmission dynamics of cholera in each setting. Conclusions Reactive vaccination campaigns using a single dose of OCV may avert more cases and deaths than a standard two-dose campaign when vaccine supplies are limited, while at the same time reducing logistical complexity. These findings should motivate consideration of the trade-offs between one- and two-dose campaigns in resource-constrained settings, though further field efficacy data are needed and should be a priority in any one-dose campaign. PMID:26305226

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.

BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

EPA Pesticide Factsheets

The purpose of this document is to provide guidance for the Agency on the application of the benchmark dose approach in determining the point of departure (POD) for health effects data, whether a linear or nonlinear low dose extrapolation is used. The guidance includes discussion on computation of benchmark doses and benchmark concentrations (BMDs and BMCs) and their lower confidence limits, data requirements, dose-response analysis, and reporting requirements. This guidance is based on today's knowledge and understanding, and on experience gained in using this approach.

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

PubMed Central

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

2015-01-01

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

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

Effective dose evaluation of NORM-added consumer products using Monte Carlo simulations and the ICRP computational human phantoms.

PubMed

Lee, Hyun Cheol; Yoo, Do Hyeon; Testa, Mauro; Shin, Wook-Geun; Choi, Hyun Joon; Ha, Wi-Ho; Yoo, Jaeryong; Yoon, Seokwon; Min, Chul Hee

2016-04-01

The aim of this study is to evaluate the potential hazard of naturally occurring radioactive material (NORM) added consumer products. Using the Monte Carlo method, the radioactive products were simulated with ICRP reference phantom and the organ doses were calculated with the usage scenario. Finally, the annual effective doses were evaluated as lower than the public dose limit of 1mSv y(-1) for 44 products. It was demonstrated that NORM-added consumer products could be quantitatively assessed for the safety regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential implications of the bystander effect on TCP and EUD when considering target volume dose heterogeneity.

PubMed

Balderson, Michael J; Kirkby, Charles

2015-01-01

In light of in vitro evidence suggesting that radiation-induced bystander effects may enhance non-local cell killing, there is potential for impact on radiotherapy treatment planning paradigms such as the goal of delivering a uniform dose throughout the clinical target volume (CTV). This work applies a bystander effect model to calculate equivalent uniform dose (EUD) and tumor control probability (TCP) for external beam prostate treatment and compares the results with a more common model where local response is dictated exclusively by local absorbed dose. The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. EUD and TCP of a prostate cancer target volume under conditions of increasing dose heterogeneity were calculated using two models: One incorporating bystander effects derived from previously published in vitro bystander data ( McMahon et al. 2012 , 2013a); and one using a common linear-quadratic (LQ) response that relies exclusively on local absorbed dose. Dose through the CTV was modelled as a normal distribution, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). Also, a representative clinical dose distribution was examined as cold (low dose) sub-volumes were systematically introduced. The bystander model suggests a moderate degree of dose heterogeneity throughout a target volume will yield as good or better outcome compared to a uniform dose in terms of EUD and TCP. For a typical intermediate risk prostate prescription of 78 Gy over 39 fractions maxima in EUD and TCP as a function of increasing SD occurred at SD ∼ 5 Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. Small, but potentially significant differences in the outcome metrics between the models were identified in the clinically-derived dose distribution as cold sub-volumes were introduced. In terms of EUD and TCP, the bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV varies. The results suggest, at least in a limiting sense, the potential for allowing some degree of dose heterogeneity within a CTV, although further investigation of the assumptions of the bystander model are warranted.

Generalised photon skyshine calculations.

PubMed

Hayes, Robert

2004-01-01

The energy-dependent dose contributions from monoenergetic photon source points located 1.5 m above the ground have been tabulated. These values are intended to be used for regulatory compliance with site boundary dose limitations and as such are all presented in effective dose units. Standard air and soil are modelled where the air has vertical density gradient approximation. Energies from 0.05 up to 10 MeV are evaluated for dose transport up to 40 mean free paths.

[Dose rate-dependent cellular and molecular effects of ionizing radiation].

PubMed

Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

2008-09-11

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

Analysis of the track- and dose-averaged LET and LET spectra in proton therapy using the GEANT4 Monte Carlo code

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

Guan, Fada; Peeler, Christopher; Taleei, Reza

Purpose: The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the GEANT 4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from GEANT 4 simulations to correlate with biological effectiveness of therapeutic protons. Methods: The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LET{sub t} and dose-averaged LET, LET{sub d}) using GEANT 4 for different tracking stepmore » size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LET{sub t} and LET{sub d} of protons with six different step limits ranging from 1 to 500 μm in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Results: Simulation results showed that the step limit effect was small for LET{sub t} but significant for LET{sub d}. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in GEANT 4 can result in incorrect LET{sub d} calculation results in the dose plateau region for small step limits. The erroneous LET{sub d} results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in GEANT 4. The incorrect LET{sub d} values lead to substantial differences in the calculated RBE. Conclusions: When the GEANT 4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 μm, the authors recommend the use of LET{sub t} in the dose plateau region and LET{sub d} around the Bragg peak. For a large step limit, i.e., 500 μm, LET{sub d} is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LET{sub d} and LET{sub t} becomes positive.« less

Radiation exposure levels within timber industries in Calabar, Nigeria

PubMed Central

Inyang, S. O.; Inyang, I. S.; Egbe, N. O.

2009-01-01

The UNSCEAR (2000) observed that there could be some exposure at work which would require regulatory control but is not really considered. This study was, therefore, set up to evaluate the effective dose in timber industries in Calabar, Nigeria to determine if the evaluated dose levels could lead to any radiological health effect in the workers, and also determine if the industries require regulatory control. The gamma ray exposure at four timber industries measured using an exposure meter were converted to effective dose and compared with the public and occupational values. The evaluated effective dose values in the timber industries were below public and occupational exposure limits and may not necessarily result in any radiological health hazard. Therefore, they may not require regulatory control. PMID:20098544

Development of a point-of-care HIV/AIDS medication dosing support system using the Android mobile platform.

PubMed

Sadasivam, Rajani S; Gathibandhe, Vaibhav; Tanik, Murat M; Willig, James H

2012-06-01

Medication dosing errors can greatly reduce HIV treatment effectiveness as incorrect dosing leads to drug resistance and non-adherence. In order to dose correctly, HIV therapy providers must balance several patient characteristics such as renal functions and weight. In developing countries and other resource-limited settings, dosing errors are more likely because treatment is provided by mid-level providers with only basic training in HIV therapy. These providers also typically lack electronic tools informing medical decisions. Widespread adoption of mobile phones in developing nations offers an opportunity to implement a point-of-care system to help providers reduce dosing errors. We discuss the development of the mHIV-Dr system prototype using the new Android mobile platform. mHIV-Dr is being designed to provide dosing recommendations for front-line providers in developing countries. We also discuss the additional challenges in the implementation of the mHIV-Dr system in a resource limited setting.

Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone.

PubMed

Poet, T S; Schlosser, P M; Rodriguez, C E; Parod, R J; Rodwell, D E; Kirman, C R

2016-04-01

The developmental effects of NMP are well studied in Sprague-Dawley rats following oral, inhalation, and dermal routes of exposure. Short-term and chronic occupational exposure limit (OEL) values were derived using an updated physiologically based pharmacokinetic (PBPK) model for NMP, along with benchmark dose modeling. Two suitable developmental endpoints were evaluated for human health risk assessment: (1) for acute exposures, the increased incidence of skeletal malformations, an effect noted only at oral doses that were toxic to the dam and fetus; and (2) for repeated exposures to NMP, changes in fetal/pup body weight. Where possible, data from multiple studies were pooled to increase the predictive power of the dose-response data sets. For the purposes of internal dose estimation, the window of susceptibility was estimated for each endpoint, and was used in the dose-response modeling. A point of departure value of 390 mg/L (in terms of peak NMP in blood) was calculated for skeletal malformations based on pooled data from oral and inhalation studies. Acceptable dose-response model fits were not obtained using the pooled data for fetal/pup body weight changes. These data sets were also assessed individually, from which the geometric mean value obtained from the inhalation studies (470 mg*hr/L), was used to derive the chronic OEL. A PBPK model for NMP in humans was used to calculate human equivalent concentrations corresponding to the internal dose point of departure values. Application of a net uncertainty factor of 20-21, which incorporates data-derived extrapolation factors, to the point of departure values yields short-term and chronic occupational exposure limit values of 86 and 24 ppm, respectively. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cumulative total effective whole-body radiation dose in critically ill patients.

PubMed

Rohner, Deborah J; Bennett, Suzanne; Samaratunga, Chandrasiri; Jewell, Elizabeth S; Smith, Jeffrey P; Gaskill-Shipley, Mary; Lisco, Steven J

2013-11-01

Uncertainty exists about a safe dose limit to minimize radiation-induced cancer. Maximum occupational exposure is 20 mSv/y averaged over 5 years with no more than 50 mSv in any single year. Radiation exposure to the general population is less, but the average dose in the United States has doubled in the past 30 years, largely from medical radiation exposure. We hypothesized that patients in a mixed-use surgical ICU (SICU) approach or exceed this limit and that trauma patients were more likely to exceed 50 mSv because of frequent diagnostic imaging. Patients admitted into 15 predesignated SICU beds in a level I trauma center during a 30-day consecutive period were prospectively observed. Effective dose was determined using Huda's method for all radiography, CT imaging, and fluoroscopic examinations. Univariate and multivariable linear regressions were used to analyze the relationships between observed values and outcomes. Five of 74 patients (6.8%) exceeded exposures of 50 mSv. Univariate analysis showed trauma designation, length of stay, number of CT scans, fluoroscopy minutes, and number of general radiographs were all associated with increased doses, leading to exceeding occupational exposure limits. In a multivariable analysis, only the number of CT scans and fluoroscopy minutes remained significantly associated with increased whole-body radiation dose. Radiation levels frequently exceeded occupational exposure standards. CT imaging contributed the most exposure. Health-care providers must practice efficient stewardship of radiologic imaging in all critically ill and injured patients. Diagnostic benefit must always be weighed against the risk of cumulative radiation dose.

Cefixime allows greater dose escalation of oral irinotecan: a phase I study in pediatric patients with refractory solid tumors.

PubMed

Furman, Wayne L; Crews, Kristine R; Billups, Catherine; Wu, Jianrong; Gajjar, Amar J; Daw, Najat C; Patrick, Christian C; Rodriguez-Galindo, Carlos; Stewart, Clinton F; Dome, Jeffrey S; Panetta, John C; Houghton, Peter J; Santana, Victor M

2006-02-01

Irinotecan is active against a variety of malignancies; however, severe diarrhea limits its usefulness. In our phase I study, the intravenous formulation of irinotecan was administered orally daily for 5 days for 2 consecutive weeks (repeated every 21 days) to children with refractory solid tumors. Our objectives were to determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of oral irinotecan and to evaluate whether coadministration of cefixime (8 mg/kg/d beginning 5 days before irinotecan and continuing throughout the course) ameliorates irinotecan-induced diarrhea. In separate cohorts, irinotecan doses were escalated from 15 to 45 mg/m2/d without cefixime and then from 45 to 60 and 75 mg/m2/d with cefixime. Without cefixime, diarrhea was dose limiting at irinotecan 45 mg/m2/d. Myelotoxicity was not significant at any dose. The MTD was 40 mg/m2/d without cefixime but 60 mg/m2/d with cefixime. Systemic exposure to SN-38 at the MTD was significantly higher with cefixime than without cefixime (mean SN-38 area under the curve: 19.5 ng x h/mL; standard deviation [SD], 6.8 ng x h/mL v 10.4 ng x h/mL; SD, 4.3 ng x h/mL, respectively; P = .030). Cefixime administered with oral irinotecan is well tolerated in children and allows greater dose escalation of irinotecan. Because diarrhea is a major adverse effect of both intravenous and oral irinotecan, further evaluation of the use of cefixime to ameliorate this adverse effect is warranted.

Limited PCB antagonism of TCDD-induced malformations in mice

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

Morrissey, R.E.; Harris, M.W.; Diliberto, J.J.

1992-01-01

Mice used to model induction of cleft palate and kidney malformations in offspring following maternal treatment with TCDD, were dosed on gestation day with hexachlorobiphenyl (HCB) and/or with tetrachlorodibenzo-p-dioxin (TCDD) to investigate the potential protective effects of HCB against TCDD-induced teratogenicity. At the doses used in the study, there was no effect of either compound on number of live or dead offspring. Fetal body weight was slightly decreased in all groups dosed with = or > 250 mg HCB/kg. HCB did not induce cleft palate at a dose of 1000 mg/kg, but did induce increases in hydronephrosis and hydroureter atmore » 500 and 1000 mg/kg. Combinations of HCB and TCDD decreased the incidence of cleft palate induced by TCDD alone, but only at doses of 15 microgram TCDD/kg combined with 125-500 mg HCB/kg. The window for antagonism of hydronephrosis (incidence and severity) appeared narrower (15 microgram TCDD/kg + 500 mg HCB/kg). HCB induced increases (3 fold) in EROD activity at doses of 500 and 1000 mg/kg, suggesting that the limited antagonism of TCDD teratogenicity by HCB would be consistent with control by Ah receptor. (Copyright (c) 1992 Elsevier Science Publishers B.V.)« less

MPC and ALI: their basis and their comparison

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

Kennedy, W.E. Jr.; Watson, E.C.

Radiation protection regulations in the United States have evolved from the recommendations of the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP). In 1959, the ICRP issued Publication 2 which contained specific recommendations on dose rate limits, permissible body burdens, metabolic data for radionuclides, and maximum permissible concentrations (MPC) in air or water. Over the next 20 years, new information became available concerning the effects of radiation, the uptake and retention of radionuclides, and the radioactive decay schemes of parent radionuclides. To include this newer information, the ICRP issued Publication 30 inmore » 1978 to supersede Publication 2. One of the secondary limits defined in Publication 30 is the annual limit of intake (ALI). Radionuclide specific ALI values are intended to replace MPC values in determining whether or not ambient air and water concentrations are sufficiently low to maintain the dose to workers within accepted dose rate limits. In this paper, we discuss the derivation of MPC and ALI values, compare inhalation committed dose equivalent factors derived from ICRP Publications 2 and 30, and discuss the practical implications of using either MPC or ALI in determining compliance with occupational exposure limits. 6 references.« less

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

PubMed Central

Vaiserman, Alexander M.

2010-01-01

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

SUDOQU, a new dose-assessment methodology for radiological surface contamination.

PubMed

van Dillen, Teun; van Dijk, Arjan

2018-06-12

A new methodology has been developed for the assessment of the annual effective dose resulting from removable and fixed radiological surface contamination. It is entitled SUDOQU (SUrface DOse QUantification) and it can for instance be used to derive criteria for surface contamination related to the import of non-food consumer goods, containers and conveyances, e.g., limiting values and operational screening levels. SUDOQU imposes mass (activity)-balance equations based on radioactive decay, removal and deposition processes in indoor and outdoor environments. This leads to time-dependent contamination levels that may be of particular importance in exposure scenarios dealing with one or a few contaminated items only (usually public exposure scenarios, therefore referred to as the 'consumer' model). Exposure scenarios with a continuous flow of freshly contaminated goods also fall within the scope of the methodology (typically occupational exposure scenarios, thus referred to as the 'worker model'). In this paper we describe SUDOQU, its applications, and its current limitations. First, we delineate the contamination issue, present the assumptions and explain the concepts. We describe the relevant removal, transfer, and deposition processes, and derive equations for the time evolution of the radiological surface-, air- and skin-contamination levels. These are then input for the subsequent evaluation of the annual effective dose with possible contributions from external gamma radiation, inhalation, secondary ingestion (indirect, from hand to mouth), skin contamination, direct ingestion and skin-contact exposure. The limiting effective surface dose is introduced for issues involving the conservatism of dose calculations. SUDOQU can be used by radiation-protection scientists/experts and policy makers in the field of e.g. emergency preparedness, trade and transport, exemption and clearance, waste management, and nuclear facilities. Several practical examples are worked out demonstrating the potential applications of the methodology. . Creative Commons Attribution license.

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

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

Potential Developmental and Early Life Health Effects of Nanomaterials: Data Gaps and Research Needs for Risk Assessment

EPA Science Inventory

Although research examining the toxicology of nanomaterials has been ongoing for many years, early studies largely focus on respiratory effects, and are limited by lack of appropriate dose metrics and a limited understanding of the role of the physicochemical properties of nanoma...

Primary Prevention of Asthma: Age and Sex Influence Sensitivity to Allergen-Induced Airway Inflammation and Contribute to Asthma Heterogeneity in Guinea Pigs

PubMed Central

Regal, Jean F.; Regal, Ronald R.; Meehan, Jessica L.; Mohrman, Margaret E.

2010-01-01

Background Limiting allergen exposure in the sensitization phase has been proposed as a means of primary prevention of asthma, but its effectiveness is debated. Hypothesis Primary prevention of asthma is more effective in limiting asthma symptoms in young guinea pigs compared with adults, whether males or females. Methods The following experimental groups were used: young/young, sensitized and challenged before sexual maturity; young/adult, sensitized young and challenged after sexual maturity; adult/adult, sensitized and challenged after sexual maturity. Males and females were sensitized intraperitoneally with varying doses of ovalbumin (OVA) and challenged intratracheally with a constant OVA dose. Cellular infiltration into lung and lavage fluid as well as airway hyperresponsiveness to intravenous methacholine was determined 24 h later. Results In unsensitized animals, density of resident inflammatory cells as well as baseline pulmonary function differed with age and sex. Maximum OVA-induced eosinophilia in females occurred at a lower sensitizing dose of OVA than in males, and the slopes of the dose-response relationship differed significantly between sexes. Young females had more pronounced increases in eosinophils compared with some adult treatment groups. The concentrations of OVA-specific antibodies were not directly related to differences in cellular infiltration. Airway hyperresponsiveness to methacholine challenge was observed in all treatment groups. Conclusion Young animals require major reductions in allergen exposure compared with adults to effectively limit airway inflammation in primary prevention. Heterogeneity of asthma symptoms seen with age and sex suggests that primary prevention by limiting allergen exposure or treatment with anti-inflammatory or bronchodilator drugs may be more effective strategies for specific age and gender populations. PMID:16931886

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

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2014 CFR

2014-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2011 CFR

2011-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2012 CFR

2012-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2010 CFR

2010-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2013 CFR

2013-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

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

PubMed Central

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

2008-01-01

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

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer

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

Inoue, Tatsuya; Widder, Joachim; Dijk, Lisanne V. van

2016-11-01

Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Methods and Materials: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2.more » The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D{sub 2} − D{sub 98}, where D{sub 2} and D{sub 98} are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. Results: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. Conclusions: In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters.« less

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

PubMed

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

2015-10-13

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

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

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

Xue, J; Park, J; Kim, L

2016-06-15

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

Meeting report: Estimating the benefits of reducing hazardous air pollutants--summary of 2009 workshop and future considerations.

PubMed

Gwinn, Maureen R; Craig, Jeneva; Axelrad, Daniel A; Cook, Rich; Dockins, Chris; Fann, Neal; Fegley, Robert; Guinnup, David E; Helfand, Gloria; Hubbell, Bryan; Mazur, Sarah L; Palma, Ted; Smith, Roy L; Vandenberg, John; Sonawane, Babasaheb

2011-01-01

Quantifying the benefits of reducing hazardous air pollutants (HAPs, or air toxics) has been limited by gaps in toxicological data, uncertainties in extrapolating results from high-dose animal experiments to estimate human effects at lower doses, limited ambient and personal exposure monitoring data, and insufficient economic research to support valuation of the health impacts often associated with exposure to individual air toxics. To address some of these issues, the U.S. Environmental Protection Agency held the Workshop on Estimating the Benefits of Reducing Hazardous Air Pollutants (HAPs) in Washington, DC, from 30 April to 1 May 2009. Experts from multiple disciplines discussed how best to move forward on air toxics benefits assessment, with a focus on developing near-term capability to conduct quantitative benefits assessment. Proposed methodologies involved analysis of data-rich pollutants and application of this analysis to other pollutants, using dose-response modeling of animal data for estimating benefits to humans, determining dose-equivalence relationships for different chemicals with similar health effects, and analysis similar to that used for criteria pollutants. Limitations and uncertainties in economic valuation of benefits assessment for HAPS were discussed as well. These discussions highlighted the complexities in estimating the benefits of reducing air toxics, and participants agreed that alternative methods for benefits assessment of HAPs are needed. Recommendations included clearly defining the key priorities of the Clean Air Act air toxics program to identify the most effective approaches for HAPs benefits analysis, focusing on susceptible and vulnerable populations, and improving dose-response estimation for quantification of benefits.

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

DOE PAGES

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

2015-12-09

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

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

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

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

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

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

Low-dose vaporized cannabis significantly improves neuropathic pain.

PubMed

Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

RADIATION DOSE DUE TO RADON AND HEAVY METAL ANALYSIS IN DRINKING WATER SAMPLES OF JAMMU DISTRICT, JAMMU & KASHMIR, INDIA.

PubMed

Kumar, A; Kaur, M; Sharma, S; Mehra, R; Sharma, D K; Mishra, R

2016-10-01

In the present investigation, radon concentration and heavy metal analysis were carried out in drinking water samples in Jammu district, Jammu & Kashmir, India. The radon concentration was measured by using RAD-7, portable alpha particle detector. The values of radon concentration in drinking water samples were also compared within the safe limit recommended by different health agencies. The total annual effective dose ranged from 53.04 to 197.29 µSv y -1 The annual effective dose from few locations from the studied area was found to be greater than the safe limit (100 µSv y -1 ) suggested by World Health Organisation (WHO) and EU Council. Heavy metal concentration was determined by atomic absorption spectrophotometer. A total of eight elements were analysed, viz. arsenic, mercury, zinc, iron, copper, chromium, manganese and cadmium. Heavy metals are considered to be the major pollutants of water sources. The results were compared with the limits of WHO, EU and Indian organisations. The trace metal analysis is not on the exceeding side of the permissible limit in all the samples. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Eye doses to staff in a nuclear medicine department.

PubMed

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

2012-05-01

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

Clinical Pharmacodynamics: Principles of Drug Response and Alterations in Kidney Disease.

PubMed

Keller, Frieder; Hann, Alexander

2018-05-16

Pharmacokinetics and pharmacodynamics follow the logic of cause and consequence. Receptor-mediated and reversible effects can be distinguished from direct and irreversible effects. Reversible effects are capacity-limited and saturable whereas irreversible effects are limited only by the number of viable targets. In the case of receptor-mediated and reversible effects a threshold and a ceiling concentration can be defined. Antimicrobial drugs with concentration-dependent action are distinguished from drugs with time-dependent action. Concentration-dependent effects are associated with a high ceiling concentration and the target is the high peak. Time-dependent effects are associated with a high threshold concentration and the target is the high trough. During kidney dysfunction, alterations of drug response are usually attributed to pharmacokinetic but rarely to pharmacodynamic changes. Dose adjustment calculations, therefore, tacitly presume that pharmacodynamic parameters remain unchanged while only pharmacokinetic parameters are altered in kidney failure. Kidney dysfunction influences the pharmacokinetic parameters of at least 50% of all essential drugs. Clinicians usually consider pharmacokinetics when kidney disease is found, but pharmacodynamics is as important. Alterations of pharmacodynamic parameters are conceivable but only rarely reported in kidney failure. Sometimes surprising dosing adjustments are needed when pharmacodynamic concepts are brought into the decision process of which dose to choose. Pharmacokinetics and pharmacodynamics should both be considered when any dosing regimen is determined. Copyright © 2018 by the American Society of Nephrology.

Esophageal Dose Tolerance in Patients Treated With Stereotactic Body Radiation Therapy.

PubMed

Nuyttens, Joost J; Moiseenko, Vitali; McLaughlin, Mark; Jain, Sheena; Herbert, Scott; Grimm, Jimm

2016-04-01

Mediastinal critical structures such as trachea, bronchus, esophagus, and heart are among the dose-limiting factors for stereotactic body radiation therapy (SBRT) to central lung lesions. The purpose of this study was to characterize the risk of esophagitis for patients treated with SBRT and to develop a statistical dose-response model to assess the equivalent uniform dose, D10%, D5cc, D1cc, and Dmax, to the esophagus and the risk of toxicity. Toxicity outcomes of a dose-escalation study of 56 patients who had taken CyberKnife treatment from 45-60Gy in 3-7 fractions at the Erasmus MC-Daniel den Hoed Cancer Center were utilized to create the dose-response model for esophagus. A total of 5 grade 2 esophageal complications were reported (Common Terminology Criteria for Adverse Events version 3.0); 4 complications were early effects and 1 complication was a late effect. All analyses were performed in terms of 5-fraction equivalent dosing. According to our study, D1cc at a dose of 32.9Gy and Dmax dose of 43.4Gy corresponded to a complication probability of 50% for grade 2 toxicity. In this series of 58 CyberKnife mediastinal lung cases, no grade 3 or higher esophageal toxicity occurred. Our estimates of esophageal toxicity are compared with the data in the literature. Further research needs to be performed to establish more reliable dose limits as longer follow-up and toxicity outcomes are reported in patients treated with SBRT for central lung lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost-effectiveness of pharmacogenetics-guided warfarin therapy vs. alternative anticoagulation in atrial fibrillation.

PubMed

Pink, J; Pirmohamed, M; Lane, S; Hughes, D A

2014-02-01

Pharmacogenetics-guided warfarin dosing is an alternative to standard clinical algorithms and new oral anticoagulants for patients with nonvalvular atrial fibrillation. However, clinical evidence for pharmacogenetics-guided warfarin dosing is limited to intermediary outcomes, and consequently, there is a lack of information on the cost-effectiveness of anticoagulation treatment options. A clinical trial simulation of S-warfarin was used to predict times within therapeutic range for different dosing algorithms. Relative risks of clinical events, obtained from a meta-analysis of trials linking times within therapeutic range with outcomes, served as inputs to an economic analysis. Neither dabigatran nor rivaroxaban were cost-effective options. Along the cost-effectiveness frontier, in relation to clinically dosed warfarin, pharmacogenetics-guided warfarin and apixaban had incremental cost-effectiveness ratios of £13,226 and £20,671 per quality-adjusted life year gained, respectively. On the basis of our simulations, apixaban appears to be the most cost-effective treatment.

Effect of Polyether Ether Ketone on Therapeutic Radiation to the Spine: A Pilot Study.

PubMed

Jackson, J Benjamin; Crimaldi, Anthony J; Peindl, Richard; Norton, H James; Anderson, William E; Patt, Joshua C

2017-01-01

Cadaveric model. To compare the effect of PEEK versus conventional implants on scatter radiation to a simulated tumor bed in the spine SUMMARY OF BACKGROUND DATA.: Given the highly vasculature nature of the spine, it is the most common place for bony metastases. After surgical treatment of a spinal metastasis, adjuvant radiation therapy is typically administered. Radiation dosing is primarily limited by toxicity to the spinal cord. The scatter effect caused by metallic implants decreases the accuracy of dosing and can unintentionally increase the effective dose seen by the spinal cord. This represents a dose-limiting factor for therapeutic radiation postoperatively. A cadaveric thorax specimen was utilized as a metastatic tumor model with two separate three-level spine constructs (one upper thoracic and one lower thoracic). Each construct was examined independently. All four groups compared included identical posterior instrumentation. The anterior constructs consisted of either: an anterior polyether ether ketone (PEEK) cage, an anterior titanium cage, an anterior bone cement cage (polymethyl methacrylate), or a control group with posterior instrumentation alone. Each construct had six thermoluminescent detectors to measure the radiation dose. The mean dose was similar across all constructs and locations. There was more variability in the upper thoracic spine irrespective of the construct type. The PEEK construct had a more uniform dose distribution with a standard deviation of 9.76. The standard deviation of the others constructs was 14.26 for the control group, 19.31 for the titanium cage, and 21.57 for the cement (polymethyl methacrylate) construct. The PEEK inter-body cage resulted in a significantly more uniform distribution of therapeutic radiation in the spine when compared with the other constructs. This may allow for the application of higher effective dosing to the tumor bed for spinal metastases without increasing spinal cord toxicity with either fractionated or hypofractionated radiotherapy. N/A.

Appropriate Use of Effective Dose in Radiation Protection and Risk Assessment.

PubMed

Fisher, Darrell R; Fahey, Frederic H

2017-08-01

Effective dose was introduced by the ICRP for the single, over-arching purpose of setting limits for radiation protection. Effective dose is a derived quantity or mathematical construct and not a physical, measurable quantity. The formula for calculating effective dose to a reference model incorporates terms to account for all radiation types, organ and tissue radiosensitivities, population groups, and multiple biological endpoints. The properties and appropriate applications of effective dose are not well understood by many within and outside the health physics profession; no other quantity in radiation protection has been more confusing or misunderstood. According to ICRP Publication 103, effective dose is to be used for "prospective dose assessment for planning and optimization in radiological protection, and retrospective demonstration of compliance for regulatory purposes." In practice, effective dose has been applied incorrectly to predict cancer risk among exposed persons. The concept of effective dose applies generally to reference models only and not to individual subjects. While conceived to represent a measure of cancer risk or heritable detrimental effects, effective dose is not predictive of future cancer risk. The formula for calculating effective dose incorporates committee-selected weighting factors for radiation quality and organ sensitivity; however, the organ weighting factors are averaged across all ages and both genders and thus do not apply to any specific individual or radiosensitive subpopulations such as children and young women. Further, it is not appropriate to apply effective dose to individual medical patients because patient-specific parameters may vary substantially from the assumptions used in generalized models. Also, effective dose is not applicable to therapeutic uses of radiation, as its mathematical underpinnings pertain only to observed late (stochastic) effects of radiation exposure and do not account for short-term adverse tissue reactions. The weighting factors incorporate substantial uncertainties, and linearity of the dose-response function at low dose is uncertain and highly disputed. Since effective dose is not predictive of future cancer incidence, it follows that effective dose should never be used to estimate future cancer risk from specific sources of radiation exposure. Instead, individual assessments of potential detriment should only be based on organ or tissue radiation absorbed dose, together with best scientific understanding of the corresponding dose-response relationships.

SOURCES AND ESTIMATED LOAD OF BIOAVAILABLE NITROGEN ATTRIBUTABLE TO CHRONIC NITROGEN EXPOSURE AND CHANGED ECOSYSTEM STRUCTURE AND FUNCTION

EPA Science Inventory

Bioavailable nitrogen is a limiting nutrient throughout the Eastern United States. Research demonstrates that exposure to large doses of nitrogen leads to deleterious environmental impacts. However, effects of chronic exposure to lower doses of nitrogen are not well known. Since...

SOURCES AND ESTIMATED LOAD OF BIOAVAILABLE NITROGEN ATTRIBUTED TO CHRONIC NITROGEN EXPOSURE AND CHANGED ECOSYSTEM STRUCTURE AND FUNCTION

EPA Science Inventory

Bioavailable nitrogen is a limiting nutrient throughout the Eastern United States. Research demonstrates that exposure to large doses of nitrogen leads to deleterious environmental impacts. However, effects of chronic exposure to lower doses of nitrogen are under-appreciated. ...

Oral Therapy of Diabetes Insipidus with Chlorpropamide

PubMed Central

Cushard, William G.; Beauchamp, Charles J.; Martin, Neil D.

1971-01-01

Chlorpropamide was found to be an effective antidiuretic agent in vasopressin-sensitive diabetes insipidus. Full clinical use of this action is limited by the frequent occurrence of hypoglycemia on higher doses. This complication can be avoided, however, by restricting the dose and by employing combination therapy with hydrochlorothiazide. PMID:5563815

Are Recommended Doses of Acetaminophen Effective for Children Aged 2 to 3 Years? A Pharmacokinetic Modeling Answer.

PubMed

Abourbih, Daniel Asher; Gosselin, Sophie; Villeneuve, Eric; Kazim, Sara

2016-01-01

Acetaminophen (APAP) elixir is a widely used pediatric antipyretic medication. It has been shown that up to 30% of febrile children presenting to a large urban pediatric emergency department received inadequate APAP dosages at home with errors primarily due to age-based dosing. Parental education material in the form of weight-based dosing guides has been proposed; however, validation of current recommended APAP dosages using pharmacokinetic models is needed. This study used a mathematical model of APAP absorption to predict plasma concentrations and to compare them with the range required to reach and achieve antipyresis (10-20 μg/mL). A common APAP preparation (Children's Tylenol Elixir) was tested (children aged 2-3 years, 10.9-15.9 kg). The manufacturer's suggested dose of 160 mg was compared with the standard 10 to 15 mg/kg dose range. The model predicts a peak plasma concentration between 6.38 and 8.55 μg/mL for 10 mg/kg dose and 9.57 and 12.8 μg/mL for 15 mg/kg dose. The manufacturer's suggested dose of 160 mg was tested across the limits of the weight range (10.9-15.9 kg). A peak plasma concentration between 9.36 and 12.6 μg/mL was found for the lower weight limit (10.9 kg child) and 6.42 to 8.61 μg/mL for the upper weight limit (15.9 kg child). With the use of this model, the 10 mg/kg dose does not reach the plasma concentration value for antipyresis (10-20 μg/mL), whereas 15 mg/kg is adequate only if assuming a greater absorption constant. The 160 mg dose is effective only for children weighing 10.9 kg. Individual differences in drug bioavailability, volume of distribution, and absorption/elimination constants undoubtedly exist, and future studies directly measuring plasma APAP concentration and pharmacokinetics are needed. However, these results indicate that dosages for APAP in children should be weight based and manufacturers should review their dosing recommendations.

Biological effects and equivalent doses in radiotherapy: A software solution

PubMed Central

Voyant, Cyril; Julian, Daniel; Roustit, Rudy; Biffi, Katia; Lantieri, Céline

2013-01-01

Background The limits of TDF (time, dose, and fractionation) and linear quadratic models have been known for a long time. Medical physicists and physicians are required to provide fast and reliable interpretations regarding delivered doses or any future prescriptions relating to treatment changes. Aim We, therefore, propose a calculation interface under the GNU license to be used for equivalent doses, biological doses, and normal tumor complication probability (Lyman model). Materials and methods The methodology used draws from several sources: the linear-quadratic-linear model of Astrahan, the repopulation effects of Dale, and the prediction of multi-fractionated treatments of Thames. Results and conclusions The results are obtained from an algorithm that minimizes an ad-hoc cost function, and then compared to an equivalent dose computed using standard calculators in seven French radiotherapy centers. PMID:24936319

Limitations of current dosimetry for intracavitary accelerated partial breast irradiation with high dose rate iridium-192 and electronic brachytherapy sources

NASA Astrophysics Data System (ADS)

Raffi, Julie A.

Intracavitary accelerated partial breast irradiation (APBI) is a method of treating early stage breast cancer using a high dose rate (HDR) brachytherapy source positioned within the lumpectomy cavity. An expandable applicator stretches the surrounding tissue into a roughly spherical or elliptical shape and the dose is prescribed to 1 cm beyond the edge of the cavity. Currently, dosimetry for these treatments is most often performed using the American Association of Physicists in Medicine Task Group No. 43 (TG-43) formalism. The TG-43 dose-rate equation determines the dose delivered to a homogeneous water medium by scaling the measured source strength with standardized parameters that describe the radial and angular features of the dose distribution. Since TG-43 parameters for each source model are measured or calculated in a homogeneous water medium, the dosimetric effects of the patient's dimensions and composition are not accounted for. Therefore, the accuracy of TG-43 calculations for intracavitary APBI is limited by the presence of inhomogeneities in and around the target volume. Specifically, the breast is smaller than the phantoms used to determine TG-43 parameters and is surrounded by air, ribs, and lung tissue. Also, the composition of the breast tissue itself can affect the dose distribution. This dissertation is focused on investigating the limitations of TG-43 dosimetry for intracavitary APBI for two HDR brachytherapy sources: the VariSource TM VS2000 192Ir source and the AxxentRTM miniature x-ray source. The dose for various conditions was determined using thermoluminescent dosimeters (TLDs) and Monte Carlo (MC) calculations. Accurate measurements and calculations were achieved through the implementation of new measurement and simulation techniques and a novel breast phantom was developed to enable anthropomorphic phantom measurements. Measured and calculated doses for phantom and patient geometries were compared with TG-43 calculated doses to illustrate the limitations of TG-43 dosimetry for intracavitary APBI. TG-43 dose calculations overestimate the dose for regions approaching the lung and breast surface and underestimate the dose for regions in and beyond less-attenuating media such as lung tissue, and for lower energies, breast tissue as well.

TU-H-207A-08: Estimating Radiation Dose From Low-Dose Lung Cancer Screening CT Exams Using Tube Current Modulation

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

Hardy, A; Bostani, M; McMillan, K

Purpose: The purpose of this work is to estimate effective and lung doses from a low-dose lung cancer screening CT protocol using Tube Current Modulation (TCM) across patient models of different sizes. Methods: Monte Carlo simulation methods were used to estimate effective and lung doses from a low-dose lung cancer screening protocol for a 64-slice CT (Sensation 64, Siemens Healthcare) that used TCM. Scanning parameters were from the AAPM protocols. Ten GSF voxelized patient models were used and had all radiosensitive organs identified to facilitate estimating both organ and effective doses. Predicted TCM schemes for each patient model were generatedmore » using a validated method wherein tissue attenuation characteristics and scanner limitations were used to determine the TCM output as a function of table position and source angle. The water equivalent diameter (WED) was determined by estimating the attenuation at the center of the scan volume for each patient model. Monte Carlo simulations were performed using the unique TCM scheme for each patient model. Lung doses were tallied and effective doses were estimated using ICRP 103 tissue weighting factors. Effective and lung dose values were normalized by scanspecific 32 cm CTDIvol values based upon the average tube current across the entire simulated scan. Absolute and normalized doses were reported as a function of WED for each patient. Results: For all ten patients modeled, the effective dose using TCM protocols was below 1.5 mSv. Smaller sized patient models experienced lower absolute doses compared to larger sized patients. Normalized effective and lung doses showed some dependence on patient size (R2 = 0.77 and 0.78, respectively). Conclusion: Effective doses for a low-dose lung screening protocol using TCM were below 1.5 mSv for all patient models used in this study. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

HLW Flexible jumper materials compatibility evaluation

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

Skidmore, T. E.

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

Radiation dose to workers due to the inhalation of dust during granite fabrication.

PubMed

Zwack, L M; McCarthy, W B; Stewart, J H; McCarthy, J F; Allen, J G

2014-03-01

There has been very little research conducted to determine internal radiation doses resulting from worker exposure to ionising radiation in granite fabrication shops. To address this issue, we estimated the effective radiation dose of granite workers in US fabrication shops who were exposed to the maximum respirable dust and silica concentrations allowed under current US regulations, and also to concentrations reported in the literature. Radiation doses were calculated using standard methods developed by the International Commission on Radiological Protection. The calculated internal doses were very low, and below both US occupational standards (50 mSv yr(-1)) and limits applicable to the general public (1 mSv yr(-1)). Workers exposed to respirable granite dust concentrations at the US Occupational Safety and Health Administration (OSHA) respirable dust permissible exposure limit (PEL) of 5 mg m(-3) over a full year had an estimated radiation dose of 0.062 mSv yr(-1). Workers exposed to respirable granite dust concentrations at the OSHA silica PEL and at the American Conference of Governmental Industrial Hygienists Threshold Limit Value for a full year had expected radiation doses of 0.007 mSv yr(-1) and 0.002 mSv yr(-1), respectively. Using data from studies of respirable granite dust and silica concentrations measured in granite fabrication shops, we calculated median expected radiation doses that ranged from <0.001 to 0.101 mSv yr(-1).

The influence of dosing on effect size of exercise therapy for musculoskeletal foot and ankle disorders: a systematic review.

PubMed

Young, Jodi L; Rhon, Daniel I; de Zoete, Rutger M J; Cleland, Joshua A; Snodgrass, Suzanne J

The purpose of this review was to identify doses of exercise therapy associated with greater treatment effect sizes in individuals with common musculoskeletal disorders of the foot and ankle, namely, achilles tendinopathy, ankle sprains and plantar heel pain. AMED, EMBASE and MEDLINE were searched from 2005 to August 2017 for randomized controlled trials related to exercise for these three diagnoses. The Physiotherapy Evidence Database scale was used for methodological quality assessment. Exercise dosing variables and outcome measures related to pain and function were extracted from the studies, and standardized mean differences were calculated for the exercise groups. Fourteen studies met the final inclusion. A majority of the studies showed large effects and two small trends were identified. Patients with plantar heel pain may benefit more from a daily home exercise program than two supervised visits per week (SMD=3.82), but this recommendation is based on weak evidence. In achilles tendinopathy, a relationship was also seen when sets and repetitions of eccentric exercise were performed as tolerated (SMD=1.08 for function, -1.29 for pain). Session duration, frequency, total number of visits, and overall length of care may all be dosing variables with limited value for determining effective exercise prescription. However, the limited number of studies prevents any definitive conclusions. Further investigation is warranted to improve our understanding of the influence exercise dosing has on treatment effect sizes. Future randomized controlled trials comparing specific exercise dose variables should be conducted to clarify the impact of these variables. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. All rights reserved.

Radiation accident dosimetry on plastics by EPR spectrometry.

PubMed

Trompier, F; Bassinet, C; Clairand, I

2010-02-01

In case of acute exposure to ionizing radiation, the dose absorbed by the victims has to be rapidly and accurately assessed in order to choose an appropriate medical treatment. Tooth enamel and bone biopsies measured by EPR spectrometry are often used as dose indicators, due to the good radiation sensitivity and the stability of EPR radiation-sensitive signals. Nevertheless, the invasive sampling of teeth and bones limits the application of this technique to retrospective dosimetry. Therefore, we have investigated an alternative non-invasive methodology. We have surveyed with EPR spectrometry the dosimetric properties of the plastics that can be found in personal effects such as glasses (CR-39, polycarbonate), mobile phones (PMMA, polycarbonate), watches and buttons. Dose response, signal stability and effects of storage conditions were investigated. Significant signal fading limits the use for radiation accident dosimetry. Few plastics present the required characteristics to be used in case of a radiation accident.

Measurement of 131I activity in thyroid of nuclear medical staff and internal dose assessment in a Polish nuclear medical hospital.

PubMed

Brudecki, K; Kowalska, A; Zagrodzki, P; Szczodry, A; Mroz, T; Janowski, P; Mietelski, J W

2017-03-01

This paper presents results of 131 I thyroid activity measurements in 30 members of the nuclear medicine personnel of the Department of Endocrinology and Nuclear Medicine Holy Cross Cancer Centre in Kielce, Poland. A whole-body spectrometer equipped with two semiconductor gamma radiation detectors served as the basic research instrument. In ten out of 30 examined staff members, the determined 131 I activity was found to be above the detection limit (DL = 5 Bq of 131 I in the thyroid). The measured activities ranged from (5 ± 2) Bq to (217 ± 56) Bq. The highest activities in thyroids were detected for technical and cleaning personnel, whereas the lowest values were recorded for medical doctors. Having measured the activities, an attempt has been made to estimate the corresponding annual effective doses, which were found to range from 0.02 to 0.8 mSv. The highest annual equivalent doses have been found for thyroid, ranging from 0.4 to 15.4 mSv, detected for a cleaner and a technician, respectively. The maximum estimated effective dose corresponds to 32% of the annual background dose in Poland, and to circa 4% of the annual limit for the effective dose due to occupational exposure of 20 mSv per year, which is in compliance with the value recommended by the International Commission on Radiological Protection.

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

NASA Astrophysics Data System (ADS)

Liu, Yingzi

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

[Treatment of subglottic laryngitis (pseudocroup): steroids instead of steam].

PubMed

Roorda, R J; Walhof, C M; Brand, P L

1998-07-18

Traditionally, steaming with warm moist air was recommended for the treatment of subglottic laryngitis (pseudocroup). However, no favourable effect has ever been demonstrated. Consequently, steaming is no longer to be advised. Systemic corticosteroids, already of proven effectiveness in severe croup, were shown to be also effective when administered in a single oral dose in moderately severe disease. Besides, in various studies, nebulisation of budesonide (2000 micrograms) with a jet nebuliser had a good effect on the clinical course of croup. However, dose-effect studies are still lacking. A single dose of corticosteroids, either systemic or inhaled via a jet nebuliser, should be the first line therapy in moderate and severe croup syndrome. In milder cases no specific treatment is needed as the disease is self-limiting.

EYE LENS DOSIMETRY FOR FLUOROSCOPICALLY GUIDED CLINICAL PROCEDURES: PRACTICAL APPROACHES TO PROTECTION AND DOSE MONITORING.

PubMed

Martin, Colin J

2016-06-01

Doses to the eye lenses of clinicians undertaking fluoroscopically guided procedures can exceed the dose annual limit of 20 mSv, so optimisation of radiation protection is essential. Ceiling-suspended shields and disposable radiation absorbing pads can reduce eye dose by factors of 2-7. Lead glasses that shield against exposures from the side can lower doses by 2.5-4.5 times. Training in effective use of protective devices is an essential element in achieving good protection and acceptable eye doses. Effective methods for dose monitoring are required to identify protection issues. Dosemeters worn adjacent to the eye provide the better option for interventional clinicians, but an unprotected dosemeter worn at the neck will give an indication of eye dose that is adequate for most interventional staff. Potential requirements for protective devices and dose monitoring can be determined from risk assessments using generic values for dose linked to examination workload. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Bone Anabolic Effect of RANKL in a Murine Model of Osteoporosis mediated through FoxP3+ CD8 T-cells

PubMed Central

Buchwald, Zachary S.; Yang, Chang; Nellore, Suman; Shashkova, Elena V.; Davis, Jennifer L.; Cline, Anna; Ko, Je; Novack, Deborah V.; DiPaolo, Richard; Aurora, Rajeev

2015-01-01

TNFα and IL-17 secreted by proinflammatory T-cells (TEFF) promote bone erosion by activating osteoclasts. We previously demonstrated that in addition to bone resorption, osteoclasts act as antigen presenting cells to induce FoxP3 in CD8 T-cells (TcREG). The osteoclast-induced regulatory CD8 T-cells limit bone resorption in ovariectomized mice (a murine model of postmenopausal osteoporosis). Here we show that while low-dose RANKL maximally induces TcREG via Notch signaling pathway to limit bone resorption, high-dose RANKL promotes bone resorption. In vitro, both TNFα and IL-17, cytokines that are abundant in ovariectomized animals, suppress TcREG induction by osteoclasts by repressing Notch ligand expression in osteoclasts but this effect can be counteracted by addition of RANKL. Ovariectomized mice treated with low-dose RANKL induced TcREG that suppressed bone resorption, decreased TEFF levels and increased bone formation. High dose RANKL had the expected osteolytic effect. Low dose RANKL administration in ovariectomized mice lacking CD8 T-cells was also osteolytic, confirming that TcREG mediate this bone anabolic effect. Our results show that while RANKL directly stimulates osteoclasts to resorb bone, it also controls the osteoclasts’ ability to induce regulatory T-cells, engaging an important negative feedback loop. In addition to the conceivable clinical relevance to treatment of osteoporosis, these observations have potential relevance to induction of tolerance and autoimmune diseases. PMID:25656537

Radiation dosimetry with fiber Bragg gratings

NASA Astrophysics Data System (ADS)

Avino, S.; D'Avino, V.; Giorgini, A.; Pacelli, R.; Liuzzi, R.; Cella, L.; Gagliardi, G.; De Natale, P.

2014-05-01

The measurement and monitoring of radiation dose delivered in patient tissues is a critical aspect in radiation therapy. Various dosimeters have proven effective in measuring radiations at low doses. However, there is a growing demand for new dosimeters based on small, non-invasive and high resolution devices. Here we report on a miniature dosimeter based on an optical fiber cavity. We demonstrate an ultimate detection limit of 160 mGy with an effective interaction region of 6 x 10-4 mm3. Due to its reliability, compactness and biomedical dose level sensitivity, our system shows itself suitable for applications in radiation therapy dosimetry.

Dose-dependent consumption of farmed Atlantic salmon (salmo salar) increases plasma phospholipid n-3 fatty acids differentially

USDA-ARS?s Scientific Manuscript database

ABSTRACT Background: Enhanced n-3 intake benefit CVD risk reduction. Increasing consumption at a population level will be better addressed by dietary modification than through supplementation. However, limited data are available on the effect of increasing doses of fish intake on circulating level...

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

Dourson, M.L.

The quantitative procedures associated with noncancer risk assessment include reference dose (RfD), benchmark dose, and severity modeling. The RfD, which is part of the EPA risk assessment guidelines, is an estimation of a level that is likely to be without any health risk to sensitive individuals. The RfD requires two major judgments: the first is choice of a critical effect(s) and its No Observed Adverse Effect Level (NOAEL); the second judgment is choice of an uncertainty factor. This paper discusses major assumptions and limitations of the RfD model.

Irradiate-anneal screening of total dose effects in semiconductor devices

NASA Technical Reports Server (NTRS)

Stanley, A. G.; Price, W. E.

1976-01-01

Judicious choice of radiation dose and parameter change acceptance criteria, absence of anomalous anneal phenomena, and absence of anomalous reirradiation effects are recognized as essential for a successful irradiation-anneal (IRAN) screening procedure to ensure that no device will fall, upon reirradiation, above parametric limits assigned for the worst case application. Reirradiation and irradiation-anneal behavior of various semiconductor devices are compared and those that do not lend themselves to IRAN screening are singled out. Information needed to judge the suitability of an IRAN type screening program is detailed. Reasons for success of the limited IRAN screening of flight parts for the Mariner Jupiter/Saturn (MJS '77) spacecraft are indicated.

Subacute toxicity of the mycotoxin cyclopiazonic acid.

PubMed

van Rensburg, S J

1984-12-01

Cyclopiazonic acid (CA) is known to contaminate processed foods, maize and peanuts. Since previously available toxicity data were limited to the effects of single doses, Wistar-derived rats were given weekly doses of 0, 12 or 21 mg CA/kg body weight in 1 N-sodium bicarbonate, using a dosage volume of 2.5 ml/kg body weight, and subgroups of eight were killed 1 wk after doses 2, 5, 9 and 14. Males on the highest dose level showed mild growth retardation initially and 25% died suddenly during wk 4. No abnormal signs were observed in the surviving males or in any of the females throughout the 15 wk of the experiment. CA induced mild cellular degenerative changes in the myocardium and in several other organs where ballooning of nuclei, especially in ductal epithelia, was also characteristic. The changes were only weakly related to dose level, sex and the number of doses given. The findings suggest that CA is probably a metabolic inhibitor requiring considerable concentrations to exert toxicity. The limited data currently available do not elicit concern in terms of human risk or warrant any particular control procedures.

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

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

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

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

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

DOE PAGES

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

2016-10-17

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

EVALUATION OF EYE LENS DOSE TO WORKERS IN THE STEAM GENERATOR AT THE KOREAN OPTIMIZED POWER REACTOR 1000.

PubMed

Maeng, Sung Jun; Kim, Jinhwan; Cho, Gyuseong

2018-03-15

ICRP (2011) revised the dose limit to the eye lens to 20 mSv/y based on a recent epidemiological study of radiation-induced cataracts. Maintenance of steam generators at nuclear power plants is one of the highest radiation-associated tasks within a non-uniform radiation field. This study aims to evaluate eye lens doses in the steam generators of the Korean OPR1000 design. The source term was characterized based on the CRUD-specific activity, and both the eye lens dose and organ dose were simulated using MCNP6 combined with an ICRP voxel phantom and a mesh phantom, respectively. The eye lens dose was determined to be 5.39E-02-9.43E-02 Sv/h, with a negligible effect by beta particles. As the effective dose was found to be 0.81-1.21 times the lens equivalent dose depending on the phantom angles, the former can be used to estimate the lens dose in the SG of the OPR1000 for radiation monitoring purposes.

Medical and occupational dose reduction in pediatric barium meal procedures

NASA Astrophysics Data System (ADS)

Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Ledesma, J. A.; Legnani, A.; Bunick, A. P.; Sauzen, J.; Yagui, A.; Vosiak, P.

2017-11-01

Doses received in pediatric Barium Meal procedure can be rather high. It is possible to reduce dose values following the recommendations of the European Communities (EC) and the International Commission on Radiological Protection (ICRP). In the present work, the modifications of radiographic techniques made in a Brazilian hospital according to the EC and the ICRP recommendations and their influence on medical and occupational exposure are reported. The procedures of 49 patients before and 44 after the optimization were studied and air kerma-area product (PK,A) values and the effective doses were evaluated. The occupational equivalent doses were measured next to the eyes, under the thyroid shield and on each hand of both professionals who remained inside the examination room. The implemented modifications reduced by 70% and 60% the PK,A and the patient effective dose, respectively. The obtained dose values are lower than approximately 75% of the results from similar studies. The occupational annual equivalent doses for all studied organs became lower than the limits set by the ICRP. The equivalent doses in one examination were on average below than 75% of similar studies.

Hormesis as a biological hypothesis.

PubMed Central

Calabrese, E J; Baldwin, L A

1998-01-01

A comprehensive effort was undertaken to identify articles demonstrating chemical hormesis. Nearly 4000 potentially relevant articles were retrieved from preliminary computer database searches by using various key word descriptors and extensive cross-referencing. A priori evaluation criteria were established including study design features (e.g., number of doses, dose range), statistical analysis, and reproducibility of results. Evidence of chemical hormesis was judged to have occurred in approximately 350 of the 4000 studies evaluated. Chemical hormesis was observed in a wide range of taxonomic groups and involved agents representing highly diverse chemical classes, many of potential environmental relevance. Numerous biological end points were assessed; growth responses were the most prevalent, followed by metabolic effects, longevity, reproductive responses, and survival. Hormetic responses were generally observed to be of limited magnitude. The average low-dose maximum stimulation was approximately 50% greater than controls. The hormetic dose-response range was generally limited to about one order of magnitude, with the upper end of the hormetic curve approaching the estimated no observable effect level for the particular end point. Based on the evaluation criteria, high to moderate evidence of hormesis was observed in studies comprised of > 6 doses; with > 3 doses in the hormetic zone. The present analysis suggests that chemical hormesis is a reproducible and relatively common biological phenomenon. A quantitative scheme is presented for future application to the database. PMID:9539030

Live Attenuated Yellow Fever 17D Vaccine: A Legacy Vaccine Still Controlling Outbreaks In Modern Day.

PubMed

Collins, Natalie D; Barrett, Alan D T

2017-03-01

Live attenuated 17D vaccine is considered one of the safest and efficacious vaccines developed to date. This review highlights what is known and the gaps in knowledge of vaccine-induced protective immunity. Recently, the World Health Organization modifying its guidance from 10-year booster doses to one dose gives lifelong protection in most populations. Nonetheless, there are some data suggesting immunity, though protective, may wane over time in certain populations and more research is needed to address this question. Despite having an effective vaccine to control yellow fever, vaccine shortages were identified during outbreaks in 2016, eventuating the use of a fractional-dosing campaign in the Democratic Republic of the Congo. Limited studies hinder identification of the underlying mechanism(s) of vaccine longevity; however, concurrent outbreaks during 2016 provide an opportunity to evaluate vaccine immunity following fractional dosing and insights into vaccine longevity in populations where there is limited information.

Tolerance limits and methodologies for IMRT measurement-based verification QA: Recommendations of AAPM Task Group No. 218.

PubMed

Miften, Moyed; Olch, Arthur; Mihailidis, Dimitris; Moran, Jean; Pawlicki, Todd; Molineu, Andrea; Li, Harold; Wijesooriya, Krishni; Shi, Jie; Xia, Ping; Papanikolaou, Nikos; Low, Daniel A

2018-04-01

Patient-specific IMRT QA measurements are important components of processes designed to identify discrepancies between calculated and delivered radiation doses. Discrepancy tolerance limits are neither well defined nor consistently applied across centers. The AAPM TG-218 report provides a comprehensive review aimed at improving the understanding and consistency of these processes as well as recommendations for methodologies and tolerance limits in patient-specific IMRT QA. The performance of the dose difference/distance-to-agreement (DTA) and γ dose distribution comparison metrics are investigated. Measurement methods are reviewed and followed by a discussion of the pros and cons of each. Methodologies for absolute dose verification are discussed and new IMRT QA verification tools are presented. Literature on the expected or achievable agreement between measurements and calculations for different types of planning and delivery systems are reviewed and analyzed. Tests of vendor implementations of the γ verification algorithm employing benchmark cases are presented. Operational shortcomings that can reduce the γ tool accuracy and subsequent effectiveness for IMRT QA are described. Practical considerations including spatial resolution, normalization, dose threshold, and data interpretation are discussed. Published data on IMRT QA and the clinical experience of the group members are used to develop guidelines and recommendations on tolerance and action limits for IMRT QA. Steps to check failed IMRT QA plans are outlined. Recommendations on delivery methods, data interpretation, dose normalization, the use of γ analysis routines and choice of tolerance limits for IMRT QA are made with focus on detecting differences between calculated and measured doses via the use of robust analysis methods and an in-depth understanding of IMRT verification metrics. The recommendations are intended to improve the IMRT QA process and establish consistent, and comparable IMRT QA criteria among institutions. © 2018 American Association of Physicists in Medicine.

Dose and Dose Risk Caused by Natural Phenomena - Proposed Powder Metallurgy Core Manufacturing Facility

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

Holmes, W.G.

2001-08-16

The offsite radiological effects from high velocity straight winds, tornadoes, and earthquakes have been estimated for a proposed facility for manufacturing enriched uranium fuel cores by powder metallurgy. Projected doses range up to 30 mrem/event to the maximum offsite individual for high winds and up to 85 mrem/event for very severe earthquakes. Even under conservative assumptions on meteorological conditions, the maximum offsite dose would be about 20 per cent of the DOE limit for accidents involving enriched uranium storage facilities. The total dose risk is low and is dominated by the risk from earthquakes. This report discusses this test.

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

PubMed

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

2016-11-09

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

Role of particle radiotherapy in the management of head and neck cancer.

PubMed

Laramore, George E

2009-05-01

Modern imaging techniques and powerful computers allow a radiation oncologist to design treatments delivering higher doses of radiation than previously possible. Dose distributions imposed by the physics of 'standard' photon and electron beams limit further dose escalation. Hadron radiotherapy offers advantages in either dose distribution and/or improved radiobiology that may significantly improve the treatment of certain head and neck malignancies. Clinical studies support the effectiveness of fast-neutron radiotherapy in the treatment of major and minor salivary gland tumors. Data show highly favorable outcomes with proton radiotherapy for skull-base malignancies and tumors near highly critical normal tissues compared with that expected with standard radiotherapy. Heavy-ion radiotherapy clinical studies are mainly being conducted with fully stripped carbon ions, and limited data seem to indicate a possible improvement over proton radiotherapy for the same subset of radioresistant tumors where neutrons show a benefit over photons. Fast-neutron radiotherapy has different radiobiological properties compared with standard radiotherapy but similar depth dose distributions. Its role in the treatment of head and neck cancer is currently limited to salivary gland malignancies and certain radioresistant tumors such as sarcomas. Protons have the same radiobiological properties as standard radiotherapy beams but more optimal depth dose distributions, making it particularly advantageous when treating tumors adjacent to highly critical structures. Heavy ions combine the radiobiological properties of fast neutrons with the physical dose distributions of protons, and preliminary data indicate their utility for radioresistant tumors adjacent to highly critical structures.

In vivo dose perturbation effects of metallic dental alloys during head and neck irradiation with intensity modulated radiation therapy.

PubMed

Fuller, Clifton D; Diaz, Irma; Cavanaugh, Sean X; Eng, Tony Y

2004-07-01

A patient with base of tongue squamous sell carcinoma, with significant CT artifact-inducing metallic alloy, non-removable dental restorations in both the mandible and maxilla was identified. Simultaneous with IMRT treatment, thermoluminescent dosimeters (TLDs) were placed in the oral cavity. After a series of three treatments, the data from the TLDs and software calculations were analyzed. Analysis of mean in vivo TLD dosimetry reveals differentials from software predicted dose calculation that fall within acceptable dose variation limits. IMRT dose calculation software is a relatively accurate predictor of dose attenuation and augmentation due to dental alloys within the treatment volume, as measured by intra-oral thermoluminescent dosimetry. IMRT represents a safe and effective methodology to treat patients with non-removable metallic dental work who have head and neck cancer.

Impact of reduced dose limits on NRC licensed activities. Major issues in the implementation of ICRP/NCRP dose limit recommendations: Final report

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

Meinhold, C.B.

This report summarizes information required to estimate, at least qualitatively, the potential impacts of reducing occupational dose limits below those given in 10 CFR 20 (Revised). For this study, a questionnaire was developed and widely distributed to the radiation protection community. The resulting data together with data from existing surveys and sources were used to estimate the impact of three dose-limit options; 10 mSv yr{sup {minus}1} (1 rem yr{sup {minus}1}), 20 mSv yr{sup {minus}1} (2 rem yr{sup {minus}1}), and a combination of an annual limit of 50 mSv yr{sup {minus}1} (5 rem yr{sup {minus}1}) coupled with a cumulative limit, inmore » rem, equal to age in years. Due to the somewhat small number of responses and the lack of data in some specific areas, a working committee of radiation protection experts from a variety of licensees was employed to ensure the exposure data were representative. The following overall conclusions were reached: (1) although 10 mSv yr{sup {minus}1} is a reasonable limit for many licensees, such a limit could be extraordinarily difficult to achieve and potentially destructive to the continued operation of some licensees, such as nuclear power, fuel fabrication, and medicine; (2) twenty mSv yr{sup {minus}1} as a limit is possible for some of these groups, but for others it would prove difficult. (3) fifty mSv yr{sup {minus}1} and age in 10s of mSv appear reasonable for all licensees, both in terms of the lifetime risk of cancer and severe genetic effects to the most highly exposed workers, and the practicality of operation.« less

Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.

PubMed

Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

2017-01-01

Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synergistic anticancer effects of combined gamma-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFkappaB signaling.

PubMed

Shirode, Amit B; Sylvester, Paul W

2010-05-01

The selective cyclooxygenase (COX)-2 inhibitor, celecoxib, and the vitamin E isoform, gamma-tocotrienol, both display potent anticancer activity. However, high dose clinical use of selective COX-2 inhibitors has been limited by gastrointestinal and cardiovascular toxicity, whereas limited absorption and transport of gamma-tocotrienol by the body has made it difficult to obtain and sustain therapeutic levels in the blood and target tissues. Studies were conducted to characterize the synergistic anticancer antiproliferative effects of combined low dose celecoxib and gamma-tocotrienol treatment on mammary tumor cells in culture. The highly malignant mouse +SA mammary epithelial cells were maintained in culture on serum-free defined control or treatment media. Treatment effects on COX-1, COX-2, Akt, NFkappaB and prostaglandin E(2) (PGE(2)) synthesis were assessed following a 3- or 4-day culture period. Treatment with 3-4 microM gamma-tocotrienol or 7.5-10 microM celecoxib alone significantly inhibited +SA cell growth in a dose-responsive manner. However, combined treatment with subeffective doses of gamma-tocotrienol (0.25 microM) and celecoxib (2.5 microM) resulted in a synergistic antiproliferative effect, as determined by isobologram analysis, and this growth inhibitory effect was associated with a reduction in PGE(2) synthesis, and decrease in COX-2, phospho-Akt (active), and phospho-NFkappaB (active) levels. These results demonstrate that the synergistic anticancer effects of combined celecoxib and gamma-tocotrienol therapy are mediated by COX-2 dependent and independent mechanisms. These findings also suggest that combination therapy with these agents may provide enhanced therapeutic response in breast cancer patients, while avoiding the toxicity associated with high-dose COX-2 inhibitor monotherapy. 2009 Elsevier Masson SAS. All rights reserved.

Synergistic anticancer effects of combined γ-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFκB signaling

PubMed Central

Shirode, Amit B.; Sylvester, Paul W.

2009-01-01

The selective cyclooxygenase (COX)-2 inhibitor, celecoxib, and the vitamin E isoform, γ-tocotrienol, both display potent anticancer activity. However, high dose clinical use of selective COX-2 inhibitors has been limited by gastrointestinal and cardiovascular toxicity, whereas limited absorption and transport of γ-tocotrienol by the body has made it difficult to obtain and sustain therapeutic levels in the blood and target tissues. Studies were conducted to characterize the synergistic anticancer antiproliferative effects of combined low dose celecoxib and γ-tocotrienol treatment on mammary tumor cells in culture. The highly malignant mouse +SA mammary epithelial cells were maintained in culture on serum-free defined control or treatment media. Treatment effects on COX-1, COX-2, Akt, NFκB and prostaglandin E2 (PGE2) synthesis was assessed following a 3- or 4-day culture period. Treatment with 3–4 μM γ-tocotrienol or 7.5–10 μM celecoxib alone significantly inhibited +SA cell growth in a dose-responsive manner. However, combined treatment with subeffective doses of γ-tocotrienol (0.25 μM) and celecoxib (2.5 μM) resulted in a synergistic antiproliferative effect, as determined by isobologram analysis, and this growth inhibitor effect was associated with a reduction in PGE2 synthesis, and decrease in COX-2, phospho-Akt (active), and phospho-NFκB (active) levels. These results demonstrate that the synergistic anticancer effects of combined celecoxib and γ-tocotrienol therapy are mediated by COX-2 dependent and independent mechanisms. These findings also suggest that combination therapy with these agents may provide enhanced therapeutic response in breast cancer patients, while avoiding the toxicity associated with high-dose COX-2 inhibitor monotherapy. PMID:19954924

10 CFR 835.208 - Limits for members of the public entering a controlled area.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Limits for members of the public entering a controlled area. 835.208 Section 835.208 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards... area. The total effective dose limit for members of the public exposed to radiation and/or radioactive...

10 CFR 835.208 - Limits for members of the public entering a controlled area.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Limits for members of the public entering a controlled area. 835.208 Section 835.208 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards... area. The total effective dose limit for members of the public exposed to radiation and/or radioactive...

10 CFR 835.208 - Limits for members of the public entering a controlled area.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Limits for members of the public entering a controlled area. 835.208 Section 835.208 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards... area. The total effective dose limit for members of the public exposed to radiation and/or radioactive...

10 CFR 835.208 - Limits for members of the public entering a controlled area.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Limits for members of the public entering a controlled area. 835.208 Section 835.208 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards... area. The total effective dose limit for members of the public exposed to radiation and/or radioactive...

Disease activity-guided dose optimisation of adalimumab and etanercept is a cost-effective strategy compared with non-tapering tight control rheumatoid arthritis care: analyses of the DRESS study.

PubMed

Kievit, Wietske; van Herwaarden, Noortje; van den Hoogen, Frank Hj; van Vollenhoven, Ronald F; Bijlsma, Johannes Wj; van den Bemt, Bart Jf; van der Maas, Aatke; den Broeder, Alfons A

2016-11-01

A disease activity-guided dose optimisation strategy of adalimumab or etanercept (TNFi (tumour necrosis factor inhibitors)) has shown to be non-inferior in maintaining disease control in patients with rheumatoid arthritis (RA) compared with usual care. However, the cost-effectiveness of this strategy is still unknown. This is a preplanned cost-effectiveness analysis of the Dose REduction Strategy of Subcutaneous TNF inhibitors (DRESS) study, a randomised controlled, open-label, non-inferiority trial performed in two Dutch rheumatology outpatient clinics. Patients with low disease activity using TNF inhibitors were included. Total healthcare costs were measured and quality adjusted life years (QALY) were based on EQ5D utility scores. Decremental cost-effectiveness analyses were performed using bootstrap analyses; incremental net monetary benefit (iNMB) was used to express cost-effectiveness. 180 patients were included, and 121 were allocated to the dose optimisation strategy and 59 to control. The dose optimisation strategy resulted in a mean cost saving of -€12 280 (95 percentile -€10 502; -€14 104) per patient per 18 months. There is an 84% chance that the dose optimisation strategy results in a QALY loss with a mean QALY loss of -0.02 (-0.07 to 0.02). The decremental cost-effectiveness ratio (DCER) was €390 493 (€5 085 184; dominant) of savings per QALY lost. The mean iNMB was €10 467 (€6553-€14 037). Sensitivity analyses using 30% and 50% lower prices for TNFi remained cost-effective. Disease activity-guided dose optimisation of TNFi results in considerable cost savings while no relevant loss of quality of life was observed. When the minimal QALY loss is compensated with the upper limit of what society is willing to pay or accept in the Netherlands, the net savings are still high. NTR3216; Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia.

PubMed

Vahdat, L; Wong, E T; Wile, M J; Rosenblum, M; Foley, K M; Warrell, R P

1994-11-15

Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation.

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

PubMed

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

2013-09-01

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

Improvement of the clinical use of computed radiography for mobile chest imaging: Image quality and patient dose

NASA Astrophysics Data System (ADS)

Rill, Lynn Neitzey

Chest radiography is technically difficult because of the wide variation of tissue attenuations in the chest and limitations of screen-film systems. Mobile chest radiography, performed bedside on hospital inpatients, presents additional difficulties due to geometrical and equipment limitations inherent to mobile x-ray procedures and the severity of illness in patients. Computed radiography (CR) offers a new approach for mobile chest radiography by utilizing a photostimulable phosphor. Photostimulable phosphors are more efficient in absorbing lower-energy x-rays than standard intensifying screens and overcome some image quality limitations of mobile chest imaging, particularly because of the inherent latitude. This study evaluated changes in imaging parameters for CR to take advantage of differences between CR and screen-film radiography. Two chest phantoms, made of acrylic and aluminum, simulated x-ray attenuation for average-sized and large- sized adult chests. The phantoms contained regions representing the lungs, heart and subdiaphragm. Acrylic and aluminum disks (1.9 cm diameter) were positioned in the chest regions to make signal-to-noise ratio (SNR) measurements for different combinations of imaging parameters. Disk thicknesses (contrast) were determined from disk visibility. Effective dose to the phantom was also measured for technique combinations. The results indicated that using an anti-scatter grid and lowering x- ray tube potential improved the SNR significantly; however, the dose to the phantom also increased. An evaluation was performed to examine the clinical applicability of the observed improvements in SNR. Parameter adjustments that improved phantom SNRs by more than 50% resulted in perceived image quality improvements in the lung region of clinical mobile chest radiographs. Parameters that produced smaller improvements in SNR had no apparent effect on clinical image quality. Based on this study, it is recommended that a 3:1 grid be used for mobile chest radiography with CR in order to improve image quality. Using a higher kVp (+15 kVp) did not have a detrimental effect on image quality and offered a patient dose savings, including effective dose and breast dose. Higher kVp techniques should be considered when using a grid is not possible.

Energy spectrum control for modulated proton beams.

PubMed

Hsi, Wen C; Moyers, Michael F; Nichiporov, Dmitri; Anferov, Vladimir; Wolanski, Mark; Allgower, Chris E; Farr, Jonathan B; Mascia, Anthony E; Schreuder, Andries N

2009-06-01

In proton therapy delivered with range modulated beams, the energy spectrum of protons entering the delivery nozzle can affect the dose uniformity within the target region and the dose gradient around its periphery. For a cyclotron with a fixed extraction energy, a rangeshifter is used to change the energy but this produces increasing energy spreads for decreasing energies. This study investigated the magnitude of the effects of different energy spreads on dose uniformity and distal edge dose gradient and determined the limits for controlling the incident spectrum. A multilayer Faraday cup (MLFC) was calibrated against depth dose curves measured in water for nonmodulated beams with various incident spectra. Depth dose curves were measured in a water phantom and in a multilayer ionization chamber detector for modulated beams using different incident energy spreads. Some nozzle entrance energy spectra can produce unacceptable dose nonuniformities of up to +/-21% over the modulated region. For modulated beams and small beam ranges, the width of the distal penumbra can vary by a factor of 2.5. When the energy spread was controlled within the defined limits, the dose nonuniformity was less than +/-3%. To facilitate understanding of the results, the data were compared to the measured and Monte Carlo calculated data from a variable extraction energy synchrotron which has a narrow spectrum for all energies. Dose uniformity is only maintained within prescription limits when the energy spread is controlled. At low energies, a large spread can be beneficial for extending the energy range at which a single range modulator device can be used. An MLFC can be used as part of a feedback to provide specified energy spreads for different energies.

Phase I Study of Vandetanib With Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma

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

Drappatz, Jan; Norden, Andrew D.; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital, Boston, MA

Purpose: Increasing evidence has suggested that angiogenesis inhibition might potentiate the effects of radiotherapy and chemotherapy in patients with glioblastoma (GBM). In addition, epidermal growth factor receptor inhibition might be of therapeutic benefit, because the epidermal growth factor receptor is upregulated in GBM and contributes to radiation resistance. We conducted a Phase I study of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, in patients with newly diagnosed GBM combined with RT and temozolomide (TMZ). Methods and Materials: A total of 13 GBM patients were treated with vandetanib, radiotherapy, and concurrent and adjuvantmore » TMZ, using a standard '3 + 3' dose escalation. The maximal tolerated dose was defined as the dose with <1 of 6 dose-limiting toxicities during the first 12 weeks of therapy. The eligible patients were adults with newly diagnosed GBM, Karnofsky performance status of {>=}60, normal organ function, who were not taking enzyme-inducing antiepileptic drugs. Results: Of the 13 patients, 6 were treated with vandetanib at a dose of 200mg daily. Of the 6 patients, 3 developed dose-limiting toxicities within the first 12 weeks, including gastrointestinal hemorrhage and thrombocytopenia in 1 patient, neutropenia in 1 patient, and diverticulitis with gastrointestinal perforation in 1 patient. The other 7 patients were treated with 100 mg daily, with no dose-limiting toxicities observed, establishing this dose as the maximal tolerated dose combined with TMZ and RT. Conclusion: Vandetanib can be safely combined with RT and TMZ in GBM patients. A Phase II study in which patients are randomized to vandetanib 100 mg daily with RT and TMZ or RT and TMZ alone is underway.« less

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

Temporal resolution required for accurate evaluation of the interplay effect in spot scanning proton therapy

NASA Astrophysics Data System (ADS)

Seo, Jeongmin; Han, Min Cheol; Yeom, Yeon Soo; Lee, Hyun Su; Kim, Chan Hyeong; Jeong, Jong Hwi; Kim, SeongHoon

2017-04-01

In proton therapy, the spot scanning method is known to suffer from the interplay effect induced from the independent movements of the proton beam and the organs in the patient during the treatment. To study the interplay effect, several investigators have performed four-dimensional (4D) dose calculations with some limited temporal resolutions (4 or 10 phases per respiratory cycle) by using the 4D computed tomography (CT) images of the patient; however, the validity of the limited temporal resolutions has not been confirmed. The aim of the present study is to determine whether the previous temporal resolutions (4 or 10 phases per respiratory cycle) are really high enough for adequate study of the interplay effect in spot scanning proton therapy. For this study, a series of 4D dose calculations were performed with a virtual water phantom moving in the vertical direction during dose delivery. The dose distributions were calculated for different temporal resolutions (4, 10, 25, 50, and 100 phases per respiratory cycle), and the calculated dose distributions were compared with the reference dose distribution, which was calculated using an almost continuously-moving water phantom ( i.e., 1000 phases per respiratory cycle). The results of the present study show that the temporal resolutions of 4 and 10 phases per respiratory cycle are not high enough for an accurate evaluation of the interplay effect for spot scanning proton therapy. The temporal resolution should be at least 14 and 17 phases per respiratory cycle for 10-mm and 20-mm movement amplitudes, respectively, even for rigid movement ( i.e., without deformation) of the homogeneous water phantom considered in the present study. We believe that even higher temporal resolutions are needed for an accurate evaluation of the interplay effect in the human body, in which the organs are inhomogeneous and deform during movement.

Measuring and statistically testing the size of the effect of a chemical compound on a continuous in-vitro pharmacological response through a new statistical model of response detection limit

PubMed Central

Diaz, Francisco J.; McDonald, Peter R.; Pinter, Abraham; Chaguturu, Rathnam

2018-01-01

Biomolecular screening research frequently searches for the chemical compounds that are most likely to make a biochemical or cell-based assay system produce a strong continuous response. Several doses are tested with each compound and it is assumed that, if there is a dose-response relationship, the relationship follows a monotonic curve, usually a version of the median-effect equation. However, the null hypothesis of no relationship cannot be statistically tested using this equation. We used a linearized version of this equation to define a measure of pharmacological effect size, and use this measure to rank the investigated compounds in order of their overall capability to produce strong responses. The null hypothesis that none of the examined doses of a particular compound produced a strong response can be tested with this approach. The proposed approach is based on a new statistical model of the important concept of response detection limit, a concept that is usually neglected in the analysis of dose-response data with continuous responses. The methodology is illustrated with data from a study searching for compounds that neutralize the infection by a human immunodeficiency virus of brain glioblastoma cells. PMID:24905187

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

PubMed

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

2018-06-04

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

Some Considerations for Chelation Treatment and Surgical Excision Following Incorporation of Plutonium in Wounds

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

Poudel, Deepesh; Bertelli, Luiz; Klumpp, John A.

After a plutonium-contaminated wound, the role of an internal dosimetrist is to inform the patient and the physician of the dosimetric considerations. The doses averted due to medical treatments (excision or chelation) are higher if the treatments are administered early; therefore, the internal dosimetrist needs to rely on limited information on wound counts and process knowledge for advising the physician. For this study, several wound cases in the literature were reviewed to obtain estimates of the efficacies of surgical excision and chelation treatment after plutonium-contaminated wounds. The dose coefficients calculated by coupling the NCRP 156 wound model with the systemicmore » model were used to derive the decision guidelines that may indicate medical treatment based on 1) the concept of saved doses proposed by the NCRP 156 wound model, 2) the limits recommended by the CEC/DOE guidebook, and 3) the Clinical Decision Guidelines proposed in NCRP Report No. 161. These guidelines by themselves, however, are of limited use for several reasons, including 1) large uncertainties associated with wound measurements, 2) exposure to forms of radionuclides that cannot be assigned to a single category in the NCRP 156 framework, 3) inability of the NCRP 156 model to explain some of the wound cases in the literature, 4) neglect of the local doses to the wound site and the pathophysiological response of the tissue, 5) poorly understood relationship between effective doses and risks of late health effects, and 6) disregard of the psychological aspects of radionuclide intake.« less

Some Considerations for Chelation Treatment and Surgical Excision Following Incorporation of Plutonium in Wounds

DOE PAGES

Poudel, Deepesh; Bertelli, Luiz; Klumpp, John A.; ...

2018-03-01

After a plutonium-contaminated wound, the role of an internal dosimetrist is to inform the patient and the physician of the dosimetric considerations. The doses averted due to medical treatments (excision or chelation) are higher if the treatments are administered early; therefore, the internal dosimetrist needs to rely on limited information on wound counts and process knowledge for advising the physician. For this study, several wound cases in the literature were reviewed to obtain estimates of the efficacies of surgical excision and chelation treatment after plutonium-contaminated wounds. The dose coefficients calculated by coupling the NCRP 156 wound model with the systemicmore » model were used to derive the decision guidelines that may indicate medical treatment based on 1) the concept of saved doses proposed by the NCRP 156 wound model, 2) the limits recommended by the CEC/DOE guidebook, and 3) the Clinical Decision Guidelines proposed in NCRP Report No. 161. These guidelines by themselves, however, are of limited use for several reasons, including 1) large uncertainties associated with wound measurements, 2) exposure to forms of radionuclides that cannot be assigned to a single category in the NCRP 156 framework, 3) inability of the NCRP 156 model to explain some of the wound cases in the literature, 4) neglect of the local doses to the wound site and the pathophysiological response of the tissue, 5) poorly understood relationship between effective doses and risks of late health effects, and 6) disregard of the psychological aspects of radionuclide intake.« less

76 FR 53847 - New International Commission on Radiological Protection; Recommendations on the Annual Dose Limit...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

... Radiological Protection; Recommendations on the Annual Dose Limit to the Lens of the Eye AGENCY: Nuclear... Protection (ICRP) recommendations for the limitation of annual dose to the lens of the eye. This significant... might be lower than previously considered. For the lens of the eye, the threshold in absorbed dose for...

Dosimetric evaluation of the staff working in a PET/CT department

NASA Astrophysics Data System (ADS)

Dalianis, K.; Malamitsi, J.; Gogou, L.; Pagou, M.; Efthimiadou, R.; Andreou, J.; Louizï, A.; Georgiou, E.

2006-12-01

The dosimetric literature data concerning the medical personnel working in positron emission tomography/computed tomography (PET/CT) departments are limited. Therefore, we measured the radiation dose of the staff working in the first PET/CT department in Greece at the Diagnostic and Therapeutic Center of Athens HYGEIA—Harvard Medical International. As, for the time being, only 2-deoxy-2-[ 18F]fluoro-d-glucose (FDG) PET studies are performed, radiation dose measurements concern those derived from dispensing of the radiopharmaceutical as well as from the patients undergoing FDG-PET imaging. Our aim is to develop more effective protective measures against radionuclide exposure. To estimate the effective dose from external exposure, all seven members of the staff (two nurses, two medical physicists, two technologists, one secretary) had TLD badges worn at the upper pocket of their overall, TLD rings on the right hand and digital dosimeters at their upper side pocket. In addition, isodose curves were measured with thermoluminescence detectors for distances of 20, 50, 70 and 100 cm away from patients who had been injected with 18F-FDG. Dose values of the PET/CT staff were measured with digital detectors, TLD badges and TLD rings over the first 8 months for a total of 160 working days of the department's operation, consisting of a workload of about 10-15 patients/week who received 250-420 MBq of 18F-FDG each. Whole - body collective doses and hand doses for the staff were the following: Nurse #1 received 1.6 mSv as a whole body dose and 2,1 as a hand dose, Nurse #2 received 1.9 and 2.4 mSv respectively. For medical physicist #1 the dose values were 1.45 mSv whole body and 1.7 mSv hand dose, for medical physicist #2 1.67 mSv wholebody dose and 1.55 mSv hand dose and for technologists #1 & #2 the whole body doses were 0.7 and 0.64 mSv respectively. Lastly, the secretary received 0.1 mSv whole body dose. These preliminary data have shown that the dose levels of our PET/CT staff are within acceptable limits.

Estimating the Effects of Astronaut Career Ionizing Radiation Dose Limits on Manned Interplanetary Flight Programs

NASA Technical Reports Server (NTRS)

Koontz, Steven L.; Rojdev, Kristina; Valle, Gerard D.; Zipay, John J.; Atwell, William S.

2013-01-01

Space radiation effects mitigation has been identified as one of the highest priority technology development areas for human space flight in the NASA Strategic Space Technology Investment Plan (Dec. 2012). In this paper we review the special features of space radiation that lead to severe constraints on long-term (more than 180 days) human flight operations outside Earth's magnetosphere. We then quantify the impacts of human space radiation dose limits on spacecraft engineering design and development, flight program architecture, as well as flight program schedule and cost. A new Deep Space Habitat (DSH) concept, the hybrid inflatable habitat, is presented and shown to enable a flexible, affordable approach to long term manned interplanetary flight today.

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

PubMed

Pfefferkorn, Jeffrey A

2009-03-01

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

[SUBSTANTIATION OF DOSE LIMITS FOR A NEW NORMATIVE DOCUMENT ON RADIATION SAFETY OF LONG-DURATION SPACE MISSIONS AT ORBIT ALTITUDES OF UP TO 500 KM].

PubMed

Ushakov, I B; Grigoriev, Yu G; Shafirkin, A V; Shurshakov, V A

2016-01-01

Review of the data of experimental radiobiology and epidemiological follow-up of large groups of people subjected to radiation exposures on Earth has been undertaken to substantiate dose limits for critical organs of cosmonauts in order to ensure good performance and vitality while on long-duration orbital missions. The career dose limits for cosmonauts and astronauts established earlier in the USSR and USA amounted to nothing more but banning the risk of cancer death increase to 3%. To apply more rigorous criteria of delayed radiation risks, the Russian limits for cosmonauts were revised to substantiate a 4-fold reduction of the average tissue equivalent dose maximum to 1 Sv. The total of cancer and non-cancer radiation risks over lifetime and probable reduction of mean life expectancy (MLE) were calculated using the model of radiation-induced mortality for mammals and taken as the main damage to health. The established dose limit is equal to the career dose for nuclear industry personnel set forth by Russian standard document NRB 99/2009. For better agreement of admissible threshold doses to critical human organs (bone marrow, lens and skin) in the revised radiation limits for long-duration space missions and radiation safety limits on Earth, reduction of dose limits for the critical organs were substantiated additionally; these limits comply with those for planned over-exposure on Earth in document NRB 99/2009.

Cost-effectiveness of hepatitis A vaccination in Indonesia.

PubMed

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

2014-01-01

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

Cost-effectiveness of hepatitis A vaccination in Indonesia

PubMed Central

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

2014-01-01

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

Nutritive Supplements - Help or Harm for Breast Cancer Patients?

PubMed

Muenstedt, Karsten; El-Safadi, Samer

2010-01-01

SUMMARY: Considerable numbers of patients and physicians believe that micronutrients may be useful with respect to prevention and treatment of breast cancer. However, the analysis of the literature shows that basic information on nutritional demands in cancer patients is lacking. It is unknown whether there is an increased demand of micro-nutrients in cancer patients in general and if there is an even more increased demand during the various types of treatment. As a result, there are only limited positive findings. Higher calcium intake in premenopausal women and higher intake of vitamin D seem to be able to lower breast cancer incidence. Vitamin E (800 IU per day) was found to have a modest effect on hot flashes during tamoxifen treatment. However, there are potential side effects especially when micronutrients are administered in high or very high doses. There is increasing evidence that dose-effect relationships are not linear but U-shaped. It seems that two thresholds exist for adverse effect, one at low doses for undersupply, and another at high doses for toxicity. Thus, arbitrary high-dose administration of micronutrients should be avoided. Supplementation of normal doses seems to be safe and acceptable from the medical point of view.

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

Enhancing the Effects of Low Dose Doxorubicin Treatment by the Radiation in T47D and SKBR3 Breast Cancer Cells

PubMed Central

Aghaee, Fahimeh; Baradaran, Behzad; Mesbahi, Asghar; Mohammadzadeh, Mohammad; Jafarabadi, Mohammad Asghari

2013-01-01

Purpose Breast cancer is the most common malignancy of women worldwide. Radiotherapy consists of a vital element in the treatment of breast cancer but relative side effects and different radioactive responses are limiting factors for a successful treatment. Doxorubicin has been used to treat cancers for over 30 years and is considered as the most effective drug in the treatment of breast cancer. There are also many chronic side effects that limit the amount of doxorubicin that can be administered. The combined radio-drug treatment, with low doses, can be an approach for reducing side effects from single modality treatments instead of suitable cure rates. Methods We have studied the effect of 1, 1.5, and 2 Gy doses of 9 MV X-rays along with 1 µM doxorubicin on inducing cell death, apoptosis and also p53 and PTEN gene expression in T47D and SKBR3 breast cancer cells. Results Doxorubicin treatment resulted in upregulation of radiation-induced levels of p53 and downregulation of PTEN at 1 and 1.5 Gy in T47D breast cancer cells, as well as downregulation of p53 mRNA level of expression and upregulation of PTEN mRNA level of expression in SKBR3 breast cancer cell line. In addition, doxorubicin in combination with radiation decreased the viability of breast cancer cell lines in the both cell lines. Conclusion Low doses of doxorubicin, with least cell toxicity, may be an effective treatment for breast cancer when used in conjunction with ionizing radiation. PMID:23843848

Cumulative radiation exposure and cancer risk estimation in children with heart disease.

PubMed

Johnson, Jason N; Hornik, Christoph P; Li, Jennifer S; Benjamin, Daniel K; Yoshizumi, Terry T; Reiman, Robert E; Frush, Donald P; Hill, Kevin D

2014-07-08

Children with heart disease are frequently exposed to imaging examinations that use ionizing radiation. Although radiation exposure is potentially carcinogenic, there are limited data on cumulative exposure and the associated cancer risk. We evaluated the cumulative effective dose of radiation from all radiation examinations to estimate the lifetime attributable risk of cancer in children with heart disease. Children ≤6 years of age who had previously undergone 1 of 7 primary surgical procedures for heart disease at a single institution between 2005 and 2010 were eligible for the study. Exposure to radiation-producing examinations was tabulated, and cumulative effective dose was calculated in millisieverts. These data were used to estimate lifetime attributable risk of cancer above baseline using the approach of the Committee on Biological Effects of Ionizing Radiation VII. The cohort included 337 children exposed to 13 932 radiation examinations. Conventional radiographs represented 92% of examinations, whereas cardiac catheterization and computed tomography accounted for 81% of cumulative exposure. Overall median cumulative effective dose was 2.7 mSv (range, 0.1-76.9 mSv), and the associated lifetime attributable risk of cancer was 0.07% (range, 0.001%-6.5%). Median lifetime attributable risk of cancer ranged widely depending on surgical complexity (0.006%-1.6% for the 7 surgical cohorts) and was twice as high in females per unit exposure (0.04% versus 0.02% per 1-mSv effective dose for females versus males, respectively; P<0.001). Overall radiation exposures in children with heart disease are relatively low; however, select cohorts receive significant exposure. Cancer risk estimation highlights the need to limit radiation dose, particularly for high-exposure modalities. © 2014 American Heart Association, Inc.

Space Radiation Cancer Risk Projections and Uncertainties - 2010

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Kim, Myung-Hee Y.; Chappell, Lori J.

2011-01-01

Uncertainties in estimating health risks from galactic cosmic rays greatly limit space mission lengths and potential risk mitigation evaluations. NASA limits astronaut exposures to a 3% risk of exposure-induced death and protects against uncertainties using an assessment of 95% confidence intervals in the projection model. Revisions to this model for lifetime cancer risks from space radiation and new estimates of model uncertainties are described here. We review models of space environments and transport code predictions of organ exposures, and characterize uncertainties in these descriptions. We summarize recent analysis of low linear energy transfer radio-epidemiology data, including revision to Japanese A-bomb survivor dosimetry, longer follow-up of exposed cohorts, and reassessments of dose and dose-rate reduction effectiveness factors. We compare these projections and uncertainties with earlier estimates. Current understanding of radiation quality effects and recent data on factors of relative biological effectiveness and particle track structure are reviewed. Recent radiobiology experiment results provide new information on solid cancer and leukemia risks from heavy ions. We also consider deviations from the paradigm of linearity at low doses of heavy ions motivated by non-targeted effects models. New findings and knowledge are used to revise the NASA risk projection model for space radiation cancer risks.

Effects of short-chain chlorinated paraffins exposure on the viability and metabolism of human hepatoma HepG2 cells.

PubMed

Geng, Ningbo; Zhang, Haijun; Zhang, Baoqin; Wu, Ping; Wang, Feidi; Yu, Zhengkun; Chen, Jiping

2015-03-03

Short-chain chlorinated paraffins (SCCPs) have attracted considerable attention for their characteristic of persistent organic pollutants. However, very limited information is available for their toxic effects at environmentally relevant doses, limiting the evaluation of their health risks. In this study, cell viability assay and targeted metabolomic approach was used to evaluate the environmental dose (<100 μg/L) effect of SCCPs on HepG2 cells. Cell viability was found to be decreased with increases in exposure dose of SCCPs. Exposure for 48 h to C10-CPs resulted in a significant reduction in cell viability compared with 24 h, even at 1 μg/L. SCCPs exposure altered the intracellular redox status and caused significant metabolic disruptions. As a kind of peroxisome proliferator, SCCPs specifically stimulated the β-oxidation of unsaturated fatty acids and long-chain fatty acids. Meanwhile, SCCPs exposure disturbed glycolysis and amino acid metabolism, and led to the up-regulation of glutamate metabolism and urea cycle. The toxic effects of SCCPs might mainly involve the perturbation of energy production, protein biosynthesis, fatty acid metabolism, and ammonia recycling.

State of the evidence: Cannabinoids and cancer pain-A systematic review.

PubMed

Tateo, Sydney

2017-02-01

Cannabinoids are widely used to alleviate intractable symptoms such as pain, nausea, and muscle spasticity. The purpose of this review was to ascertain the current state of the science regarding use of cannabinoids for cancer pain. Four electronic databases were searched for randomized control trials of cannabinoids and cancer pain. Studies included examined the analgesic effects of cannabinoids for cancer pain. Methodological quality was assessed using the Jadad scale. Eight randomized control trials met the inclusion criteria for review. Most trials found analgesic effects from cannabinoids when compared to placebo, although not all associations reached statistical significance. The analgesic effects of cannabinoids were also limited by dose-dependent side effects. Side effects most commonly reported were changes in cognition, sedation, and dizziness. There is evidence that cannabinoids are effective adjuvants for cancer pain not completely relieved by opioid therapy, but there is a dearth of high-quality studies to support a stronger conclusion. Cannabinoids appear to be safe in low and medium doses. Methodological limitations of the trials limited the ability to make sound conclusions. Further research is warranted before efficacy, safety, and utility of cannabinoids for cancer pain can be determined. ©2016 American Association of Nurse Practitioners.

Estimating the Effects of Astronaut Career Ionizing Radiation Dose Limits on Manned Interplanetary Flight Programs

NASA Technical Reports Server (NTRS)

Koontz, Steven L.; Rojdev, Kristina; Valle, Gerard D.; Zipay, John J.; Atwell, William S.

2013-01-01

The Hybrid Inflatable DSH combined with electric propulsion and high power solar-electric power systems offer a near TRL-now solution to the space radiation crew dose problem that is an inevitable aspect of long term manned interplanetary flight. Spreading program development and launch costs over several years can lead to a spending plan that fits with NASA's current and future budgetary limitations, enabling early manned interplanetary operations with space radiation dose control, in the near future while biomedical research, nuclear electric propulsion and active shielding research and development proceed in parallel. Furthermore, future work should encompass laboratory validation of HZETRN calculations, as previous laboratory investigations have not considered large shielding thicknesses and the calculations presented at these thicknesses are currently performed via extrapolation.

Radiation protection issues in galactic cosmic ray risk assessment

NASA Technical Reports Server (NTRS)

Sinclair, W. K.

1994-01-01

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

Radiation protection issues in galactic cosmic ray risk assessment.

PubMed

Sinclair, W K

1994-01-01

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

A Comprehensive Toxicological Safety Assessment of an Extract of Olea Europaea L. Leaves (Bonolive™).

PubMed

Clewell, Amy E; Béres, Erzsébet; Vértesi, Adél; Glávits, Róbert; Hirka, Gábor; Endres, John R; Murbach, Timothy S; Szakonyiné, Ilona Pasics

2016-01-01

A battery of toxicological studies was conducted to investigate the genotoxicity and repeated-dose oral toxicity of Bonolive™, a proprietary water-soluble extract of the leaves of the olive tree (Olea europaea L.), in accordance with internationally accepted protocols. There was no evidence of mutagenicity in a bacterial reverse mutation test and in an vitro mammalian chromosomal aberration test nor was any genotoxic activity observed in an in vivo mouse micronucleus test at concentrations up to the limit dose of 2000 mg/kg bw/d. Bonolive™ did not cause mortality or toxic effects in Crl:(WI)BR Wistar rats in a 90-day repeated-dose oral toxicity study at doses of 360, 600, and 1000 mg/kg bw/d. The no observed adverse effect level in the 90-day study was 1000 mg/kg bw/d for both male and female rats, the highest dose tested. © The Author(s) 2015.

Ultralow dose effects in ion-beam induced grafting of polymethylmethacrylate (PMMA)

NASA Astrophysics Data System (ADS)

Corelli, J. C.; Steckl, A. J.; Pulver, D.; Randall, J. N.

We have investigated the process of image enhancement in high resolution lithography through polymer grafting techniques. Sensitivity gains of 10 3-10 4 were obtained for H +, X-ray, e-beam and deep-UV irradiations. Ultralow dose effects in 60 keV H + irradiated PMMA have been observed through the use of the acrylic acid (AA) monomer grafting with irradiated PMMA. At conventional doses of 10 10 cm -2 an inner structure of each feature is revealed. At doses of (1-2) X 10 9 cm -2, discrete events within the exposed regions are observable. This is the first time that individual events have been observable in a lithography process and sets the upper limit in the useful sensitivity of the resist and ion lithography process. This effect is directly observable only with ions, because of their higher efficiency per particle than either photons or electrons.

Limiting CT radiation dose in children with craniosynostosis: phantom study using model-based iterative reconstruction.

PubMed

Kaasalainen, Touko; Palmu, Kirsi; Lampinen, Anniina; Reijonen, Vappu; Leikola, Junnu; Kivisaari, Riku; Kortesniemi, Mika

2015-09-01

Medical professionals need to exercise particular caution when developing CT scanning protocols for children who require multiple CT studies, such as those with craniosynostosis. To evaluate the utility of ultra-low-dose CT protocols with model-based iterative reconstruction techniques for craniosynostosis imaging. We scanned two pediatric anthropomorphic phantoms with a 64-slice CT scanner using different low-dose protocols for craniosynostosis. We measured organ doses in the head region with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Numerical simulations served to estimate organ and effective doses. We objectively and subjectively evaluated the quality of images produced by adaptive statistical iterative reconstruction (ASiR) 30%, ASiR 50% and Veo (all by GE Healthcare, Waukesha, WI). Image noise and contrast were determined for different tissues. Mean organ dose with the newborn phantom was decreased up to 83% compared to the routine protocol when using ultra-low-dose scanning settings. Similarly, for the 5-year phantom the greatest radiation dose reduction was 88%. The numerical simulations supported the findings with MOSFET measurements. The image quality remained adequate with Veo reconstruction, even at the lowest dose level. Craniosynostosis CT with model-based iterative reconstruction could be performed with a 20-μSv effective dose, corresponding to the radiation exposure of plain skull radiography, without compromising required image quality.

Regulation of X-Ray Security Scanners in Michigan.

PubMed

Parry, Donald E

2016-02-01

In January of 2013 the Transportation Security Administration (TSA) ordered the removal of x-ray security scanners from airports by June of 2013. Since that time several of these scanners have been purchased at a reduced cost by various state and county governments for use in screening individuals entering or leaving their facilities. To address this issue the Radiation Safety Section of the State of Michigan drafted a set of registration conditions for facilities to follow when using these security scanners. Inspection procedures and measurement protocols were developed to estimate the dose to screened individuals. Inspections were performed on nine of the 16 registered backscatter scanners in the state and the one transmission scanner. The average estimated effective dose to screened individuals was ∼11 nSv for a two view scan from a backscatter system. The effective dose was 0.446 μSv, 0.330 μSv, and 0.150 μSv for a transmission system operated in the high, medium, and low dose modes, respectively. The limit suggested in the new registration condition is 0.25 μSv for a general use system and 10 μSv for a limited use system.

Background of Civil Defense and Current Damage Limiting Studies.

ERIC Educational Resources Information Center

Romm, Joseph

A brief history of civil defense administration precedes analysis of nuclear attack conditions and the influence of protective measures. Damage limitation procedure is explained in terms of--(1) blast effects, (2) radiation doses, (3) geographical fallout distribution patterns, and (4) national shelter needs. Major concept emphasis relates to--(1)…

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.

Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

PubMed

Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

2016-05-01

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effective Dose Radon 222 of the Tap Water in Children and Adults People; Minab City, Iran.

PubMed

Fakhri, Yadolah; Kargosha, Morteza; Langarizadeh, Ghazaleh; Zandsalimi, Yahya; Rasouli Amirhajeloo, Leila; Moradi, Mahboobeh; Moradi, Bigard; Mirzaei, Maryam

2015-09-01

(222)Rn is a radioactive, odorless, and colorless element which has a half-life of 3.83 days. One of (222)Rn main resources are Groundwater (wells, springs, etc.). Hence, the use of groundwater with high concentration of (222)Rn can increase the risk of lung and stomach cancers. Concentration of (222)Rn in tap water of Minab city in two temperatures 5 and 15 ºC was measured by radon meter model RTM1668-2. The effective dose was calculated by equations proposed by UNSCEAR. Geometric mean concentration of (222)Rn in drinking water was found to be 0.78±0.06 and 0.46±0.04 Bq/l at 5 and 15 ̊C (p value<0.05), respectively. The effective doses were 0.006 and 0.003 mSv/y for adults, and 0.011 and 0.007 mSv/y for the children, respectively (p value<0.05). Besides, the effective dose for adult through inhaling (222)Rn at 5 and 15 ̊C were estimated 0.0021 and 0.0012mSv/y, respectively. Geometric mean concentration in (222)Rn drinking water and effective dose received from drinking water and inhalation of (222)Rn is lower than WHO and EPA standard limits. Increasing temperature of drinking water will decrease the effective dose received. Annual Effective dose received from inhalation and consumption of (222)Rn in drinking water in children is more than adults.

Effective Dose Radon 222 of the Tap Water in Children and Adults People; Minab City, Iran

PubMed Central

Fakhri, Yadolah; Kargosha, Morteza; Langarizadeh, Ghazaleh; Zandsalimi, Yahya; Amirhajeloo, Leila Rasouli; Moradi, Mahboobeh; Moradi, Bigard; Mirzaei, Maryam

2016-01-01

222Rn is a radioactive, odorless, and colorless element which has a half-life of 3.83 days. One of 222Rn main resources are Groundwater (wells, springs, etc.). Hence, the use of groundwater with high concentration of 222Rn can increase the risk of lung and stomach cancers. Concentration of 222Rn in tap water of Minab city in two temperatures 5 and 15 ºC was measured by radon meter model RTM1668-2. The effective dose was calculated by equations proposed by UNSCEAR. Geometric mean concentration of 222Rn in drinking water was found to be 0.78±0.06 and 0.46±0.04 Bq/l at 5 and 15 °C (p value<0.05), respectively. The effective doses were 0.006 and 0.003 mSv/y for adults, and 0.011 and 0.007 mSv/y for the children, respectively (p value<0.05). Besides, the effective dose for adult through inhaling 222Rn at 5 and 15 °C were estimated 0.0021 and 0.0012mSv/y, respectively. Geometric mean concentration in 222Rn drinking water and effective dose received from drinking water and inhalation of 222Rn is lower than WHO and EPA standard limits. Increasing temperature of drinking water will decrease the effective dose received. Annual Effective dose received from inhalation and consumption of 222Rn in drinking water in children is more than adults. PMID:26573047

Chemical and radiological risk factors associated with waste from energy production.

PubMed

Christensen, T; Fuglestvedt, J; Benestad, C; Ehdwall, H; Hansen, H; Mustonen, R; Stranden, E

1992-04-01

We have tried to estimate the toxic potential of waste from nuclear power plants and from power plants burning fossil fuels. The potential risks have been expressed as 'risk potentials' or 'person equivalents.' These are purely theoretical units and represent only an attempt to quantify the potential impact of different sources and substances on human health. Existing concentration limits for effects on human health are used. The philosophy behind establishing limits for several carcinogenic chemicals is based on a linear dose-effect curve. That is, no lower concentration of no effect exists and one has to accept a certain small risk by accepting the concentration limit. This is in line with the establishment of limits for radiation. Waste products from coal combustion have the highest potential risk among the fossil fuel alternatives. The highest risk is caused by metals, and the fly ash represents the effluent stream giving the largest contribution to the potential risk. The waste from nuclear power production has a lower potential risk than coal if today's limit values re used. If one adjusts the limits for radiation dose and the concentration limit values so that a similar risk is accepted by the limits, nuclear waste seems to have a much higher potential risk than waste from fossil fuel. The possibility that such risk estimates may be used as arguments for safe storage of the different types of waste is discussed. In order to obtain the actual risk from the potential risk, the dispersion of the waste in the environment and its uptake and effects in man have to be taken into account.

Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

PubMed Central

2012-01-01

Background According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Results Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv). Conclusions At this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed. PMID:22540409

Construction of new skin models and calculation of skin dose coefficients for electron exposures

NASA Astrophysics Data System (ADS)

Yeom, Yeon Soo; Kim, Chan Hyeong; Nguyen, Thang Tat; Choi, Chansoo; Han, Min Cheol; Jeong, Jong Hwi

2016-08-01

The voxel-type reference phantoms of the International Commission on Radiological Protection (ICRP), due to their limited voxel resolutions, cannot represent the 50- μm-thick radiosensitive target layer of the skin necessary for skin dose calculations. Alternatively, in ICRP Publication 116, the dose coefficients (DCs) for the skin were calculated approximately, averaging absorbed dose over the entire skin depth of the ICRP phantoms. This approximation is valid for highly-penetrating radiations such as photons and neutrons, but not for weakly penetrating radiations like electrons due to the high gradient in the dose distribution in the skin. To address the limitation, the present study introduces skin polygon-mesh (PM) models, which have been produced by converting the skin models of the ICRP voxel phantoms to a high-quality PM format and adding a 50- μm-thick radiosensitive target layer into the skin models. Then, the constructed skin PM models were implemented in the Geant4 Monte Carlo code to calculate the skin DCs for external exposures of electrons. The calculated values were then compared with the skin DCs of the ICRP Publication 116. The results of the present study show that for high-energy electrons (≥ 1 MeV), the ICRP-116 skin DCs are, indeed, in good agreement with the skin DCs calculated in the present study. For low-energy electrons (< 1 MeV), however, significant discrepancies were observed, and the ICRP-116 skin DCs underestimated the skin dose as much as 15 times for some energies. Besides, regardless of the small tissue weighting factor of the skin ( w T = 0.01), the discrepancies in the skin dose were found to result in significant discrepancies in the effective dose, demonstarting that the effective DCs in ICRP-116 are not reliable for external exposure to electrons.

The internal dosimetry of Rubidium-82 based on dynamic PET/CT imaging in humans

NASA Astrophysics Data System (ADS)

Hunter, Chad R.

Rubidium-82 (Rb-82) is a useful blood flow tracer, and has become important in recent years due to the shutdown of the Chalk River reactor. Published effective dose estimates for Rb-82 vary widely, and as yet no comprehensive study in man has been conducted with PET/CT, and no effective dose estimates for Rb-82 during pharmacological stress testing has been published. 30 subjects were recruited for rest, and 25 subjects were recruited for stress. The subjects consisted of both cardiac patients and normal subjects. For rest, a total of 283 organs were measured across 60 scans. For stress, a total of 171 organs were measured across 25 scans. Effective dose estimates were calculated using the ICRP 60, 80, and 103 tissue weighting factors. Relative differences between this study and the published in-vivo estimates showed agreement for the lungs. Relative differences between this study and the blood flow models showed differences> 5 times in the thyroid contribution to the effective dose demonstrating a limitation in these models. Comparisons between rest and stress effective dose estimates revealed no significant difference. The average 'adult' effective dose for Rb-82 was found to be 0.00084+/-0.00018 mSv/MBq. The highest dose organs were the lungs, kidneys and stomach wall. These dose estimates for Rb-82 are the first to be measured directly with PET/CT in humans, and are 4 times lower than previous ICRP 60 values based on a theoretical blood flow model. The total adult effective dose from a typical Rb-82 study including CT for attenuation correction and potential Sr-85 breakthrough is 1.5 +/- 0.4 mSv.

The effects of cannabinoids on serum cortisol and prolactin in humans

PubMed Central

Ranganathan, Mohini; Braley, Gabriel; Pittman, Brian; Cooper, Thomas; Perry, Edward; Krystal, John; D’Souza, Deepak Cyril

2010-01-01

Background Cannabis is one of the most widely used illicit substances, and there is growing interest in the therapeutic applications of cannabinoids. While known to modulate neuroendocrine function, the precise acute and chronic dose-related effects of cannabinoids in humans are not well-known. Furthermore, the existing literature on the neuroendocrine effects of cannabinoids is limited by small sample sizes (n=6–22), heterogeneous samples with regard to cannabis exposure (lumping users and nonusers), lack of controlling for chronic cannabis exposure, differing methodologies, and limited dose–response data. Delta-9-tetrahydrocannabinol (Δ-9-THC) was hypothesized to produce dose-related increases in plasma cortisol levels and decreases in plasma prolactin levels. Furthermore, relative to controls, frequent users of cannabis were hypothesized to show altered baseline levels of these hormones and blunted Δ-9-THC-induced changes of these hormones. Materials and methods Pooled data from a series of laboratory studies with multiple doses of intravenous Δ-9-THC in healthy control subjects (n=36) and frequent users of cannabis (n=40) was examined to characterize the acute, chronic, and acute on chronic effects of cannabinoids on plasma cortisol and prolactin levels. Hormone levels were measured before (baseline) and 70 min after administration of each dose of Δ-9-THC. Data were analyzed using linear mixed models with +70 min hormonal levels as the dependant variable and baseline hormonal level as the covariate. Results At socially relevant doses, Δ-9-THC raised plasma cortisol levels in a dose-dependent manner but frequent users showed blunted increases relative to healthy controls. Frequent users also had lower baseline plasma prolactin levels relative to healthy controls. Conclusions These group differences may be related to the development of tolerance to the neuroendocrine effects of cannabinoids. Alternatively, these results may reflect inherent differences in neuroendocrine function in frequent users of cannabis and not a consequence of cannabis use. PMID:19083209

Dental cone-beam CT reconstruction from limited-angle view data based on compressed-sensing (CS) theory for fast, low-dose X-ray imaging

NASA Astrophysics Data System (ADS)

Je, Uikyu; Cho, Hyosung; Lee, Minsik; Oh, Jieun; Park, Yeonok; Hong, Daeki; Park, Cheulkyu; Cho, Heemoon; Choi, Sungil; Koo, Yangseo

2014-06-01

Recently, reducing radiation doses has become an issue of critical importance in the broader radiological community. As a possible technical approach, especially, in dental cone-beam computed tomography (CBCT), reconstruction from limited-angle view data (< 360°) would enable fast scanning with reduced doses to the patient. In this study, we investigated and implemented an efficient reconstruction algorithm based on compressed-sensing (CS) theory for the scan geometry and performed systematic simulation works to investigate the image characteristics. We also performed experimental works by applying the algorithm to a commercially-available dental CBCT system to demonstrate its effectiveness for image reconstruction in incomplete data problems. We successfully reconstructed CBCT images with incomplete projections acquired at selected scan angles of 120, 150, 180, and 200° with a fixed angle step of 1.2° and evaluated the reconstruction quality quantitatively. Both simulation and experimental demonstrations of the CS-based reconstruction from limited-angle view data show that the algorithm can be applied directly to current dental CBCT systems for reducing the imaging doses and further improving the image quality.

Role of the standard deviation in the estimation of benchmark doses with continuous data.

PubMed

Gaylor, David W; Slikker, William

2004-12-01

For continuous data, risk is defined here as the proportion of animals with values above a large percentile, e.g., the 99th percentile or below the 1st percentile, for the distribution of values among control animals. It is known that reducing the standard deviation of measurements through improved experimental techniques will result in less stringent (higher) doses for the lower confidence limit on the benchmark dose that is estimated to produce a specified risk of animals with abnormal levels for a biological effect. Thus, a somewhat larger (less stringent) lower confidence limit is obtained that may be used as a point of departure for low-dose risk assessment. It is shown in this article that it is important for the benchmark dose to be based primarily on the standard deviation among animals, s(a), apart from the standard deviation of measurement errors, s(m), within animals. If the benchmark dose is incorrectly based on the overall standard deviation among average values for animals, which includes measurement error variation, the benchmark dose will be overestimated and the risk will be underestimated. The bias increases as s(m) increases relative to s(a). The bias is relatively small if s(m) is less than one-third of s(a), a condition achieved in most experimental designs.

Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP

PubMed Central

Kusuhara, Hiroyuki; Furuie, Hidetoshi; Inano, Akihiro; Sunagawa, Akihiro; Yamada, Saiko; Wu, Chunyong; Fukizawa, Shinya; Morimoto, Nozomi; Ieiri, Ichiro; Morishita, Mariko; Sumita, Kiminobu; Mayahara, Hiroshi; Fujita, Takuya; Maeda, Kazuya; Sugiyama, Yuichi

2012-01-01

BACKGROUND AND PURPOSE An ATP-binding cassette (ABC) transporter, breast cancer resistance protein (BCRP)/ABCG2, limits oral bioavailability of sulphasalazine. Here we examined the effect of curcumin, the principal curcuminoid of turmeric, on oral bioavailability of microdoses and therapeutic doses of sulphasalazine in humans. EXPERIMENTAL APPROACH Effects of curcumin were measured on the ATP-dependent sulphasalazine uptake by hBCRP-expressing membrane vesicles and on oral bioavailability of sulphasalazine in wild-type and Bcrp(–/–) mice. Eight healthy Japanese subjects received an oral dose of sulphasalazine suspension (100 µg) or tablets (2 g) alone or after curcumin tablets (2 g). Uptake of sulphasalazine was studied in HEK293 cells transfected with the influx transporter (OATP)2B1. KEY RESULTS Curcumin was a potent hBCRP inhibitor in vitro (Ki 0.70 ± 0.41 µM). Curcumin increased the area under the curve (AUC)0–8 of plasma sulphasalazine eightfold in wild-type mice at 300 and 400 mg·kg−1, but not in Bcrp(–/–) mice. Curcumin increased AUC0–24 of plasma sulphasalazine 2.0-fold at microdoses and 3.2-fold at therapeutic doses in humans. Non-linearity of the dose–exposure relationship was observed between microdoses and therapeutic doses of sulphasalazine. Sulphasalazine was a substrate for OATP2B1 (Km 1.7 ± 0.3 µM). Its linear index (dose/Km) at the therapeutic dose was high and may saturate OATP2B1. CONCLUSIONS AND IMPLICATIONS Curcumin can be used to investigate effects of BCRP on oral bioavailability of drugs in humans. Besides the limited dissolution, OATP2B1 saturation is a possible mechanism underlying non-linearity in the dose–exposure relationship of sulphasalazine. PMID:22300367

Dose-related beneficial and harmful effects of gabapentin in postoperative pain management – post hoc analyses from a systematic review with meta-analyses and trial sequential analyses

PubMed Central

Fabritius, Maria Louise; Wetterslev, Jørn; Mathiesen, Ole; Dahl, Jørgen B

2017-01-01

Background During the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients. Materials and methods Data in this paper were derived from an original review, and the subgroup analyses were predefined in an International Prospective Register of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library’s CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin versus placebo were included. Four different dose intervals were investigated: 0–350, 351–700, 701–1050, and >1050 mg. Primary co-outcomes were 24-hour morphine consumption and serious adverse events (SAEs), with emphasis put on trials with low risk of bias. Results One hundred and twenty-two randomized clinical trials, with 8466 patients, were included. Sixteen were overall low risk of bias. No consistent increase in morphine-sparing effect was observed with increasing doses of gabapentin from the trials with low risk of bias. Analyzing all trials, the smallest and the highest dose subgroups demonstrated numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin. Conclusion Data were sparse, and the small number of trials with low risk of bias is a major limitation for firm conclusions. Taking these limitations into account, we were not able to demonstrate a clear relationship between the dosage of gabapentin and opioid-sparing or harmful effects. These subgroup analyses are exploratory and hypothesis-generating for future trialists. PMID:29138592

The effects of acute alcohol on psychomotor, set-shifting, and working memory performance in older men and women.

PubMed

Hoffman, Lauren A; Sklar, Alfredo L; Nixon, Sara Jo

2015-05-01

A limited number of publications have documented the effects of acute alcohol administration among older adults. Among these, only a few have investigated sex differences within this population. The current project examined the behavioral effects of acute low- and moderate-dose alcohol on 62 older (ages 55-70) male and female, healthy, light to moderate drinkers. Participants were randomly assigned to one of three dose conditions: placebo (peak breath alcohol concentration [BrAC] of 0 mg/dL), low (peak BrAC of 40 mg/dL), and moderate (peak BrAC of 65 mg/dL). Tasks assessed psychomotor, set-shifting, and working memory performance. Better set-shifting abilities were observed among women, whereas men demonstrated more efficient working memory, regardless of dose. The moderate-dose group did not significantly differ from the placebo group on any task. However, the low-dose group performed better than the moderate-dose group across measures of set shifting and working memory. Relative to the placebo group, the low-dose group exhibited better working memory, specifically for faces. Interestingly, there were no sex by dose interactions. These data suggest that, at least for our study's task demands, low and moderate doses of alcohol do not significantly hinder psychomotor, set-shifting, or working memory performance among older adults. In fact, low-dose alcohol may facilitate certain cognitive abilities. Furthermore, although sex differences in cognitive abilities were observed, these alcohol doses did not differentially affect men and women. Further investigation is necessary to better characterize the effects of sex and alcohol dose on cognition in older adults. Copyright © 2015 Elsevier Inc. All rights reserved.

Critical evaluation of taeniacidal antibiotic S15-1 (SQ 21, 704) for removal of natural tapeworm infections in dogs and cats.

PubMed

Szanto, J; Lillis, W G; Brown, W E; Sutphin, C F; Maplesden, D C

1979-05-01

The new taeniacidal antibiotic S15-1 (SQ 21,704) was evaluated against naturally occuring infections of Taenia pisiformis in 53 dogs, Dipylidium caninum in 35 dogs, T taeniaformis in 18 cats, and D caninum in 33 cats. It all instances, the compound was administered in gelatine capsules in a single oral dose. The doses tested were between and 200 mg/kg of body weight in dogs and between 15 and 45 mg/kg in cats. In dogs, doses of 25 mg/kg and greater were 100% effective against T pisiformis, whereas a dose of 50 mg/kg was necessary to clear D caninum. In cats, a single oral dose of 22.5 mg/kg was 100% efficacious against T taeniaeformis, and a single dose of 45 mg/kg (the largest dose tested) clearly seven of eight cats of D caninum. The efficacy was limited to tapeworms only; there was no efficacy against nematodes. The antibiotic was well tolerated by both species with no drug-related vomiting or other side-effects observed.

Radiological dose in Muria peninsula from SB-LOCA event

NASA Astrophysics Data System (ADS)

Sunarko; Suud, Zaki

2017-01-01

Dose assessment for accident condition is performed for Muria Peninsula region using source-term from Three-Mile Island unit 2 SB-LOCA accident. Xe-133, Kr-88, 1-131 and Cs-137 isotopes are considered in the calculation. The effluent is assumed to be released from a 50 m stack. Lagrangian particle dispersion method (LPDM) employing non-Gaussian dispersion coefficient in 3-dimensional mass-consistent wind-field is employed to obtain periodic surface-level concentration which is then time-integrated to obtain spatial distribution of ground-level dose. In 1-hour simulation, segmented plumes with 60 seconds duration with a total of 18.000 particles involved. Simulations using 6-hour worst-case meteorological data from Muria peninsula results in a peak external dose of around 1.668 mSv for low scenario and 6.892 mSv for high scenario in dry condition. In wet condition with 5 mm/hour and 10 mm/hour rain for the whole duration of the simulation provides only minor effect to dose. The peak external dose is below the regulatory limit of 50 mSv for effective skin dose from external gamma exposure.

High-dose hook effect in six automated human chorionic gonadotrophin assays.

PubMed

Al-Mahdili, Huda A; Jones, Graham R D

2010-07-01

The high-dose hook effect is a well-known phenomenon of two-site immunoassays including those for human chorionic gonadotrophin (hCG). We investigated the occurrence of a high-dose hook effect in six routinely available hCG assays using a sample with a total hCG concentration of approximately 3,600,000 IU/L. Dilutions of a sample with high hCG concentration were analysed using six common methods: Advia Centaur, Immulite 2000, Dimension RxL, Unicel DxI 800, Roche E170 and Abbott Architect. The measured concentrations and corresponding assay signals were obtained for each method. Performance was compared with manufacturer claims. Four of the tested platforms demonstrated a clear high-dose hook effect, while the other methods showed no hook effect at the highest level tested. Our results indicate that the hook effect may occur in some hCG assays, although the risk of reporting falsely low results was in most cases at higher concentrations than those indicated in manufacturers' product information. Assay design plays a major role in its occurrence. Laboratories should be aware of the assay limitations in this regard.

A calpain-2 selective inhibitor enhances learning & memory by prolonging ERK activation.

PubMed

Liu, Yan; Wang, Yubin; Zhu, Guoqi; Sun, Jiandong; Bi, Xiaoning; Baudry, Michel

2016-06-01

While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occupational radiation dose to eyes from endoscopic retrograde cholangiopancreatography procedures in light of the revised eye lens dose limit from the International Commission on Radiological Protection.

PubMed

O'Connor, U; Gallagher, A; Malone, L; O'Reilly, G

2013-02-01

Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure that combines the use of X-ray fluoroscopy and endoscopy for examination of the bile duct. Published data on ERCP doses are limited, including staff eye dose from ERCP. Occupational eye doses are of particular interest now as the International Commission on Radiological Protection (ICRP) has recommended a reduction in the dose limit to the lens of the eye. The aim of this study was to measure occupational eye doses obtained from ERCP procedures. A new eye lens dosemeter (EYE-D(™), Radcard, Krakow, Poland) was used to measure the ERCP eye dose, H(p)(3), at two endoscopy departments in Ireland. A review of radiation protection practice at the two facilities was also carried out. The mean equivalent dose to the lens of the eye of a gastroenterologist is 0.01 mSv per ERCP procedure with an undercouch X-ray tube and 0.09 mSv per ERCP procedure with an overcouch X-ray tube. Staff eye dose normalised to patient kerma area product is also presented. Staff eye doses in ERCP have the potential to exceed the revised ICRP limit of 20 mSv per annum when an overcouch X-ray tube is used. The EYE-D dosemeter was found to be a convenient method for measuring lens dose. Eye doses in areas outside of radiology departments should be kept under review, particularly in light of the new ICRP eye dose limit. Occupational eye lens doses from ERCP procedures have been established using a new commercially available dedicated H(p)(3) dosemeter.

Dialysis Cannot be Dosed

PubMed Central

Meyer, Timothy W.; Sirich, Tammy L.; Hostetter, Thomas H.

2014-01-01

Adequate dialysis is difficult to define because we have not identified the toxic solutes that contribute most to uremic illness. Dialysis prescriptions therefore cannot be adjusted to control the levels of these solutes. The current solution to this problem is to define an adequate dose of dialysis on the basis of fraction of urea removed from the body. This has provided a practical guide to treatment as the dialysis population has grown over the past 25 years. Indeed, a lower limit to Kt/Vurea (or the related urea reduction ratio) is now established as a quality indicator by the Centers for Medicare and Medicaid for chronic hemodialysis patients in the United States. For the present, this urea-based standard provides a useful tool to avoid grossly inadequate dialysis. Dialysis dosing, however, based on measurement of a single, relatively nontoxic solute can provide only a very limited guide toward improved treatment. Prescriptions which have similar effects on the index solute can have widely different effects on other solutes. The dose concept discourages attempts to increase the removal of such solutes independent of the index solute. The dose concept further assumes that important solutes are produced at a constant rate relative to body size, and discourages attempts to augment dialysis treatment by reducing solute production. Identification of toxic solutes would provide a more rational basis for the prescription of dialysis and ultimately for improved treatment of patients with renal failure. PMID:21929590

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

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

Schüler, Emil; Trovati, Stefania; King, Gregory

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

High dose bystander effects in spatially fractionated radiation therapy

PubMed Central

Asur, Rajalakshmi; Butterworth, Karl T.; Penagaricano, Jose A.; Prise, Kevin M.; Griffin, Robert J.

2014-01-01

Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. PMID:24246848

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2013 CFR

2013-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2014 CFR

2014-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2012 CFR

2012-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2011 CFR

2011-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2010 CFR

2010-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing.

PubMed

Natale, Stephanie; Bradley, John; Nguyen, William Huy; Tran, Tri; Ny, Pamela; La, Kirsten; Vivian, Eva; Le, Jennifer

2017-03-01

Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966-July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs' properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients. © 2017 Pharmacotherapy Publications, Inc.

Cancer mortality among coke oven workers.

PubMed Central

Redmond, C K

1983-01-01

The OSHA standard for coke oven emissions, which went into effect in January 1977, sets a permissible exposure limit to coke oven emissions of 150 micrograms/m3 benzene-soluble fraction of total particulate matter (BSFTPM). Review of the epidemiologic evidence for the standard indicates an excess relative risk for lung cancer as high as 16-fold in topside coke oven workers with 15 years of exposure or more. There is also evidence for a consistent dose-response relationship in lung cancer mortality when duration and location of employment at the coke ovens are considered. Dose-response models fitted to these same data indicate that, while excess risks may still occur under the OSHA standard, the predicted levels of increased relative risk would be about 30-50% if a linear dose-response model is assumed and 3-7% if a quadratic model is assumed. Lung cancer mortality data for other steelworkers suggest the predicted excess risk has probably been somewhat overestimated, but lack of information on important confounding factors limits further dose-response analysis. PMID:6653539

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.

A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.

PubMed

Chiu, Weihsueh A; Slob, Wout

2015-12-01

When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

Analysis of Exposure-Dose Variation of Inhaled Particles in Adult Subjects.

EPA Science Inventory

Although internal dose is a key factor for determining the health risk of inhaled pollutant particles, available dose information is largely limited to young healthy adults under a few typical exposure conditions. Extrapolation of the limited dose information to different populat...

Dose limits to the lens of the eye: International Basic Safety Standards and related guidance.

PubMed

Boal, T J; Pinak, M

2015-06-01

The International Atomic Energy Agency (IAEA) safety requirements: 'General Safety Requirements Part 3--Radiation protection and safety of radiation sources: International Basic Safety Standards' (BSS) was approved by the IAEA Board of Governors at its meeting in September 2011, and was issued as General Safety Requirements Part 3 in July 2014. The equivalent dose limit for the lens of the eye for occupational exposure in planned exposure situations was reduced from 150 mSv year(-1) to 20 mSv year(-1), averaged over defined periods of 5 years, with no annual dose in a single year exceeding 50 mSv. This reduction in the dose limit for the lens of the eye followed the recommendation of the International Commission on Radiological Protection in its statement on tissue reactions of 21 April 2011. IAEA has developed guidance on the implications of the new dose limit for the lens of the eye. This paper summarises the process that led to the inclusion of the new dose limit for the lens of the eye in the BSS, and the implications of the new dose limit. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

PubMed

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

2005-06-01

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

A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system.

PubMed

Ma, Jiasen; Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G

2014-12-01

Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. For relatively large and complex three-field head and neck cases, i.e., >100,000 spots with a target volume of ∼ 1000 cm(3) and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45,000 dollars. The fast calculation and optimization make the system easily expandable to robust and multicriteria optimization.

Phase I study of 6-diazo-5-oxo-L-norleucine (DON).

PubMed

Sklaroff, R B; Casper, E S; Magill, G B; Young, C W

1980-01-01

We conducted a phase I study of 6-diazo-5-oxo-L-norleucine given iv on a twice weekly schedule. Twenty-six evaluable patients received 31 courses of the drug. Doses ranged from 100 to 500 mg/m2. Nausea with vomiting was the dose-limiting toxic effect, transient thrombocytopenia was seen frequently, and mucositis occurred in 39% of the patients. No definite therapeutic responses were observed in 18 patients with measurable lesions. The recommended dose for phase II studies is 200-300 mg/m2 iv twice weekly.

Profiling primaquine metabolites in primary human hepatocytes by UPLC-QTOF-MS with 13c stable isotope labeling

USDA-ARS?s Scientific Manuscript database

Primaquine (PQ) is an important antimalarial agent because of its activity against exoerythrocytic forms of Plasmodium spp. However, hemolytic anemia is a dose-limiting side effect of primaquine therapy that limits its widespread use. The major plasma metabolite identified in humans and animals, car...

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

NASA Astrophysics Data System (ADS)

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

2012-07-01

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

BET 2: Low-dose ketamine for acute pain in the ED.

PubMed

Duncan, Colby; Riley, Brad

2016-12-01

A short cut review was carried out to establish whether low-dose ketamine is better than morphine at safely and effectively reducing pain scores in ED patients with acute pain who do not respond to conventional therapies. One hundred and thirty-two papers were found using the reported searches, of these three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that the evidence is limited, but that ketamine can be an effective alternative or adjunct to intravenous opioid pain medications and in some instances may provide more effective pain relief when compared with opioids. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Biological dosimetry in a group of radiologists by the analysis of dicentrics and translocations.

PubMed

Montoro, A; Rodríguez, P; Almonacid, M; Villaescusa, J I; Verdú, G; Caballín, M R; Barrios, L; Barquinero, J F

2005-11-01

The results of a cytogenetic study carried out in a group of nine radiologists are presented. Chromosome aberrations were detected by fluorescence plus Giemsa staining and fluorescence in situ hybridization. Dose estimates were obtained by extrapolating the yield of dicentrics and translocations to their respective dose-effect curves. In seven individuals, the 95% confidence limits of the doses estimated by dicentrics did not include 0 Gy. The 99 dicentrics observed in 17,626 cells gave a collective estimated dose of 115 mGy (95% confidence limits 73-171). For translocations, five individuals had estimated doses that were clearly higher than the total accumulated recorded dose. The 82 total apparently simple translocations observed in 9722 cells gave a collective estimated dose of 275 mGy (132-496). The mean genomic frequencies (x100 +/- SE) of complete and total apparently simple translocations observed in the group of radiologists (1.91 +/- 0.30 and 2.67 +/- 0.34, respectively) were significantly higher than those observed in a matched control group (0.53 +/- 0.10 and 0.87 +/- 0.13, P < 0.01 in both cases) and in another occupationally exposed matched group (0.79 +/- 0.12 and 1.14 +/-0.14, P < 0.03 and P < 0.01, respectively). The discrepancies observed between the physically recorded doses and the biologically estimated doses indicate that the radiologists did not always wear their dosimeters or that the dosimeters were not always in the radiation field.

Radiation exposure to nuclear medicine staffs during 18F-FDG PET/CT procedures at Ramathibodi Hospital

NASA Astrophysics Data System (ADS)

Donmoon, T.; Chamroonrat, W.; Tuntawiroon, M.

2016-03-01

The aim of this study is to estimate the whole body and finger radiation doses per study received by nuclear medicine staff involved in dispensing, administration of 18F-FDG and interacting with radioactive patients during PET/CT imaging procedures in a PET/CT facility. The whole-body doses received by radiopharmacists, technologists and nurses were measured by electronic dosimeter and the finger doses by ring dosimeter during a period of 4 months. In 70 PET/CT studies, the mean whole-body dose per study to radiopharmacist, technologist, and nurse were 1.07±0.09, 1.77±0.46, μSv, and not detectable respectively. The mean finger doses per study received by radiopharmacist, technologist, and nurse were 265.65±107.55, 4.84±1.08 and 19.22±2.59 μSv, respectively. The average time in contact with 18F-FDG was 5.88±0.03, 39.06±1.89 and 1.21±0.02 minutes per study for radiopharmacist, technologist and nurse respectively. Technologists received highest mean effective whole- body dose per study and radiopharmacist received the highest finger dose per study. When compared with the ICRP dose limit, each individual worker can work with many more 18F- FDG PET/CT studies for a whole year without exceeding the occupational dose limits. This study confirmed that low levels of radiation does are received by our medical personnel involved in 18F-FDG PET/CT procedures.

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

NASA Astrophysics Data System (ADS)

Evangeliou, Nikolaos; Stohl, Andreas; Balkanski, Yves

2017-04-01

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

Radiation Therapy and Hearing Loss

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

Bhandare, Niranjan; Jackson, Andrew; Eisbruch, Avraham

2010-03-01

A review of literature on the development of sensorineural hearing loss after high-dose radiation therapy for head-and-neck tumors and stereotactic radiosurgery or fractionated stereotactic radiotherapy for the treatment of vestibular schwannoma is presented. Because of the small volume of the cochlea a dose-volume analysis is not feasible. Instead, the current literature on the effect of the mean dose received by the cochlea and other treatment- and patient-related factors on outcome are evaluated. Based on the data, a specific threshold dose to cochlea for sensorineural hearing loss cannot be determined; therefore, dose-prescription limits are suggested. A standard for evaluating radiation therapy-associatedmore » ototoxicity as well as a detailed approach for scoring toxicity is presented.« less

The New Radiobiology: Returning to Our Roots

PubMed Central

Ulsh, Brant A.

2012-01-01

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

Therapeutic drug monitoring in pregnancy.

PubMed

Matsui, Doreen M

2012-10-01

Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

Assessment of the risk of solar ultraviolet radiation to amphibians. III. Prediction of impacts in selected northern midwestern wetlands.

PubMed

Diamond, Stephen A; Peterson, Gregory S; Tietge, Joseph E; Ankley, Gerald T

2002-07-01

Solar ultraviolet radiation, especially UVB (280-320 nm), has been hypothesized to be at least partially responsible for adverse effects (e.g., declines and malformations) in amphibian species throughout the world. Evaluation of this hypothesis has been limited by the paucity of high-quality UV dose-response data and reliable estimates of typical UV doses that occur in amphibian habitats. In this preliminary risk assessment for effects of UV radiation on amphibians, dose-response relationships quantified in outdoor experiments were compared with UV exposure estimates for 26 wetlands in northern Minnesota and Wisconsin. A comparison of wetland doses, derived from model prediction, historical data, and dissolved organic carbon (DOC) characterization, with experimental effects levels for green (R. clamitans), northern leopard (R. pipiens), and mink (R. septentrionalis) frogs indicated that the risk of mortality and malformations due to UV exposure is low for the majority of wetlands evaluated. Wetland UV dose, averaged over the entire breeding season, exceeded effects doses for mortality for all three species in two of the 26 wetlands examined and for one species in an additional wetland. On the basis of evidence that shorter term doses caused mortality in amphibian larvae, 3-day doses were also evaluated. In three of the wetlands examined, 3-day doses in excess of 85% of full sunlight (the level that appeared to trigger effects in controlled experimentation) occurred at frequencies ranging 22-100% for all three species and at frequencies ranging from 15% to 58% for R. pipiens and R. septentrionalis in three additional wetlands. Risk of malformation in R. pipiens was apparent in five of the 26 wetlands evaluated. Overall, estimated UVB doses in 21 of the wetlands never exceeded experimental effects doses for mortality or malformations. These results suggest that most amphibians are not currently at significant risk for UVB effects in northern Minnesota and Wisconsin wetlands. However, continued reduction of ozone and other global climate change effects may increase UV doses in wetlands, suggesting that the risk of UV to amphibians should continue to be monitored and studied.

76 FR 8157 - National Ambient Air Quality Standards for Carbon Monoxide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... alternative mechanisms of CO- induced effects independent of limited oxygen availability (2000 AQCD, section 5... Concentrations B. Health Effects Information 1. Carboxyhemoglobin as Biomarker and Mechanism of Toxicity 2. Nature of Effects 3. At-Risk Populations 4. Potential Impacts on Public Health C. Human Exposure and Dose...

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

PubMed

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

2012-01-01

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

[Mechanisms of opioid-induced overdose: experimental approach to clinical concerns].

PubMed

Baud, F-J

2009-09-01

The widely used term "overdose" denotes a toxic effect: opioid-induced intoxication and a mechanism: the poisoning results only from an overdose. Surprisingly, our understanding of the pathophysiology of this deadly complication is limited. In drug users, we attempted to: (1) improve knowledge of drug-induced respiratory effects; (2) clarify the mechanisms of drug interactions; (3) identify factors of variability and vulnerability. A prospective study of opioid overdoses confirmed that poisonings involving buprenorphine do exist. However, the mechanisms of buprenorphine poisoning are more complex than only an overdose, particularly the severity is less than that induced by heroin. In contrast, methadone overdose is life-threatening. Experimental studies addressed several clinical questions and also showed limited discrepancies. At pharmacological doses, opioids decrease the ventilatory response to CO(2). However, this effect does not account for the morbimortality of opioid poisonings. The mechanisms of opioid-induced morbimortality are different. Buprenorphine at doses near its median lethal dose did not induce acute respiratory failure as defined by a decrease in the partial pressure of oxygen in arterial blood (PaO(2)). In contrast, the combination of buprenorphine with flunitrazepam results in a decrease in PaO(2). This harmful interaction does not exist with other benzodiazepines in the rat, except for very high doses of nordazepam. The interaction results from a pharmacokinetic process. In contrast, methadone causes a dose-dependent decrease in PaO(2,) even significant before hypercapnia. We are assessing the relationships between on one hand alterations of ventilatory pattern and of arterial blood gas and on the other hand the different types of opiate receptors in the rats.

Sci—Fri PM: Topics — 04: What if bystander effects influence cell kill within a target volume? Potential consequences of dose heterogeneity on TCP and EUD on intermediate risk prostate patients

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

Balderson, M.J.; Kirkby, C.; Department of Medical Physics, Tom Baker Cancer Centre, Calgary, Alberta

In vitro evidence has suggested that radiation induced bystander effects may enhance non-local cell killing which may influence radiotherapy treatment planning paradigms. This work applies a bystander effect model, which has been derived from published in vitro data, to calculate equivalent uniform dose (EUD) and tumour control probability (TCP) and compare them with predictions from standard linear quadratic (LQ) models that assume a response due only to local absorbed dose. Comparisons between the models were made under increasing dose heterogeneity scenarios. Dose throughout the CTV was modeled with normal distributions, where the degree of heterogeneity was then dictated by changingmore » the standard deviation (SD). The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. The bystander model suggests a moderate degree of dose heterogeneity yields as good or better outcome compared to a uniform dose in terms of EUD and TCP. Intermediate risk prostate prescriptions of 78 Gy over 39 fractions had maximum EUD and TCP values at SD of around 5Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. The bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV is varies. The results suggest the potential for allowing some degree of dose heterogeneity within a CTV, although further investigations of the assumptions of the bystander model are warranted.« less

Improved dosimetry techniques for intravascular brachytherapy

NASA Astrophysics Data System (ADS)

Sehgal, Varun

Coronary artery disease leads to the accumulation of atheromatous plaque leading to coronary stenosis. Coronary intervention techniques such as balloon angioplasty and atherectomy are used to address coronary stenosis and establish a stable lumen thus enhancing blood flow to the myocardium. Restenosis or re-blockage of the arteries is a major limitation of the above mentioned interventional techniques. Neointimal hyperplasia or proliferation of cells in response to the vascular injury as a result of coronary intervention is considered to be one of the major causes of restenosis. Recent studies indicated that irradiation of the coronary lesion site, with radiation doses ranging from 15 to 30 Gy, leads to diminishing neointimal hyperplasia with subsequent reduction in restenosis. The radiation dose is given by catheter-based radiation delivery systems using beta-emitters 90Sr/90Y, 32P and gamma-emitting 192Ir among others. However the dose schema used for dose prescription for these sources are relatively simplistic, and are based on calculations using uniform homogenous water or tissue media and simple cylinder geometry. Stenotic coronary vessels are invariably lined with atheromatous plaque of heterogeneous composition, the radiation dose distribution obtained from such dosimetry data can cause significant variations in the actual dose received by a given patient. Such discrepancies in dose calculation can introduce relatively large uncertainties in the limits of dose window for effective and safe application of intravascular brachytherapy, and consequently in the clinical evaluation of the efficacy of this modality. In this research study we investigated the effect of different geometrical and material heterogeneities, including residual plaque, catheter non-centering, lesion eccentricity and cardiac motion on the radiation dose delivered at the lesion site. Correction factors including dose perturbation factors and dose variation factors have been calculated using Monte Carlo-based radiation transport code MCNP and tabulated for a range of different coronary geometries and different radionuclides. A new technique using imaging techniques such as intravascular ultrasound and angiography to assess dosimetry for realistic coronary arteries is also introduced. The results indicate the need for accurate assessment of post-intervention clinical measurements such as minimal lumen diameter and residual plaque burden and incorporating them into dose calculations.

Using probabilistic criteria in an assessment of the potential radiological consequences of the decommissioning of a nuclear research reactor

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

Wallner, Christian; Rall, Anna-Maria; Thummerer, Severin

In order to assess the risk of radiological consequences of incidents and accidents in nuclear facilities it is important to contemplate their frequency of occurrence. It has to be shown that incidents and accidents occur sufficiently seldom according to their radiological consequences i. e. the occurrence frequency of radiological doses has to be limited. This is even demanded by the German radiation protection ordinance (StrlSchV), which says that in nuclear facilities other than nuclear power plants (NPP) in operation and for decommissioning, the occurrence frequency of incidents and accidents shall be contemplated in order to prove the design of safetymore » measures and safety installations. Based on the ideas of the ICRP64, we developed a risk based assessment concept for nuclear facilities, which fulfils the requirements of the German regulations concerning dose limits in normal operation and design basis accidents. The general use of the concept is dedicated to nuclear facilities other than nuclear power plants (NPP) in operation and for decommissioning, where the regulation of risk assessment is less sophisticated. The concept specifies occurrence frequency limits for radiation exposure dose ranges, i. e. the occurrence frequency of incidents and accidents has to be limited according to their radiological effects. To apply this concept, scenarios of incidents and accidents are grouped in exposition classes according to their resulting potential effective dose to members of the general public. The occurrence frequencies of the incidents and accidents are summarized in each exposition class whereas the sum must not exceed the frequency limits mentioned above. In the following we introduce the application of this concept in the assessment of the potential radiological consequences of the decommissioning of a nuclear research reactor. We carried out this assessment for the licensing process of the decommissioning on behalf of German authorities. (authors)« less

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

PubMed

Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

2018-05-01

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

Dose-dependent changes in the levels of free and peptide forms of hydroxyproline in human plasma after collagen hydrolysate ingestion.

PubMed

Shigemura, Yasutaka; Kubomura, Daiki; Sato, Yoshio; Sato, Kenji

2014-09-15

The presence of hydroxyproline (Hyp)-containing peptides in human blood after collagen hydrolysate ingestion is believed to exert beneficial effects on human health. To estimate the effective beneficial dose of these peptides, we examined the relationship between ingested dose and food-derived Hyp levels in human plasma. Healthy volunteers (n=4) ingested 30.8, 153.8 and 384.6 mg per kg body weight of collagen hydrolysate. The average plasma concentration of Hyp-containing peptides was dose-dependent, reaching maximum levels of 6.43, 20.17 and 32.84 nmol/ml following ingestion of 30.8, 153.8 and 384.6-mg doses of collagen hydrolysate, respectively. Ingesting over 153.8 mg of collagen hydrolysate significantly increased the average concentrations of the free and peptide forms of Hyp in plasma. The Hyp absorption limit was not reached with ingestion of as much as 384.6 mg of collagen hydrolysate. These finding suggest that ingestion of less than 30.8 mg of collagen hydrolysate is not effective for health benefits. Copyright © 2014 Elsevier Ltd. All rights reserved.

A generic biokinetic model for noble gases with application to radon

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

Leggett, Richard Wayne; Marsh, James; Gregoratto, Demetrio

The International Commission for Radiological Protection (ICRP) currently uses a dose conversion coefficient to calculate effective dose per unit exposure to radon and its progeny. The coefficient is derived by dividing the detriment associated with unit exposure to radon, as estimated from epidemiological studies, by the detriment per unit effective dose, as estimated mainly from atomic bomb survivor data and animal studies. In a recent statement the ICRP indicated that future guidance on exposure to radon and its progeny will be developed in the same way as guidance for any other radionuclide. That is, intake of radon and progeny willmore » be limited on the basis of effective dose coefficients derived from biokinetic and dosimetric models. This paper proposes a biokinetic model for systemic (absorbed) radon for use in the calculation of dose coefficients for inhaled or ingested radon. The model is based largely on physical laws governing transfer of a non-reactive and soluble gas between materials. Model predictions are shown to be consistent with results of controlled studies of the fate of internally deposited radon in human subjects.« less

Correlation of Noncancer Benchmark Doses in Short- and Long-Term Rodent Bioassays.

PubMed

Kratchman, Jessica; Wang, Bing; Fox, John; Gray, George

2018-05-01

This study investigated whether, in the absence of chronic noncancer toxicity data, short-term noncancer toxicity data can be used to predict chronic toxicity effect levels by focusing on the dose-response relationship instead of a critical effect. Data from National Toxicology Program (NTP) technical reports have been extracted and modeled using the Environmental Protection Agency's Benchmark Dose Software. Best-fit, minimum benchmark dose (BMD), and benchmark dose lower limits (BMDLs) have been modeled for all NTP pathologist identified significant nonneoplastic lesions, final mean body weight, and mean organ weight of 41 chemicals tested by NTP between 2000 and 2012. Models were then developed at the chemical level using orthogonal regression techniques to predict chronic (two years) noncancer health effect levels using the results of the short-term (three months) toxicity data. The findings indicate that short-term animal studies may reasonably provide a quantitative estimate of a chronic BMD or BMDL. This can allow for faster development of human health toxicity values for risk assessment for chemicals that lack chronic toxicity data. © 2017 Society for Risk Analysis.

Effects of an oral iron chelator, deferasirox, on advanced hepatocellular carcinoma.

PubMed

Saeki, Issei; Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Maeda, Masaki; Fujisawa, Koichi; Iwamoto, Takuya; Matsumoto, Toshihiko; Hidaka, Isao; Ishikawa, Tsuyoshi; Uchida, Koichi; Tani, Kenji; Sakaida, Isao

2016-10-28

To evaluate the inhibitory effects of deferasirox (DFX) against hepatocellular carcinoma (HCC) through basic and clinical studies. In the basic study, the effect of DFX was investigated in three hepatoma cell lines (HepG2, Hep3B, and Huh7), as well as in an N-nitrosodiethylamine-induced murine HCC model. In the clinical study, six advanced HCC patients refractory to chemotherapy were enrolled. The initial dose of DFX was 10 mg/kg per day and was increased by 10 mg/kg per day every week, until the maximum dose of 30 mg/kg per day. The duration of a single course of DFX therapy was 28 consecutive days. In the event of dose-limiting toxicity (according to the Common Terminology Criteria for Adverse Events v.4.0), DFX dose was reduced. Administration of DFX inhibited the proliferation of hepatoma cell lines and induced the activation of caspase-3 in a dose-dependent manner in vitro . In the murine model, DFX treatment significantly suppressed the development of liver tumors ( P < 0.01), and significantly upregulated the mRNA expression levels of hepcidin ( P < 0.05), transferrin receptor 1 ( P < 0.05), and hypoxia inducible factor-1α ( P < 0.05) in both tumor and non-tumor tissues, compared with control mice. In the clinical study, anorexia and elevated serum creatinine were observed in four and all six patients, respectively. However, reduction in DFX dose led to decrease in serum creatinine levels in all patients. After the first course of DFX, one patient discontinued the therapy. We assessed the tumor response in the remaining five patients; one patient exhibited stable disease, while four patients exhibited progressive disease. The one-year survival rate of the six patients was 17%. We demonstrated that DFX inhibited HCC in the basic study, but not in the clinical study due to dose-limiting toxicities.

Simplifying anemia management in hemodialysis patients: ESAs administered at longer dosing intervals can enhance opportunities to provide patient-focused care.

PubMed

Schiller, Brigitte; Besarab, Anatole

2011-08-01

To review issues and challenges in caring for hemodialysis patients with anemia of chronic kidney disease, specifically focusing on the effects of longer erythropoiesis-stimulating agent (ESA) dosing intervals on processes of care. PubMed searches were performed limited to the last 10 years to February 2011, focusing on articles in English that were 'clinical trials,' assessed processes of care, measured associations of hemoglobin (Hb) with outcomes, and explored/analyzed extended dosing intervals of ESAs in hemodialysis patients and recommendations for increasing the quality of care of these patients. Some limitations included the fact that a meta-analysis was not conducted; many studies were associative and therefore unable to prove causality; and none of the clinical trials directly compared the impact of more frequent or less frequent ESA dosing strategies on patient care and outcomes. Progress over the past several decades has been substantial; however, unmet needs remain and there is room for improvement in efficiencies of care. Many patients fail to meet Hb targets, and nephrology professionals' time is consumed with preparing, administering, and monitoring therapy. Direct interaction between patients and care providers has been lost as attention has shifted to 'cost-effective' (not necessarily patient-centered) ways to deliver care. Use of ESAs at longer dosage intervals represents one opportunity to improve efficiency of care. Newer ESAs have been developed for less frequent dosing. Once-monthly dosing decreases time spent administering/monitoring therapy and allows nephrology professionals to provide comprehensive renal care, wherein the patient rather than task-oriented processes becomes the primary focus. A fragmented, uncoordinated care-delivery model heightens the urgency to systematically address issues related to delivery of care and improve efficiencies in anemia management as part of the patient-centered approach. ESAs designed for administration at longer intervals may effectively and reliably achieve Hb targets with once-monthly dosing, thereby decreasing time spent administering/monitoring therapy.

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.

Space radiation dosimetry in low-Earth orbit and beyond.

PubMed

Benton, E R; Benton, E V

2001-09-01

Space radiation dosimetry presents one of the greatest challenges in the discipline of radiation protection. This is a result of both the highly complex nature of the radiation fields encountered in low-Earth orbit (LEO) and interplanetary space and of the constraints imposed by spaceflight on instrument design. This paper reviews the sources and composition of the space radiation environment in LEO as well as beyond the Earth's magnetosphere. A review of much of the dosimetric data that have been gathered over the last four decades of human space flight is presented. The different factors affecting the radiation exposures of astronauts and cosmonauts aboard the International Space Station (ISS) are emphasized. Measurements made aboard the Mir Orbital Station have highlighted the importance of both secondary particle production within the structure of spacecraft and the effect of shielding on both crew dose and dose equivalent. Roughly half the dose on ISS is expected to come from trapped protons and half from galactic cosmic rays (GCRs). The dearth of neutron measurements aboard LEO spacecraft and the difficulty inherent in making such measurements have led to large uncertainties in estimates of the neutron contribution to total dose equivalent. Except for a limited number of measurements made aboard the Apollo lunar missions, no crew dosimetry has been conducted beyond the Earth's magnetosphere. At the present time we are forced to rely on model-based estimates of crew dose and dose equivalent when planning for interplanetary missions, such as a mission to Mars. While space crews in LEO are unlikely to exceed the exposure limits recommended by such groups as the NCRP, dose equivalents of the same order as the recommended limits are likely over the course of a human mission to Mars. c2001 Elsevier Science B.V. All rights reserved.

Leaded eyeglasses substantially reduce radiation exposure of the surgeon's eyes during acquisition of typical fluoroscopic views of the hip and pelvis.

PubMed

Burns, Sean; Thornton, Raymond; Dauer, Lawrence T; Quinn, Brian; Miodownik, Daniel; Hak, David J

2013-07-17

Despite recommendations to do so, few orthopaedists wear leaded glasses when performing operative fluoroscopy. Radiation exposure to the ocular lens causes cataracts, and regulatory limits for maximum annual occupational exposure to the eye continue to be revised downward. Using anthropomorphic patient and surgeon phantoms, radiation dose at the surgeon phantom's lens was measured with and without leaded glasses during fluoroscopic acquisition of sixteen common pelvic and hip views. The magnitude of lens dose reduction from leaded glasses was calculated by dividing the unprotected dose by the dose measured behind leaded glasses. On average, the use of leaded glasses reduced radiation to the surgeon phantom's eye by tenfold, a 90% reduction in dose. However, there was widespread variation in the amount of radiation that reached the phantom surgeon's eye among the various radiographic projections we studied. Without leaded glasses, the dose measured at the surgeon's lens varied more than 250-fold among these sixteen different views. In addition to protecting the surgeon's eye from the deleterious effects of radiation, the use of leaded glasses could permit an orthopaedist to perform fluoroscopic views on up to ten times more patients before reaching the annual dose limit of 20 mSv of radiation to the eye recommended by the International Commission on Radiological Protection. Personal safety and adherence to limits of occupational radiation exposure should compel orthopaedists to wear leaded glasses for fluoroscopic procedures if other protective barriers are not in use. Leaded glasses are a powerful tool for reducing the orthopaedic surgeon's lens exposure to radiation during acquisition of common intraoperative fluoroscopic views.

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

Podonsky, Glenn S.

The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2012 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protectionmore » of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past 5-year period, the occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site. As an indicator of the overall amount of radiation dose received during the conduct of operations at DOE, the report includes information on collective total effective dose (TED). The TED is comprised of the effective dose (ED) from external sources, which includes neutron and photon radiation, and the internal committed effective dose (CED), which results from the intake of radioactive material into the body. The collective ED from photon exposure decreased by 23% between 2011 and 2012, while the neutron dose increased by 5%. The internal dose components of the collective TED decreased by 7%. Over the past 5-year period, 99.99% of the individuals receiving measurable TED have received doses below the 2 roentgen equivalent in man (rems) (20 millisievert [mSv]) TED administrative control level (ACL), which is well below the DOE regulatory limit of 5 rems (50 mSv) TED annually. The occupational radiation exposure records show that in 2012, DOE facilities continued to comply with DOE dose limits and ACLs and worked to minimize exposure to individuals. The DOE collective TED decreased 17.1% from 2011 to 2012. The collective TED decreased at three of the five sites with the largest collective TED. u Idaho Site – Collective dose reductions were achieved as a result of continuing improvements at the Advanced Mixed Waste Treatment Project (AMWTP) through the planning of drum movements that reduced the number of times a container is handled; placement of waste containers that created highradiation areas in a centralized location; and increased worker awareness of high-dose rate areas. In addition, Idaho had the largest decrease in the total number of workers with measurable TED (1,143 fewer workers). u Hanford Site (Hanford) – An overall reduction of decontamination and decommissioning (D&D) activities at the Plutonium Finishing Plant (PFP) and Transuranic (TRU) retrieval activities resulted in collective dose reductions. u Savannah River Site (SRS) – Reductions were achieved through ALARA initiatives employed site wide. The Solid Waste Management Facility used extended specialty tools, cameras and lead shield walls to facilitate removal of drums. These tools and techniques reduce exposure time through improved efficiency, increase distance from the source of radiation by remote monitoring, shield the workers to lower the dose rate, and reduce the potential for contamination and release of material through repacking of waste. Overall, from 2011 to 2012, there was a 19% decrease in the number of workers with measurable dose. Furthermore, due to a slight decrease in both the DOE workforce (7%) and monitored workers (10%), the ratio of workers with measurable doses to monitored workers decreased to 13%. Another primary indicator of the level of radiation exposure covered in this report is the average measurable dose, which normalizes the collective dose over the population of workers who actually received a measurable dose. The average measurable TED increased by 3% from 2011 to 2012. Additional analyses show that the dose distribution in 2012 was similar to the distribution in 2011. In 2012, 13% of the monitored workers received a measurable TED and the average measurable TED, 0.069 rem, was less than 2% of the DOE limit. From 2011 to 2012, the collective TED and the number of individuals with measurable TED decreased 17.1% and 19%, respectively. These decreases were mainly due to an overall reduction of D&D activities at the PFP and TRU retrieval activities at Hanford; a 78% decrease in the number of targeted waste drums that were processed at the Idaho Site’s Accelerated Retrieval Project (ARP) from 5,566 drums in 2011 to a total of 1,211 drums processed in 2012; and ALARA initiatives employed site wide at SRS. In addition, the decreases were the result of decreased American Recovery and Reinvestment Act (ARRA) activities and continuing D&D, particularly at the DOE sites that comprise the majority of DOE collective dose. Over the past 5 years, the size of the monitored workforce has remained at a fairly stable level (within 12%), while the collective dose has varied up to 37%. No reported doses exceeded the DOE occupational limit of 5 rems TED in 2012 and no reported doses exceeded the DOE ACL of 2 rems TED.« less

Review of proton pump inhibitors for the initial treatment of heartburn: is there a dose ceiling effect?

PubMed

Kushner, Pamela R; Peura, David A

2011-05-01

Proton pump inhibitors (PPIs) are widely used in clinical practice. However, concerns have been expressed about their long-term use, particularly with regard to bone health, Clostridium difficile infections, and drug interactions with platelet aggregation inhibitors. There has been limited guidance for clinicians concerning appropriate dose selection of PPIs for the initial treatment of heartburn. This review explored whether published clinical trials provide evidence of a ceiling above which higher PPI doses do not provide additional clinical benefit over the lowest approved dose. All articles of randomized, controlled clinical trials in nonerosive gastroesophageal reflux disease (GERD) in which the effects of two or more doses of the same PPI on symptomatic relief of heartburn were quantified as a study endpoint were identified and analyzed through PubMed searches up to the end of September 2010. The majority of trials evaluated provided no evidence that higher PPI doses were superior to the lowest approved dose for the initial treatment of heartburn. There were no clinically relevant findings with respect to dose dependence and safety outcomes in these studies. Efficacy outcomes from the trials suggest there may be a dose ceiling effect and highlight the need for further research on the use of the lowest effective PPI doses as an appropriate strategy in the initial treatment of uncomplicated heartburn. Observational studies and some meta-analyses have suggested that long-term PPI pharmacotherapy might be associated with safety concerns, which necessitate the periodic evaluation of therapeutic benefit in terms of symptom resolution and regimen tolerability. However, evidence to date suggests that use of the lowest effective dose for the indication is not associated with significant adverse events, particularly in the short term. Clinical practice suggests that patients requiring long-term treatment should be maintained on the lowest dose necessary to control symptoms, and monitored for potentially confounding factors that may lead to safety concerns.

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.

PubMed

Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5-3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. Published by Elsevier Inc.

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

PubMed Central

Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

2014-01-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; Mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA- activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32%–87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. PMID:24971906

Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I.

PubMed

Wheldon, T E; O'Donoghue, J A; Hilditch, T E; Barrett, A

1988-02-01

A simple analysis is developed to evaluate the likely effectiveness of treatment of micrometastases by antibody-targeted 131I. Account is taken of the low levels of tumour uptake of antibody-conjugated 131I presently achievable and of the "energy wastage" in targeting microscopic tumours with a radionuclide whose disintegration energy is widely dissipated. The analysis shows that only modest doses can be delivered to micrometastases when total body dose is restricted to levels which allow recovery of bone marrow. Much higher doses could be delivered to micrometastases when bone marrow rescue is used. A rationale is presented for targeted systemic radiotherapy used in combination with external beam total body irradiation (TBI) and bone marrow rescue. This has some practical advantages. The effect of the targeted component is to impose a biological non-uniformity on the total body dose distribution with regions of high tumour cell density receiving higher doses. Where targeting results in high doses to particular normal organs (e.g. liver, kidney) the total dose to these organs could be kept within tolerable limits by appropriate shielding of the external beam radiation component of the treatment. Greater levels of tumour cell kill should be achievable by the combination regime without any increase in normal tissue damage over that inflicted by conventional TBI. The predicted superiority of the combination regime is especially marked for tumours just below the threshold for detectability (e.g. approximately 1 mm-1 cm diameter). This approach has the advantage that targeted radiotherapy provides only a proportion of the total body dose, most of which is given by a familiar technique. The proportion of dose given by the targeted component could be increased as experience is gained. The predicted superiority of the combination strategy should be experimentally testable using laboratory animals. Clinical applications should be cautiously approached, with due regard to the limitations of the theoretical analysis.

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.

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

PubMed

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

2014-02-01

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

Long-active granulocyte colony-stimulating factor for peripheral blood hematopoietic progenitor cell mobilization.

PubMed

Martino, Massimo; Laszlo, Daniele; Lanza, Francesco

2014-06-01

Peg-filgrastim (PEG-FIL), a polyethylene glycol-conjugated form of granulocyte colony-stimulating factor (G-CSF), has been introduced in clinical practice and is effective in shortening the time of neutropenia after cytotoxic chemotherapy. G-CSF has emerged as the preferred cytokine for hematopoietic progenitor cells' (HPC) mobilization. Nevertheless, data on the ability of PEG-FIL in this field have been published. We review publications in the field with the goal of providing an overview of this approach. PEG-FIL may be able to mobilize CD34(+) cells in a more timely fashion than G-CSF, with the advantages of only a single-dose administration, an earlier start and a reduction in the number of apheresis procedures. The main controversies concern the dosage of the drug and the optimal dose. In the context of chemo-mobilization, a single dose of 6 mg PEG-FIL seems effective in terms of HPC's mobilization and there is no increase in this effect if the dose is doubled to 12 mg. Steady-state mobilization requires higher doses of PEG-FIL and this approach is not cost-effective when compared with G-CSF. The experiences with PEG-FIL in the healthy donor setting are very limited.

Investigation of J-shaped dose-responses induced by exposure to the alkylating agent N-methyl-N-nitrosourea.

PubMed

Chapman, Katherine E; Hoffmann, George R; Doak, Shareen H; Jenkins, Gareth J S

2017-07-01

Hormesis is defined as a biphasic dose-response where biological effects of low doses of a stressor demonstrate the opposite effect to high-dose effects of the same stressor. Hormetic, or J-shaped, dose-response relationships are relatively rarely observed in toxicology, resulting in a limited understanding and even some skepticism of the concept. Low dose-response studies for genotoxicity endpoints have been performed at Swansea University for over a decade. However, no statistically significant decreases below control genotoxicity levels have been detected until recently. A hormetic-style dose-response following a 24h exposure to the alkylating agent N-methyl-N-nitrosourea (MNU) was observed in a previous study for HPRT mutagenesis in the human lymphoblastoid cell line AHH-1. A second recent study demonstrated a J-shaped dose-response for the induction of micronuclei by MNU in a 24h treatment in a similar test system. Following mechanistic investigations, it was hypothesized that p53 may be responsible for the observed hormetic phenomenon. As genotoxic carcinogens are a major causative factor of many cancers, consideration of hormesis in carcinogenesis could be important in safety assessment. The data examined here offer possible insights into hormesis, including its estimated prevalence, underlying mechanisms and lack of generalizability. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Clonidine Reduces Nociceptive Responses in Mouse Orofacial Formalin Model: Potentiation by Sigma-1 Receptor Antagonist BD1047 without Impaired Motor Coordination.

PubMed

Yoon, Seo-Yeon; Kang, Suk-Yun; Kim, Hyun-Woo; Kim, Hyung-Chan; Roh, Dae-Hyun

2015-01-01

Although the administration of clonidine, an alpha-2 adrenoceptor agonist, significantly attenuates nociception and hyperalgesia in several pain models, clinical trials of clonidine are limited by its side effects such as drowsiness, hypotension and sedation. Recently, we determined that the sigma-1 receptor antagonist BD1047 dose-dependently reduced nociceptive responses in a mouse orofacial formalin model. Here we examined whether intraperitoneal injection of clonidine suppressed the nociceptive responses in the orofacial formalin test, and whether co-administration with BD1047 enhances lower-dose clonidine-induced anti-nociceptive effects without the disruption of motor coordination and blood pressure. Formalin (5%, 10 µL) was subcutaneously injected into the right upper lip, and the rubbing responses with the ipsilateral fore- or hind-paw were counted for 45 min. Clonidine (10, 30 or 100 µg/kg) was intraperitoneally administered 30 min before formalin injection. Clonidine alone dose-dependently reduced nociceptive responses in both the first and second phases. Co-localization for alpha-2A adrenoceptors and sigma-1 receptors was determined in trigeminal ganglion cells. Interestingly, the sub-effective dose of BD1047 (3 mg/kg) significantly potentiated the anti-nociceptive effect of lower-dose clonidine (10 or 30 µg/kg) in the second phase. In particular, the middle dose of clonidine (30 µg/kg) in combination with BD1047 produced an anti-nociceptive effect similar to that of the high-dose clonidine, but without a significant motor dysfunction or hypotension. In contrast, mice treated with the high dose of clonidine developed severe impairment in motor coordination and blood pressure. These data suggest that a combination of low-dose clonidine with BD1047 may be a novel and safe therapeutic strategy for orofacial pain management.

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

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

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

Zhu, M.; Kearfott, K.J.

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

The comparative short-term effectiveness of iron dosing and formulations in US hemodialysis patients.

PubMed

Kshirsagar, Abhijit V; Freburger, Janet K; Ellis, Alan R; Wang, Lily; Winkelmayer, Wolfgang C; Brookhart, M Alan

2013-06-01

Intravenous iron is used widely in hemodialysis, yet there are limited data on the effectiveness of contemporary dosing strategies or formulation type. We conducted a retrospective cohort study using data from the clinical database of a large dialysis provider (years 2004-2008) merged with administrative data from the US Renal Data System to compare the effects of intravenous iron use on anemia management. Dosing comparisons were bolus (consecutive doses ≥100 mg exceeding 600 mg during 1 month) versus maintenance (all other iron doses during the month); and high (>200 mg over 1 month) versus low dose (≤200 mg over 1 month). Formulation comparison was administration of ferric gluconate versus iron sucrose over 1 month. Outcomes were hemoglobin, epoetin dose, transferrin saturation, and serum ferritin during 6 weeks of follow-up. We identified 117,050 patients for the dosing comparison, and 66,207 patients for the formulation comparison. Bolus dosing was associated with higher average adjusted hemoglobin (+0.23 g/dL; 95% confidence interval [CI], 0.21-0.26), transferrin saturation (+3.31%; 95% CI, 2.99-3.63), serum ferritin (+151 μg/L; 95% CI, 134.9-168.7), and lower average epoetin dose (-464 units; 95% CI, -583 to -343) compared with maintenance. Similar trends were observed with high-dose iron versus low-dose. Iron sucrose was associated with higher adjusted average hemoglobin (+0.16 g/dL; 95% CI, 0.12-0.19) versus ferric gluconate. Strategies favoring large doses of intravenous iron or iron sucrose lead to improved measures of anemia management. These potential benefits should be weighed against risks, which currently remain incompletely characterized. Copyright © 2013 Elsevier Inc. All rights reserved.

Autonomous functioning thyroid nodules and 131I in diagnosis and therapy after 50 years of experience: what is still open to debate?

PubMed

Ronga, Giuseppe; Filesi, Mauro; D'Apollo, Rosaria; Toteda, Maria; Di Nicola, Angelo Domenico; Colandrea, Marzia; Travascio, Laura; Vestri, Anna Rita; Montesano, Teresa

2013-05-01

Autonomous functioning thyroid nodules (AFTN), defined as "hot nodules" at thyroid scan, are often cured by radioiodine treatment. The aim of our study was to investigate the long-term outcome in patients treated with an 131I calculated dose, to identify a possible "size-tailored" dose, and to simplify follow-up procedures. Retrospective analysis was carried out on 1402 cases, covering a period of 50 years, of AFTN treated with an 131I calculated dose. Our study focused on nodular size and mean administered dose. Concordance between thyroid scan and serum TSH levels at 3-6 months from treatment was considered. A single 131I dose was effective for the vast majority of patients (93%). The outcome was influenced by nodular size. On the basis of the Italian dose limit for outpatient treatment, our population was divided into subgroups according to administered doses (more or less than 16 mCi) and nodular dimensions: no differences in outcome were observed for each class of nodule size. A dose ≤10 mCi was effective on the smaller nodules (50.1% of our population). The agreement between TSH and scan after treatment was 90.3% at 3 months and 94.5% at 6 months. 131I therapy with a calculated dose is an effective treatment of AFTN. If a fixed dose is chosen, 16 mCi is often resolutive and for nodules <3 cm a dose of 10 mCi can suffice. Nodules >5 cm are eligible for surgery. TSH is the only parameter required to evaluate the outcome.

Effective dose in the manufacturing process of rutile covered welding electrodes.

PubMed

Herranz, M; Rozas, S; Pérez, C; Idoeta, R; Núñez-Lagos, R; Legarda, F

2013-03-01

Shielded metal arc welding using covered electrodes is the most common welding process. Sometimes the covering contains naturally occurring radioactive materials (NORMs). In Spain the most used electrodes are those covered with rutile mixed with other materials. Rutile contains some detectable natural radionuclides, so it can be considered a NORM. This paper mainly focuses on the use of MCNP (Monte Carlo N-Particle Transport Code) as a predictive tool to obtain doses in a factory which produces this type of electrode and assess the radiological impact in a specific facility after estimating the internal dose.To do this, in the facility, areas of highest radiation and positions of workers were identified, radioactive content of rutile and rutile covered electrodes was measured, and, considering a worst possible scenario, external dose at working points has been calculated using MCNP. This procedure has been validated comparing the results obtained with those from a pressurised ionisation chamber and TLD dosimeters. The internal dose has been calculated using DCAL (dose and risk calculation). The doses range between 8.8 and 394 μSv yr(-1), always lower than the effective dose limit for the public, 1 mSv yr(-1). The highest dose corresponds to the mixing area.

Occupational radiation dose to eyes from interventional radiology procedures in light of the new eye lens dose limit from the International Commission on Radiological Protection

PubMed Central

Walsh, C; Gallagher, A; Dowling, A; Guiney, M; Ryan, J M; McEniff, N; O'Reilly, G

2015-01-01

Objective: In 2011, the International Commission on Radiological Protection (ICRP) recommended a substantial reduction in the equivalent dose limit for the lens of the eye, in line with a reduced threshold of absorbed dose for radiation-induced cataracts. This is of particular relevance in interventional radiology (IR) where it is well established that staff doses can be significant, however, there is a lack of data on IR eye doses in terms of Hp(3). Hp(3) is the personal dose equivalent at a depth of 3 mm in soft tissue and is used for measuring lens dose. We aimed to obtain a reliable estimate of eye dose to IR operators. Methods: Lens doses were measured for four interventional radiologists over a 3-month period using dosemeters specifically designed to measure Hp(3). Results: Based on their typical workloads, two of the four interventional radiologists would exceed the new ICRP dose limit with annual estimated doses of 31 and 45 mSv to their left eye. These results are for an “unprotected” eye, and for IR staff who routinely wear lead glasses, the dose beneath the glasses is likely to be significantly lower. Staff eye dose normalized to patient kerma–area product and eye dose per procedure have been included in the analysis. Conclusion: Eye doses to IR operators have been established using a dedicated Hp(3) dosemeter. Estimated annual doses have the potential to exceed the new ICRP limit. Advances in knowledge: We have estimated lens dose to interventional radiologists in terms of Hp(3) for the first time in an Irish hospital setting. PMID:25761211

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.

American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance.

PubMed

Manchikanti, Laxmaiah; Abdi, Salahadin; Atluri, Sairam; Balog, Carl C; Benyamin, Ramsin M; Boswell, Mark V; Brown, Keith R; Bruel, Brian M; Bryce, David A; Burks, Patricia A; Burton, Allen W; Calodney, Aaron K; Caraway, David L; Cash, Kimberly A; Christo, Paul J; Damron, Kim S; Datta, Sukdeb; Deer, Timothy R; Diwan, Sudhir; Eriator, Ike; Falco, Frank J E; Fellows, Bert; Geffert, Stephanie; Gharibo, Christopher G; Glaser, Scott E; Grider, Jay S; Hameed, Haroon; Hameed, Mariam; Hansen, Hans; Harned, Michael E; Hayek, Salim M; Helm, Standiford; Hirsch, Joshua A; Janata, Jeffrey W; Kaye, Alan D; Kaye, Adam M; Kloth, David S; Koyyalagunta, Dhanalakshmi; Lee, Marion; Malla, Yogesh; Manchikanti, Kavita N; McManus, Carla D; Pampati, Vidyasagar; Parr, Allan T; Pasupuleti, Ramarao; Patel, Vikram B; Sehgal, Nalini; Silverman, Sanford M; Singh, Vijay; Smith, Howard S; Snook, Lee T; Solanki, Daneshvari R; Tracy, Deborah H; Vallejo, Ricardo; Wargo, Bradley W

2012-07-01

Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. ( good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. ( limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. ( good to fair) D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. ( good) 2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. ( good) B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient, to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. ( good) C) Stratify patients into one of the 3 risk categories - low, medium, or high risk. D) A pain management consultation, may assist non-pain physicians, if high-dose opioid therapy is utilized. ( fair) 3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. ( good) 4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. ( good) 5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. ( fair) B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. ( fair to limited) 6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. ( fair) 7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. ( fair for short-term effectiveness, limited for long-term effectiveness) B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. ( fair) C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. ( good) 8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. ( limited) B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. ( fair) 9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. ( fair) 10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. ( good) 11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. ( fair). The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Naloxegol: A Novel Therapy in the Management of Opioid-Induced Constipation.

PubMed

Jones, Rachel; Prommer, Eric; Backstedt, David

2016-11-01

Opioid-related bowel dysfunction is a common and potentially severe adverse effect from treatment with opioid analgesics. Its development is not dose related, nor do patients develop tolerance. Opioid-induced constipation (OIC) can lead to fecal impaction, bowel obstruction, and bowel perforation as well as noncompliance with opioid analgesics and poor quality of life. Routine administration of laxatives is necessary to maintain bowel function, and, in refractory cases, other modalities must be pursued. Available options are limited but include peripherally acting μ-opioid receptor antagonists (PAMORAs), including methylnaltrexone. Naloxegol is a newly developed PAMORA that is available through the oral route. At the therapeutic dose of 25 mg daily, naloxegol is effective and safe, with a limited side effect profile and is associated with preservation of centrally mediated analgesia. In this article, we discuss the pharmacokinetics, pharmacodynamics, adverse effects, clinical trials, and cost considerations of naloxegol. Finally, we discuss its potential role as a novel key treatment for OIC in palliative medicine patients. © The Author(s) 2015.

Solar particle dose rate buildup and distribution in critical body organs

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

Microbial quality evaluation and effective decontamination of nutraceutically valued lotus seeds by electron beams and gamma irradiation

NASA Astrophysics Data System (ADS)

Bhat, Rajeev; Sridhar, K. R.; Karim, A. A.

2010-09-01

Lotus seeds are nutraceutically valued natural plant produce, which succumbs to microbial contamination, predominantly to toxigenic moulds. Results of the present study revealed seed coat portion to harbor higher proportion of microbial load, particularly fungi than cotyledon portion. Among the mycotoxins analyzed, aflatoxins (B 1, B 2, G 1 and G 2) were below detectable limits, while the seeds were devoid of Ochratoxin-A (OTA). Application of different doses of electron beam and gamma irradiation (0, 2.5, 5, 7.5, 10, 15 and 30 kGy) for decontamination purpose revealed significant dose-dependent decrease in the fungal contaminants ( P<0.05). However, the contaminant yeasts could survive up to 10 kGy dose, which could be completely eliminated at 15 kGy. From the results obtained, a dose range between 10 and 15 kGy is recommended for complete decontamination, as these doses have also been shown earlier to have minimal effects on nutritional and functional properties of lotus seeds.

Plasma Membrane Permeabilization by 60- and 600-ns Electric Pulses Is Determined by the Absorbed Dose

PubMed Central

Ibey, Bennett L.; Xiao, Shu; Schoenbach, Karl H.; Murphy, Michael R.; Pakhomov, Andrei G.

2008-01-01

We explored how the effect of plasma membrane permeabilization by nanosecond-duration electric pulses (nsEP) depends on the physical characteristics of exposure. The resting membrane resistance (Rm) and membrane potential (MP) were measured in cultured GH3 and CHO cells by conventional whole-cell patch-clamp technique. Intact cells were exposed to a single nsEP (60 or 600 ns duration, 0-22 kV/cm), followed by patch-clamp measurements after a 2-3 min delay. Consistent with earlier findings, nsEP caused long-lasting Rm decrease, accompanied by the loss of MP. The threshold for these effects was about 6 kV/cm for 60 ns pulses, and about 1 kV/cm for 600 ns pulses. Further analysis established that it was neither pulse duration nor the E-field amplitude per se, but the absorbed dose that determined the magnitude of the biological effect. In other words, exposure to nsEP at either pulse duration caused equal effects if the absorbed doses were equal. The threshold absorbed dose to produce plasma membrane effects in either GH3 or CHO cells at either pulse duration was found to be at or below 10 mJ/g. Despite being determined by the dose, the nsEP effect clearly is not thermal, as the maximum heating at the threshold dose is less than 0.01 °C. The use of the absorbed dose as a universal exposure metric may help to compare and quantify nsEP sensitivity of different cell types and of cells in different physiological conditions. The absorbed dose may also prove to be a more useful metric than the incident E-field in determining safety limits for high peak, lowaverage power EMF emissions. PMID:18839412

Radon activity concentrations and effective doses in ancient Egyptian tombs of the Valley of the Kings.

PubMed

Hafez, A F; Hussein, A S

2001-09-01

Radon concentrations and equilibrium factors were measured in three pharaonic tombs during the year 1998. The tombs, which are open to the public are located in a limestone wadi on the West Bank of the River Nile at Luxor, 650 km south of Cairo. The radon activity concentration and equilibrium factor were measured monthly by two-integral nuclear track detectors (bare and diffusion detectors). Seasonal variation of radon concentrations, with summer maximum and winter minimum were observed in all tombs investigated. The yearly mean radon activity concentrations insidc the tombs ranged from 540 to 3115 Bq m(-3). The mean equilibrium factor over a year was found to be 0.25 and 0.32 inside and at the entrance, respectively. Estimated annual effective doses to tour guides ranged from 0.33 to 1.90 mSv, visitors receive doses from 0.65 to 3.80 microSv per visit. The effective dose to tomb workers did not exceed the 20 mSv yr(-1) limit.

Utilizing placebo mechanisms for dose reduction in pharmacotherapy.

PubMed

Doering, Bettina K; Rief, Winfried

2012-03-01

The knowledge and systematic application of the placebo effect remains limited, although its importance to the treatment of various medical conditions has increasingly been recognized. A possible application of the placebo effect to pharmacotherapy is seen in conditioning processes that aim at a placebo-controlled dose reduction of drugs while maintaining the efficacy of the medical treatment. The pairing of a placebo and a pharmacological agent may achieve satisfactory treatment outcomes in combination with a lower dose of medication. This procedure includes classic and instrumental conditioning processes that involve both conscious and non-conscious information processing. Although recent studies have gathered preliminary evidence for the efficacy of placebo-controlled dose reduction (e.g. in psoriasis and attention deficit hyperactivity disorder [ADHD]), they have also illustrated the difficulties that are inherent to this approach. We critically review previous approaches and discuss designs for clinical trials that seem appropriate to the investigation of conditioned placebo effects in pharmacotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

PubMed

Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B

1992-02-01

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

Effects of gamma irradiation dose-rate on sterile male Aedesaegypti

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection.

PubMed

Namour, Florence; Diderichsen, Paul Matthias; Cox, Eugène; Vayssière, Béatrice; Van der Aa, Annegret; Tasset, Chantal; Van't Klooster, Gerben

2015-08-01

Filgotinib (GLPG0634) is a selective inhibitor of Janus kinase 1 (JAK1) currently in development for the treatment of rheumatoid arthritis and Crohn's disease. While less selective JAK inhibitors have shown long-term efficacy in treating inflammatory conditions, this was accompanied by dose-limiting side effects. Here, we describe the pharmacokinetics of filgotinib and its active metabolite in healthy volunteers and the use of pharmacokinetic-pharmacodynamic modeling and simulation to support dose selection for phase IIB in patients with rheumatoid arthritis. Two trials were conducted in healthy male volunteers. In the first trial, filgotinib was administered as single doses from 10 mg up to multiple daily doses of 200 mg. In the second trial, daily doses of 300 and 450 mg for 10 days were evaluated. Non-compartmental analysis was used to determine individual pharmacokinetic parameters for filgotinib and its metabolite. The overall pharmacodynamic activity for the two moieties was assessed in whole blood using interleukin-6-induced phosphorylation of signal-transducer and activator of transcription 1 as a biomarker for JAK1 activity. These data were used to conduct non-linear mixed-effects modeling to investigate a pharmacokinetic/pharmacodynamic relationship. Modeling and simulation on the basis of early clinical data suggest that the pharmacokinetics of filgotinib are dose proportional up to 200 mg, in agreement with observed data, and support that both filgotinib and its metabolite contribute to its pharmacodynamic effects. Simulation of biomarker response supports that the maximum pharmacodynamic effect is reached at a daily dose of 200 mg filgotinib. Based on these results, a daily dose range up to 200 mg has been selected for phase IIB dose-finding studies in patients with rheumatoid arthritis.

[Driving under the influence of amphetamine and metamphetamine].

PubMed

Lia, Kjersti; Spigset, Olav; Slørdal, Lars

2009-01-15

The CNS stimulatory agents amphetamine and methamphetamine are often detected in blood samples from apprehended subjects driving under the influence of drugs. Relevant literature was identified through searches in PubMed and Google Scholar. The current state of knowledge regarding effects of amphetamines on traffic behaviour is reviewed and discussed. Limited epidemiological data and a small number of experimental studies using low doses of amphetamines are available. Low amphetamine doses have been associated with enhanced performance in studies of sleep-deprived subjects. Theoretical considerations and empirical observations suggest that higher doses may impede performance, but not in accordance with usual concentration/effect relationships. There is a conspicuous lack of data on how to handle cases of driving under the influence of amphetamines.

Use of CroFab antivenin in the management of a very young pediatric copperhead envenomation.

PubMed

Trinh, Hai H; Hack, Jason B

2005-08-01

The use of crotalid Fab antivenin (CroFab) in the treatment of snake envenomations in the pediatric population is still an underexplored area. There are very limited data to confirm the efficacy and safety of dosing children the same as adults and even less information available to evaluate this antivenin use in copperhead snake bites in children. We report the first use of crotalid Fab antivenin in an adult dose for a copperhead snake envenomation in a 2-year-old child. She had rapid resolution of symptoms with no adverse effects. The report serves to increase the literature supporting the current dosing recommendations of crotalid Fab antivenin in very young pediatric patients evidenced by its effectiveness in this patient.

Opioid Challenge Evaluation of Blockade by Extended-Release Naltrexone in Opioid-Abusing Adults: Dose-Effects and Time-Course

PubMed Central

Bigelow, George E.; Preston, Kenzie L.; Schmittner, John; Dong, Qunming; Gastfriend, David R.

2013-01-01

Background Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. Methods Outpatient non-dependent opioid abusers (N=27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300 mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6 mg IM in ascending order at 1-hr intervals [up to 13.5 mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) Visual Analog Scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. Results Blockade of the VAS “any drug effect” response to 3 mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150 and 300 mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300 mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. Conclusions These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment. PMID:22079773

Pulsed-dosing with oral sodium phenylbutyrate increases hemoglobin F in a patient with sickle cell anemia.

PubMed

Hines, Patrick; Dover, George J; Resar, Linda M S

2008-02-01

Increasing hemoglobin F (HbF) appears to be beneficial for patients with sickle cell anemia. We previously demonstrated that daily, oral sodium phenylbutyrate (OSPB) induces HbF synthesis in pediatric and adult patients with hemoglobin SS (HbSS). The high doses and need for daily therapy, however, have limited its use. Here, we report a patient treated with pulsed-dosing of OSPB for over 3 years. This patient developed a modest, but sustained elevation in HbF over the course of therapy without side effects. Although larger studies are needed, this case demonstrates that pulsed-dosing with OSPB enhances HbF synthesis. (c) 2007 Wiley-Liss, Inc.

Modifiers of radiation effects in the eye

NASA Astrophysics Data System (ADS)

Kleiman, Norman J.; Stewart, Fiona A.; Hall, Eric J.

2017-11-01

World events, including the threat of radiological terrorism and the fear of nuclear accidents, have highlighted an urgent need to develop medical countermeasures to prevent or reduce radiation injury. Similarly, plans for manned spaceflight to a near-Earth asteroid or journey to Mars raise serious concerns about long-term effects of space radiation on human health and the availability of suitable therapeutic interventions. At the same time, the need to protect normal tissue from the deleterious effects of radiotherapy has driven considerable research into the design of effective radioprotectors. For more than 70 years, animal models of radiation cataract have been utilized to test the short and long-term efficacy of various radiation countermeasures. While some compounds, most notably the Walter Reed (WR) class of radioprotectors, have reported limited effectiveness when given before exposure to low-LET radiation, the human toxicity of these molecules at effective doses limits their usefulness. Furthermore, while there has been considerable testing of eye responses to X- and gamma irradiation, there is limited information about using such models to limit the injurious effects of heavy ions and neutrons on eye tissue. A new class of radioprotector molecules, including the sulfhydryl compound PrC-210, are reported to be effective at much lower doses and with far less side effects. Their ability to modify ocular radiation damage has not yet been examined. The ability to non-invasively measure sensitive, radiation-induced ocular changes over long periods of time makes eye models an attractive option to test the radioprotective and radiation mitigating abilities of new novel compounds.

Liquid Medication Dosing Errors by Hispanic Parents: Role of Health Literacy and English Proficiency

PubMed Central

Harris, Leslie M.; Dreyer, Benard; Mendelsohn, Alan; Bailey, Stacy C.; Sanders, Lee M.; Wolf, Michael S.; Parker, Ruth M.; Patel, Deesha A.; Kim, Kwang Youn A.; Jimenez, Jessica J.; Jacobson, Kara; Smith, Michelle; Yin, H. Shonna

2016-01-01

Objective Hispanic parents in the US are disproportionately affected by low health literacy and limited English proficiency (LEP). We examined associations between health literacy, LEP, and liquid medication dosing errors in Hispanic parents. Methods Cross-sectional analysis of data from a multisite randomized controlled experiment to identify best practices for the labeling/dosing of pediatric liquid medications (SAFE Rx for Kids study); 3 urban pediatric clinics. Analyses were limited to Hispanic parents of children <8 years, with health literacy and LEP data (n=1126). Parents were randomized to 5 groups that varied by pairing of units of measurement on the label/dosing tool. Each parent measured 9 doses [3 amounts (2.5,5,7.5 mL) using 3 tools (2 syringes (0.2,0.5 mL increment), 1 cup)] in random order. Dependent variable: Dosing error=>20% dose deviation. Predictor variables: health literacy (Newest Vital Sign) [limited=0–3; adequate=4–6], LEP (speaks English less than “very well”). Results 83.1% made dosing errors (mean(SD) errors/parent=2.2(1.9)). Parents with limited health literacy and LEP had the greatest odds of making a dosing error compared to parents with adequate health literacy who were English proficient (% trials with errors/parent=28.8 vs. 12.9%; AOR=2.2[1.7–2.8]). Parents with limited health literacy who were English proficient were also more likely to make errors (% trials with errors/parent=18.8%; AOR=1.4[1.1–1.9]). Conclusion Dosing errors are common among Hispanic parents; those with both LEP and limited health literacy are at particular risk. Further study is needed to examine how the redesign of medication labels and dosing tools could reduce literacy and language-associated disparities in dosing errors. PMID:28477800

The lens of the eye: exposures in the UK medical sector and mechanistic studies of radiation effects.

PubMed

Bouffler, S D; Peters, S; Gilvin, P; Slack, K; Markiewicz, E; Quinlan, R A; Gillan, J; Coster, M; Barnard, S; Rothkamm, K; Ainsbury, E

2015-06-01

The recommendation from the International Commission on Radiological Protection that the occupational equivalent dose limit for the lens of the eye should be reduced to 20 mSv year(-1), averaged over 5 years with no year exceeding 50 mSv, has stimulated a discussion on the practicalities of implementation of this revised dose limit, and the most appropriate risk and protection framework to adopt. This brief paper provides an overview of some of the drivers behind the move to a lower recommended dose limit. The issue of implementation in the medical sector in the UK has been addressed through a small-scale survey of doses to the lens of the eye amongst interventional cardiologists and radiologists. In addition, a mechanistic study of early and late post-irradiation changes in the lens of the eye in in-vivo-exposed mice is outlined. Surveys and studies such as those described can contribute to a deeper understanding of fundamental and practical issues, and therefore contribute to a robust evidence base for ensuring adequate protection of the eye while avoiding undesirable restrictions to working practices. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

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

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

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

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

PubMed

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

2011-01-01

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

Influence of ACTG4-7-PGP (Semax) on Morphofunctional State of Hepatocytes in Chronic Emotional and Painful Stress.

PubMed

Ivanov, A V; Bobyntsev, I I; Shepeleva, O M; Kryukov, A A; Andreeva, L A; Myasoedov, N F

2017-05-01

We studied the effect of intraperitoneal administration of peptide ACTG 4-7 -PGP to male Wistar rats in doses of 5, 50, 150, and 450 μg/kg on the morphofunctional state of hepatocytes in chronic emotional and painful stress. A dose-dependent stress-limiting effect of the peptide was observed: it normalized the protein synthesis function of the liver and serum activity of ALT. The anticytolytic effect of the peptide increased with increasing its dose against the background of the increase in the relative number of multinucleated and multinucleolated cells and deceleration of the recovery of serum protein concentration. The decrease of hepatocyte cytolysis against the background of more intense morphological signs of protein synthesis processes attests to activation of reparative processes in the liver parenchyma via enhanced constitutional synthesis of protein.

Estimating Radiation Dose Metrics for Patients Undergoing Tube Current Modulation CT Scans

NASA Astrophysics Data System (ADS)

McMillan, Kyle Lorin

Computed tomography (CT) has long been a powerful tool in the diagnosis of disease, identification of tumors and guidance of interventional procedures. With CT examinations comes the concern of radiation exposure and the associated risks. In order to properly understand those risks on a patient-specific level, organ dose must be quantified for each CT scan. Some of the most widely used organ dose estimates are derived from fixed tube current (FTC) scans of a standard sized idealized patient model. However, in current clinical practice, patient size varies from neonates weighing just a few kg to morbidly obese patients weighing over 200 kg, and nearly all CT exams are performed with tube current modulation (TCM), a scanning technique that adjusts scanner output according to changes in patient attenuation. Methods to account for TCM in CT organ dose estimates have been previously demonstrated, but these methods are limited in scope and/or restricted to idealized TCM profiles that are not based on physical observations and not scanner specific (e.g. don't account for tube limits, scanner-specific effects, etc.). The goal of this work was to develop methods to estimate organ doses to patients undergoing CT scans that take into account both the patient size as well as the effects of TCM. This work started with the development and validation of methods to estimate scanner-specific TCM schemes for any voxelized patient model. An approach was developed to generate estimated TCM schemes that match actual TCM schemes that would have been acquired on the scanner for any patient model. Using this approach, TCM schemes were then generated for a variety of body CT protocols for a set of reference voxelized phantoms for which TCM information does not currently exist. These are whole body patient models representing a variety of sizes, ages and genders that have all radiosensitive organs identified. TCM schemes for these models facilitated Monte Carlo-based estimates of fully-, partially- and indirectly-irradiated organ dose from TCM CT exams. By accounting for the effects of patient size in the organ dose estimates, a comprehensive set of patient-specific dose estimates from TCM CT exams was developed. These patient-specific organ dose estimates from TCM CT exams will provide a more complete understanding of the dose impact and risks associated with modern body CT scanning protocols.

Relieving Pain using Dose-Extending Placebos: A Scoping Review

PubMed Central

Colloca, Luana; Enck, Paul; DeGrazia, David

2017-01-01

Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Importantly, provided that nondisclosure is pre-authorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated. PMID:27023425

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

NASA Astrophysics Data System (ADS)

Hajdas, Wojtek; Mrigakshi, Alankrita; Xiao, Hualin

2017-04-01

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

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

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

Low dose radiation interactions with the transformation growth factor (TFG)-beta pathway

NASA Astrophysics Data System (ADS)

Maslowski, Amy Jesse

A major limiting factor for long-term, deep-space missions is the radiation dose to astronauts. Because the dose to the astronauts is a mixed field of low- and high-LET radiation, there is a need to understand the effects of both radiation types on whole tissue; however, there are limited published data on the effects of high-LET (linear-energy-transfer) radiation on tissue. Thus, we designed a perfusion chamber system for rat trachea in order to mimic in vivo respiratory tissue. We successfully maintained the perfused tracheal tissue ex vivo in a healthy and viable condition for up to three days. In addition, this project studied the effects of high-LET Fe particles on the overall transformation growth factor (TGF)-beta response after TGF-beta inactivation and compared the results to the TGF-beta response post x-ray irradiation. It was found that a TGF-beta response could be measured in the perfused tracheal tissue, for x-ray and Fe particle irradiations, despite the high autofluorescent background intrinsic to tissue. However, after comparing the TGF-beta response of x-ray irradiation to High-Z-High-energy (HZE) irradiation, there was not a significant difference in radiation types. The TGF-beta response in x-ray and HZE irradiated perfusion chambers was also measured over time post irradiation. It was found that for 6 hour and 8 hour post irradiation, the TGF-beta response was higher for lower doses of radiation than for higher doses. This is in contrast to the 0 hour fixation which found the TGF-beta response to increase with increased dose. The inverse relationship found for 6 hour and 8 hour fixation times may indicate a threshold response for TGF-beta response; i.e., for low doses, a threshold of dose must be reached for an immediate TGF-beta response, otherwise the tissue responds more slowly to the irradiation damage. This result was unexpected and will require further investigation to determine if the threshold can be determined for the 250 kVp x-rays and 1 Gev Fe particles.

Pharmacotherapy of Essential Tremor

PubMed Central

Hedera, Peter; Cibulčík, František; Davis, Thomas L.

2013-01-01

Essential tremor (ET) is a common movement disorder but its pathogenesis remains poorly understood. This has limited the development of effective pharmacotherapy. The current therapeutic armamentaria for ET represent the product of careful clinical observation rather than targeted molecular modeling. Here we review their pharmacokinetics, metabolism, dosing, and adverse effect profiles and propose a treatment algorithm. We also discuss the concept of medically refractory tremor, as therapeutic trials should be limited unless invasive therapy is contraindicated or not desired by patients. PMID:24385718

Environmental radiology assessment in Lahad Datu, Sabah

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

Proof of concept and dose estimation with binary responses under model uncertainty.

PubMed

Klingenberg, B

2009-01-30

This article suggests a unified framework for testing Proof of Concept (PoC) and estimating a target dose for the benefit of a more comprehensive, robust and powerful analysis in phase II or similar clinical trials. From a pre-specified set of candidate models, we choose the ones that best describe the observed dose-response. To decide which models, if any, significantly pick up a dose effect, we construct the permutation distribution of the minimum P-value over the candidate set. This allows us to find critical values and multiplicity adjusted P-values that control the familywise error rate of declaring any spurious effect in the candidate set as significant. Model averaging is then used to estimate a target dose. Popular single or multiple contrast tests for PoC, such as the Cochran-Armitage, Dunnett or Williams tests, are only optimal for specific dose-response shapes and do not provide target dose estimates with confidence limits. A thorough evaluation and comparison of our approach to these tests reveal that its power is as good or better in detecting a dose-response under various shapes with many more additional benefits: It incorporates model uncertainty in PoC decisions and target dose estimation, yields confidence intervals for target dose estimates and extends to more complicated data structures. We illustrate our method with the analysis of a Phase II clinical trial. Copyright (c) 2008 John Wiley & Sons, Ltd.

Assessment of the benefits and impacts in the U.S. Nuclear Power Industry of hypothesized lower occupational dose limits

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

Andersen, R.L.; Schmitt, J.F.

1995-03-01

The International Commission on Radiological Protection and the National Council on Radiation Protection and Measurements have issued recommendations that would limit occupational exposure of individuals to doses lower than regulatory limits contained in the Nuclear Regulatory Commission`s 10 CFR Part 20, {open_quotes}Standards for Protection Against Radiation{close_quotes}. Because of this situation, there is interest in the potential benefits and impacts that would be associated with movement of the NRC regulatory limits toward the advisory bodies recommendations. The records of occupational worker doses in the U.S. commercial nuclear power industry show that the vast majority of these workers have doses that aremore » significantly below the regulatory limit of 50 mSv (5 rem) per year. Some workers doses do approach the limits, however. This is most common in the case of specially skilled workers, especially those with skills utilized in support of plant outage work. Any consideration of the potential benefits and impacts of hypothesized lower dose limits must address these workers as an important input to the overall assessment. There are also, of course, many other areas in which the benefits and impacts must be evaluated. To prepare to provide valid, constructive input on this matter, the U.S. nuclear power industry is undertaking an assessment, facilitated by the Nuclear Energy Institute (NEI), of the potential benefits and impacts at its facilities associated with hypothesized lower occupational dose limits. Some preliminary results available to date from this assessment are provided.« less

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

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Botas, Pablo; Faculty of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg

Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dosemore » objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.« less

Thyroid Dysfunction and Autoimmune Thyroid Diseases Among Atomic Bomb Survivors Exposed in Childhood.

PubMed

Imaizumi, Misa; Ohishi, Waka; Nakashima, Eiji; Sera, Nobuko; Neriishi, Kazuo; Yamada, Michiko; Tatsukawa, Yoshimi; Takahashi, Ikuno; Fujiwara, Saeko; Sugino, Keizo; Ando, Takao; Usa, Toshiro; Kawakami, Atsushi; Akahoshi, Masazumi; Hida, Ayumi

2017-07-01

The risk of thyroid cancer increases and persists for decades among individuals exposed to ionizing radiation in childhood, although the long-term effects of childhood exposure to medium to low doses of radiation on thyroid dysfunction and autoimmune thyroid diseases have remained unclear. To evaluate radiation dose responses for the prevalence of thyroid dysfunction and autoimmune thyroid disease among atomic bomb survivors exposed in childhood. Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years old at exposure underwent thyroid examinations at the Radiation Effects Research Foundation between 2007 and 2011, which was 62 to 66 years after the bombing. Data from 2668 participants (mean age, 68.2 years; 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; dose range, 0 to 4.040 Gy) were analyzed. Dose-response relationships between atomic bomb radiation dose and the prevalence of hypothyroidism, hyperthyroidism (Graves' disease), and positive for antithyroid antibodies. Prevalences were determined for hypothyroidism (129 cases, 7.8%), hyperthyroidism (32 cases of Graves' disease, 1.2%), and positive for antithyroid antibodies (573 cases, 21.5%). None of these was associated with thyroid radiation dose. Neither thyroid antibody-positive nor -negative hypothyroidism was associated with thyroid radiation dose. Additional analyses using alternative definitions of hypothyroidism and hyperthyroidism found that radiation dose responses were not significant. Radiation effects on thyroid dysfunction and autoimmune thyroid diseases were not observed among atomic bomb survivors exposed in childhood, at 62 to 66 years earlier. The cross-sectional design and survival bias were limitations of this study. Copyright © 2017 Endocrine Society

Status epilepticus induction has prolonged effects on the efficacy of antiepileptic drugs in the 6-Hz seizure model.

PubMed

Leclercq, Karine; Kaminski, Rafal M

2015-08-01

Several factors may influence the efficacy of antiepileptic drugs (AEDs) in patients with epilepsy, and treatment resistance could be related to genetics, neuronal network alterations, and modification of drug transporters or targets. Consequently, preclinical models used for the identification of potential new, more efficacious AEDs should reflect at least a few of these factors. Previous studies indicate that induction of status epilepticus (SE) may alter drug efficacy and that this effect could be long-lasting. In this context, we wanted to assess the protective effects of mechanistically diverse AEDs in mice subjected to pilocarpine-induced SE in another seizure model. We first determined seizure thresholds in mice subjected to pilocarpine-induced SE in the 6-Hz model, 2 weeks and 8 weeks following SE. We then evaluated the protective effects of mechanistically diverse AEDs in post-SE and control animals. No major differences in 6-Hz seizure susceptibility were observed between control groups, while the seizure threshold of pilocarpine mice at 8 weeks after SE was higher than at 2 weeks and higher than in control groups. Treatment with AEDs revealed major differences in drug response depending on their mechanism of action. Diazepam produced a dose-dependent protection against 6-Hz seizures in control and pilocarpine mice, both at 2 weeks and 8 weeks after SE, but with a more pronounced increase in potency in post-SE animals at 2 weeks. Levetiracetam induced a potent and dose-dependent protection in pilocarpine mice, 2 weeks after SE, while its protective effects were observed only at much higher doses in control mice. Its potency decreased in post-SE mice at 8 weeks and was very limited (30% protection at the highest tested dose) in the control group. Carbamazepine induced a dose-dependent protection at 2 weeks in control mice but only limited effect (50% at the highest tested dose) in pilocarpine mice. Its efficacy deeply decreased in post-SE mice at 8 weeks after SE. Perampanel and phenytoin showed almost comparable protective effects in all groups of mice. These experiments confirm that prior SE may have an impact on both potency and efficacy of AEDs and indicate that this effect may be dependent on the underlying epileptogenic processes. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Absorbed Dose Rate Due to Intake of Natural Radionuclides by Tilapia Fish (Tilapia nilotica,Linnaeus, 1758) Estimated Near Uranium Mining at Caetité, Bahia, Brazil

NASA Astrophysics Data System (ADS)

Pereira, Wagner de S.; Kelecom, Alphonse; Py Júnior, Delcy de Azevedo

2008-08-01

The uranium mining at Caetité (Uranium Concentrate Unit—URA) is in its operational phase. Aiming to estimate the radiological environmental impact of the URA, a monitoring program is underway. In order to preserve the biota of the deleterious effects from radiation and to act in a pro-active way as expected from a licensing body, the present work aims to use an environmental protection methodology based on the calculation of absorbed dose rate in biota. Thus, selected target organism was the Tilapia fish (Tilapia nilotica, Linnaeus, 1758) and the radionuclides were: uranium (U-238), thorium (Th-232), radium (Ra-226 and Ra-228) and lead (Pb-210). As, in Brazil there are no radiation exposure limits adopted for biota the value proposed by the Department of Energy (DOE) of the United States of 3.5×103 μGy y-1 has been used. The derived absorbed dose rate calculated for Tilapia was 2.51×100 μGy y-1, that is less than 0.1% of the dose limit established by DOE. The critical radionuclide was Ra-226, with 56% of the absorbed dose rate, followed by U-238 with 34% and Th-232 with 9%. This value of 0.1% of the limit allows to state that, in the operational conditions analyzed, natural radionuclides do not represent a radiological problem to biota.

Absorbed Dose Rate Due to Intake of Natural Radionuclides by Tilapia Fish (Tilapia nilotica,Linnaeus, 1758) Estimated Near Uranium Mining at Caetite, Bahia, Brazil

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

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

2008-08-07

The uranium mining at Caetite (Uranium Concentrate Unit--URA) is in its operational phase. Aiming to estimate the radiological environmental impact of the URA, a monitoring program is underway. In order to preserve the biota of the deleterious effects from radiation and to act in a pro-active way as expected from a licensing body, the present work aims to use an environmental protection methodology based on the calculation of absorbed dose rate in biota. Thus, selected target organism was the Tilapia fish (Tilapia nilotica, Linnaeus, 1758) and the radionuclides were: uranium (U-238), thorium (Th-232), radium (Ra-226 and Ra-228) and lead (Pb-210).more » As, in Brazil there are no radiation exposure limits adopted for biota the value proposed by the Department of Energy (DOE) of the United States of 3.5x10{sup 3} {mu}Gy y{sup -1} has been used. The derived absorbed dose rate calculated for Tilapia was 2.51x10{sup 0} {mu}Gy y{sup -1}, that is less than 0.1% of the dose limit established by DOE. The critical radionuclide was Ra-226, with 56% of the absorbed dose rate, followed by U-238 with 34% and Th-232 with 9%. This value of 0.1% of the limit allows to state that, in the operational conditions analyzed, natural radionuclides do not represent a radiological problem to biota.« less

A Phase I Trial and Pharmacokinetic Study of Aflibercept (VEGF Trap) in Children with Refractory Solid Tumors: A Children’s Oncology Group Phase I Consortium Report

PubMed Central

Bender, Julia Glade; Blaney, Susan M.; Borinstein, Scott; Reid, Joel M.; Baruchel, Sylvain; Ahern, Charlotte; Ingle, Ashish M.; Yamashiro, Darrell J.; Chen, Alice; Weigel, Brenda; Adamson, Peter C.; Park, Julie R.

2012-01-01

Background Aflibercept is a novel decoy receptor that efficiently neutralizes circulating vascular endothelial growth factor (VEGF). A pediatric phase 1 trial was performed to define the dose limiting toxicities (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of aflibercept. Methods Cohorts of 3–6 children with refractory solid tumors received aflibercept intravenously over 60 minutes every 14 days, at 2.0, 2.5 or 3.0 mg/kg/dose. PK sampling and analysis of peripheral blood biomarkers were performed with the initial dose. Results 21 eligible patients were enrolled; 18 were fully evaluable for toxicity. One of 6 patients receiving 2.0 mg/kg/dose developed dose-limiting intra-tumoral hemorrhage and 2 of 6 receiving 3.0 mg/kg/dose developed either dose-limiting tumor pain or tissue necrosis. None of the 6 patients receiving 2.5 mg/kg/dose developed DLT, defining this as the MTD. The most common non-dose limiting toxicities were hypertension and fatigue. Three patients with hepatocellular carcinoma, hepatoblastoma and clear cell sarcoma had stable disease for >13 weeks. At the MTD, the ratio of free to bound aflibercept serum concentration was 2.10 on day 8, but only 0.44 by day 15. A rapid decrease in VEGF (p<0.05) and increase in PlGF (p<0.05) from baseline was observed in response to aflibercept by day 2. Conclusion The aflibercept MTD in children of 2.5 mg/kg/dose every 14 days is lower that the adult recommended dose of 4.0 mg/kg. This dose achieves, but does not sustain, free aflibercept concentrations in excess of bound. Tumor pain and hemorrhage may be evidence of anti-tumor activity, but were dose-limiting. PMID:22791883

Antidepressant-like effects of scopolamine in mice are enhanced by the group II mGlu receptor antagonist LY341495.

PubMed

Podkowa, Karolina; Podkowa, Adrian; Sałat, Kinga; Lenda, Tomasz; Pilc, Andrzej; Pałucha-Poniewiera, Agnieszka

2016-12-01

Clinical studies have shown that the muscarinic receptor antagonist scopolamine induces a potent and rapid antidepressant effect relative to conventional antidepressants. However, potential undesirable effects, including memory impairment, partially limit the use of scopolamine in psychiatry. In the present study, we propose to overcome these limitations and enhance the therapeutic effects of scopolamine via administration in combination with the group II metabotropic glutamate (mGlu) receptor antagonist, LY341495. Joint administration of sub-effective doses of scopolamine (0.03 or 0.1 mg/kg, i.p.) with a sub-effective dose of LY341495 (0.1 mg/kg, i.p.) induced a profound antidepressant effect in the tail suspension test (TST) and in the forced swim test (FST) in mice. This drug combination did not impair memory, as measured using the Morris water maze (MWM), and did not influence the locomotor activity of mice. Furthermore, we found that an AMPA receptor antagonist, NBQX (10 mg/kg), completely reversed the antidepressant-like activity of a mixture of scopolamine and LY341495 in the TST. However, this effect was not influenced by para-chlorophenylalanine (PCPA) pre-treatment, indicating a lack of involvement of serotonergic system activation in the antidepressant-like effects of jointly given scopolamine and LY341495. Therefore, the combined administration of low doses of the antimuscarinic drug scopolamine and the group II mGlu receptor antagonist LY341495 might be a new, effective and safe strategy in the therapy of depression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Short communication: a repeated simian human immunodeficiency virus reverse transcriptase/herpes simplex virus type 2 cochallenge macaque model for the evaluation of microbicides.

PubMed

Kenney, Jessica; Derby, Nina; Aravantinou, Meropi; Kleinbeck, Kyle; Frank, Ines; Gettie, Agegnehu; Grasperge, Brooke; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Zydowsky, Thomas M; Robbiani, Melissa

2014-11-01

Epidemiological studies suggest that prevalent herpes simplex virus type 2 (HSV-2) infection increases the risk of HIV acquisition, underscoring the need to develop coinfection models to evaluate promising prevention strategies. We previously established a single high-dose vaginal coinfection model of simian human immunodeficiency virus (SHIV)/HSV-2 in Depo-Provera (DP)-treated macaques. However, this model does not appropriately mimic women's exposure. Repeated limiting dose SHIV challenge models are now used routinely to test prevention strategies, yet, at present, there are no reports of a repeated limiting dose cochallenge model in which to evaluate products targeting HIV and HSV-2. Herein, we show that 20 weekly cochallenges with 2-50 TCID50 simian human immunodeficiency virus reverse transcriptase (SHIV-RT) and 10(7) pfu HSV-2 results in infection with both viruses (4/6 SHIV-RT, 6/6 HSV-2). The frequency and level of vaginal HSV-2 shedding were significantly greater in the repeated exposure model compared to the single high-dose model (p<0.0001). We used this new model to test the Council's on-demand microbicide gel, MZC, which is active against SHIV-RT in DP-treated macaques and HSV-2 and human papillomavirus (HPV) in mice. While MZC reduced SHIV and HSV-2 infections in our repeated limiting dose model when cochallenging 8 h after each gel application, a barrier effect of carrageenan (CG) that was not seen in DP-treated animals precluded evaluation of the significance of the antiviral activity of MZC. Both MZC and CG significantly (p<0.0001) reduced the frequency and level of vaginal HSV-2 shedding compared to no gel treatment. This validates the use of this repeated limiting dose cochallenge model for testing products targeting HIV and HSV-2.

Effect of fluconazole on fungicidal activity of flucytosine in murine cryptococcal meningitis.

PubMed Central

Larsen, R A; Bauer, M; Weiner, J M; Diamond, D M; Leal, M E; Ding, J C; Rinaldi, M G; Graybill, J R

1996-01-01

Both animal and in vitro studies have demonstrated that combinations of flucytosine with amphotericin B and with fluconazole have significantly improved activity against cryptococcal meningitis compared with the activity of each drug used alone. However, very few dose levels of these agents have been tested in combination. This study evaluated the efficacy of fluconazole plus flucytosine in a murine model of cryptococcal meningitis over a broad range of dose combinations (fluconazole, 0 to 40 micrograms/g of body weight per day; flucytosine, 0 to 200 micrograms/g/day). Both drugs were dissolved in drinking water, with treatment on days 2 to 11. In this highly reproducible model, fluconazole had a dramatic effect on the fungicidal activity of flucytosine. Flucytosine at dose levels of as much as 200 micrograms/g/day alone or in combination with low doses of fluconazole had minimal fungicidal activity, whereas in combination with fluconazole at 24 to 40 micrograms/g/day, flucytosine showed fungicidal activity in the range of 45 to 65% of the animals treated at doses of 40 to 100 micrograms/g/day. This striking effect of fluconazole is consistent with the results of both in vitro and clinical studies. In the clinic, the use of flucytosine is often limited by severe toxicity, while toxicity is rarely observed with fluconazole. These results suggest that when flucytosine is given with higher doses of fluconazole, the maximum therapeutic effect of the former in the clinic may be observed at dose levels that are far less than the doses commonly employed (150 micrograms/g daily). PMID:8878602

Radiation Exposure of Interventional Radiologists During Computed Tomography Fluoroscopy-Guided Renal Cryoablation and Lung Radiofrequency Ablation: Direct Measurement in a Clinical Setting.

PubMed

Matsui, Yusuke; Hiraki, Takao; Gobara, Hideo; Iguchi, Toshihiro; Fujiwara, Hiroyasu; Kawabata, Takahiro; Yamauchi, Takatsugu; Yamaguchi, Takuya; Kanazawa, Susumu

2016-06-01

Computed tomography (CT) fluoroscopy-guided renal cryoablation and lung radiofrequency ablation (RFA) have received increasing attention as promising cancer therapies. Although radiation exposure of interventional radiologists during these procedures is an important concern, data on operator exposure are lacking. Radiation dose to interventional radiologists during CT fluoroscopy-guided renal cryoablation (n = 20) and lung RFA (n = 20) was measured prospectively in a clinical setting. Effective dose to the operator was calculated from the 1-cm dose equivalent measured on the neck outside the lead apron, and on the left chest inside the lead apron, using electronic dosimeters. Equivalent dose to the operator's finger skin was measured using thermoluminescent dosimeter rings. The mean (median) effective dose to the operator per procedure was 6.05 (4.52) μSv during renal cryoablation and 0.74 (0.55) μSv during lung RFA. The mean (median) equivalent dose to the operator's finger skin per procedure was 2.1 (2.1) mSv during renal cryoablation, and 0.3 (0.3) mSv during lung RFA. Radiation dose to interventional radiologists during renal cryoablation and lung RFA were at an acceptable level, and in line with recommended dose limits for occupational radiation exposure.

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

Matsui, Yusuke, E-mail: wckyh140@yahoo.co.jp; Hiraki, Takao, E-mail: takaoh@tc4.so-net.ne.jp; Gobara, Hideo, E-mail: gobara@cc.okayama-u.ac.jp

IntroductionComputed tomography (CT) fluoroscopy-guided renal cryoablation and lung radiofrequency ablation (RFA) have received increasing attention as promising cancer therapies. Although radiation exposure of interventional radiologists during these procedures is an important concern, data on operator exposure are lacking.Materials and MethodsRadiation dose to interventional radiologists during CT fluoroscopy-guided renal cryoablation (n = 20) and lung RFA (n = 20) was measured prospectively in a clinical setting. Effective dose to the operator was calculated from the 1-cm dose equivalent measured on the neck outside the lead apron, and on the left chest inside the lead apron, using electronic dosimeters. Equivalent dose to the operator’s finger skinmore » was measured using thermoluminescent dosimeter rings.ResultsThe mean (median) effective dose to the operator per procedure was 6.05 (4.52) μSv during renal cryoablation and 0.74 (0.55) μSv during lung RFA. The mean (median) equivalent dose to the operator’s finger skin per procedure was 2.1 (2.1) mSv during renal cryoablation, and 0.3 (0.3) mSv during lung RFA.ConclusionRadiation dose to interventional radiologists during renal cryoablation and lung RFA were at an acceptable level, and in line with recommended dose limits for occupational radiation exposure.« less

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

PubMed Central

Sasaki, Masao S.; Tachibana, Akira; Takeda, Shunichi

2014-01-01

Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. PMID:24366315

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

PubMed

Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

2014-05-01

Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

PubMed Central

Lücke, Caroline; Heidegger, Tonio; Röhner, Mirjam; Toennes, Stefan W; Krivanekova, Lucia; Müller-Dahlhaus, Florian; Ziemann, Ulf

2014-01-01

Ingesting ethanol (EtOH) at low doses during social drinking is a common human behavior for its facilitating effects on social interactions. However, low-dose EtOH may have also detrimental effects that so far are underexplored. Here we sought to test the effects of low-dose EtOH on long-term potentiation (LTP)-like plasticity in human motor cortex. Previous cellular experiments showed that low-dose EtOH potentiates extrasynaptic GABAAR and reduces NMDAR-mediated currents, processes that would limit the expression of LTP. Paired associative transcranial magnetic stimulation (PASLTP) was employed in nine healthy subjects for induction of LTP-like plasticity, indexed by a long-term increase in motor-evoked potential input–output curves. Synaptic α1-GABAAR function was measured by saccadic peak velocity (SPV). Very low doses of EtOH (resulting in blood concentrations of <5 mM) suppressed LTP-like plasticity but did not affect SPV when compared with a placebo condition. In contrast, 1 mg of alprazolam, a classical benzodiazepine, or 10 mg of zolpidem, a non-benzodiazepine hypnotic, decreased SPV but did not significantly affect LTP-like plasticity when compared with placebo. This double dissociation of low-dose EtOH vs alprazolam/zolpidem effects is best explained by the putatively high affinity of EtOH but not alprazolam/zolpidem to extrasynaptic GABAARs and to NMDARs. Findings suggest that enhancement of extrasynaptic GABAAR-mediated tonic inhibition and/or reduction of NMDAR-mediated neurotransmission by EtOH blocks LTP-like plasticity in human cortex at very low doses that are easily reached during social drinking. Therefore, low-dose EtOH may jeopardize LTP-dependent processes, such as learning and memory formation. PMID:24385131

Ionizing diagnostic radiation exposure in patients with Crohn's disease: A retrospective study in a medium hospital and its predictive factors.

PubMed

Merino Rodríguez, Esther; Carrera Alonso, Elisa; Torralba González de Suso, Miguel; Sánchez da Silva, Marta; Martínez López, María; Sánchez-Tembleque Zarandona, María Dolores

2018-02-01

It is estimated that diagnostic medical radiation exposure may be responsable for 0.5-2% of cancers worldwide. Because of the relapsing course of Crohn's disease (CD), these patients usually requiere multiple ionizing radiation test. Stimating the total cumulative effective dose received by our CD patients and identifying the risk factors associated with the exposure to a cumulative effective dose due to the disease (CEED) > 50mSv. Retrospective cohort study (2001-2014). patients with CD. Risk dose >50mSv. For calculating de cumulative effective dose and the CEED, all the ionizing test done were taken. For identifying predictive factors for receiving a CEDD >50mSv, an univariate and a multivariate logistic regression analyses were performed using a >50mSv dose as dependent variable. Of the 267 patients analyzed the 24.6% of them received a cumulative effective dose > 50mSv and the 15.2% a CEED>50mSv. In the multivariate analysis, the following variables were identified as independent predictors associated with a CEDD >50mSv: major surgery (OR= 2.1; IC 95% [1.1-3.8]; p=.019) and severity (OR= 20.6; IC 95% [4.5-94.8]; p<.01). Patients with CD are more at risk of receiving risk CEED, so it would be advisable to monitor the cumulative effective dose received to anticipate our intervention in order to avoid reaching that dose. The ultrasounds and abdominal resonance enterography are alternatives in these cases, although their accessibility is limited in some centers. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Comparative Effectiveness of Mesalamine, Sulfasalazine, Corticosteroids, and Budesonide for the Induction of Remission in Crohn's Disease: A Bayesian Network Meta-analysis.

PubMed

Coward, Stephanie; Kuenzig, M Ellen; Hazlewood, Glen; Clement, Fiona; McBrien, Kerry; Holmes, Rebecca; Panaccione, Remo; Ghosh, Subrata; Seow, Cynthia H; Rezaie, Ali; Kaplan, Gilaad G

2017-03-01

Induction treatment of mild-to-moderate Crohn's disease is controversial. To compare the induction of remission between different doses of mesalamine, sulfasalazine, corticosteroids, and budesonide for active Crohn's disease. We identified randomized controlled trials from existing Cochrane reviews and an updated literature search in Medline, EMBASE, and CENTRAL to November 2015. We included randomized controlled trials (n = 22) in adult patients with Crohn's disease that compared budesonide, sulfasalazine, mesalamine, or corticosteroids with placebo or each other, for the induction of remission (8-17 wks). Mesalamine (above and below 2.4 g/d) and budesonide (above and below 6 mg/d) were stratified into low and high doses. Our primary outcome was remission, defined as a Crohn's Disease Activity Index score <150. A Bayesian random-effects network meta-analysis was performed on the proportion in remission. Corticosteroids (odds ratio [OR] = 3.80; 95% credible interval [CrI]: 2.48-5.66), high-dose budesonide (OR = 2.96; 95% CrI: 2.06-4.30), and high-dose mesalamine (OR = 2.29; 95% CrI: 1.58-3.33) were superior to placebo. Corticosteroids were similar to high-dose budesonide (OR = 1.21; 95% CrI: 0.84-1.76), but more effective than high-dose mesalamine (OR = 1.83; 95% CrI: 1.16-2.88). Sulfasalazine was not significantly superior to any therapy including placebo. Randomized controlled trials that use a strict definition of induction of remission and disease severity at enrollment to assess effectiveness in treating mild-to-moderate Crohn's disease are limited. Corticosteroids and high-dose budesonide were effective treatments for inducing remission in mild-to-moderate Crohn's disease. High-dose mesalamine is an option among patients preferring to avoid steroids.

MEASUREMENT OF RADIATION DOSES TO THE EYE LENS DURING ORTHOPEDIC SURGERY USING AN C-ARM X-RAY SYSTEM.

PubMed

Suzuki, Akira; Matsubara, Kosuke; Sasa, Yuko

2018-04-01

The present study aimed to determine doses delivered to the eye lenses of surgeons while using the inverted-C-arm technique and the protective effect of leaded spectacles during orthopedic surgery. The kerma in air was measured at five positions on leaded glasses positioned near the eye lens and on the neck using small optically stimulated luminescence (OSL) dosemeters. The lens equivalent dose was also measured at the neck using an OSL dosemeter. The maximum equivalent dose to the eye lens and the maximum kerma were 0.8 mSv/month and 0.66 mGy/month, respectively. The leaded glasses reduced the exposure by ~60%. Even if the surgeons are exposed to the maximum dose of X-ray radiation for 5 years, the equivalent doses to the eye lens will not exceed the present limit recommended by the ICRP.

JOURNAL CLUB: Quantification of Fetal Dose Reduction if Abdominal CT Is Limited to the Top of the Iliac Crests in Pregnant Patients With Trauma.

PubMed

Corwin, Michael T; Seibert, J Anthony; Fananapazir, Ghaneh; Lamba, Ramit; Boone, John M

2016-04-01

The purposes of this study were to correlate fetal z-axis location within the maternal abdomen on CT with gestational age and estimate fetal dose reduction of a study limited to the abdomen only, with its lower aspect at the top of the iliac crests, compared with full abdominopelvic CT in pregnant trauma patients. We performed a study of pregnant patients who underwent CT of the abdomen and pelvis for trauma at a single institution over a 10-year period. The inferior aspect of maternal liver, spleen, gallbladder, pancreas, adrenals, and kidneys was recorded as above or below the iliac crests. The distance from the iliac crest to the top of the fetus or gestational sac was determined. The CT images of the limited and full scanning studies were independently reviewed by two blinded radiologists to identify traumatic injuries. Fetal dose profiles, including both scatter and primary radiation, were computed analytically along the central axis of the patient to estimate fetal dose reduction. Linear regression analysis was performed between gestational age and distance of the fetus to the iliac crests. Thirty-five patients were included (mean age, 26.2 years). Gestational age ranged from 5 to 38 weeks, with 5, 19, and 11 gestations in the first, second, and third trimesters, respectively. All solid organs were above the iliac crests in all patients. In three of six patients, traumatic findings in the pelvis would have been missed with the limited study. There was high correlation between gestational age and distance of the fetus to the iliac crests (R(2) = 0.84). The mean gestational age at which the top of the fetus was at the iliac crest was 17.3 weeks. Using the limited scanning study, fetuses at 5, 20, and 40 weeks of gestation would receive an estimated 4.3%, 26.2%, and 59.9% of the dose, respectively, compared with the dose for the full scanning study. In pregnant patients in our series with a history of trauma, CT of the abdomen only was an effective technique to reduce fetal radiation exposure compared with full abdomen and pelvis CT.

Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study.

PubMed

Hurwitz, Herbert I; Smith, David C; Pitot, Henry C; Brill, Jeffrey M; Chugh, Rashmi; Rouits, Elisabeth; Rubin, Joseph; Strickler, John; Vuagniaux, Gregoire; Sorensen, J Mel; Zanna, Claudio

2015-04-01

To assess safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of DEBIO1143, an antagonist of inhibitor apoptosis proteins. This first-in-man study in patients with advanced cancer used an accelerated dose titration design. DEBIO1143 was given orally once daily on days 1-5 every 2 or 3 weeks until disease progressed or patients dropped out. The starting dose of 5 mg was escalated by 100% in single patients until related grade 2 toxicity occurred. This triggered expansion to cohorts of three and subsequently six patients and reduction in dose increments to 50%. Maximum tolerated dose (MTD) was exceeded when any two patients within the same cohort experienced dose-limiting toxicity (DLT). On days 1 and 5, PK and PD samples were taken. Thirty-one patients received doses from 5 to 900 mg. Only one DLT was reported at 180 mg. No MTD was found. Most common adverse drug reactions were fatigue (26%), nausea (23%), and vomiting (13%). Average t max and T 1/2 was about 1 and 6 h, respectively. Exposure increased proportionally with doses from 80 to 900 mg, without accumulation over 5 days. Plasma CCL2 increased at 3-6 h postdose and epithelial apoptosis marker M30 on day 5; cIAP-1 levels in PBMCs decreased at all doses >80 mg. Five patients (17%) had stable disease as the best treatment response. DEBIO1143 was well tolerated at doses up to 900 mg and elicited PD effects at doses greater 80 mg. Limited antitumor activity may suggest development rather as adjunct treatment.

A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

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

Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.

2015-07-15

Purpose: Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials: We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor wasmore » contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results: We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion: We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted.« 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.

A Micronutrient Fortified Beverage Given at Different Dosing Frequencies Had Limited Impact on Anemia and Micronutrient Status in Filipino Schoolchildren.

PubMed

Angeles-Agdeppa, Imelda; Magsadia, Clarita R; Aaron, Grant J; Lloyd, Beate B; Hilmers, David C; Bhutta, Zulfiqar A

2017-09-12

This study evaluated the effects of a multi-micronutrient fortified juice drink given in different frequencies of consumption on hemoglobin (Hb) concentration of schoolchildren. Hb was measured in 2423 schoolchildren aged 6- to 9-years-old at baseline. All anemic children ( n = 246) were randomly allocated into groups: Daily dose (HD: high dose), 5X/week (MD: Moderate Dose), 3X/week (LD: Low Dose) and unfortified (Control). Pre- and post-study measurements of micronutrients were collected from 228 children. At the endpoint, significant Hb increases were observed in all groups, but there was no significant difference between groups. There was a significant reduction in anemia prevalence in all groups from 100% to 36% (Control), 30% (LD), 23% (MD) and 26% (HD). No dose-response effect was observed in Hb in this population. Most likely, this resulted from better than expected micronutrient status and lower than expected severity of anemia and micronutrient deficiencies in this cohort. It is unlikely that the addition of a fortified beverage to school feeding programs in this population would have a positive impact. Whether such an intervention would be cost-effective as a preventative approach needs to be assessed. This study demonstrates the importance of targeting such interventions to appropriate populations.

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

PubMed

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

2016-08-02

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

A Micronutrient Fortified Beverage Given at Different Dosing Frequencies Had Limited Impact on Anemia and Micronutrient Status in Filipino Schoolchildren

PubMed Central

Angeles-Agdeppa, Imelda; Magsadia, Clarita R.; Aaron, Grant J.; Lloyd, Beate B.; Hilmers, David C.; Bhutta, Zulfiqar A.

2017-01-01

This study evaluated the effects of a multi-micronutrient fortified juice drink given in different frequencies of consumption on hemoglobin (Hb) concentration of schoolchildren. Hb was measured in 2423 schoolchildren aged 6- to 9-years-old at baseline. All anemic children (n = 246) were randomly allocated into groups: Daily dose (HD: high dose), 5X/week (MD: Moderate Dose), 3X/week (LD: Low Dose) and unfortified (Control). Pre- and post-study measurements of micronutrients were collected from 228 children. At the endpoint, significant Hb increases were observed in all groups, but there was no significant difference between groups. There was a significant reduction in anemia prevalence in all groups from 100% to 36% (Control), 30% (LD), 23% (MD) and 26% (HD). No dose-response effect was observed in Hb in this population. Most likely, this resulted from better than expected micronutrient status and lower than expected severity of anemia and micronutrient deficiencies in this cohort. It is unlikely that the addition of a fortified beverage to school feeding programs in this population would have a positive impact. Whether such an intervention would be cost-effective as a preventative approach needs to be assessed. This study demonstrates the importance of targeting such interventions to appropriate populations. PMID:28895887

Defence strategies and antibiotic resistance gene abundance in enterococci under stress by exposure to low doses of peracetic acid.

PubMed

Turolla, Andrea; Sabatino, Raffaella; Fontaneto, Diego; Eckert, Ester M; Colinas, Noemi; Corno, Gianluca; Citterio, Barbara; Biavasco, Francesca; Antonelli, Manuela; Mauro, Alessandro; Mangiaterra, Gianmarco; Di Cesare, Andrea

2017-10-01

Peracetic acid (PAA) is an organic compound used efficiently as disinfectant in wastewater treatments. Yet, at low doses it may cause selection; thus, the effect of low doses of PAA on Enterococcus faecium as a proxy of human-related microbial waste was evaluated. Bacteria were treated with increasing doses of PAA (from 0 to 25 mg L -1 min) and incubated in regrowth experiments under non-growing, limiting conditions and under growing, favorable conditions. The changes in bacterial abundance, in bacterial phenotype (number and composition of small cell clusters), and in the abundance of an antibiotic resistance gene (ARG) was evaluated. The experiment demonstrated that the selected doses of PAA efficiently removed enterococci, and induced a long-lasting effect after PAA inactivation. The relative abundance of small clusters increased during the experiment when compared with that of the inoculum. Moreover, under growing favorable conditions the relative abundance of small clusters decreased and the number of cells per cluster increased with increasing PAA doses. A strong stability of the measured ARG was found, not showing any effect during the whole experiment. The results demonstrated the feasibility of low doses of PAA to inactivate bacteria. However, the stress induced by PAA disinfection promoted a bacterial adaptation, even if potentially without affecting the abundance of the ARG. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ambient dose equivalent and effective dose from scattered x-ray spectra in mammography for Mo/Mo, Mo/Rh and W/Rh anode/filter combinations.

PubMed

Künzel, R; Herdade, S B; Costa, P R; Terini, R A; Levenhagen, R S

2006-04-21

In this study, scattered x-ray distributions were produced by irradiating a tissue equivalent phantom under clinical mammographic conditions by using Mo/Mo, Mo/Rh and W/Rh anode/filter combinations, for 25 and 30 kV tube voltages. Energy spectra of the scattered x-rays have been measured with a Cd(0.9)Zn(0.1)Te (CZT) detector for scattering angles between 30 degrees and 165 degrees . Measurement and correction processes have been evaluated through the comparison between the values of the half-value layer (HVL) and air kerma calculated from the corrected spectra and measured with an ionization chamber in a nonclinical x-ray system with a W/Mo anode/filter combination. The shape of the corrected x-ray spectra measured in the nonclinical system was also compared with those calculated using semi-empirical models published in the literature. Scattered x-ray spectra measured in the clinical x-ray system have been characterized through the calculation of HVL and mean photon energy. Values of the air kerma, ambient dose equivalent and effective dose have been evaluated through the corrected x-ray spectra. Mean conversion coefficients relating the air kerma to the ambient dose equivalent and to the effective dose from the scattered beams for Mo/Mo, Mo/Rh and W/Rh anode/filter combinations were also evaluated. Results show that for the scattered radiation beams the ambient dose equivalent provides an overestimate of the effective dose by a factor of about 5 in the mammography energy range. These results can be used in the control of the dose limits around a clinical unit and in the calculation of more realistic protective shielding barriers in mammography.

Dose-Dependent Effects of Statins for Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Regression Analysis.

PubMed

To, Minh-Son; Prakash, Shivesh; Poonnoose, Santosh I; Bihari, Shailesh

2018-05-01

The study uses meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DIND), and mortality in aneurysmal subarachnoid hemorrhage. Prospective, retrospective observational studies, and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo). Meta-regression using inverse variance weighting and robust variance estimation was performed to assess the effect of statin dose on transformed AR in a random effects model. Dose-dependence of predicted AR with 95% confidence interval (CI) was recovered by using Miller's Freeman-Tukey inverse. The database search and study selection criteria yielded 18 studies (2594 patients) for analysis. These included 12 RCTs, 4 retrospective observational studies, and 2 prospective observational studies. Twelve studies investigated simvastatin, whereas the remaining studies investigated atorvastatin, pravastatin, or pitavastatin, with simvastatin-equivalent doses ranging from 20 to 80 mg. Meta-regression revealed dose-dependent reductions in Freeman-Tukey-transformed AR of vasospasm (slope coefficient -0.00404, 95% CI -0.00720 to -0.00087; P = 0.0321), DIND (slope coefficient -0.00316, 95% CI -0.00586 to -0.00047; P = 0.0392), and mortality (slope coefficient -0.00345, 95% CI -0.00623 to -0.00067; P = 0.0352). The present meta-regression provides weak evidence for dose-dependent reductions in vasospasm, DIND and mortality associated with acute statin use after aneurysmal subarachnoid hemorrhage. However, the analysis was limited by substantial heterogeneity among individual studies. Greater dosing strategies are a potential consideration for future RCTs. Copyright © 2018 Elsevier Inc. All rights reserved.

First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent.

PubMed

Allen, Joshua E; Crowder, Roslyn N; Crowder, Roslyn; El-Deiry, Wafik S

2015-01-01

We previously identified ONC201 (TIC10) as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL) was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer.

First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent

PubMed Central

Allen, Joshua E.; Crowder, Roslyn; El-Deiry, Wafik S.

2015-01-01

We previously identified ONC201 (TIC10) as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL) was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer. PMID:26580220

Analysis of dose to patient, spouse/caretaker, and staff, from an implanted trackable radioactive fiducial for use in the radiation treatment of prostate cancer

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

Neustadter, David; Barnea, Gideon; Stokar, Saul

Purpose: A fiducial tracking system based on a novel radioactive tracking technology is being developed for real-time target tracking in radiation therapy. In this study, the authors calculate the radiation dose to the patient, the spouse/caretaker, and the medical staff that would result from a 100 {mu}Ci Ir192 radioactive fiducial marker permanently implanted in the prostate of a radiation therapy patient. Methods: Local tissue dose was calculated by Monte Carlo simulation. The patient's whole body effective dose equivalent was calculated by summing the doses to the sensitive organs. Exposure of the spouse/caretaker was calculated from the NRC guidelines. Exposure ofmore » the medical staff was based on estimates of proximity to and time spent with the patient. Results: The local dose is below 40 Gy at 5 mm from the marker and below 10 Gy at 10 mm from the marker. The whole body effective dose equivalent to the patient is 64 mSv. The dose to the spouse/caretaker is 0.25 mSv. The annual exposures of the medical staff are 0.2 mSv for a doctor performing implantations and 0.34 mSv for a radiation therapist positioning patients for therapy. Conclusions: The local dose is not expected to have any clinically significant effect on the surrounding tissue which is irradiated during therapy. The dose to the patient is small in comparison to the whole body dose received from the therapy itself. The exposure of all other people is well below the recommended limits. The authors conclude that there is no radiation exposure related contraindication for use of this technology in the radiation treatment of prostate cancer.« less

TU-C-18A-01: Models of Risk From Low-Dose Radiation Exposures: What Does the Evidence Say?

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

Bushberg, J; Boreham, D; Ulsh, B

2014-06-15

At dose levels of (approximately) 500 mSv or more, increased cancer incidence and mortality have been clearly demonstrated. However, at the low doses of radiation used in medical imaging, the relationship between dose and cancer risk is not well established. As such, assumptions about the shape of the dose-response curve are made. These assumptions, or risk models, are used to estimate potential long term effects. Common models include 1) the linear non-threshold (LNT) model, 2) threshold models with either a linear or curvilinear dose response above the threshold, and 3) a hormetic model, where the risk is initially decreased belowmore » background levels before increasing. The choice of model used when making radiation risk or protection calculations and decisions can have significant implications on public policy and health care decisions. However, the ongoing debate about which risk model best describes the dose-response relationship at low doses of radiation makes informed decision making difficult. This symposium will review the two fundamental approaches to determining the risk associated with low doses of ionizing radiation, namely radiation epidemiology and radiation biology. The strengths and limitations of each approach will be reviewed, the results of recent studies presented, and the appropriateness of different risk models for various real world scenarios discussed. Examples of well-designed and poorly-designed studies will be provided to assist medical physicists in 1) critically evaluating publications in the field and 2) communicating accurate information to medical professionals, patients, and members of the general public. Equipped with the best information that radiation epidemiology and radiation biology can currently provide, and an understanding of the limitations of such information, individuals and organizations will be able to make more informed decisions regarding questions such as 1) how much shielding to install at medical facilities, 2) at what dose level are risk vs. benefit discussions with patients appropriate, 3) at what dose level should we tell a pregnant woman that the baby’s health risk from a prenatal radiation exposure is “significant”, 4) is informed consent needed for patients undergoing medical imaging, and 5) at what dose level is evacuation appropriate after a radiological accident. Examples of the tremendous impact that choosing different risks models can have on the answers to these types of questions will be given.A moderated panel discussion will allow audience members to pose questions to the faculty members, each of whom is an established expert in his respective discipline. Learning Objectives: Understand the fundamental principles, strengths and limitations of radiation epidemiology and radiation biology for determining the risk from exposures to low doses of ionizing radiation Become familiar with common models of risk used to describe the dose-response relationship at low dose levels Learn to identify strengths and weaknesses in studies designed to measure the effect of low doses of ionizing radiation Understand the implications of different risk models on public policy and health care decisions.« less

Too Late to Vaccinate? The Incremental Benefits and Cost-effectiveness of a Delayed Catch-up Program Using the 4-Valent Human Papillomavirus Vaccine in Norway

PubMed Central

Burger, Emily A.; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar S.; Kim, Jane J.

2015-01-01

Background Human papillomavirus (HPV) vaccines are ideally administered before HPV exposure; therefore, catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway. Methods We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with 8 HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity. Results The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 years remained below Norway's willingness-to-pay threshold (approximately $83 000/quality-adjusted life year gained); extension to age 22 years was cost-effective at a lower cost per dose ($50–$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 years was cost-effective. Results were stable with lower coverage. Conclusions HPV vaccination catch-up programs, 5 years after routine implementation, may be warranted; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 years remains uncertain. PMID:25057044

Effectiveness of sheltering in buildings and vehicles for plutonium

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

Engelmann, R.J.

1990-07-30

The purpose of this paper is to collect and present current knowledge relevant to the protection offered by sheltering against exposure to plutonium particles released to the atmosphere during accidents. For those many contaminants for which effects are linear with the airborne concentration, it is convenient to define a Dose Reduction Factor (DRF). In the past, the DRF has been defined as the ratio of the radiological dose that may be incurred within the shelter to that in the outdoors. As such, it includes the dose through shine from plumes aloft and from material deposited on the surface. For thismore » paper, which is concerned only with the inhalation pathway, the DRF is the ratio of the time-integrated concentration inside the shelter to that outdoors. It is important to note that the range over which effects are linear with concentration may be limited for many contaminants. Examples are when concentrations produce effects that are irreversible, or when concentrations are below effects threshold levels. 71 refs., 4 figs., 8 tabs.« less

Sub-efficacious doses of phosphodiesterase 4 and 5 inhibitors improve memory in a mouse model of Alzheimer's disease.

PubMed

Gulisano, Walter; Tropea, Maria Rosaria; Arancio, Ottavio; Palmeri, Agostino; Puzzo, Daniela

2018-06-06

Cyclic nucleotides cAMP and cGMP cooperate to ensure memory acquisition and consolidation. Increasing their levels by phosphodiesterase inhibitors (PDE-Is) enhanced cognitive functions and rescued memory loss in different models of aging and Alzheimer's disease (AD). However, side effects due to the high doses used limited their application in humans. Based on previous studies suggesting that combinations of sub-efficacious doses of cAMP- and cGMP-specific PDE-Is improved synaptic plasticity and memory in physiological conditions, here we aimed to study whether this treatment was effective to counteract the AD phenotype in APPswe mice. We found that a 3-week chronic treatment with a combination of sub-efficacious doses of the cAMP-specific PDE4-I roflumilast (0.01 mg/kg) and the cGMP-specific PDE5-I vardenafil (0.1 mg/kg) improved recognition, spatial and contextual fear memory. Importantly, the cognitive enhancement persisted for 2 months beyond administration. This long-lasting action, and the possibility to minimize side effects due to the low doses used, might open feasible therapeutic strategies against AD. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effects of tramadol on postoperative shivering after sevoflurane and remifentanil anesthesia.

PubMed

Nakagawa, Taku; Hashimoto, Miki; Hashimoto, Yasunori; Shirozu, Kazuhiro; Hoka, Sumio

2017-01-03

Remifentanil has been reported to cause post-anesthetic shivering (PAS). Higher doses of remifentanil reportedly induce more intense PAS. Tramadol, a synthetic opioid that acts at multiple sites, is considered to be an effective treatment for PAS, but the evidence for its therapeutic benefit after remifentanil anesthesia is limited. We investigated the effect of tramadol on the incidence of PAS after remifentanil anesthesia. Sixty-three patients who had undergone upper abdominal surgery under general anesthesia were studied retrospectively. Tramadol was administered at induction of anesthesia. The patients were divided into four groups: HT(+), high dose remifentanil (1-1.5 μg/kg/min) with tramadol; HT(-), high dose remifentanil without tramadol; LT(+), low dose remifentanil (0.15-0.25 μg/kg/min) with tramadol; and LT(-), low dose remifentanil without tramadol. We recorded perioperative changes in nasopharyngeal temperature and episodes of PAS on emergence from anesthesia. The incidences of PAS in both tramadol treatment groups were significantly lower than the groups that did not receive tramadol. Nasopharyngeal temperature after surgery fell significantly more from baseline in the tramadol treatment groups compared with the non-treatment groups. Tramadol administered at induction of anesthesia appears to suppress PAS following remifentanil anesthesia.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents.

PubMed

Albuquerque, Edson X; Pereira, Edna F R; Aracava, Yasco; Fawcett, William P; Oliveira, Maristela; Randall, William R; Hamilton, Tracey A; Kan, Robert K; Romano, James A; Adler, Michael

2006-08-29

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents

PubMed Central

Albuquerque, Edson X.; Pereira, Edna F. R.; Aracava, Yasco; Fawcett, William P.; Oliveira, Maristela; Randall, William R.; Hamilton, Tracey A.; Kan, Robert K.; Romano, James A.; Adler, Michael

2006-01-01

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer’s disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning. PMID:16914529

Prevention of murine cerebral malaria by low-dose cyclosporin A.

PubMed Central

Grau, G E; Gretener, D; Lambert, P H

1987-01-01

The effects of cyclosporin A (CsA) were investigated in an experimental model of cerebral malaria. In this model, Plasmodium berghei ANKA-infected CBA/Ca mice develop a clinically and histologically characterized neurological syndrome which is considered to be the result of immunopathological reactions mediated by L3T4+ T cells. It was shown that CsA displayed a strong protective effect on neurological complications when given at a dose 1 mg/kg/day for 5 consecutive days (Days 4-8), which had no effect on the parasite. Paradoxically, this protection against neurological complications was not seen when parasiticidal doses were used during this limited 5-day period. A similar protective effect was observed with two CsA derivatives, C5-34 and H7-94. The mechanisms by which CsA and the two derivatives could prevent murine cerebral malaria are unknown but can be related to exquisite effects on some lymphocyte functions. In view of these results, it might be conceivable to investigate the benefits of using low doses of CsA in man, in conjunction with the classical antiparasite therapy, for the management of cerebral malaria. PMID:3327806

Prevention of murine cerebral malaria by low-dose cyclosporin A.

PubMed

Grau, G E; Gretener, D; Lambert, P H

1987-08-01

The effects of cyclosporin A (CsA) were investigated in an experimental model of cerebral malaria. In this model, Plasmodium berghei ANKA-infected CBA/Ca mice develop a clinically and histologically characterized neurological syndrome which is considered to be the result of immunopathological reactions mediated by L3T4+ T cells. It was shown that CsA displayed a strong protective effect on neurological complications when given at a dose 1 mg/kg/day for 5 consecutive days (Days 4-8), which had no effect on the parasite. Paradoxically, this protection against neurological complications was not seen when parasiticidal doses were used during this limited 5-day period. A similar protective effect was observed with two CsA derivatives, C5-34 and H7-94. The mechanisms by which CsA and the two derivatives could prevent murine cerebral malaria are unknown but can be related to exquisite effects on some lymphocyte functions. In view of these results, it might be conceivable to investigate the benefits of using low doses of CsA in man, in conjunction with the classical antiparasite therapy, for the management of cerebral malaria.

Compendium of Single Event Effects, Total Ionizing Dose, and Displacement Damage for Candidate Spacecraft Electronics for NASA

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.; OBryan, Martha V.; Chen, Dakai; Campola, Michael J.; Casey, Megan C.; Pellish, Jonathan A.; Lauenstein, Jean-Marie; Wilcox, Edward P.; Topper, Alyson D.; Ladbury, Raymond L.;

Improving microbiological safety and maintaining sensory and nutritional quality of pre-cut tomato and carrot by gamma irradiation

NASA Astrophysics Data System (ADS)

Mohácsi-Farkas, Cs.; Nyirő-Fekete, B.; Daood, H.; Dalmadi, I.; Kiskó, G.

2014-06-01

Pre-cut tomato and carrot were irradiated with doses of 1.0, 1.5 and 2 kGy. Unirradiated control and irradiated samples were compared organoleptically by a sensory panel. Microbiological analyses were performed directly after irradiation and during post-irradiation storage for 8 days at 5 °C. Ascorbic acid contents, composition of carotenoids and tocopherols were determined. Statistically significant differences of sensory scores between unirradiated and irradiated samples were observed only in the texture of sliced carrots. Total aerobic viable cell counts have been reduced by about two log cycles with 1.5 kGy dose. Total coliforms and moulds were below the detection limit of 15 CFU/g in the irradiated samples during the refrigerated storage. Yeasts were relatively resistant part of the microbiota of pre-cut tomatoes, but 2 kGy dose reduced them below the detection limit. In pre-cut tomatoes, alpha-tocopherol and some carotenoids seemed to be the most radio-sensitive losing approximately one-third of their original concentrations at the dose of 2 kGy. At this dose tocopherols and the level of ascorbic acid decreased also one-third of the initial level in sliced carrots. Additional experiments were conducted to study the effect of irradiation and storage on the population of Listeria monocytogenes and Listeria innocua artificially inoculated on cut tomato and carrot. Cell numbers of both test organisms decreased by at least two log-cycles as an effect of 1 kGy dose. Our studies confirmed earlier findings on a temporary antilisterial effect of freshly cut carrot tissue. No re-growth of Listeria was observed during the studied storage period. The results of these studies suggest that irradiation with 1 kGy gamma rays could improve sufficiently the microbiological safety of the investigated pre-cut produce to satisfy the requirement of low microbial raw diets with acceptable nutritional quality and without diminishing significantly the organoleptic parameters of the commodities.

Dose of physical activity, physical functioning and disability risk in mobility-limited older adults: Results from the LIFE study randomized trial

PubMed Central

Guralnik, Jack M.; King, Abby C.; Pahor, Marco; McDermott, Mary M.; Tudor-Locke, Catrine; Manini, Todd M.; Glynn, Nancy W.; Marsh, Anthony P.; Axtell, Robert S.; Hsu, Fang-Chi; Rejeski, W. Jack

2017-01-01

Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70–89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P < 0.001) (highest versus the lowest quartile of physical activity change HR 0.23 ((95% CI:0.10–0.52) P = 0.001) in the physical activity arm. We observed a dose-dependent effect of objectively monitored physical activity on physical functioning and onset of major mobility disability. Relatively small increases (> 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes. Trial registration: ClinicalsTrials.gov NCT00116194 PMID:28820909

Dose of physical activity, physical functioning and disability risk in mobility-limited older adults: Results from the LIFE study randomized trial.

PubMed

Fielding, Roger A; Guralnik, Jack M; King, Abby C; Pahor, Marco; McDermott, Mary M; Tudor-Locke, Catrine; Manini, Todd M; Glynn, Nancy W; Marsh, Anthony P; Axtell, Robert S; Hsu, Fang-Chi; Rejeski, W Jack

2017-01-01

Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70-89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P < 0.001) (highest versus the lowest quartile of physical activity change HR 0.23 ((95% CI:0.10-0.52) P = 0.001) in the physical activity arm. We observed a dose-dependent effect of objectively monitored physical activity on physical functioning and onset of major mobility disability. Relatively small increases (> 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes. ClinicalsTrials.gov NCT00116194.

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

PubMed

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

2016-05-01

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

Evaluation of the reinforcing and subjective effects of heroin in combination with dextromethorphan and quinidine

PubMed Central

Vosburg, Suzanne K.; Sullivan, Maria A.; Comer, Sandra D.

2015-01-01

Objective Studies have suggested that the N-methyl-d-aspartate antagonist dextromethorphan may be useful in the treatment of opioid dependence. Design This double-blinded, placebo-controlled inpatient study evaluated the effects of 0, 30, and 60 mg of dextromethorphan and quinidine (DMQ) on the reinforcing and subjective effects of heroin in recently detoxified heroin abusers. Participants Nine heroin-dependent participants were admitted and then detoxified from heroin over the course of several days. Interventions Participants were subsequently stabilized on 0, 30, or 60 mg of DMQ. Each dose of DMQ was administered for two consecutive weeks, and the effects of heroin (0, 12.5, and 50 mg) were studied under each DMQ maintenance dose condition. DMQ and heroin dose were administered in random order both within and between participants. Results Planned comparisons revealed statistically significant increases in progressive ratio breakpoint values and positive subjective ratings as a function of heroin dose. There were no consistent changes in any of the responses as a function of DMQ maintenance dose, other than a modest reduction in craving. Conclusions In summary, results from this study suggest that maintenance on dextromethorphan in combination with quinidine has a limited role in the treatment of opioid dependence. PMID:22320027

Exjade® (deferasirox, ICL670) in the treatment of chronic iron overload associated with blood transfusion

PubMed Central

Cappellini, Maria Domenica

2007-01-01

Although blood transfusions are important for patients with anemia, chronic transfusions inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. Although the current reference standard iron chelator deferoxamine has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Deferasirox (Exjade®, ICL670, Novartis Pharma AG, Basel, Switzerland) is a once-daily, oral iron chelator approved for the treatment of transfusional iron overload in adult and pediatric patients. The efficacy and safety of deferasirox have been established in a comprehensive clinical development program involving patients with various transfusion-dependent anemias. Deferasirox has a dose-dependent effect on iron burden, and is as efficacious as deferoxamine at comparable therapeutic doses. Deferasirox therapy can be tailored to a patient’s needs, as response is related to both dose and iron intake. Since deferasirox has a long half-life and is present in the plasma for 24 hours with once-daily dosing, it is unique in providing constant chelation coverage with a single dose. The availability of this convenient, effective, and well tolerated therapy represents a significant advance in the management of transfusional iron overload. PMID:18360637

The FLUKA Monte Carlo code coupled with the NIRS approach for clinical dose calculations in carbon ion therapy

NASA Astrophysics Data System (ADS)

Magro, G.; Dahle, T. J.; Molinelli, S.; Ciocca, M.; Fossati, P.; Ferrari, A.; Inaniwa, T.; Matsufuji, N.; Ytre-Hauge, K. S.; Mairani, A.

2017-05-01

Particle therapy facilities often require Monte Carlo (MC) simulations to overcome intrinsic limitations of analytical treatment planning systems (TPS) related to the description of the mixed radiation field and beam interaction with tissue inhomogeneities. Some of these uncertainties may affect the computation of effective dose distributions; therefore, particle therapy dedicated MC codes should provide both absorbed and biological doses. Two biophysical models are currently applied clinically in particle therapy: the local effect model (LEM) and the microdosimetric kinetic model (MKM). In this paper, we describe the coupling of the NIRS (National Institute for Radiological Sciences, Japan) clinical dose to the FLUKA MC code. We moved from the implementation of the model itself to its application in clinical cases, according to the NIRS approach, where a scaling factor is introduced to rescale the (carbon-equivalent) biological dose to a clinical dose level. A high level of agreement was found with published data by exploring a range of values for the MKM input parameters, while some differences were registered in forward recalculations of NIRS patient plans, mainly attributable to differences with the analytical TPS dose engine (taken as reference) in describing the mixed radiation field (lateral spread and fragmentation). We presented a tool which is being used at the Italian National Center for Oncological Hadrontherapy to support the comparison study between the NIRS clinical dose level and the LEM dose specification.

Research on radiation exposure from CT part of hybrid camera and diagnostic CT

NASA Astrophysics Data System (ADS)

Solný, Pavel; Zimák, Jaroslav

2014-11-01

Research on radiation exposure from CT part of hybrid camera in seven different Departments of Nuclear Medicine (DNM) was conducted. Processed data and effective dose (E) estimations led to the idea of phantom verification and comparison of absorbed doses and software estimation. Anonymous data from about 100 examinations from each DNM was gathered. Acquired data was processed and utilized by dose estimation programs (ExPACT, ImPACT, ImpactDose) with respect to the type of examination and examination procedures. Individual effective doses were calculated using enlisted programs. Preserving the same procedure in dose estimation process allows us to compare the resulting E. Some differences and disproportions during dose estimation led to the idea of estimated E verification. Consequently, two different sets of about 100 of TLD 100H detectors were calibrated for measurement inside the Aldersnon RANDO Anthropomorphic Phantom. Standard examination protocols were examined using a 2 Slice CT- part of hybrid SPECT/CT. Moreover, phantom exposure from body examining protocol for 32 Slice and 64 Slice diagnostic CT scanner was also verified. Absorbed dose (DT,R) measured using TLD detectors was compared with software estimation of equivalent dose HT values, computed by E estimation software. Though, only limited number of cavities for detectors enabled measurement within the regions of lung, liver, thyroid and spleen-pancreas region, some basic comparison is possible.

Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy Through Science – Addressing the ODWAC New Recommendation

PubMed Central

Dingwall, S.; Mills, C.E.; Phan, N.; Taylor, K.; Boreham, D.R.

2011-01-01

Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered. The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from tritium exposure at 20 Bq/L would be orders of magnitude less than that from exposure to natural background sources of radiation. The new proposed standard would set the radiation dose limit for drinking water to 0.0003 mSv/year, which is equivalent to approximately three times the dose from naturally occurring tritium in drinking water. This new standard is incongruent with national and international standards for safe levels of radiation exposure, currently set at 1 mSv/year for the general public. Scientific research from leading authorities on the carcinogenic health effects of tritium exposure supports the notion that the current standard of 7,000 Bq/L (annual dose of 0.1 mSv) is a safe standard for human health. Policy-making for the purpose of regulating tritium levels in drinking water is a dynamic multi-stage process that is influenced by more than science alone. Ethics, economics, and public perception also play important roles in policy development; however, these factors sometimes undermine the scientific evidence that should form the basis of informed decision making. Consequently, implementing a new standard without a scientific basis may lead the public to perceive that risks from tritium have been historically underestimated. It was concluded that the new recommendation is not supported by any new scientific insight regarding negative consequences of low dose effects, and may be contrary to new data on the potential benefits of low dose effects. Given the lack of cost versus benefit analysis, this type of dramatic policy change could have detrimental effects to society from an ethical, economical, and public perception perspective. PMID:21431084

Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy Through Science - Addressing the ODWAC New Recommendation.

PubMed

Dingwall, S; Mills, C E; Phan, N; Taylor, K; Boreham, D R

2011-02-22

Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered.The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from tritium exposure at 20 Bq/L would be orders of magnitude less than that from exposure to natural background sources of radiation. The new proposed standard would set the radiation dose limit for drinking water to 0.0003 mSv/year, which is equivalent to approximately three times the dose from naturally occurring tritium in drinking water. This new standard is incongruent with national and international standards for safe levels of radiation exposure, currently set at 1 mSv/year for the general public. Scientific research from leading authorities on the carcinogenic health effects of tritium exposure supports the notion that the current standard of 7,000 Bq/L (annual dose of 0.1 mSv) is a safe standard for human health.Policy-making for the purpose of regulating tritium levels in drinking water is a dynamic multi-stage process that is influenced by more than science alone. Ethics, economics, and public perception also play important roles in policy development; however, these factors sometimes undermine the scientific evidence that should form the basis of informed decision making. Consequently, implementing a new standard without a scientific basis may lead the public to perceive that risks from tritium have been historically underestimated. It was concluded that the new recommendation is not supported by any new scientific insight regarding negative consequences of low dose effects, and may be contrary to new data on the potential benefits of low dose effects. Given the lack of cost versus benefit analysis, this type of dramatic policy change could have detrimental effects to society from an ethical, economical, and public perception perspective.

Evaluation and mitigation of the interplay effects for intensity modulated proton therapy for lung cancer in a clinical setting

PubMed Central

Kardar, Laleh; Li, Yupeng; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y.; Liao, Li; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D.; Lim, Gino; Zhang, Xiaodong

2015-01-01

Purpose The primary aim of this study was to evaluate the impact of interplay effects for intensity-modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of iso-layered re-scanning for mitigating these interplay effects. Methods and Materials Single-fraction 4D dynamic dose without considering re-scanning (1FX dynamic dose) was used as a metric to determine the magnitude of dosimetric degradation caused by 4D interplay effects. The 1FX dynamic dose was calculated by simulating the machine delivery processes of proton spot scanning on moving patient described by 4D computed tomography (4DCT) during the IMPT delivery. The dose contributed from an individual spot was fully calculated on the respiratory phase corresponding to the life span of that spot, and the final dose was accumulated to a reference CT phase by using deformable image registration. The 1FX dynamic dose was compared with the 4D composite dose. Seven patients with various tumor volumes and motions were selected. Results The CTV prescription coverage for the 7 patients were 95.04%, 95.38%, 95.39%, 95.24%, 95.65%, 95.90%, and 95.53%, calculated with use of the 4D composite dose, and were 89.30%, 94.70%, 85.47%, 94.09%, 79.69%, 91.20%, and 94.19% with use of the 1FX dynamic dose. For the 7 patients, the CTV coverage, calculated by using single-fraction dynamic dose, were 95.52%, 95.32%, 96.36%, 95.28%, 94.32%, 95.53%, and 95.78%, using maximum MU limit value of 0.005. In other words, by increasing the number of delivered spots in each fraction, the degradation of CTV coverage improved up to 14.6%. Conclusions Single-fraction 4D dynamic dose without re-scanning was validated as a surrogate to evaluate the interplay effects for IMPT for lung cancer in the clinical setting. The interplay effects can be potentially mitigated by increasing the number of iso-layered re-scanning in each fraction delivery. PMID:25407877

Evaluation and mitigation of the interplay effects of intensity modulated proton therapy for lung cancer in a clinical setting.

PubMed

Kardar, Laleh; Li, Yupeng; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y; Liao, Li; Zhu, Ronald X; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D; Lim, Gino; Zhang, Xiaodong

2014-01-01

The primary aim of this study was to evaluate the impact of the interplay effects of intensity modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of isolayered rescanning to mitigate these interplay effects. A single-fraction 4-dimensional (4D) dynamic dose without considering rescanning (1FX dynamic dose) was used as a metric to determine the magnitude of dosimetric degradation caused by 4D interplay effects. The 1FX dynamic dose was calculated by simulating the machine delivery processes of proton spot scanning on a moving patient, described by 4D computed tomography during IMPT delivery. The dose contributed from an individual spot was fully calculated on the respiratory phase that corresponded to the life span of that spot, and the final dose was accumulated to a reference computed tomography phase by use of deformable image registration. The 1FX dynamic dose was compared with the 4D composite dose. Seven patients with various tumor volumes and motions were selected for study. The clinical target volume (CTV) prescription coverage for the 7 patients was 95.04%, 95.38%, 95.39%, 95.24%, 95.65%, 95.90%, and 95.53% when calculated with the 4D composite dose and 89.30%, 94.70%, 85.47%, 94.09%, 79.69%, 91.20%, and 94.19% when calculated with the 1FX dynamic dose. For these 7 patients, the CTV coverage calculated by use of a single-fraction dynamic dose was 95.52%, 95.32%, 96.36%, 95.28%, 94.32%, 95.53%, and 95.78%, with a maximum monitor unit limit value of 0.005. In other words, by increasing the number of delivered spots in each fraction, the degradation of CTV coverage improved up to 14.6%. A single-fraction 4D dynamic dose without rescanning was validated as a surrogate to evaluate the interplay effects of IMPT for lung cancer in the clinical setting. The interplay effects potentially can be mitigated by increasing the amount of isolayered rescanning in each fraction delivery.

Minimum Detectable Dose as a Measure of Bioassay Programme Capability

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

Carbaugh, Eugene H.

2003-01-01

This paper suggests that minimum detectable dose (MDD) be used to describe the capability of bioassay programs for which intakes are expected to be rare. This allows expression of the capability in units that correspond directly to primary dose limits. The concept uses the well-established analytical statistic minimum detectable amount (MDA) as the starting point and assumes MDA detection at a prescribed time post intake. The resulting dose can then be used as an indication of the adequacy or capability of the program for demonstrating compliance with the performance criteria. MDDs can be readily tabulated or plotted to demonstrate themore » effectiveness of different types of monitoring programs. The inclusion of cost factors for bioassay measurements can allow optimisation.« less

Minimum detectable dose as a measure of bioassay programme capability.

PubMed

Carbaugh, E H

2003-01-01

This paper suggests that minimum detectable dose (MDD) be used to describe the capability of bioassay programmes for which intakes are expected to be rare. This allows expression of the capability in units that correspond directly to primary dose limits. The concept uses the well established analytical statistic minimum detectable amount (MDA) as the starting point, and assumes MDA detection at a prescribed time post-intake. The resulting dose can then be used as an indication of the adequacy or capability of the programme for demonstrating compliance with the performance criteria. MDDs can be readily tabulated or plotted to demonstrate the effectiveness of different types of monitoring programmes. The inclusion of cost factors for bioassay measurements can allow optimisation.

Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System

PubMed Central

Alwood, Joshua S.; Tran, Luan H.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Kumar, Akhilesh; Hilton, Diane; Tahimic, Candice G. T.; Globus, Ruth K.

2017-01-01

Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET 56Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA’s Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed by RT-PCR during the proliferative or mineralizing phase of growth, and differentiation was analyzed by imaging mineralized nodules. As expected, a high dose (200 cGy), but not lower doses, of either 56Fe or protons caused a loss of cancellous bone volume/total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; 56Fe (200 cGy) inhibited osteoblastogenesis by more than 90% (5 weeks and 1 year post-IR). After 5 weeks, irradiation (protons or 56Fe) caused few changes in gene expression levels during osteoblastogenesis, although a high dose 56Fe (200 cGy) increased Catalase and Gadd45. The addition of exogenous superoxide dismutase (SOD) protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET (137Cs γ) when irradiated in vitro, but had limited protective effects on high-LET 56Fe-exposed cells. In sum, either protons or 56Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET 56Fe increased redox-related gene expression, albeit to a limited extent, and inhibited osteoblastogenesis. Doses below 50 cGy did not elicit widespread responses in any parameter measured. We conclude that high-LET irradiation at 200 cGy impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss. PMID:28994728

Does oral polio vaccine have non-specific effects on all-cause mortality? Natural experiments within a randomised controlled trial of early measles vaccine.

PubMed

Aaby, Peter; Andersen, Andreas; Martins, Cesário L; Fisker, Ane B; Rodrigues, Amabelia; Whittle, Hilton C; Benn, Christine S

2016-12-23

BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs). If an unplanned intervention with a vaccine (a natural experiment) modifies the estimated effect in a randomised controlled trial (RCT), this suggests NSEs. We used this approach to test NSEs of triple oral polio vaccine (OPV). During an RCT of 2 doses of MV at 4.5 and 9 months versus 1 dose of MV at 9 months of age, we experienced 2 natural experiments with OPV. We assessed whether these OPV experiments modified the effect of 2-dose MV in the MV trial. MV RCT conducted in urban Guinea-Bissau 2003-2009. Natural experiments with OPV due to missing vaccine and the implementation of OPV campaigns. Changes in the mortality rate ratio (MRR) for 2-dose MV versus 1-dose MV. First, the MRR (2-dose/1-dose MV) overall was 0.70 (0.52 to 0.94), but the MRR was 1.04 (0.53 to 2.04) when OPV at birth (OPV0) was not given, suggesting that early priming with OPV was important for the effect of 2-dose MV. The effect of OPV0 depended on age of administration; the MRR (2-dose/1-dose MV) was 0.45 (0.29 to 0.71) for children receiving OPV0 in the first week of life, but 3.63 (0.87 to 15.2) for those receiving OPV0 after the first month of life (p=0.007, test of no interaction). Second, campaign-OPV may have reduced the difference between the randomisation groups since the MRR (2-dose/1-dose MV) was 0.60 (0.42 to 0.85) for children who had not received campaign-OPV before RCT-enrolment versus 0.72 (0.23 to 2.31) and 1.42 (0.70 to 2.90) for children who had received 1 or 2 doses of campaign-OPV-before-enrolment, respectively. Bissau had no polio infection during this trial, so OPV0 and campaign-OPV may have NSEs since they modified the effect of 2-dose MV in an RCT. Different interventions may interact to a much larger effect than usually assumed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Radiation dose to physicians’ eye lens during interventional radiology

NASA Astrophysics Data System (ADS)

Bahruddin, N. A.; Hashim, S.; Karim, M. K. A.; Sabarudin, A.; Ang, W. C.; Salehhon, N.; Bakar, K. A.

2016-03-01

The demand of interventional radiology has increased, leading to significant risk of radiation where eye lens dose assessment becomes a major concern. In this study, we investigate physicians' eye lens doses during interventional procedures. Measurement were made using TLD-100 (LiF: Mg, Ti) dosimeters and was recorded in equivalent dose at a depth of 0.07 mm, Hp(0.07). Annual Hp(0.07) and annual effective dose were estimated using workload estimation for a year and Von Boetticher algorithm. Our results showed the mean Hp(0.07) dose of 0.33 mSv and 0.20 mSv for left and right eye lens respectively. The highest estimated annual eye lens dose was 29.33 mSv per year, recorded on left eye lens during fistulogram procedure. Five physicians had exceeded 20 mSv dose limit as recommended by international commission of radiological protection (ICRP). It is suggested that frequent training and education on occupational radiation exposure are necessary to increase knowledge and awareness of the physicians’ thus reducing dose during the interventional procedure.

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2010-01-01 2010-01-01 false Occupational dose limits for general employees. 835.202...

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2014-01-01 2014-01-01 false Occupational dose limits for general employees. 835.202...

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2012-01-01 2012-01-01 false Occupational dose limits for general employees. 835.202...

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2013-01-01 2013-01-01 false Occupational dose limits for general employees. 835.202...

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2011-01-01 2011-01-01 false Occupational dose limits for general employees. 835.202...

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

PubMed

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

2003-07-01

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

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

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

PubMed

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

2016-01-01

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

Doses to medical workers operating in a PET/CT department after the use of new dynamic techniques.

NASA Astrophysics Data System (ADS)

Dalianis, K.; Kollias, G.; Malamitsi, J.; Euthimiadou, R.; Andreou, J.; Georgiou, E.; Prassopoulos, V.

2015-09-01

Since new radiopharmaceuticals are used like [18F]-fluoro-3'-deoxy-3'-L- fluorothymidine and 18F fluoromethylcholine, also new dynamic techniques of imaging are used, measurements concerning the doses to medical staff are needed. The aim of this study was to measure the effective whole body dose of the personnel and compare them with the oldest. Estimation of equivalent dose for all members of the staff was monitored with the use of TLDs badges and electronic dosimeters. The duration of the study was year 2011 (983 patients).Concerning the nurses, we measured 10% increase in the wholebody doses and that is due to the longer time they spent near the patient (dynamic protocol). For technologist we measure 15-21% increase for they come near the patient immediately after administration. We can observe that there is an increase of the doses for technologists and nurses the numbers are significantly lower than the recommended annual dose limit by Euratrom 97/43.

Replacing the Measles Ten-Dose Vaccine Presentation with the Single-Dose Presentation in Thailand

PubMed Central

Lee, Bruce Y.; Assi, Tina-Marie; Rookkapan, Korngamon; Connor, Diana L.; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T.; Welling, Joel S.; Norman, Bryan A.; Chen, Sheng-I; Bailey, Rachel R.; Wiringa, Ann E.; Wateska, Angela R.; Jana, Anirban; Van Panhuis, Willem G.; Burke, Donald S.

2011-01-01

Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes entailed to deliver vaccines from manufacturers to patients). We developed a computational model of Thailand’s Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose Measles-Mumps-Rubella vaccine (which Thailand is currently considering) and a single-dose measles vaccine. While the Trang province vaccine supply chain would generally have enough storage and transport capacity to accommodate the switches, the added volume could push some locations’ storage and transport space utilization close to their limits. Single-dose vaccines would allow for more precise ordering and decrease open vial waste, but decrease reserves for unanticipated demand. Moreover, the added disposal and administration costs could far outweigh the costs saved from preventing open vial wastage. PMID:21439313

COMPREHENSIVE DATA CONCERNING COSMIC RADIATION DOSES AT GROUND LEVEL AND IN-FLIGHTS FOR TURKEY.

PubMed

Parmaksız, A

2016-12-01

Cosmic radiation doses of individuals living in 81 cities in Turkey were estimated by using CARI-6 software. Annual cosmic radiation doses of individuals were found to be between 308 and 736 µSv y -1 at ground level. The population-weighted annual effective dose from cosmic radiation was determined to be 387 µSv y -1 for Turkey. Cosmic radiation doses on-board for 137 (60 domestic and 77 international) flights varied from 1.2 to 83 µSv. It was estimated that six or over long-route round-trip air travels may cause cosmic radiation dose above the permissible limit for member of the public, i.e. 1 mSv y -1 According to the assumption of flights throughout 800 h on each route, cosmic radiation doses were found to be between 1.0 and 4.8 mSv for aircrew. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Combined Hazard Index Fire Test Methodology for Aircraft Cabin Materials. Volume I.

DTIC Science & Technology

1982-04-01

PROGRAM TEST PANEL NO. 1 ....... 52 5 SUMARY OF EXPERIMTAL CHAS/SATS DATA FOR CI PRGRAM TEST PANEL 2, 3 & 4...As indicated in Figure 2, the dose of each hazard building up in CHI zone 13 is approaching an "effective dose" limit which prevents occupant escape...per minute. During a test, flow into SATS was stopped when CO reached peak concentrations to prevent dilution thereafter at decreasing sample CO

Small-spot laser-exposure effects on visual function

NASA Astrophysics Data System (ADS)

Zwick, Harry; Robbins, David O.; Stuck, Bruce E.; Lund, David J.; Reynolds, Scottie B.; Nawim, Maqsood; Schuschereba, Steven T.

1990-07-01

Laser field exposure effects on visual function involve produc tJon of minimal spot irradiation on or near the huntan fovea. Functional effects of such exposure may involve transient or perinanent change in visual function depending upon exposure dose. While Maximun Permissible Exposure (MPE) lirrtits define exposure in terins of threshold retinal niorphological change such limits are not applicable with regard to transient changes in visual function below MPE limits induced by alteration in retinal physiological processes. Mechanisms of transient and permanent functional change reported in these exper iments point out the need to examine laser safety limits in terms of both the functional as well as the morphological disturbance induced in retinal tissue. L

Chronic tiagabine administration and aggressive responding in individuals with a history of substance abuse and antisocial behavior.

PubMed

Gowin, Joshua L; Green, Charles E; Alcorn, Joseph L; Swann, Alan C; Moeller, F Gerard; Lane, Scott D

2012-07-01

Anticonvulsants, notably those which modulate GABA activity, have shown efficacy in reducing aggressive behavior. Previously, we found dose-related decreases in human aggressive responding following acute tiagabine administration. Here, we examined the effects of chronic tiagabine over a 5-week period. Twelve individuals at increased risk for aggressive and violent behavior (currently on parole/probation with personality and/or substance use disorders) were randomly assigned to placebo (n = 6) or an escalating dose sequence of placebo, 4 mg, 8 mg, 12 mg, placebo (n = 6). Data were analyzed using both frequentist and Bayesian mixed models, evaluating aggressive behavior as a function of time, dose condition, and their interaction. For aggressive responding, there was a significant interaction of drug condition and time. Aggression in the tiagabine condition decreased for each additional week in the study, while participants in the placebo condition failed to demonstrate similar change over time. For monetary-reinforced responding, no drug or drug by time interactions were observed, suggesting specificity of drug effects on aggression. The small number of subjects limits the generality of the findings, and previous studies with tiagabine are limited to acute dosing and case report investigations. However, the present data provide an indication that tiagabine merits further examination as an agent for management of impulsive aggression.

Radiation-induced cataracts: the Health Protection Agency's response to the ICRP statement on tissue reactions and recommendation on the dose limit for the eye lens.

PubMed

Bouffler, Simon; Ainsbury, Elizabeth; Gilvin, Phil; Harrison, John

2012-12-01

This paper presents the response of the Health Protection Agency (HPA) to the 2011 statement from the International Commission on Radiological Protection (ICRP) on tissue reactions and recommendation of a reduced dose limit for the lens of the eye. The response takes the form of a brief review of the most recent epidemiological and mechanistic evidence. This is presented together with a discussion of dose limits in the context of the related risk and the current status of eye dosimetry, which is relevant for implementation of the limits. It is concluded that although further work is desirable to quantify better the risk at low doses and following protracted exposures, along with research into the mechanistic basis for radiation cataractogenesis to inform selection of risk projection models, the HPA endorses the conclusion reached by the ICRP in their 2011 statement that the equivalent dose limit for the lens of the eye should be reduced from 150 to 20 mSv per year, averaged over a five year period, with no year's dose exceeding 50 mSv.

Measurement of the natural radioactivity in building materials used in Ankara and assessment of external doses.

PubMed

Turhan, S; Baykan, U N; Sen, K

2008-03-01

A total of 183 samples of 20 different commonly used structural and covering building materials were collected from housing and other building construction sites and from suppliers in Ankara to measure the natural radioactivity due to the presence of (226)Ra, (232)Th and (40)K. The measurements were carried out using gamma-ray spectrometry with two HPGe detectors. The specific activities of the different building materials studied varied from 0.5 +/- 0.1 to 144.9 +/- 4.9 Bq kg(-1), 0.6 +/- 0.2 to 169.9 +/- 6.6 Bq kg(-1) and 2.0 +/- 0.1 to 1792.3 +/- 60.8 Bq kg(-1) for (226)Ra, (232)Th and (40)K, respectively. The results show that the lowest mean values of the specific activity of (226)Ra, (232)Th and (40)K are 0.8 +/- 0.5, 0.9 +/- 0.4 and 4.1 +/- 1.4 Bq kg(-1), respectively, measured in travertine tile while the highest mean values of the specific activity of the same radionuclides are 78.5 +/- 18.1 (ceramic wall tile), 77.4 +/- 53.0 (granite tile) and 923.4 +/- 161.0 (white brick), respectively. The radium equivalent activity (Ra(eq)), the gamma-index, the indoor absorbed dose rate and the corresponding annual effective dose were evaluated to assess the potential radiological hazard associated with these building materials. The mean values of the gamma-index and the estimated annual effective dose due to external gamma radiation inside the room for structural building materials ranged from 0.15 to 0.89 and 0.2 to 1.1 mSv, respectively. Applying criteria recently recommended for building materials in the literature, four materials meet the exemption annual dose criterion of 0.3 mSv, five materials meet the annual dose limit of 1 mSv and only one material slightly exceeds this limit. The mean values of the gamma-index for all building materials were lower than the upper limit of 1.

Assessment of the occupational eye lens dose for clinical staff in interventional radiology, cardiology and neuroradiology.

PubMed

Omar, Artur; Kadesjö, Nils; Palmgren, Charlotta; Marteinsdottir, Maria; Segerdahl, Tony; Fransson, Annette

2017-03-20

In accordance with recommendations by the International Commission on Radiological Protection, the current European Basic Safety Standards has adopted a reduced occupational eye lens dose limit of 20 mSv yr -1 . The radiation safety implications of this dose limit is of concern for clinical staff that work with relatively high dose x-ray angiography and interventional radiology. Presented in this work is a thorough assessment of the occupational eye lens dose based on clinical measurements with active personal dosimeters worn by staff during various types of procedures in interventional radiology, cardiology and neuroradiology. Results are presented in terms of the estimated equivalent eye lens dose for various medical professions. In order to compare the risk of exceeding the regulatory annual eye lens dose limit for the widely different clinical situations investigated in this work, the different medical professions were separated into categories based on their distinct work pattern: staff that work (a) regularly beside the patient, (b) in proximity to the patient and (c) typically at a distance from the patient. The results demonstrate that the risk of exceeding the annual eye lens dose limit is of concern for staff category (a), i.e. mainly the primary radiologist/cardiologist. However, the results also demonstrate that the risk can be greatly mitigated if radiation protection shields are used in the clinical routine. The results presented in this work cover a wide range of clinical situations, and can be used as a first indication of the risk of exceeding the annual eye lens dose limit for staff at other medical centres.

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

PubMed

Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

2017-02-01

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (<75 mg) on sustained attention are limited and use short-term tests. Therefore, we investigated the acute effects of a 60 mg dose of caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

Repeated doses of cardiac mesenchymal cells are therapeutically superior to a single dose in mice with old myocardial infarction.

PubMed

Guo, Yiru; Wysoczynski, Marcin; Nong, Yibing; Tomlin, Alex; Zhu, Xiaoping; Gumpert, Anna M; Nasr, Marjan; Muthusamy, Senthikumar; Li, Hong; Book, Michael; Khan, Abdur; Hong, Kyung U; Li, Qianhong; Bolli, Roberto

2017-03-01

We have recently demonstrated that repeated administrations of c-kit POS cardiac progenitor cells (CPCs) have cumulative beneficial effects in rats with old myocardial infarction (MI), resulting in markedly greater improvement in left ventricular (LV) function compared with a single administration. To determine whether this paradigm applies to other species and cell types, mice with a 3-week-old MI received one or three doses of cardiac mesenchymal cells (CMCs), a novel cell type that we have recently described. CMCs or vehicle were infused percutaneously into the LV cavity, 14 days apart. Compared with vehicle-treated mice, the single-dose group exhibited improved LV ejection fraction (EF) after the 1st infusion (consisting of CMCs) but not after the 2nd and 3rd (vehicle). In contrast, in the multiple-dose group, LV EF improved after each CMC infusion, so that at the end of the study, LV EF averaged 35.5 ± 0.7% vs. 32.7 ± 0.6% in the single-dose group (P < 0.05). The multiple-dose group also exhibited less collagen in the non-infarcted region vs. the single-dose group. Engraftment and differentiation of CMCs were negligible in both groups, indicating paracrine effects. These results demonstrate that, in mice with ischemic cardiomyopathy, the beneficial effects of three doses of CMCs are significantly greater than those of one dose, supporting the concept that multiple treatments are necessary to properly evaluate the full therapeutic potential of cell therapy. Thus, the repeated-treatment paradigm is not limited to c-kit POS CPCs or to rats, but applies to other cell types and species. The generalizability of this concept dramatically augments its significance.

SU-F-J-48: Effect of Scan Length On Magnitude of Imaging Dose in KV CBCT

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

Deshpande, S; Naidu, S; Sutar, A

Purpose: To study effect of scan length on magnitude of imaging dose deposition in Varian kV CBCT for head & neck and pelvis CBCT. Methods: To study effect of scan length we measured imaging dose at depth of 8 cm for head and neck Cone Beam Computed Tomography (CBCT) acquisition ( X ray beam energy is used 100kV and 200 degree of gantry rotation) and at 16 cm depth for pelvis CBCT acquisition ( X ray beam energy used is 125 kV and 360 degree of gantry rotation) in specially designed phantom. We used farmer chamber which was calibrated inmore » kV X ray range for measurements .Dose was measured with default field size, and reducing field size along y direction to 10 cm and 5 cm. Results: As the energy of the beam decreases the scattered radiation increases and this contributes significantly to the dose deposited in the patient. By reducing the scan length to 10 Cm from default 20.6 cm we found a dose reduction of 14% for head and neck CBCT protocol and a reduction of 26% for pelvis CBCT protocol. Similarly for a scan length of 5cm compared to default the dose reduction in head and neck CBCT protocol is 36% while in the pelvis CBCT protocol the dose reduction is 50%. Conclusion: By limiting the scan length we can control the scatter radiation generated and hence the dose to the patient. However the variation in dose reduction for same length used in two protocols is because of the scan geometry. The pelvis CBCT protocol uses a full rotation and head and neck CBCT protocol uses partial rotation.« less

The Effect of High-Dose Ionizing Radiation on the Isolated Photobiont of the Astrobiological Model Lichen Circinaria gyrosa

NASA Astrophysics Data System (ADS)

Meeßen, Joachim; Backhaus, Theresa; Brandt, Annette; Raguse, Marina; Böttger, Ute; de Vera, Jean-Pierre; de la Torre, Rosa

2017-02-01

Lichen symbioses between fungi and algae represent successful life strategies to colonize the most extreme terrestrial habitats. Consequently, space exposure and simulation experiments have demonstrated lichens' high capacity for survival, and thus, they have become models in astrobiological research with which to discern the limits and limitations of terrestrial life. In a series of ground-based irradiation experiments, the STARLIFE campaign investigated the resistance of astrobiological model organisms to galactic cosmic radiation, which is one of the lethal stressors of extraterrestrial environments. Since previous studies have identified that the alga is the more sensitive lichen symbiont, we chose the isolated photobiont Trebouxia sp. of the astrobiological model Circinaria gyrosa as a subject in the campaign. Therein, γ radiation was used to exemplify the deleterious effects of low linear energy transfer (LET) ionizing radiation at extremely high doses up to 113 kGy in the context of astrobiology. The effects were analyzed by chlorophyll a fluorescence of photosystem II (PSII), cultivation assays, live/dead staining and confocal laser scanning microscopy (CLSM), and Raman laser spectroscopy (RLS). The results demonstrate dose-dependent impairment of photosynthesis, the cessation of cell proliferation, cellular damage, a decrease in metabolic activity, and degradation of photosynthetic pigments. While previous investigations on other extraterrestrial stressors have demonstrated a high potential of resistance, results of this study reveal the limits of photobiont resistance to ionizing radiation and characterize γ radiation-induced damages. This study also supports parallel STARLIFE studies on the lichens Circinaria gyrosa and Xanthoria elegans, both of which harbor a Trebouxia sp. photobiont.

Prophylaxis of thromboembolism in bariatric surgery with parnaparin.

PubMed

Forestieri, Pietro; Quarto, Gennaro; De Caterina, Maurizio; Cuocolo, Alberto; Pilone, Vincenzo; Formato, Antonio; Ruocco, Aldo; Ferrari, Patrizio

2007-12-01

There are limited data on appropriate dosing of low-molecular-weight heparins (LMWHs) for venous thromboembolism (VTE) prophylaxis in bariatric surgery. The primary objective of this preliminary study was to evaluate the preoperative effects of increasing doses of the LMWH parnaparin on coagulation in severely obese patients undergoing bariatric surgery. Severely obese patients (BMI > 50 kg/m(2)) were administered three increasing single doses of parnaparin (3200, 4250, and 6400 IU) on the three consecutive days leading up to biliointestinal bypass surgery. Activated partial thromboplastin time (APTT), anti-factor IIa and anti-factor Xa levels were measured 1 h before and 4 h after dosing. The highest dose (6400 IU/day) was continued from the day of surgery until day 30 (recovery period). Intermittent pneumatic compression and stockings were applied during surgery and the recovery period, respectively. Lower limb echoDoppler and phleboscintigraphy, and pulmonary scintigraphy were used for VTE detection. Ten patients (mean BMI 52.4 kg/m(2)) were recruited into this study. During the preoperative dosing phase, parnaparin dose-dependently prolonged APTT, with the 6400 IU dose significantly prolonging APTT versus the lower doses. Meanwhile, anti-factor Xa and anti-factor IIa activity was increased by the 4250 and 6400 IU doses. After surgery, one patient with heparin resistance experienced pulmonary embolization. No bleeding complications were observed. The dose-response data reported in this preliminary study suggest that parnaparin doses of 4250 and 6400 IU may provide effective prophylaxis for VTE in patients undergoing bariatric surgery. However, given the small number of patients, larger, well-controlled trials are required to confirm these findings.

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

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

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

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

COBALT 60 KILOCURIE TELETHERAPY ADVANTAGES AND LIMITATIONS--TECHNICAL PROBLEMS

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

Patricio, M.B.

1961-12-01

The advantages of Co/sup 60/ therapy over conventional x-ray therapy, stemming from the fact that in the lst instance energy absorption within the tissues is by the Compton effect and in the 2nd case by the photoelectric effect, are: (1) increased skin tolerance, (2) reduced bone absorption, (3) increase in depth dose, (4) diminished radiation sickness, and (5) simplicity of operation. As a disadvantage, possibility of injury to adjacent organs is greater with Co/ sup 60/ therapy, since skin reactions, indicative of overdosage with x-ray therapy, may be absent. Some tumors at limited skin depth, such as in the larynx,more » are not amenable to Co/sup 60/ therapy because of the high exit dose. Various technical problems of Co/sup 60/ therapy are discussed, including precise localization of the tumor, calculation of dosage, use of filters to evenly distribute radiation and prevent hot spots, immobilization and positioning of the patient, and direct dosimetry for affirmation of calculated dosage. Favorable results are described in patients with urinary bladder tumors administered l50- to 200-rad daily doses, for a total of 6000 to 8000 rads over 6 to 8 weeks. (H.H.D.)« less

Medical and health physics management of a plutonium wound

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

Carbaugh, E.H.; Decker, W.A.; Swint, M.J.

1988-04-01

A puncture wound contaminated with plutonium and americium has provided an excellent case study for dealing with internal contamination. This case provides an opportunity to examine the effectiveness of diagnostic techniques, therapeutic techniques, dose assessment practices, and case management philosophy. The wound deposited 48 kBq of transuranic alpha activity in the right index finger. Minor surgery reduced the long-term wound burden to about 5.4 kBq. Chelation therapy with DTPA lasted 17 months and resulted in urinary excretion of about 7 kBq of the deposited activity. Therapy appears to have been effective in limiting early uptake and internal doses from thismore » wound. However, the possibility of slow future uptake from the wound exists. Thus, estimating long-term uptake and dose is difficult. In vivo measurements indicate that residual wound contamination is essentially constant. Within three weeks of the injury, an initial measurable liver burden was reduced by chelation therapy to below detectable limits, and no subsequent build-up has been observed. However, there is indication of a gradually increasing skeleton burden. The axillary lymph nodes have shown relatively constant, detectable activity. 8 refs., 3 figs.« less

Comparison of the therapeutic dose of warfarin in HIV-infected and HIV-uninfected patients: a study of clinical practice.

PubMed

Jackson, B S; Mokoena, T

2017-02-08

People infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims of this study were to determine whether the therapeutic dose of warfarin and induction time to therapeutic dose in HIV-infected patients differ from that in HIV-uninfected patients. A prospective and retrospective descriptive study of induction time to therapeutic warfarin dose, as well as of ambulant therapeutic warfarin dose, was performed. HIV-infected and HIV-uninfected patients being treated after deep venous thrombosis with or without pulmonary embolism were compared. Sex and use of antiretroviral drugs (ARVs) were also compared in the groups. 234 patients were entered into the study. Induction time to therapeutic warfarin dose did not differ between the 2 groups. The mean therapeutic dose of warfarin was higher in the HIV-infected than the HIV-uninfected group: 6.06 vs 5.72 mg/day, but this was not statistically significant (p=0.29). There was no difference in therapeutic warfarin dose between ARV-naïve groups-HIV-uninfected and HIV-infected patients not on ARVs. There appears to be little effect of HIV infection on warfarin dosing. Warfarin therapy should be administered conventionally in HIV-infected patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Time-resolved dosimetry using a pinpoint ionization chamber as quality assurance for IMRT and VMAT

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

Louwe, Robert J. W., E-mail: rob.louwe@ccdbh.org.nz; Satherley, Thomas; Day, Rebecca A.

Purpose: To develop a method to verify the dose delivery in relation to the individual control points of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) using an ionization chamber. In addition to more effective problem solving during patient-specific quality assurance (QA), the aim is to eventually map out the limitations in the treatment chain and enable a targeted improvement of the treatment technique in an efficient way. Methods: Pretreatment verification was carried out for 255 treatment plans that included a broad range of treatment indications in two departments using the equipment of different vendors. In-house developed softwaremore » was used to enable calculation of the dose delivery for the individual beamlets in the treatment planning system (TPS), for data acquisition, and for analysis of the data. The observed deviations were related to various delivery and measurement parameters such as gantry angle, field size, and the position of the detector with respect to the field edge to distinguish between error sources. Results: The average deviation of the integral fraction dose during pretreatment verification of the planning target volume dose was −2.1% ± 2.2% (1 SD), −1.7% ± 1.7% (1 SD), and 0.0% ± 1.3% (1 SD) for IMRT at the Radboud University Medical Center (RUMC), VMAT (RUMC), and VMAT at the Wellington Blood and Cancer Centre, respectively. Verification of the dose to organs at risk gave very similar results but was generally subject to a larger measurement uncertainty due to the position of the detector at a high dose gradient. The observed deviations could be related to limitations of the TPS beam models, attenuation of the treatment couch, as well as measurement errors. The apparent systematic error of about −2% in the average deviation of the integral fraction dose in the RUMC results could be explained by the limitations of the TPS beam model in the calculation of the beam penumbra. Conclusions: This study showed that time-resolved dosimetry using an ionization chamber is feasible and can be largely automated which limits the required additional time compared to integrated dose measurements. It provides a unique QA method which enables identification and quantification of the contribution of various error sources during IMRT and VMAT delivery.« less

SU-E-T-759: To Replan Or Not To Replan for Each Fraction Using Inverse Optimization for Multichannel Vaginal Cylinder

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

Balik, M; Rybak, M; Strongosky, M

2015-06-15

Purpose: This study investigates whether replanning each fraction for vaginal cuff HDR therapy using a multichannel cylinder (MC) and brachytherapy inverse optimization (BIO) provides dosimetric benefits to organs-at-risk (OAR). The goal was to appropriately cover the target and limit dose to OAR, as well as evaluate dosimetric changes for each fraction, while doing this in a timely and cost effective manner. Methods: From an initial selection of 57 patients that were treated with 3 fractions using a MC and BIO, a subset of n=12 patients was selected based on the criterion that one plan was used for all 3 fractions.more » A simulation CT was acquired prior to each fraction. CT scans for fractions 2 and 3 were fused to the initial CT. Contours for the bladder and rectum were manually drawn on CTs for all 3 fractions, and the clinical treatment volume (PTVeval) was defined. Cylinders were reconstructed using applicator modeling library, influencing time and cost effectiveness. Planning objectives were at least 95% prescription dose to 95% (D95%) of target volume and limiting high dose to OAR. Dose to 2 cm{sup 3} (D2cc) for each OAR was analyzed using a t-test. Results: This study concentrated on comparing 2cm{sup 3} of highest dose to OAR (D2cc), for each fraction for the plans that were used to treat all 3 fraction. Based on statistical analysis, using the initial plan for fractions 2 and 3 resulted in approximately 6% change to the highest D2cc of the bladder (p=0.03). Conclusion: Performing CT fusion and contours of each OAR on each fraction allows objective plan evaluation and supports decision making on the necessity of replanning based on improved dose sparing for OAR. Future studies will investigate the effects of replanning on maximum dose (D0.1cc) using the same physician-drawn OAR contours to avoid subjectivity.« less

Physics considerations in MV-CBCT multi-layer imager design.

PubMed

Hu, Yue-Houng; Fueglistaller, Rony; Myronakis, Marios E; Rottmann, Joerg; Wang, Adam; Shedlock, Daniel; Morf, Daniel; Baturin, Paul; Huber, Pascal; Star-Lack, Josh M; Berbeco, Ross I

2018-05-30

Megavoltage (MV) cone-beam computed tomography (CBCT) using an electronic portal imaging (EPID) offers advantageous features, including 3D mapping, treatment beam registration, high-z artifact suppression, and direct radiation dose calculation. Adoption has been slowed by image quality limitations and concerns about imaging dose. Developments in imager design, including pixelated scintillators, structured phosphors, inexpensive scintillation materials, and multi-layer imager (MLI) architecture have been explored to improve EPID image quality and reduce imaging dose. The present study employs a hybrid Monte Carlo and linear systems model to determine the effect of detector design elements, such as multi-layer architecture and scintillation materials. We follow metrics of image quality including modulation transfer function (MTF) and noise power spectrum (NPS) from projection images to 3D reconstructions to in-plane slices and apply a task based figure-of-merit, the ideal observer signal-to-noise ratio (d') to determine the effect of detector design on object detectability. Generally, detectability was limited by detector noise performance. Deploying an MLI imager with a single scintillation material for all layers yields improvement in noise performance and d' linear with the number of layers. In general, improving x-ray absorption using thicker scintillators results in improved DQE(0). However, if light yield is low, performance will be affected by electronic noise at relatively high doses, resulting in rapid image quality degradation. Maximizing image quality in a heterogenous MLI detector (i.e. multiple different scintillation materials) is most affected by limiting imager noise. However, while a second-order effect, maximizing total spatial resolution of the MLI detector is a balance between the intensity contribution of each layer against its individual MTF. So, while a thinner scintillator may yield a maximal individual-layer MTF, its quantum efficiency will be relatively low in comparison to a thicker scintillator and thus, intensity contribution may be insufficient to noticeably improve the total detector MTF. © 2018 Institute of Physics and Engineering in Medicine.

Review article: Efficacy and safety of methoxyflurane analgesia in the emergency department and prehospital setting.

PubMed

Grindlay, Joanne; Babl, Franz E

2009-02-01

This article reviews the evidence for the analgesic efficacy of methoxyflurane in both prehospital and ED settings, as well as the adverse event profile associated with methoxyflurane use. Although there are no published controlled trials of methoxyflurane in sub-anaesthetic doses, available data indicate that it is an efficacious analgesic. There is inadequate evidence regarding its use as an agent for procedural pain. Despite the potential for renal impairment evident when it was used in anaesthetic doses, no significant adverse effects have been reported in the literature, neither in patients nor occupationally, when the dose used is limited to that currently recommended.

SU-E-T-284: Dose Plan Optimization When Using Hydrogel Prostate-Rectum Spacer: A Single Institution Experience

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

Rajecki, M; Thurber, A; Catalfamo, F

2015-06-15

Purpose: To describe rectal dose reduction achieved and techniques used to take advantage of the increased peri-rectal spacing provided by injected polyethylene-glycol. Methods: Thirty prostate cancer patents were 2:1 randomized during a clinical trial to evaluate the effectiveness of injected poly-ethylene glycol hydrogel (SpaceOAR System) in creating space between the prostate and the anterior rectal wall. All patients received a baseline CT/MR scan and baseline IMRT treatment plan. Patients were randomized to receive hydrogel injection (n=20) or Control (n=10), followed by another CT/MR scan and treatment plan (single arc VMAT, 6 MV photons, 79.2 Gy, 44 fractions). Additional optimization structuresmore » were employed to constrain the dose to the rectum; specifically an avoidance structure to limit V75 <15%, and a control structure to limit the maximum relative dose <105% in the interface region of the anterior rectal wall and the prostate planning target volume. Dose volumetric data was analyzed for rectal volumes receiving 60 through 80 Gy. Results: Rectal dose reduction was observed in all patients who received the hydrogel. Volumetric analysis indicates a median rectal volume and (reduction from baseline plan) following spacer application of 4.9% (8.9%) at V60Gy, 3.8% (8.1%) at V65Gy, 2.5% (7.2%) at V70Gy, 1.6% (5.8%) at V75Gy, and 0.5% (2.5%) at V80Gy. Conclusion: Relative to planning without spacers, rectal dose constraints of 5%, 4%, 3%, 2%, 1% for V60, V65, V70, V75, and V80, should be obtainable when peri-rectal spacers are used. The combined effect of increased peri-rectal space provided by the hydrogel, with strict optimization objectives, resulted in reduced dose to the rectum. To maximize benefit, strict optimization objectives and reduced rectal dose constraints should be employed when creating plans for patients with perirectal spacers. Clinical Trial for SpaceOAR product conducted by Augmenix,Inc. The research site was paid to be a participating site.« less

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

PubMed

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

2013-06-04

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

Biological monitoring to determine worker dose in a butadiene processing plant

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

Bechtold, W.E.; Hayes, R.B.

1995-12-01

Butadiene (BD) is a reactive gas used extensively in the rubber industry and is also found in combustion products. Although BD is genotoxic and acts as an animal carcinogen, the evidence for carcinogenicity in humans is limited. Extrapolation from animal studies on BD carcinogenicity to risk in humans has been controversial because of uncertainties regarding relative biologic exposure and related effects in humans vs. experimental animals. To reduce this uncertainty, a study was designed to characterize exposure to BD at a polymer production facility and to relate this exposure to mutational and cytogenetic effects. Biological monitoring was used to bettermore » assess the internal dose of BD received by the workers. Measurement of 1,2-dihydroxy-4-(N-acetylcysteinyl) butane (M1) in urine served as the biomarker in this study. M1 has been shown to correlate with area monitoring in previous studies. Most studies that relate exposure to a toxic chemical with its biological effects rely on exposure concentration as the dose metric; however, exposure concentration may or may not reflect the actual internal dose of the chemical.« less

Reduced suppression of CO2-induced ventilatory stimulation by endomorphins relative to morphine.

PubMed

Czapla, Marc A; Zadina, James E

2005-10-19

Opioids are among the most effective analgesics, but a major limitation for their therapeutic usefulness is their induction of respiratory depression. Endomorphin-1 (EM1), in contrast to several other mu opioids, exhibits a threshold for respiratory depression that is well above its threshold for analgesia. Its effect on sensitivity to CO(2), however, remains unknown. Minute ventilation (V(E)) in 2, 4, and 6% CO(2) was measured before and after systemic administration of EM1, endomorphin-2 (EM2), DAMGO, and morphine in the conscious rat. EM1 and EM2 attenuated the hypercapnic ventilatory response (HCVR) only in high doses, while DAMGO and morphine diminished the HCVR in much lower doses. The ventilatory effects of high doses of all 4 agonists were blocked by the mu-opioid antagonist naloxone (0.4 mg/kg i.v.), but not by the peripherally restricted mu-opioid antagonist, methyl-naloxone (0.4 mg/kg i.v.). It was concluded that the endomorphins attenuated the HCVR only in large doses, well beyond the analgesic threshold, and did so through a centrally mediated mu-opioid mechanism.

Exploring the collaboration between antibiotics and the immune response in the treatment of acute, self-limiting infections.

PubMed

Ankomah, Peter; Levin, Bruce R

2014-06-10

The successful treatment of bacterial infections is the product of a collaboration between antibiotics and the host's immune defenses. Nevertheless, in the design of antibiotic treatment regimens, few studies have explored the combined action of antibiotics and the immune response to clearing infections. Here, we use mathematical models to examine the collective contribution of antibiotics and the immune response to the treatment of acute, self-limiting bacterial infections. Our models incorporate the pharmacokinetics and pharmacodynamics of the antibiotics, the innate and adaptive immune responses, and the population and evolutionary dynamics of the target bacteria. We consider two extremes for the antibiotic-immune relationship: one in which the efficacy of the immune response in clearing infections is directly proportional to the density of the pathogen; the other in which its action is largely independent of this density. We explore the effect of antibiotic dose, dosing frequency, and term of treatment on the time before clearance of the infection and the likelihood of antibiotic-resistant bacteria emerging and ascending. Our results suggest that, under most conditions, high dose, full-term therapy is more effective than more moderate dosing in promoting the clearance of the infection and decreasing the likelihood of emergence of antibiotic resistance. Our results also indicate that the clinical and evolutionary benefits of increasing antibiotic dose are not indefinite. We discuss the current status of data in support of and in opposition to the predictions of this study, consider those elements that require additional testing, and suggest how they can be tested.

Dengue and chikungunya viruses in plasma are effectively inactivated after treatment with methylene blue and visible light.

PubMed

Fryk, Jesse J; Marks, Denese C; Hobson-Peters, Jody; Prow, Natalie A; Watterson, Daniel; Hall, Roy A; Young, Paul R; Reichenberg, Stefan; Sumian, Chryslain; Faddy, Helen M

2016-09-01

Arboviruses, such as dengue viruses (DENV) and chikungunya virus (CHIKV), pose a risk to the safe transfusion of blood components, including plasma. Pathogen inactivation is an approach to manage this transfusion transmission risk, with a number of techniques being used worldwide for the treatment of plasma. In this study, the efficacy of the THERAFLEX MB-Plasma system to inactivate all DENV serotypes (DENV-1, DENV-2, DENV-3, DENV-4) or CHIKV in plasma, using methylene blue and light illumination at 630 nm, was investigated. Pooled plasma units were spiked with DENV-1, DENV-2, DENV-3 DENV-4, or CHIKV and treated with the THERAFLEX MB-Plasma system at four light illumination doses: 20, 40, 60, and 120 (standard dose) J/cm(2) . Pre- and posttreatment samples were collected and viral infectivity was determined. The reduction in viral infectivity was calculated for each dose. Treatment of plasma with the THERAFLEX MB-Plasma system resulted in at least a 4.46-log reduction in all DENV serotypes and CHIKV infectious virus. The residual infectivity for each was at the detection limit of the assay used at 60 J/cm(2) , with dose dependency also observed. Our study demonstrated the THERAFLEX MB-Plasma system can reduce the infectivity of all DENV serotypes and CHIKV spiked into plasma to the detection limit of the assay used at half of the standard illumination dose. This suggests this system has the capacity to be an effective option for managing the risk of DENV or CHIKV transfusion transmission in plasma. © 2016 AABB.

Relative radiological risks derived from different TENORM wastes in Malaysia.

PubMed

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

2011-11-01

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

User Guide for GoldSim Model to Calculate PA/CA Doses and Limits

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

Smith, F.

2016-10-31

A model to calculate doses for solid waste disposal at the Savannah River Site (SRS) and corresponding disposal limits has been developed using the GoldSim commercial software. The model implements the dose calculations documented in SRNL-STI-2015-00056, Rev. 0 “Dose Calculation Methodology and Data for Solid Waste Performance Assessment (PA) and Composite Analysis (CA) at the Savannah River Site”.

Effects of clinically relevant doses of methyphenidate on spatial memory, behavioral sensitization and open field habituation: a time related study.

PubMed

Haleem, Darakhshan Jabeen; Inam, Qurrat-ul-Aen; Haleem, Muhammad Abdul

2015-03-15

The psychostimulant methylphenidate (MPD) is a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD). Despite acceptable therapeutic efficacy, there is limited data regarding the long-term consequences of MPD exposure over extended periods. The present study concerns effects of clinically relevant doses of MPD, administered orally to rats for an extended period, on spatial memory, behavioral sensitization and habituation to an open field. Water maze test was used to monitor memory acquisition (2 h after training), retention (day next to training), extinction (1 week after training) and reconsolidation (weekly for 4 weeks). Administration of MPD at doses of 0.25-1.0 mg/kg improved memory acquisition, retention, reconsolidation and impaired memory extinction. Treatment with 0.25 and 0.5 mg/kg MPD for 6 weeks produced a sustained increase in motor activity but higher dose (1.0 mg/kg) elicited behavioral sensitization. High as well as low doses MPD impaired open field habituation. We conclude that clinically relevant doses of MPD enhance memory even if used for extended period. It is suggested that higher (1.0 mg/kg) clinically relevant doses of MPD, if used for extended period, may exacerbate hyperactivity and impulsivity associated with the disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of the MCNP5 code to the Modeling of vaginal and intra-uterine applicators used in intracavitary brachytherapy: a first approach

NASA Astrophysics Data System (ADS)

Gerardy, I.; Rodenas, J.; Van Dycke, M.; Gallardo, S.; Tondeur, F.

2008-02-01

Brachytherapy is a radiotherapy treatment where encapsulated radioactive sources are introduced within a patient. Depending on the technique used, such sources can produce high, medium or low local dose rates. The Monte Carlo method is a powerful tool to simulate sources and devices in order to help physicists in treatment planning. In multiple types of gynaecological cancer, intracavitary brachytherapy (HDR Ir-192 source) is used combined with other therapy treatment to give an additional local dose to the tumour. Different types of applicators are used in order to increase the dose imparted to the tumour and to limit the effect on healthy surrounding tissues. The aim of this work is to model both applicator and HDR source in order to evaluate the dose at a reference point as well as the effect of the materials constituting the applicators on the near field dose. The MCNP5 code based on the Monte Carlo method has been used for the simulation. Dose calculations have been performed with *F8 energy deposition tally, taking into account photons and electrons. Results from simulation have been compared with experimental in-phantom dose measurements. Differences between calculations and measurements are lower than 5%.The importance of the source position has been underlined.

Exhaled breath malondialdehyde as a matter of effect of exposure to airpollution in children with asthma

EPA Science Inventory

BACKGROUND: Assessment of the adverse effects of oxidative stress related to air pollution is limited by the lack of biological markers of dose to the lungs. OBJECTIVE: We evaluated the use of exhaled breath condensate (EBC) malondialdehyde as a biomarker of exposure to traffic-r...

A procedure to determine the planar integral spot dose values of proton pencil beam spots

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

Anand, Aman; Sahoo, Narayan; Zhu, X. Ronald

2012-02-15

Purpose: Planar integral spot dose (PISD) of proton pencil beam spots (PPBSs) is a required input parameter for beam modeling in some treatment planning systems used in proton therapy clinics. The measurement of PISD by using commercially available large area ionization chambers, like the PTW Bragg peak chamber (BPC), can have large uncertainties due to the size limitation of these chambers. This paper reports the results of our study of a novel method to determine PISD values from the measured lateral dose profiles and peak dose of the PPBS. Methods: The PISDs of 72.5, 89.6, 146.9, 181.1, and 221.8 MeVmore » energy PPBSs were determined by area integration of their planar dose distributions at different depths in water. The lateral relative dose profiles of the PPBSs at selected depths were measured by using small volume ion chambers and were investigated for their angular anisotropies using Kodak XV films. The peak spot dose along the beam's central axis (D{sub 0}) was determined by placing a small volume ion chamber at the center of a broad field created by the superposition of spots at different locations. This method allows eliminating positioning uncertainties and the detector size effect that could occur when measuring it in single PPBS. The PISD was then calculated by integrating the measured lateral relative dose profiles for two different upper limits of integration and then multiplying it with corresponding D{sub 0}. The first limit of integration was set to radius of the BPC, namely 4.08 cm, giving PISD{sub RBPC}. The second limit was set to a value of the radial distance where the profile dose falls below 0.1% of the peak giving the PISD{sub full}. The calculated values of PISD{sub RBPC} obtained from area integration method were compared with the BPC measured values. Long tail dose correction factors (LTDCFs) were determined from the ratio of PISD{sub full}/PISD{sub RBPC} at different depths for PPBSs of different energies. Results: The spot profiles were found to have angular anisotropy. This anisotropy in PPBS dose distribution could be accounted in a reasonable approximate manner by taking the average of PISD values obtained using the in-line and cross-line profiles. The PISD{sub RBPC} values fall within 3.5% of those measured by BPC. Due to inherent dosimetry challenges associated with PPBS dosimetry, which can lead to large experimental uncertainties, such an agreement is considered to be satisfactory for validation purposes. The PISD{sub full} values show differences ranging from 1 to 11% from BPC measured values, which are mainly due to the size limitation of the BPC to account for the dose in the long tail regions of the spots extending beyond its 4.08 cm radius. The dose in long tail regions occur both for high energy beams such as 221.8 MeV PPBS due to the contributions of nuclear interactions products in the medium, and for low energy PPBS because of their larger spot sizes. The calculated LTDCF values agree within 1% with those determined by the Monte Carlo (MC) simulations. Conclusions: The area integration method to compute the PISD from PPBS lateral dose profiles is found to be useful both to determine the correction factors for the values measured by the BPC and to validate the results from MC simulations.« less

Characterization of the Antinociceptive Effects of the Individual Isomers of Methadone Following Acute and Chronic Administration

PubMed Central

Morgan, Richard W.; Nicholson, Katherine L.

2011-01-01

Methadone is a long-acting opioid used in the treatment of various pain states and substitution therapy in heroin addiction. Extensive behavioral characterization has been carried out utilizing the racemate, but limited investigation has been performed with the individual isomers. While the l-isomer is a potent opioid agonist, the d-isomer has weak μ opioid activity and has also been shown to possess N-methyl-d-aspartate (NMDA) antagonist properties in vitro. The acute antinociceptive effects of the isomers were evaluated in rats using a warm water tail withdrawal procedure at two stimulus intensities (50° and 55° C). Increasing dose ratios of d- to l-methadone were administered chronically to determine the ability of the d-isomer to modulate antinociceptive tolerance to the l-isomer. Acutely, both l- (0.1-5.6 mg/kg, sc) and d- (3.0-56.0 mg/kg, sc) methadone produced antinociception though the efficacy of the d-isomer was limited at 55° C. These effects were dose-dependently blocked by naltrexone (0.01-1.0 mg/kg, sc). Administered chronically, d-methadone (1.7-10 mg/kg, sc) dose-dependently blocked tolerance development to the l-isomer (1.7 mg/kg, sc). These findings support the antinociceptive effects of the isomers being opioid receptor mediated with the l-isomer functioning as a full efficacy agonist whereas the d-isomer appears to have lower efficacy. The ability of nonracemic doses of the d-isomer to prevent tolerance development to the l-isomer may be attributed to partial μ agonist activity however NMDA antagonist activity cannot be discounted. PMID:21836464

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

PubMed

Kum, Oyeon

2018-06-01

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

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

PubMed

Sakai, K

2018-01-01

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

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men. Copyright © 2017 by the American Society of Nephrology.

The effect of phenytoin, phenobarbitone, dexamethasone and flurbiprofen on misonidazole neurotoxicity in mice.

PubMed Central

Sheldon, P. W.; Clarke, C.; Dawson, K. B.

1984-01-01

Using a quantitative cytochemical technique for measuring beta-glucuronidase activity in the peripheral nerves of mice, we have investigated the effectiveness of four potential adjuncts for reducing the dose limiting neurotoxicity of misonidazole (MISO) in the clinic. Under the conditions used, the most effective adjunct was the steroid anti-inflammatory agent dexamethasone. When given over the week previous to MISO treatment, this agent almost completely eliminated the MISO neurotoxicity as determined at week 4 after commencement of MISO dosing. The second most effective adjunct was phenytoin, the third flurbiprofen and the last adjunct, phenobarbitone, was ineffective. Dexamethasone, phenytoin and phenobarbitone all reduced the clearance half-life of MISO and hence the drug exposure dose calculated as the area under the curve of MISO tissue concentration against time. However, no correlation was evident with these parameters and MISO neurotoxicity in the mouse. Dexamethasone, whilst affording protection against MISO toxicity, did not alter the radiosensitivity of the anaplastic MT tumour. PMID:6696821

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

PubMed

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

2017-10-01

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

Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

PubMed

Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

2016-01-27

Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation.

Rationale behind high-dose amoxicillin therapy for acute otitis media due to penicillin-nonsusceptible pneumococci: support from in vitro pharmacodynamic studies.

PubMed Central

Lister, P D; Pong, A; Chartrand, S A; Sanders, C C

1997-01-01

To evaluate whether increased doses of amoxicillin should be used to treat acute pneumococcal otitis media, an in vitro pharmacokinetic model was used to evaluate the killing of pneumococci by amoxicillin when middle ear pharmacokinetics were simulated. Logarithmic-phase cultures were exposed to peak concentrations of 3, 6, and 9 microg of amoxicillin per ml every 12 h, and an elimination half-life of 1.6 h was simulated. Changes in viable bacterial counts were measured over 36 h. All three doses rapidly decreased the viable bacterial counts of penicillin-susceptible strains below the 10-CFU/ml limit of detection by 6 to 10 h and maintained counts below this limit through 36 h. The 3-microg/ml peak dose was much less effective against two of three strains with intermediate penicillin resistance and all three penicillin-resistant strains, with bacterial counts approaching those in drug-free control cultures by 12 h. The 6-microg/ml peak dose completely eliminated two of three strains with intermediate penicillin resistance and maintained viable counts of the other nonsusceptible strains at 1.5 to 2 logs below the initial inoculum through 36 h. The 9-microg/ml peak dose was most effective, completely eliminating all three strains with intermediate penicillin resistance and maintaining the viable counts of the resistant strains at 3 to 4 logs below the original inoculum. The pharmacodynamics observed in this study suggest that peak concentrations of amoxicillin of 6 to 9 microg/ml may be sufficient for the elimination of penicillin-nonsusceptible pneumococcal strains causing otitis media, especially those with intermediate resistance to amoxicillin. In vivo pharmacokinetic studies are needed to determine if these levels can be achieved in middle ear fluid with amoxicillin at 70 to 90 mg/kg/day divided into two daily doses. If these levels are reliably achieved, then clinical studies are warranted. PMID:9303386

Directionality of Skyshine Radiation

NASA Astrophysics Data System (ADS)

Kernan, Warnick; Conlin, Kenneth; Kouzes, Richard; Mace, Emily; Siciliano, Edward; Woodring, Mitchell

2010-02-01

Skyshine reflection, or the scattering off of the air above a source, is frequently observed in situations where large sources are incompletely shielded, such as radiography sources in shielding pits that are open to the sky. Originally, concern about skyshine regarded limiting the dose from the source. However, even in situations where dose is minimal, the contribution of skyshine may interfere with sensitive measurement instruments operating near background limits, such as with border security applications. To help determine effective methods for shielding sensitive detection systems from skyshine interference, a series of measurements and model simulations have been conducted using a specially configured, portable collimated detector and an iridium-192 source. This paper will report these results, and also show their similarity when compared to other measurements using different sources. )

Facial exposure to ultraviolet radiation: Predicted sun protection effectiveness of various hat styles.

PubMed

Backes, C; Religi, A; Moccozet, L; Vuilleumier, L; Vernez, D; Bulliard, J-L

2018-04-23

Solar ultraviolet radiation (UVR) doses received by individuals are highly influenced by behavioural and environmental factors. This study aimed at quantifying hats' sun protection effectiveness in various exposure conditions, by predicting UVR exposure doses and their anatomical distributions. A well-defined three-dimensional head morphology and four hat styles (a cap, a helmet, a middle- and a wide-brimmed hat) were added to a previously published model. Midday (12:00-14:00) and daily (08:00 - 17:00) seasonal UVR doses were estimated at various facial skin zones, with and without hat-wear, accounting for each UVR component. Protection effectiveness was calculated by the relative reduction of predicted UVR dose, expressed as a predictive protection factor (PPF). The unprotected entire face received 2.5 times higher UVR doses during a summer midday compared to a winter midday (3.3 vs. 1.3 SED) with highest doses received at the nose (6.1 SED). During a cloudless summer day, the lowest mean UVR dose is received by the entire face protected by a wide-brimmed hat (1.7 SED). No hat reached 100% protection at any facial skin zone (PPF max : 76%). Hats' sun protection effectiveness varied highly with environmental conditions and were mainly limited by the high contribution of diffuse UVR, irrespective of hat style. Larger brim sizes afforded greater facial protection than smaller brim sizes except around midday when the sun position is high. Consideration of diffuse and reflected UVR in sun educational messages could improve sun protection effectiveness. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clozapine Titration for People in Early Psychosis: A Chart Review and Treatment Guideline.

PubMed

Ballon, Jacob S; Ashfaq, Hera; Noordsy, Douglas L

2018-06-01

The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis. We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine. People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis. We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This approach resulted in clinical response at remarkably low maintenance doses of clozapine among people within their first year of illness, but not in those with longer duration of symptoms. Slow titration also led to good tolerability and acceptance of clozapine treatment for some patients.

Towards improved quantification of post-fire conifer mortality and recovery: Impacts of fire radiative flux on seedling and mature tree mortality, physiology, and growth

NASA Astrophysics Data System (ADS)

Sparks, A. M.; Kolden, C.; Smith, A. M.

2016-12-01

Fire activity, in terms of intensity, frequency, and total area burned, is expected to increase with changing climate. A challenge for landscape level assessment of fire effects, termed burn severity, is that current assessments provide very little information regarding vegetation physiological performance and recovery, limiting our understanding of fire effects on ecosystem services such as carbon storage/cycling. To address these limitations, we evaluated an alternative dose-response methodology for quantifying fire effects that attempts to bridge fire combustion dynamics and ecophysiology. Specifically, we conducted a highly controlled, laboratory assessment of seedling response to increasing doses of fire radiative energy applied through surface fires, for two western U.S. conifer species. Seedling physiology and spectral reflectance were acquired pre- and up to 1 year post-fire. Post-fire mortality, physiological performance, and spectral reflectance were strongly related with fire radiative energy density (FRED: J m-2) dose. To examine how these relationships change with tree size and age, we conducted small prescribed fires at the tree scale (35 m2) in a mature conifer stand. Radial growth and resin duct defenses were assessed on the mature conifer trees following the prescribed fires. Differences in dose-response relationships between seedlings and mature trees indicate the importance of fire behavior (e.g., flaming-dominated versus smoldering-dominated combustion) in characterizing these relationships. Ultimately, these results suggest that post-fire impacts on growth of surviving seedlings and mature trees require modes of heat transfer to impact tree canopies.

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

PubMed

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

1996-07-01

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

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

NASA Astrophysics Data System (ADS)

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

2015-05-01

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

Natural radioactivity measurements and dosimetric evaluations in soil samples with a high content of NORM

NASA Astrophysics Data System (ADS)

Caridi, F.; Marguccio, S.; Durante, G.; Trozzo, R.; Fullone, F.; Belvedere, A.; D'Agostino, M.; Belmusto, G.

2017-01-01

In this article natural radioactivity measurements and dosimetric evaluations in soil samples contaminated by Naturally Occurring Radioactive Materials (NORM) are made, in order to assess any possible radiological hazard for the population and for workers professionally exposed to ionizing radiations. Investigated samples came from the district of Crotone, Calabria region, South of Italy. The natural radioactivity investigation was performed by high-resolution gamma-ray spectrometry. From the measured gamma spectra, activity concentrations were determined for 226Ra , 234-mPa , 224Ra , 228Ac and 40K and compared with their clearance levels for NORM. The total effective dose was calculated for each sample as due to the committed effective dose for inhalation and to the effective dose from external irradiation. The sum of the total effective doses estimated for all investigated samples was compared to the action levels provided by the Italian legislation (D.Lgs.230/95 and subsequent modifications) for the population members (0.3mSv/y) and for professionally exposed workers (1mSv/y). It was found to be less than the limit of no radiological significance (10μSv/y).

The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit

NASA Astrophysics Data System (ADS)

Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K.

2008-11-01

Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e. predict the volume dependence. In recent studies of the volume effect of a rat spinal cord after irradiation with narrow and broad proton beams the authors claim that none of the existing NTCP models is able to describe their results. Published experimental data have been used here to try to quantify the change in the effective dose (D50) causing 50% response for different field sizes. The present study was initiated to describe the induction of white matter necrosis in a rat spinal cord after irradiation with narrow proton beams in terms of the mean dose to the effective volume of the functional subunit (FSU). The physically delivered dose distribution was convolved with a function describing the effective size or, more accurately, the sensitivity distribution of the FSU to obtain the effective mean dose deposited in it. This procedure allows the determination of the mean D50 value of the FSUs of a certain size which is of interest for example if the cell nucleus of the oligodendrocyte is the sensitive target. Using the least-squares method to compare the effective doses for different sizes of the functional subunits with the experimental data the best fit was obtained with a length of about 9 mm. For the non-uniform dose distributions an effective FSU length of 8 mm gave the optimal fit with the probit dose-response model. The method could also be used to interpret the so-called bath and shower experiments where the heterogeneous dose delivery was used in the convolution process. The assumption of an effective FSU size is consistent with most of the effects seen when different portions of the rat spinal cord are irradiated to different doses. The effective FSU length from these experiments is about 8.5 ± 0.5 mm. This length could be interpreted as an effective size of the functional subunits in a rat spinal cord, where multiple myelin sheaths are connected by a single oligodendrocyte and repair is limited by the range of oligodendrocyte progenitor cell diffusion. It was even possible to suggest a more likely than uniform effective FSU sensitivity distribution from the experimental data.

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

PubMed

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

2017-10-01

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

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

PubMed Central

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

2017-01-01

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

Investigating the Implications of a Variable RBE on Proton Dose Fractionation Across a Clinical Pencil Beam Scanned Spread-Out Bragg Peak

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

Marshall, Thomas I.; Chaudhary, Pankaj; Michaelidesová, Anna

2016-05-01

Purpose: To investigate the clinical implications of a variable relative biological effectiveness (RBE) on proton dose fractionation. Using acute exposures, the current clinical adoption of a generic, constant cell killing RBE has been shown to underestimate the effect of the sharp increase in linear energy transfer (LET) in the distal regions of the spread-out Bragg peak (SOBP). However, experimental data for the impact of dose fractionation in such scenarios are still limited. Methods and Materials: Human fibroblasts (AG01522) at 4 key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subjected to various fractionation regimens with an interfractionmore » period of 24 hours at Proton Therapy Center in Prague, Czech Republic. Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and parameterized using a linear quadratic formalism. Results: Significant variations in the cell killing RBE for fractionated exposures along the proton dose profile were observed. RBE increased sharply toward the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect was more pronounced at smaller doses per fraction. Experimental survival fractions were adequately predicted using a linear quadratic formalism assuming full repair between fractions. Data were also used to validate a parameterized variable RBE model based on linear α parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimens. Conclusions: The RBE-weighted absorbed dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE, particularly in fractionation regimens with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, our study provides an RBE dataset that can be used by the modeling community for the optimization of fractionated proton therapy.« less

Chernobyl doses. Volume 1. Analysis of forest canopy radiation response from multispectral imagery and the relationship to doses. Technical report, 29 July 1987-30 September 1993

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

McClennan, G.E.; Anno, G.H.; Whicker, F.W.

1994-09-01

This volume of the report Chernobyl Doses presents details of a new, quantitative method for remotely sensing ionizing radiation dose to vegetation. Analysis of Landsat imagery of the area within a few kilometers of the Chernobyl nuclear reactor station provides maps of radiation dose to pine forest canopy resulting from the accident of April 26, 1986. Detection of the first date of significant, persistent deviation from normal of the spectral reflectance signature of pine foliage produces contours of radiation dose in the 20 to 80 Gy range extending up to 4 km from the site of the reactor explosion. Themore » effective duration of exposure for the pine foliage is about 3 weeks. For this exposure time, the LD50 of Pinus sylvestris (Scotch pine) is about 23 Gy. The practical lower dose limit for the remote detection of radiation dose to pine foliage with the Landsat Thematic Mapper is about 5 Gy or 1/4 of the LD50.« less

Occupational Exposure of the Eye Lens in Interventional Procedures: How to Assess and Manage Radiation Dose.

PubMed

Ciraj-Bjelac, Olivera; Carinou, Eleftheria; Ferrari, Paolo; Gingaume, Merce; Merce, Marta Sans; O'Connor, Una

2016-11-01

Occupational exposure from interventional x-ray procedures is one of the areas in which increased eye lens exposure may occur. Accurate dosimetry is an important element to investigate the correlation of observed radiation effects with radiation dose, to verify the compliance with regulatory dose limits, and to optimize radiation protection practice. The objective of this work is to review eye lens dose levels in clinical practice that may occur from the use of ionizing radiation. The use of a dedicated eye lens dosimeter is the recommended methodology; however, in practice it cannot always be easily implemented. Alternatively, the eye lens dose could be assessed from measurements of other dosimetric quantities or other indirect parameters, such as patient dose. The practical implementation of monitoring eye lens doses and the use of adequate protective equipment still remains a challenge. The use of lead glasses with a good fit to the face, appropriate lateral coverage, and/or ceiling-suspended screens is recommended in workplaces with potential high eye lens doses. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Calculation of Radiation Protection Quantities and Analysis of Astronaut Orientation Dependence

NASA Technical Reports Server (NTRS)

Clowdsley, Martha S.; Nealy, John E.; Atwell, William; Anderson, Brooke M.; Luetke, Nathan J.; Wilson, John W.

2006-01-01

Health risk to astronauts due to exposure to ionizing radiation is a primary concern for exploration missions and may become the limiting factor for long duration missions. Methodologies for evaluating this risk in terms of radiation protection quantities such as dose, dose equivalent, gray equivalent, and effective dose are described. Environment models (galactic cosmic ray and solar particle event), vehicle/habitat geometry models, human geometry models, and transport codes are discussed and sample calculations for possible lunar and Mars missions are used as demonstrations. The dependence of astronaut health risk, in terms of dosimetric quantities, on astronaut orientation within a habitat is also examined. Previous work using a space station type module exposed to a proton spectrum modeling the October 1989 solar particle event showed that reorienting the astronaut within the module could change the calculated dose equivalent by a factor of two or more. Here the dose equivalent to various body tissues and the whole body effective dose due to both galactic cosmic rays and a solar particle event are calculated for a male astronaut in two different orientations, vertical and horizontal, in a representative lunar habitat. These calculations also show that the dose equivalent at some body locations resulting from a solar particle event can vary by a factor of two or more, but that the dose equivalent due to galactic cosmic rays has a much smaller (<15%) dependence on astronaut orientation.

Cost-effectiveness analysis of individualized mycophenolate mofetil dosing in kidney transplant patients in the APOMYGRE trial.

PubMed

Rousseau, Annick; Laroche, Marie-Laure; Venisse, Nicolas; Loichot-Roselmac, Cecile; Turcant, Alain; Hoizey, Guillaume; Compagnon, Patricia; Hary, Lionel; Debruyne, Danièle; Saivin, Sylvie; Jacqz-Aigrain, Evelyne; Buchler, Mathias; Villeneuve, Claire; Vergnenègre, Alain; Le Meur, Yannick; Marquet, Pierre

2010-05-27

In the prospective, randomized, multicenter APOMYGRE trial conducted in France, concentration-controlled mycophenolate mofetil (MMF) dosing based on mycophenolic acid (MPA) exposure significantly reduced the treatment failure and acute rejection during the first posttransplantation year compared with fixed-dose MMF. This analysis investigated the cost effectiveness of dose individualization. The study included 65 patients per group (intent-to-treat population). Treatment failure (primary efficacy endpoint) was defined as death, graft loss, acute rejection, or MMF discontinuation because of adverse effects. Data on hospitalizations, drugs prescribed, physicians' fees, laboratory expenses, ambulatory visits, and transportation were retrieved. Costs were calculated from the French National Health System perspective. The mean (95% confidence interval) total yearly cost per patient was Euro 47,477 (Euro 43,933; Euro 51,020) in the concentration-controlled group and Euro 46,783 ( Euro 44,152; Euro 49,414) in the fixed-dose group (P=0.7). The observed incremental cost-effectiveness ratio was Euro 3757 per treatment failure (Purchasing Power Parities United States/France: $4129). Hospitalization and drug costs accounted for approximately 50% and 25% of total costs, respectively. The cost for MPA area under the concentration-time curve and dose calculation was Euro 452 per patient, less than 1% of the total cost. In the APOMYGRE trial, therapeutic MPA monitoring using a limited sampling strategy reduced the risk of treatment failure and acute rejection in renal allograft recipients during the first 12 months posttransplantation, at neutral cost.

Improvement of attention with amphetamine in low- and high-performing rats.

PubMed

Turner, Karly M; Burne, Thomas H J

2016-09-01

Attentional deficits occur in a range of neuropsychiatric disorders, such as schizophrenia and attention deficit hyperactivity disorder. Psychostimulants are one of the main treatments for attentional deficits, yet there are limited reports of procognitive effects of amphetamine in preclinical studies. Therefore, task development may be needed to improve predictive validity when measuring attention in rodents. This study aimed to use a modified signal detection task (SDT) to determine if and at what doses amphetamine could improve attention in rats. Sprague-Dawley rats were trained on the SDT prior to amphetamine challenge (0.1, 0.25, 0.75 and 1.25 mg/kg). This dose range was predicted to enhance and disrupt cognition with the effect differing between individuals depending on baseline performance. Acute low dose amphetamine (0.1 and 0.25 mg/kg) improved accuracy, while the highest dose (1.25 mg/kg) significantly disrupted performance. The effects differed for low- and high-performing groups across these doses. The effect of amphetamine on accuracy was found to significantly correlate with baseline performance in rats. This study demonstrates that improvement in attentional performance with systemic amphetamine is dependent on baseline accuracy in rats. Indicative of the inverted U-shaped relationship between dopamine and cognition, there was a baseline-dependent shift in performance with increasing doses of amphetamine. The SDT may be a useful tool for investigating individual differences in attention and response to psychostimulants in rodents.

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

Escalation to High Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease

PubMed Central

Triplett, Brandon M.; Kuttab, Hani I.; Kang, Guolian; Leung, Wing

2015-01-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those utilized in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial, 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. There was no observed increase in toxicity until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10–100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, while those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (p=0.008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose escalation strategy remains unclear, as outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. PMID:26278046

[The absence of the facts connected with the genomic instability after the irradiation in low doses by radiation with low LET].

PubMed

Koterov A N

2006-01-01

In the review which is a brief account of more complete document (Koterov A.N. // Int. J. Low Radiat. 2005. V. 1. No. 4. P. 376-451) the data of world researches devoted to a phenomenon of radiation-induced genomic instability (RIGI) are considered. The purpose of the review is the definition of the bottom limit of radiation doses which induced of RIGI in experiments at different methodical approaches (irradiation in vitro, in vivo, in utero, bystander effect and transgeneration effects of radiation). The action only radiation with low LET is examined. Among several hundreds works wasn't revealed any fact, when RIGI induced by low doses irradiation (up to 0.2 Gy) for normal cells and for organism left from maternal womb. Six exceptions are revealed which are named as "apparent" so in all cases the abnormal, unstable, defective objects or ambiguous final parameter were used. Thus, RIGI at low doses of radiation with low LET is a myth.

THE CHALLENGE OF CIEMAT INTERNAL DOSIMETRY SERVICE FOR ACCREDITATION ACCORDING TO ISO/IEC 17025 STANDARD, FOR IN VIVO AND IN VITRO MONITORING AND DOSE ASSESSMENT OF INTERNAL EXPOSURES.

PubMed

Lopez, M A; Martin, R; Hernandez, C; Navarro, J F; Navarro, T; Perez, B; Sierra, I

2016-09-01

The accreditation of an Internal Dosimetry Service (IDS) according to ISO/IEC 17025 Standard is a challenge. The aim of this process is to guarantee the technical competence for the monitoring of radionuclides incorporated in the body and for the evaluation of the associated committed effective dose E(50). This publication describes the main accreditation issues addressed by CIEMAT IDS regarding all the procedures involving good practice in internal dosimetry, focussing in the difficulties to ensure the traceability in the whole process, the appropriate calculation of detection limit of measurement techniques, the validation of methods (monitoring and dose assessments), the description of all the uncertainty sources and the interpretation of monitoring data to evaluate the intake and the committed effective dose. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

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

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

1996-06-01

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

Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer: a phase 1b study.

PubMed

Czito, Brian G; Deming, Dustin A; Jameson, Gayle S; Mulcahy, Mary F; Vaghefi, Houman; Dudley, Matthew W; Holen, Kyle D; DeLuca, Angela; Mittapalli, Rajendar K; Munasinghe, Wijith; He, Lei; Zalcberg, John R; Ngan, Samuel Y; Komarnitsky, Philip; Michael, Michael

2017-06-01

Further optimisation of present standard chemoradiation is needed in patients with locally advanced rectal cancer. Veliparib, an oral poly(ADP-ribose) polymerase inhibitor, has been shown to enhance the antitumour activity of chemotherapy and radiotherapy in preclinical models. We aimed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy. This phase 1b, open-label, multicentre, dose-escalation study was done at six hospitals (one in Australia and five in the USA). Patients were eligible if they were aged 18 years or more and were newly diagnosed with stage II to III locally advanced, resectable adenocarcinoma of the rectum with a distal tumour border of less than 12 cm from anal verge. Patients were ineligible if they had received anticancer therapy or surgery (except colostomy or ileostomy) 28 days or less before the first dose of study drug, previous pelvic radiotherapy, or previous treatment with poly (ADP-ribose) polymerase inhibitors. Enrolled patients received capecitabine (825 mg/m 2 orally twice daily) with radiotherapy (50·4 Gy in 1·8 Gy fractions daily, approximately 5 days consecutively per week for about 5·5 weeks). Veliparib (20-400 mg orally twice daily) was administered daily starting on day 2 of week 1 and continuing until 2 days after radiotherapy completion. Patients underwent total mesorectal excision 5-10 weeks after radiotherapy completion. The primary objectives were to establish the maximum tolerated dose and recommended phase 2 dose of veliparib plus capecitabine and radiotherapy, with an exposure-adjusted continual reassessment methodology. Efficacy and safety analyses were done per protocol. The reported study has completed accrual and all analyses are final. This trial is registered with ClinicalTrials.gov, number NCT01589419. Between June 12, 2012, and Jan 13, 2015, 32 patients received veliparib (22 in the dose-escalation group; ten in the safety expansion group); 31 were assessable for efficacy (<400 mg, n=16; 400 mg, n=15). During dose escalation, grade 2 dose-limiting toxic effects occurred in two patients; no grade 3-4 dose-limiting toxic effects were noted. Therefore, the maximum tolerated dose was not reached; the recommended phase 2 dose was selected as 400 mg twice daily. The most common treatment-emergent adverse events in all 32 patients were nausea (17 [53%]), diarrhoea (16 [50%]), and fatigue (16 [50%]). Grade 3 diarrhoea was noted in three (9%) of 32 patients; no grade 4 events were reported. Veliparib pharmacokinetics were dose proportional, with no effect on capecitabine pharmacokinetics. Tumour downstaging after surgery was noted in 22 (71%) of 31 patients; nine (29%) of 31 patients achieved a pathological complete response. Veliparib plus capecitabine and radiotherapy had an acceptable safety profile and showed a dose-proportional pharmacokinetic profile with no effect on the pharmacokinetics of capecitabine. Preliminary antitumour activity warrants further evaluation. AbbVie Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Surfactant-Enhanced Desorption and Biodegradation of Polycyclic Aromatic Hydrocarbons in Contaminated Soil

PubMed Central

Zhu, Hongbo; Aitken, Michael D.

2010-01-01

We evaluated two nonionic surfactants, one hydrophobic (Brij 30) and one hydrophilic (C12E8), for their ability to enhance the biodegradation of polycyclic aromatic hydrocarbons (PAHs) in contaminated soil after it had been treated in an aerobic bioreactor. The effects of each surfactant were evaluated at doses corresponding to equilibrium aqueous-phase concentrations well above the surfactant’s critical micelle concentration (CMC), slightly above the CMC, and below the CMC. The concentrations of all 3- and 4-ring PAHs were significantly lower in the soil amended with Brij 30 at the two lower doses compared to controls, whereas removal of only the 3-ring PAHs was significantly enhanced at the highest Brij 30 dose. In contrast, C12E8 did not enhance PAH removal at any dose. In the absence of surfactant, <5% of any PAH desorbed from the soil over an 18-d period. Brij 30 addition at the lowest dose significantly increased the desorption of most PAHs, whereas the addition of C12E8 at the lowest dose actually decreased the desorption of all PAHs. These findings suggest that the effects of the two surfactants on PAH biodegradation could be explained by their effects on PAH bioavailability. Overall, this study demonstrates that the properties of the surfactant and its dose relative to the corresponding aqueous-phase concentration are important factors in designing systems for surfactant-enhanced bioremediation of PAH-contaminated soils in which PAH bioavailability is limited. PMID:20586488

MIRD Pamphlet No. 21: A Generalized Schema for Radiopharmaceutical Dosimetry-Standardization of Nomenclature

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

Bolch, W E; Eckerman, Keith F; Sgouros, George

2009-03-01

The internal dosimetry schema of the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine has provided a broad framework for assessment of the absorbed dose to whole organs, tissue subregions, voxelized tissue structures, and individual cellular compartments for use in both diagnostic and therapeutic nuclear medicine. The schema was originally published in 1968, revised in 1976, and republished in didactic form with comprehensive examples as the MIRD primer in 1988 and 1991. The International Commission on Radiological Protection (ICRP) is an organization that also supplies dosimetric models and technical data, for use in providing recommendations formore » limits on ionizing radiation exposure to workers and members of the general public. The ICRP has developed a dosimetry schema similar to that of the MIRD Committee but has used different terminology and symbols for fundamental quantities such as the absorbed fraction, specific absorbed fraction, and various dose coefficients. The MIRD Committee objectives for this pamphlet are 3-fold: to restate its schema for assessment of absorbed dose in a manner consistent with the needs of both the nuclear medicine and the radiation protection communities, with the goal of standardizing nomenclature; to formally adopt the dosimetry quantities equivalent dose and effective dose for use in comparative evaluations of potential risks of radiation-induced stochastic effects to patients after nuclear medicine procedures; and to discuss the need to identify dosimetry quantities based on absorbed dose that address deterministic effects relevant to targeted radionuclide therapy.« less

The Pollution Hazard Assessment System: Documentation and Users Manual

DTIC Science & Technology

1989-10-01

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

Disruption of the Putative Vascular Leak Peptide Sequence in the Stabilized Ricin Vaccine Candidate RTA1-33/44-198

DTIC Science & Technology

2013-01-29

Time- dependence of calculated LD50. The data shown in Panel A were submitted to probit analysis to determine the LD50 of ricin at every 0.5-day...degenerate neutrophils and necrotic debris evident; (C) Only a limited region of the epithelium lining a bronchus remains viable (arrowheads); the...quantitative analysis of the dose dependent protective effects of the immunizations. All vaccine doses (2.5, 10 or 40 μg immunogen) resulted in significant

Allele doses of apolipoprotein E type {epsilon}4 in sporadic late-onset Alzheimer`s disease

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

Lucotte, G.; Aouizerate, A.; Gerard, N.

1995-12-18

Apoliprotein E, type {epsilon}4 allele (ApoE-{epsilon}4) is associated with late-onset sporadic Alzheimer`s disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-{epsilon}4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging. 26 refs., 2 figs., 1 tab.

Browns Ferry Nuclear Plant radiological impact assessment report, January-June 1988

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

Lee, B.E.

1988-01-01

Potential doses to maximum individuals and the population around Browns Ferry are calcuated for each quarter. Measured plant releases for the reporting period are used to estimate these doses. Dispersion of radioactive effluents in the environment is estimated in accordance with the guidance provided and measuring during the period. Using dose calculation methodologies which are described in detail in the Browns Ferry Offsite Dose Calculation Manual, the doses are calculated and used to determine compliance with the dose limits contained in Browns Ferry's Operating License. In this report, the doses resulting from releases are described and compared to quarterly andmore » annual limits established for Browns Ferry.« less

Radiological risk assessment of cosmic radiation at aviation altitudes (a trip from Houston Intercontinental Airport to Lagos International Airport).

PubMed

Enyinna, Paschal Ikenna

2016-01-01

Radiological risk parameters associated with aircrew members traveling from Houston Intercontinental Airport to Lagos International Airport have been computed using computer software called EPCARD (version 3.2). The mean annual effective dose of radiation was computed to be 2.94 mSv/year. This result is above the standard permissible limit of 1 mSv/year set for the public and pregnant aircrew members but below the limit set for occupationally exposed workers. The Risk of cancer mortality and excess career time cancer risk computed ranged from 3.5 × 10(-5) to 24.5 × 10(-5) (with average of 14.7 × 10(-5)) and 7 × 10(-4) to 49 × 10(-4) (with average of 29.4 × 10(-4)). Passengers and aircrew members should be aware of the extra cosmic radiation doses taken in during flights. All aircraft operators should monitor radiation doses incurred during aviation trips.

Radiological risk assessment of cosmic radiation at aviation altitudes (a trip from Houston Intercontinental Airport to Lagos International Airport)

PubMed Central

Enyinna, Paschal Ikenna

2016-01-01

Radiological risk parameters associated with aircrew members traveling from Houston Intercontinental Airport to Lagos International Airport have been computed using computer software called EPCARD (version 3.2). The mean annual effective dose of radiation was computed to be 2.94 mSv/year. This result is above the standard permissible limit of 1 mSv/year set for the public and pregnant aircrew members but below the limit set for occupationally exposed workers. The Risk of cancer mortality and excess career time cancer risk computed ranged from 3.5 × 10−5 to 24.5 × 10−5 (with average of 14.7 × 10−5) and 7 × 10−4 to 49 × 10−4 (with average of 29.4 × 10−4). Passengers and aircrew members should be aware of the extra cosmic radiation doses taken in during flights. All aircraft operators should monitor radiation doses incurred during aviation trips. PMID:27651568

TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases

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

Pinkham, D.W.; Shultz, D.; Loo, B.W.

Purpose: The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer. Methods: A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions inmore » various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros-BV-1.5.0). Results: With EMG-HDR, an average of 83% (+/−9% standard deviation) of each patient’s GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/−5%). EMG-HDR enabled a 59% (+/−12%) decrease in the aorta maximum dose, a 63% (+/−26%) decrease in the spinal cord max dose, and 57% (+/−23%) and 70% (+/−17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively. Conclusion: EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.« less

Estimation of body surface area in the musk shrew ( Suncus murinus): a small animal for testing chemotherapy-induced emesis.

PubMed

Eiseman, Julie L; Sciullo, Michael; Wang, Hong; Beumer, Jan H; Horn, Charles C

2017-10-01

Several cancer chemotherapies cause nausea and vomiting, which can be dose-limiting. Musk shrews are used as preclinical models for chemotherapy-induced emesis and for antiemetic effectiveness. Unlike rats and mice, shrews possess a vomiting reflex and demonstrate an emetic profile similar to humans, including acute and delayed phases. As with most animals, dosing of shrews is based on body weight, while translation of such doses to clinically equivalent exposure requires doses based on body surface area. In the current study body surface area in musk shrews was directly assessed to determine the Meeh constant (K m ) conversion factor (female = 9.97, male = 9.10), allowing estimation of body surface area based on body weight. These parameters can be used to determine dosing strategies for shrew studies that model human drug exposures, particularly for investigating the emetic liability of cancer chemotherapeutic agents.

Calibration of an eye lens dosemeter in terms of Hp(3) to be used in interventional radiology

NASA Astrophysics Data System (ADS)

Borges, F. L. S.; Guimarães, M. C.; Da Silva, T. A.; Nogueira Tavares, M. S.

2014-11-01

Recently, the International Commission on Radiological Protection has reviewed epidemiological evidences suggesting that there were tissue reaction effects in the eye lens below the previously considered absorbed dose threshold. A new statement related to the eye lens was issued that changed the absorbed dose threshold and reduced the dose limits for occupationally exposed persons. As consequence, some planned exposures require eye lens dosimetry and a debate was raised on the adequacy of the dosimetric quantity and on its method of measurement. The aim of this work was to study the methodology for calibrating the EYE-DTM holder with a TLD-100H Harshaw chip detector and to determine its angular and energy dependences in terms of personal dose equivalent, Hp(3).

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

PubMed

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

2013-01-15

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

Radiation exposure in interventional radiology

NASA Astrophysics Data System (ADS)

Pinto, N. G. V.; Braz, D.; Vallim, M. A.; Filho, L. G. P.; Azevedo, F. S.; Barroso, R. C.; Lopes, R. T.

2007-09-01

The aim of this study is to evaluate dose values in patients and staff involved in some interventional radiology procedures. Doses have been measured using thermoluminescent dosemeters for single procedures (such as renal and cerebral arteriography, transjungular intrahepatic portasystemic shunt (TIPS) and chemoembolization). The magnitude of doses through the hands of interventional radiologists has been studied. Dose levels were evaluated in three points for patients (eye, thyroid and gonads). The dose-area product (DAP) was also investigated using a Diamentor (PTW-M2). The dose in extremities was estimated for a professional who generally performed one TIPS, two chemoembolizations, two cerebral arteriographies and two renal arteriographies in a week. The estimated annual radiation dose was converted to effective dose as suggested by the 453-MS/Brazil norm The annual dose values were 137.25 mSv for doctors, 40.27 mSv for nurses and 51.95 mSv for auxiliary doctors, and all these annual dose values are below the limit established. The maximum values of the dose obtained for patients were 6.91, 10.92 and 15.34 mGy close to eye, thyroid and gonads, respectively. The DAP values were evaluated for patients in the same interventional radiology procedures. The dose and DAP values obtained are in agreement with values encountered in the literature.

The pharmacokinetic and pharmacodynamic effects of SL65.1498, a GABA-A alpha2,3 selective agonist, in comparison with lorazepam in healthy volunteers.

PubMed

de Haas, S L; Franson, K L; Schmitt, J A J; Cohen, A F; Fau, J B; Dubruc, C; van Gerven, J M A

2009-08-01

Benzodiazepines are effective short-term treatments for anxiety disorders, but their use is limited by undesirable side effects related to Central Nervous System impairment and tolerance development. SL65.1498 is a new compound that acts in vitro as a full agonist at the gamma-aminobutyric acid(A) 2 and 3 receptor and as a partial agonist at the 1 and 5 receptor subtypes. It is thought that the compound could be anxiolytic by its activation at the alpha2 and alpha3 receptor subtypes, without causing unfavourable side effects, which are believed to be mediated by the alpha1 and alpha5 subtypes. This study was a double-blind, five-way cross-over study to investigate the effects of three doses of SL65.1498 in comparison with placebo and lorazepam 2 mg in healthy volunteers. The objective was to select a dose level (expected to be therapeutically active), free of any significant deleterious effect. Psychomotor and cognitive effects were measured using a validated battery of measurements, including eye movements, body sway, memory tests, reaction-time assessments, and visual analogue scales. The highest dose of SL65.1498 showed slight effects on saccadic peak velocity and smooth pursuit performance, although to a much lesser extent than lorazepam. In contrast to lorazepam, none of the SL65.1498 doses affected body sway, visual analogue scale alertness, attention, or memory tests. This study showed that the three doses of SL65.1498 were well tolerated and induced no impairments on memory, sedation, psychomotor, and cognitive functions.

Too late to vaccinate? The incremental benefits and cost-effectiveness of a delayed catch-up program using the 4-valent human papillomavirus vaccine in Norway.

PubMed

Burger, Emily A; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar S; Kim, Jane J

2015-01-15

Human papillomavirus (HPV) vaccines are ideally administered before HPV exposure; therefore, catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway. We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with 8 HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity. The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 years remained below Norway's willingness-to-pay threshold (approximately $83 000/quality-adjusted life year gained); extension to age 22 years was cost-effective at a lower cost per dose ($50-$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 years was cost-effective. Results were stable with lower coverage. HPV vaccination catch-up programs, 5 years after routine implementation, may be warranted; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 years remains uncertain. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dosimetry study for a new in vivo X-ray fluorescence (XRF) bone lead measurement system

NASA Astrophysics Data System (ADS)

Nie, Huiling; Chettle, David; Luo, Liqiang; O'Meara, Joanne

2007-10-01

A new 109Cd γ-ray induced bone lead measurement system has been developed to reduce the minimum detectable limit (MDL) of the system. The system consists of four 16 mm diameter detectors. It requires a stronger source compared to the "conventional" system. A dosimetry study has been performed to estimate the dose delivered by this system. The study was carried out by using human-equivalent phantoms. Three sets of phantoms were made to estimate the dose delivered to three age groups: 5-year old, 10-year old and adults. Three approaches have been applied to evaluate the dose: calculations, Monte Carlo (MC) simulations, and experiments. Experimental results and analytical calculations were used to validate MC simulation. The experiments were performed by placing Panasonic UD-803AS TLDs at different places in phantoms that representing different organs. Due to the difficulty of obtaining the organ dose and the whole body dose solely by experiments and traditional calculations, the equivalent dose and effective dose were calculated by MC simulations. The result showed that the doses delivered to the organs other than the targeted lower leg are negligibly small. The total effective doses to the three age groups are 8.45/9.37 μSv (female/male), 4.20 μSv, and 0.26 μSv for 5-year old, 10-year old and adult, respectively. An approval to conduct human measurements on this system has been received from the Research Ethics Board based on this research.

A comparison of quantum limited dose and noise equivalent dose

NASA Astrophysics Data System (ADS)

Job, Isaias D.; Boyce, Sarah J.; Petrillo, Michael J.; Zhou, Kungang

2016-03-01

Quantum-limited-dose (QLD) and noise-equivalent-dose (NED) are performance metrics often used interchangeably. Although the metrics are related, they are not equivalent unless the treatment of electronic noise is carefully considered. These metrics are increasingly important to properly characterize the low-dose performance of flat panel detectors (FPDs). A system can be said to be quantum-limited when the Signal-to-noise-ratio (SNR) is proportional to the square-root of x-ray exposure. Recent experiments utilizing three methods to determine the quantum-limited dose range yielded inconsistent results. To investigate the deviation in results, generalized analytical equations are developed to model the image processing and analysis of each method. We test the generalized expression for both radiographic and fluoroscopic detectors. The resulting analysis shows that total noise content of the images processed by each method are inherently different based on their readout scheme. Finally, it will be shown that the NED is equivalent to the instrumentation-noise-equivalent-exposure (INEE) and furthermore that the NED is derived from the quantum-noise-only method of determining QLD. Future investigations will measure quantum-limited performance of radiographic panels with a modified readout scheme to allow for noise improvements similar to measurements performed with fluoroscopic detectors.

Combined autophagy and proteasome inhibition

PubMed Central

Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-01-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy. PMID:24991834

Enhanced brain penetration of hexamethonium in complexes with derivatives of fullerene C60.

PubMed

Piotrovskiy, L B; Litasova, E V; Dumpis, M A; Nikolaev, D N; Yakovleva, E E; Dravolina, O A; Bespalov, A Yu

2016-05-01

The present report describes development of hexamethonium complexes based on fullerene C60. Hexamethonium has a limited penetration into CNS and therefore can antagonize central effects of nicotine only when given at high doses. In the present studies conducted in laboratory rodents, intraperitoneal administration of hexamethonium-fullerene complexes blocked effects of nicotine (convulsions and locomotor stimulation). When compared to equimolar doses of hexamethonium, complexes of hexamethonium with derivatives of fullerene C60 were 40 times more potent indicating an enhanced ability to interact with central nicotine receptors. Thus, fullerene C60 derivatives should be explored further as potential carrier systems for polar drug delivery into CNS.

Characterization of adaptive statistical iterative reconstruction algorithm for dose reduction in CT: A pediatric oncology perspective

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

Brady, S. L.; Yee, B. S.; Kaufman, R. A.

Purpose: This study demonstrates a means of implementing an adaptive statistical iterative reconstruction (ASiR Trade-Mark-Sign ) technique for dose reduction in computed tomography (CT) while maintaining similar noise levels in the reconstructed image. The effects of image quality and noise texture were assessed at all implementation levels of ASiR Trade-Mark-Sign . Empirically derived dose reduction limits were established for ASiR Trade-Mark-Sign for imaging of the trunk for a pediatric oncology population ranging from 1 yr old through adolescence/adulthood. Methods: Image quality was assessed using metrics established by the American College of Radiology (ACR) CT accreditation program. Each image quality metricmore » was tested using the ACR CT phantom with 0%-100% ASiR Trade-Mark-Sign blended with filtered back projection (FBP) reconstructed images. Additionally, the noise power spectrum (NPS) was calculated for three common reconstruction filters of the trunk. The empirically derived limitations on ASiR Trade-Mark-Sign implementation for dose reduction were assessed using (1, 5, 10) yr old and adolescent/adult anthropomorphic phantoms. To assess dose reduction limits, the phantoms were scanned in increments of increased noise index (decrementing mA using automatic tube current modulation) balanced with ASiR Trade-Mark-Sign reconstruction to maintain noise equivalence of the 0% ASiR Trade-Mark-Sign image. Results: The ASiR Trade-Mark-Sign algorithm did not produce any unfavorable effects on image quality as assessed by ACR criteria. Conversely, low-contrast resolution was found to improve due to the reduction of noise in the reconstructed images. NPS calculations demonstrated that images with lower frequency noise had lower noise variance and coarser graininess at progressively higher percentages of ASiR Trade-Mark-Sign reconstruction; and in spite of the similar magnitudes of noise, the image reconstructed with 50% or more ASiR Trade-Mark-Sign presented a more smoothed appearance than the pre-ASiR Trade-Mark-Sign 100% FBP image. Finally, relative to non-ASiR Trade-Mark-Sign images with 100% of standard dose across the pediatric phantom age spectrum, similar noise levels were obtained in the images at a dose reduction of 48% with 40% ASIR Trade-Mark-Sign and a dose reduction of 82% with 100% ASIR Trade-Mark-Sign . Conclusions: The authors' work was conducted to identify the dose reduction limits of ASiR Trade-Mark-Sign for a pediatric oncology population using automatic tube current modulation. Improvements in noise levels from ASiR Trade-Mark-Sign reconstruction were adapted to provide lower radiation exposure (i.e., lower mA) instead of improved image quality. We have demonstrated for the image quality standards required at our institution, a maximum dose reduction of 82% can be achieved using 100% ASiR Trade-Mark-Sign ; however, to negate changes in the appearance of reconstructed images using ASiR Trade-Mark-Sign with a medium to low frequency noise preserving reconstruction filter (i.e., standard), 40% ASiR Trade-Mark-Sign was implemented in our clinic for 42%-48% dose reduction at all pediatric ages without a visually perceptible change in image quality or image noise.« less

On the interplay effects with proton scanning beams in stage III lung cancer.

PubMed

Li, Yupeng; Kardar, Laleh; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y; Liao, Li; Zhu, Ronald X; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D; Lim, Gino; Zhang, Xiaodong

2014-02-01

To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery.

Acute antidepressant effects of right unilateral ultra-brief ECT: a double-blind randomised controlled trial.

PubMed

Mayur, Prashanth; Byth, Karen; Harris, Anthony

2013-07-01

Shortening the pulse width to 0.3 ms holds neurophysiological and clinical promise of making ECT safer by limiting cognitive side effects. However, the antidepressant effects of right ultra-brief unilateral ECT are under contention. In an acute ECT course, antidepressant equivalence of ultra-brief right unilateral ECT to the high-dose brief pulse right unilateral ECT was investigated. Severely depressed patients were randomised to 1 ms-brief pulse (n=18) or 0.3 ms ultra-brief pulse (n=17) right unilateral ECT, both at high-dose (6 times threshold stimulus dose) given thrice weekly. Depression severity was measured using the Montgomery Asberg Depression Rating Scale at baseline, after 8 treatments and after the acute course of ECT. Depression severity declined equally in both groups: F (1.27,41.97)=0.31, p=0.63. Median time in days to remission (95%CI) was in brief pulse ECT: 26 (18.6-33.4) and ultra-brief pulse ECT:28 (17.9-38.0). The small sample study in the study increases the likelihood of type 2 error. In severe depression, high-dose ultra-brief right unilateral ECT appears to show matching acute antidepressant response to an equally high-dose brief pulse right unilateral ECT. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-01-01

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

Human coffee drinking: manipulation of concentration and caffeine dose.

PubMed Central

Griffiths, R R; Bigelow, G E; Liebson, I A; O'Keeffe, M; O'Leary, D; Russ, N

1986-01-01

In a residential research ward coffee drinking was studied in 9 volunteer human subjects with histories of heavy coffee drinking. A series of five experiments was undertaken to characterize adlibitum coffee consumption and to investigate the effects of manipulating coffee concentration, caffeine dose per cup, and caffeine preloads prior to coffee drinking. Manipulations were double-blind and scheduled in randomized sequences across days. When cups of coffee were freely available, coffee drinking tended to be rather regularly spaced during the day with intercup intervals becoming progressively longer throughout the day; experimental manipulations showed that this lengthening of intercup intervals was not due to accumulating caffeine levels. Number of cups of coffee consumed was an inverted U-shaped function of both coffee concentration and caffeine dose per cup; however, coffee-concentration and dose-per-cup manipulations did not produce similar effects on other measures of coffee drinking (intercup interval, time to drink a cup, within-day distribution of cups). Caffeine preload produced dose-related decreases in number of cups consumed. As a whole, these experiments provide some limited evidence for both the suppressive and the reinforcing effects of caffeine on coffee consumption. Examination of total daily coffee and caffeine intake across experiments, however, provides no evidence for precise regulation (i.e., titration) of coffee or caffeine intake. PMID:3958660

Oak Ridge Reservation Environmental Protection Rad Neshaps Radionuclide Inventory Web Database and Rad Neshaps Source and Dose Database

DOE PAGES

Scofield, Patricia A.; Smith, Linda Lenell; Johnson, David N.

2017-07-01

The U.S. Environmental Protection Agency promulgated national emission standards for emissions of radionuclides other than radon from US Department of Energy facilities in Chapter 40 of the Code of Federal Regulations (CFR) 61, Subpart H. This regulatory standard limits the annual effective dose that any member of the public can receive from Department of Energy facilities to 0.1 mSv. As defined in the preamble of the final rule, all of the facilities on the Oak Ridge Reservation, i.e., the Y–12 National Security Complex, Oak Ridge National Laboratory, East Tennessee Technology Park, and any other U.S. Department of Energy operations onmore » Oak Ridge Reservation, combined, must meet the annual dose limit of 0.1 mSv. At Oak Ridge National Laboratory, there are monitored sources and numerous unmonitored sources. To maintain radiological source and inventory information for these unmonitored sources, e.g., laboratory hoods, equipment exhausts, and room exhausts not currently venting to monitored stacks on the Oak Ridge National Laboratory campus, the Environmental Protection Rad NESHAPs Inventory Web Database was developed. This database is updated annually and is used to compile emissions data for the annual Radionuclide National Emission Standards for Hazardous Air Pollutants (Rad NESHAPs) report required by 40 CFR 61.94. It also provides supporting documentation for facility compliance audits. In addition, a Rad NESHAPs source and dose database was developed to import the source and dose summary data from Clean Air Act Assessment Package—1988 computer model files. As a result, this database provides Oak Ridge Reservation and facility-specific source inventory; doses associated with each source and facility; and total doses for the Oak Ridge Reservation dose.« less

The impact of various protective tools on the dose reduction in the eye lens in an interventional cardiology-clinical study.

PubMed

Domienik, J; Bissinger, A; Grabowicz, W; Jankowski, Ł; Kręcki, R; Makowski, M; Masiarek, K; Plewka, M; Lubiński, A; Peruga, J Z

2016-06-01

The aim of the study was to check, in clinical practice, the potential for the dose reduction of lead eyewear and a ceiling-suspended shield used to protect the eye lens of physicians working in interventional cardiology. To this end, for the lead eyewear, the dose reduction factors were derived to correct the readings from a dosimeter used routinely outside the glasses. Four types of lead eyewear with attached loose thermoluminescent dosimeters and EYE-D dosimeters were worn by physicians in two clinical centres, for two-month periods, during coronary angiography (CA), percutaneous coronary intervention (PCI), and pacemaker procedures. In order to analyse, separately, how a ceiling-suspended lead screen absorbs the scattered radiation, a series of measurements was carried out during single CA/PCI procedures performed with and without the protection. The lead eyewear may reduce the doses to the eye closest to the x-ray tube by a factor between 1.1 and 3.4, depending on its model and the physician's position. The effectiveness of the eyewear may, however, vary-even for the same model and physician-almost twofold between different working periods. The ceiling-suspended shield decreases the doses in clinical practice by a factor of 2.3. The annual eye lens doses without the eyewear estimated from routine measurements are high-above or close to the new eye lens dose limit established by the recent EU Basic Safety Standards, even though the ceiling-suspended shield was used. Therefore, to comply with the new dose limit that is set in the Directive, protection of the eyes of physicians with high workloads might require the use of both the eyewear and the ceiling-suspended shield.

Oak Ridge Reservation Environmental Protection Rad Neshaps Radionuclide Inventory Web Database and Rad Neshaps Source and Dose Database.

PubMed

Scofield, Patricia A; Smith, Linda L; Johnson, David N

2017-07-01

The U.S. Environmental Protection Agency promulgated national emission standards for emissions of radionuclides other than radon from US Department of Energy facilities in Chapter 40 of the Code of Federal Regulations (CFR) 61, Subpart H. This regulatory standard limits the annual effective dose that any member of the public can receive from Department of Energy facilities to 0.1 mSv. As defined in the preamble of the final rule, all of the facilities on the Oak Ridge Reservation, i.e., the Y-12 National Security Complex, Oak Ridge National Laboratory, East Tennessee Technology Park, and any other U.S. Department of Energy operations on Oak Ridge Reservation, combined, must meet the annual dose limit of 0.1 mSv. At Oak Ridge National Laboratory, there are monitored sources and numerous unmonitored sources. To maintain radiological source and inventory information for these unmonitored sources, e.g., laboratory hoods, equipment exhausts, and room exhausts not currently venting to monitored stacks on the Oak Ridge National Laboratory campus, the Environmental Protection Rad NESHAPs Inventory Web Database was developed. This database is updated annually and is used to compile emissions data for the annual Radionuclide National Emission Standards for Hazardous Air Pollutants (Rad NESHAPs) report required by 40 CFR 61.94. It also provides supporting documentation for facility compliance audits. In addition, a Rad NESHAPs source and dose database was developed to import the source and dose summary data from Clean Air Act Assessment Package-1988 computer model files. This database provides Oak Ridge Reservation and facility-specific source inventory; doses associated with each source and facility; and total doses for the Oak Ridge Reservation dose.

Oak Ridge Reservation Environmental Protection Rad Neshaps Radionuclide Inventory Web Database and Rad Neshaps Source and Dose Database

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

Scofield, Patricia A.; Smith, Linda Lenell; Johnson, David N.

The U.S. Environmental Protection Agency promulgated national emission standards for emissions of radionuclides other than radon from US Department of Energy facilities in Chapter 40 of the Code of Federal Regulations (CFR) 61, Subpart H. This regulatory standard limits the annual effective dose that any member of the public can receive from Department of Energy facilities to 0.1 mSv. As defined in the preamble of the final rule, all of the facilities on the Oak Ridge Reservation, i.e., the Y–12 National Security Complex, Oak Ridge National Laboratory, East Tennessee Technology Park, and any other U.S. Department of Energy operations onmore » Oak Ridge Reservation, combined, must meet the annual dose limit of 0.1 mSv. At Oak Ridge National Laboratory, there are monitored sources and numerous unmonitored sources. To maintain radiological source and inventory information for these unmonitored sources, e.g., laboratory hoods, equipment exhausts, and room exhausts not currently venting to monitored stacks on the Oak Ridge National Laboratory campus, the Environmental Protection Rad NESHAPs Inventory Web Database was developed. This database is updated annually and is used to compile emissions data for the annual Radionuclide National Emission Standards for Hazardous Air Pollutants (Rad NESHAPs) report required by 40 CFR 61.94. It also provides supporting documentation for facility compliance audits. In addition, a Rad NESHAPs source and dose database was developed to import the source and dose summary data from Clean Air Act Assessment Package—1988 computer model files. As a result, this database provides Oak Ridge Reservation and facility-specific source inventory; doses associated with each source and facility; and total doses for the Oak Ridge Reservation dose.« less

Comparative dosimetry of volumetric modulated arc therapy and limited-angle static intensity-modulated radiation therapy for early-stage larynx cancer

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

Riegel, Adam C.; Antone, Jeffrey; Schwartz, David L., E-mail: dschwartz3@nshs.edu

2013-04-01

To compare relative carotid and normal tissue sparing using volumetric-modulated arc therapy (VMAT) or intensity-modulated radiation therapy (IMRT) for early-stage larynx cancer. Seven treatment plans were retrospectively created on 2 commercial treatment planning systems for 11 consecutive patients with T1-2N0 larynx cancer. Conventional plans consisted of opposed-wedged fields. IMRT planning used an anterior 3-field beam arrangement. Two VMAT plans were created, a full 360° arc and an anterior 180° arc. Given planning target volume (PTV) coverage of 95% total volume at 95% of 6300 cGy and maximum spinal cord dose below 2500 cGy, mean carotid artery dose was pushed asmore » low as possible for each plan. Deliverability was assessed by comparing measured and planned planar dose with the gamma (γ) index. Full-arc planning provided the most effective carotid sparing but yielded the highest mean normal tissue dose (where normal tissue was defined as all soft tissue minus PTV). Static IMRT produced next-best carotid sparing with lower normal tissue dose. The anterior half-arc produced the highest carotid artery dose, in some cases comparable with conventional opposed fields. On the whole, carotid sparing was inversely related to normal tissue dose sparing. Mean γ indexes were much less than 1, consistent with accurate delivery of planned treatment. Full-arc VMAT yields greater carotid sparing than half-arc VMAT. Limited-angle IMRT remains a reasonable alternative to full-arc VMAT, given its ability to mediate the competing demands of carotid and normal tissue dose constraints. The respective clinical significance of carotid and normal tissue sparing will require prospective evaluation.« less

Decorporation Approach after Rat Lung Contamination with Plutonium: Evaluation of the Key Parameters Influencing the Efficacy of a Protracted Chelation Treatment.

PubMed

Grémy, Olivier; Coudert, Sylvie; Renault, Daniel; Miccoli, Laurent

2017-11-01

While the efficacy of a protracted zinc (Zn)- or calcium (Ca)-diethylenetriaminepentaacetic acid (DTPA) treatment in reducing transuranic body burden has already been demonstrated, questions about therapeutic variables remain. In response to this, we designed animal experiments primarily to assess both the effect of fractionation of a given dose and the effect of the frequency of dose fraction, with the same total dose. In our study, rats were contaminated intravenously with plutonium (Pu) then treated several days later with Ca-DTPA given at once or in various split-dose regimens cumulating to the same total dose and spread over several days. Similar efficacies were induced by the injection of the total dose or by splitting the dose in several smaller doses, independent of the number of doses and the dose level per injection. In a second study, rats were pulmonary contaminated, and three weeks later they received a Ca-DTPA dose 11-fold higher than the maximal daily recommended dose, administered either as a single bolus or as numerous multiple injections cumulating to the same dose, based on different injection frequency schedules. Independent of frequency schedule, the various split-dose regimens spread over weeks/months were as efficient as single delivery of the total dose in mobilizing lung plutonium, and had a therapeutic advantage for removal of retained hepatic and bone plutonium burdens. We concluded that cumulative dose level was a therapeutic variable of greater importance than the distribution of split doses for the success of a repeated treatment regimen on retained tissue plutonium. In addition, pulmonary administration of clodronate, which aims at killing alveolar macrophages and subsequently releasing their plutonium content, and which is associated with a continuous Ca-DTPA infusion regimen, suggested that the efficacy of injected Ca-DTPA in decorporating lung deposit is limited, due to its restricted penetration into alveolar macrophages and not because plutonium, as a physicochemical form, is unavailable for chelation.

Dose-finding design for multi-drug combinations

PubMed Central

Wages, Nolan A; Conaway, Mark R; O'Quigley, John

2012-01-01

Background Most of the current designs used for Phase I dose finding trials in oncology will either involve only a single cytotoxic agent or will impose some implicit ordering among the doses. The goal of the studies is to estimate the maximum tolerated dose (MTD), the highest dose that can be administered with an acceptable level of toxicity. A key working assumption of these methods is the monotonicity of the dose–toxicity curve. Purpose Here we consider situations in which the monotonicity assumption may fail. These studies are becoming increasingly common in practice, most notably, in phase I trials that involve combinations of agents. Our focus is on studies where there exist pairs of treatment combinations for which the ordering of the probabilities of a dose-limiting toxicity cannot be known a priori. Methods We describe a new dose-finding design which can be used for multiple-drug trials and can be applied to this kind of problem. Our methods proceed by laying out all possible orderings of toxicity probabilities that are consistent with the known orderings among treatment combinations and allowing the continual reassessment method (CRM) to provide efficient estimates of the MTD within these orders. The design can be seen to simplify to the CRM when the full ordering is known. Results We study the properties of the design via simulations that provide comparisons to the Bayesian approach to partial orders (POCRM) of Wages, Conaway, and O'Quigley. The POCRM was shown to perform well when compared to other suggested methods for partial orders. Therefore, we comapre our approach to it in order to assess the performance of the new design. Limitations A limitation concerns the number of possible orders. There are dose-finding studies with combinations of agents that can lead to a large number of possible orders. In this case, it may not be feasible to work with all possible orders. Conclusions The proposed design demonstrates the ability to effectively estimate MTD combinations in partially ordered dosefinding studies. Because it relaxes the monotonicity assumption, it can be considered a multivariate generalization of the CRM. Hence, it can serve as a link between single and multiple-agent dosefinding trials. PMID:21652689

Dose-volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study.

PubMed

Raghubar, Kimberly P; Lamba, Michael; Cecil, Kim M; Yeates, Keith Owen; Mahone, E Mark; Limke, Christina; Grosshans, David; Beckwith, Travis J; Ris, M Douglas

2018-06-01

Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning. © 2018 Wiley Periodicals, Inc.

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

PubMed

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

2017-02-01

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

A phase I human trial of mitoguazone and gemcitabine sequential bi-weekly treatment of cancer patients.

PubMed

Ishmael, D Richard; Chen, Wei R; Hamilton, Steven A; Liu, Hong; Nordquist, Robert E

2003-01-01

Our previous studies have demonstrated the existence of synergism in a combination therapy using mitoguazone and gemcitabine when the mitoguazone is administered 24 hours before gemcitabine. Based on the cell culture and animal experimental results, a phase I clinical trial was performed in order to determine the toxicity of the combined treatment. Mitoguazone and gemcitabine were administered sequentially: mitoguazone on day 1 and gemcitabine on day 2. This cycle was repeated every 2 weeks. The dosages of these two drugs were varied between patients. Ten patients were enrolled in the study. Six patients began treatment at dose level 1 (mitoguazone 500 mg/m2, gemcitabine 1500 mg/m2), three at dose level 2 (mitoguazone 500 mg/m2, gemcitabine 2000 mg/m2), and one at dose level 3 (mitoguazone 600 mg/m2, gemcitabine 2000 mg/m2). Dose-limiting toxicity (DLT) was only observed in two patients treated at dose level 1 and one patient treated at dose level 3, while all the other patients only experienced nonhematologic toxicity, such as asthenia and mucositis. Two melanoma patients showed responses (one partial and one minor) to the treatment. One lymphoma patient also showed a brief partial response. This phase I trial indicated that the combination of mitoguazone and gemcitabine had limited but noticeable activity for treatment of cancer patients. Further study on the toxicity and on the effect of the scheduled mitoguazone-gemcitabine combination is needed.

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

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

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

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

Spatial interpolation of gamma dose in radioactive waste storage facility

NASA Astrophysics Data System (ADS)

Harun, Nazran; Fathi Sujan, Muhammad; Zaidi Ibrahim, Mohd

2018-01-01

External radiation measurement for a radioactive waste storage facility in Malaysian Nuclear Agency is a part of Class G License requirement under Atomic Licensing Energy Board (AELB). The objectives of this paper are to obtain the distribution of radiation dose, create dose database and generate dose map in the storage facility. The radiation dose measurement is important to fulfil the radiation protection requirement to ensure the safety of the workers. There are 118 sampling points that had been recorded in the storage facility. The highest and lowest reading for external radiation recorded is 651 microSv/hr and 0.648 microSv/hour respectively. The calculated annual dose shows the highest and lowest reading is 1302 mSv/year and 1.3 mSv/year while the highest and lowest effective dose reading is 260.4 mSv/year and 0.26 mSv/year. The result shows that the ALARA concept along time, distance and shield principles shall be adopted to ensure the dose for the workers is kept below the dose limit regulated by AELB which is 20 mSv/year for radiation workers. This study is important for the improvement of planning and the development of shielding design for the facility.

Optimization of equivalent uniform dose using the L-curve criterion.

PubMed

Chvetsov, Alexei V; Dempsey, James F; Palta, Jatinder R

2007-10-07

Optimization of equivalent uniform dose (EUD) in inverse planning for intensity-modulated radiation therapy (IMRT) prevents variation in radiobiological effect between different radiotherapy treatment plans, which is due to variation in the pattern of dose nonuniformity. For instance, the survival fraction of clonogens would be consistent with the prescription when the optimized EUD is equal to the prescribed EUD. One of the problems in the practical implementation of this approach is that the spatial dose distribution in EUD-based inverse planning would be underdetermined because an unlimited number of nonuniform dose distributions can be computed for a prescribed value of EUD. Together with ill-posedness of the underlying integral equation, this may significantly increase the dose nonuniformity. To optimize EUD and keep dose nonuniformity within reasonable limits, we implemented into an EUD-based objective function an additional criterion which ensures the smoothness of beam intensity functions. This approach is similar to the variational regularization technique which was previously studied for the dose-based least-squares optimization. We show that the variational regularization together with the L-curve criterion for the regularization parameter can significantly reduce dose nonuniformity in EUD-based inverse planning.

The benefit of low dose prophylaxis in the treatment of hemophilia: a focus on China.

PubMed

Wu, Runhui; Luke, Koon Hung

2017-11-01

Currently full dose prophylaxis is the standard of care in the treatment of hemophilia (World Federation of Hemophilia). However, the high costs prevent the use of standard or intermediate dose prophylaxis in China and other developing countries. Low dose prophylaxis would be a viable alternative treatment. At present global research data on the use of low dose prophylaxis is limited. Areas covered: Since 2007, China has been developing low dose prophylaxis as a high priority (90 % of moderate and severe hemophilia boys suffer joint disease by age 6 - 9). 11 studies were successfully conducted and published results showing evidence of the benefits of low dose prophylaxis to reduce joint bleeding. This new knowledge has been implemented into clinical practice in China. However the long-term outcome of arthropathy remains unclear and obstacles in execution exist. Expert commentary: In 2016, the first phenotype-based individualized prophylaxis study using four escalating low dose regimens on severe Chinese hemophilia A boys (China Individualized Prophylaxis Study (CHIP China)) launched. Using the previously published and imminent CHIP data, the goal for China is to establish an effective escalating low dose prophylaxis protocol for use in China as a standard of care.

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

Cost-Effectiveness Analysis of Ixekizumab vs Etanercept and Their Manufacturer-Recommended Dosing Regimens in Moderate to Severe Plaque Psoriasis.

PubMed

Udkoff, Jeremy; Eichenfield, Lawrence F

2017-10-01

Biologic therapies have revolutionized the treatment of psoriasis; however, their use is limited by costs. Ixekizumab was more effective than etanercept in the UNCOVER trials, and the Food and Drug Administration (FDA) approved ixekizumab for treating psoriasis. Evaluating the cost-effectiveness of these therapies is crucial for medical decision making and our objective was to determine the cost-effectiveness of various ixekizumab dosing frequencies compared with etanercept. We utilized published data from the UNCOVER comparative efficacy trials, including transitional probabilities and treatment response rates, to create a Markov model simulating the clinical course and cost-effectiveness of three treatment algorithms for patients with moderate to severe plaque psoriasis over 60-weeks: (1) ixekizumab every 2 weeks for 12 weeks then every 4 weeks, (2) ixekizumab every 4 weeks throughout the treatment period, (3) biweekly etanercept for 12 weeks then once weekly. We utilized a standard willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) and Medicaid drug acquisition costs for our calculations. Ixekizumab every 4 weeks was $28,681 (USD) less expensive than biweekly etanercept, and $21,375 less expensive, and 0.006 QALY less effective, than ixekizumab every 2 weeks-- a savings of $28.7 and $21.4 million, respectively, per 1,000 patients. A 95.6% cost reduction to $197.83 per dose is required for ixekizumab every 2 weeks to be more cost-effective than every 4 weeks. Biweekly etanercept requires a 29.5% cost reduction ($743.82 per dose) to be competitive with ixekizumab every 4 weeks. This cost-effectiveness model utilizes strong input data but is a limited approximation of real-life scenarios. Treatment with ixekizumab every 2 weeks is unlikely to be cost-effective compared with ixekizumab every 4 weeks at current U.S. market prices. Yet, the U.S. FDA approval and manufacturer's recommendation are for ixekizumab every 2 weeks. Accordingly, we suggested selecting biologic therapies using cost-effectiveness analyses.

J Drugs Dermatol. 2017;16(10):964-970.

Effect of Pain Management on Immunization Efficacy in Mice

PubMed Central

Kolstad, April M; Rodriguiz, Ramona M; Kim, Caroline J; Hale, Laura P

2012-01-01

Immunization with complete Freund adjuvant (CFA) or incomplete Freund adjuvant (IFA) is commonly viewed as painful, yet rodents may not receive analgesics due to concerns that these drugs affect the desired immune responses. Here we tested the hypothesis that pain associated with immunization with CFA or IFA in mice can be relieved without compromising the effectiveness of the immune response. After subcutaneous immunization in the leg with antigen in CFA or IFA, mice were assessed for signs of pain by using behavioral tests, including unrestricted locomotion in an open field, forced running on an automated treadmill, and voluntary wheel running. Effects of the analgesics acetaminophen, meloxicam, and buprenorphine on behavioral and antibody responses were assessed after primary and secondary immunization with the model antigen ovalbumin and after repeated immunization with a limiting dose of recombinant protective antigen from Bacillus anthracis. Open field activity and the distance traveled during forced gait analysis and voluntary wheel running both decreased after immunization. Treatment with each of the analgesics normalized some but not all of these behaviors but did not decrease the mean or maximal antibody titer after primary or repeated immunization with a moderate dose of ovalbumin or after repeated immunization with a limiting dose of protective antigen. In summary, after immunization with CFA or IFA, mice showed behavioral responses suggestive of pain. Acetaminophen, meloxicam, and buprenorphine attenuated these effects without decreasing antibody responses. Therefore, the use of these analgesics for managing rodent pain associated with CFA- or IFA-containing vaccines can be encouraged. PMID:23043810

Individual and combined effects of multiple pathogens on Pacific treefrogs.

PubMed

Romansic, John M; Johnson, Pieter T J; Searle, Catherine L; Johnson, James E; Tunstall, Tate S; Han, Barbara A; Rohr, Jason R; Blaustein, Andrew R

2011-08-01

In nature, individual hosts often encounter multiple pathogens simultaneously, which can lead to additive, antagonistic, or synergistic effects on hosts. Synergistic effects on infection prevalence or severity could greatly affect host populations. However, ecologists and managers often overlook the influence of pathogen combinations on hosts. This is especially true in amphibian conservation, even though multiple pathogens coexist within amphibian populations, and several pathogens have been implicated in amphibian population declines and extinctions. Using an amphibian host, Pseudacris regilla (Pacific treefrog), we experimentally investigated interactive effects among three pathogens: the trematode Ribeiroia sp. (hereafter, Ribeiroia), the fungus Batrachochytrium dendrobatidis (hereafter, BD), and the water mold Achlya flagellata. We detected no effects of A. flagellata, but did find effects of Ribeiroia and BD that varied depending on context. Low doses of Ribeiroia caused relatively few malformations, while higher Ribeiroia doses caused numerous deformities dominated by missing and reduced limbs and limb elements. Exposure to low doses of BD accelerated larval host development, despite there being no detectable BD infections, while exposure to higher BD doses caused infection but did not alter developmental rate. Hosts exposed to both Ribeiroia and BD exhibited the highest mortality, although overall evidence of interactive effects of multiple pathogens was limited. We suggest further research on the influence of multi-pathogen assemblages on amphibians, particularly under a variety of ecological conditions and with a wider diversity of hosts and pathogens.

A phase I dose escalation study of TTI-237 in patients with advanced malignant solid tumors.

PubMed

Wang-Gillam, Andrea; Arnold, Susanne M; Bukowski, Ronald M; Rothenberg, Mace L; Cooper, Wendy; Wang, Kenneth K; Gauthier, Eric; Lockhart, A Craig

2012-02-01

This study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug, administered weekly in patients with refractory solid tumors. Using an accelerated dose escalation design, patients with refractory solid tumors were enrolled in this study and treated with TTI-237 intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m(2). Pharmacokinetic studies were performed in patients at all dose levels. Twenty-eight patients were enrolled and treated with TTI-237 at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m(2). One dose-limiting toxicity neutropenia fever was observed at 31.5 mg/m(2), and all seven patients developed grade 3 or 4 neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18 mg/m(2). Six patients were treated at the 18 mg/m(2) dose level without dose-limiting toxicity prior to trial termination. The mean terminal-phase elimination half-life (t(1/2)) for TTI-237 was 25-29 h, and the mean area under the concentration time curve at 31.5 mg/m(2) was 2,768 ng•h/mL. A protocol defined maximum tolerated dose was not determined because of early termination of the TTI-237 trial by the sponsor. 18 mg/m(2) may be a tolerable dose of TTI-237.

Statin myopathy: the fly in the ointment for the prevention of cardiovascular disease in the 21st century?

PubMed

Keen, Helen I; Krishnarajah, Janakan; Bates, Timothy R; Watts, Gerald F

2014-09-01

Cardiovascular disease (CVD) remains the leading cause of death in industrialized nations. Despite clear evidence of CVD risk reduction with HMG-CoA reductase inhibitors (statins), the side effects of these medications, particularly myopathy, limit their effectiveness. Studies into the mechanisms, aetiology and management of statin myopathy are limited by lack of an internationally agreed clinical definition and tools for assessing outcomes. Currently there is a paucity of evidence to guide the management of patients affected by statin myopathy; with the exception of dose reduction, there is little evidence that other strategies can improve statin tolerance, and even less evidence to suggest these alternate dosing strategies reduce cardiovascular risk. This review will cover current definitions, clinical presentations, risk factors, pathogenesis and management. PubMed was searched (English language, to 2014) for key articles pertaining to statin myopathy. This review then briefly describes our experience of managing this condition in a tertiary lipid disorders clinic, in the setting of limited guiding evidence. Knowledge gaps in the field of statin myopathy are identified and future research directions are suggested. We urge the need for international attention to address this important, but largely neglected clinical problem, that if unresolved will remain an impediment to the effective prevention and treatment of CVD.

A review of the efficacy and safety of oral antidiabetic drugs

PubMed Central

Stein, Stephanie Aleskow; Lamos, Elizabeth Mary; Davis, Stephen N

2014-01-01

Introduction Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes. Areas covered The efficacy and safety of metformin, SUs, TZDs, dipeptidyl peptidase-IV (DPP-4) inhibitors, meglitinide analogs, α-glucosidase inhibitors (AGIs), bile-acid sequestrants (BAS) and bromocriptine will be reviewed. Expert opinion Several new oral agents have been approved for type 2 diabetes management in recent years. It is important to understand the efficacy and safety of these medications in addition to the older agents to best maximize oral drug therapy for diabetes. Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin. They are a recommended alternative when metformin use is limited by gastrointestinal (GI) side effects or when SU treatment results in significant hypoglycemia or weight gain. Meglitinide analogs are limited by their frequent dosing, expense and hypoglycemia (repaglinide > nateglinide), while AGIs are also limited by their dosing schedule and GI side-effect profile. BAS and bromocriptine have the lowest efficacy with regard to HbA1c reduction, also are plagued by GI adverse reactions, but have a low risk of hypoglycemia. PMID:23241069

Skeletal effects of central nervous system active drugs: anxiolytics, sedatives, antidepressants, lithium and neuroleptics.

PubMed

Vestergaard, Peter

2008-09-01

Many central nervous system active drugs can alter postural balance, increasing the risk of fractures. Anxiolytics and sedatives include the benzodiazepines, and these have been associated with a limited increase in the risk of fractures, even at low doses, probably from an increased risk of falls. No systematic differences have been shown between benzodiazepines with long and short half-lives. Although the increase in risk of fractures was limited, care must still be taken when prescribing for older fall-prone subjects at risk of osteoporosis. Neuroleptics may be associated with a decrease in bone mineral density and a very limited increase in fracture risk. Antidepressants are associated with a dose-dependent increase in the risk of fractures. The increase in relative risk of fractures seems to be larger with selective serotonin reuptake inhibitors (SSRIs) than with tricyclic antidepressants. The reason for this is not known but may be linked to serotonin effects on bone cells and the risk of falls. With the wide use of SSRIs, more research is needed. Lithium is associated with a decrease in the risk of fractures. This may be linked to its effects on the Wnt glycoprotein family, which is a specialised signalling system for certain cell types.

Subpart B: National Emission Standards for Radon Emissions From Underground Uranium Mines

EPA Pesticide Factsheets

Subpart B sets a limit on the emission of radon-222 that ensures that no member of the public in any year receives an effective dose equivalent of more than 10 mrem/year from an underground uranium mine.

Evaluation and implementation of triple‐channel radiochromic film dosimetry in brachytherapy

PubMed Central

Bradley, David; Nisbet, Andrew

2014-01-01

The measurement of dose distributions in clinical brachytherapy, for the purpose of quality control, commissioning or dosimetric audit, is challenging and requires development. Radiochromic film dosimetry with a commercial flatbed scanner may be suitable, but careful methodologies are required to control various sources of uncertainty. Triple‐channel dosimetry has recently been utilized in external beam radiotherapy to improve the accuracy of film dosimetry, but its use in brachytherapy, with characteristic high maximum doses, steep dose gradients, and small scales, has been less well researched. We investigate the use of advanced film dosimetry techniques for brachytherapy dosimetry, evaluating uncertainties and assessing the mitigation afforded by triple‐channel dosimetry. We present results on postirradiation film darkening, lateral scanner effect, film surface perturbation, film active layer thickness, film curling, and examples of the measurement of clinical brachytherapy dose distributions. The lateral scanner effect in brachytherapy film dosimetry can be very significant, up to 23% dose increase at 14 Gy, at ± 9 cm lateral from the scanner axis for simple single‐channel dosimetry. Triple‐channel dosimetry mitigates the effect, but still limits the useable width of a typical scanner to less than 8 cm at high dose levels to give dose uncertainty to within 1%. Triple‐channel dosimetry separates dose and dose‐independent signal components, and effectively removes disturbances caused by film thickness variation and surface perturbations in the examples considered in this work. The use of reference dose films scanned simultaneously with brachytherapy test films is recommended to account for scanner variations from calibration conditions. Postirradiation darkening, which is a continual logarithmic function with time, must be taken into account between the reference and test films. Finally, films must be flat when scanned to avoid the Callier‐like effects and to provide reliable dosimetric results. We have demonstrated that radiochromic film dosimetry with GAFCHROMIC EBT3 film and a commercial flatbed scanner is a viable method for brachytherapy dose distribution measurement, and uncertainties may be reduced with triple‐channel dosimetry and specific film scan and evaluation methodologies. PACS numbers: 87.55.Qr, 87.56.bg, 87.55.km PMID:25207417

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.

PubMed

Laino, Carlos Horacio; Garcia, Pilar; Podestá, María Fernanda; Höcht, Christian; Slobodianik, Nora; Reinés, Analía

2014-10-01

We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Low dose elective brain irradiation in small cell carcinoma of the lung

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

Beiler, D.D.; Kane, R.C.; Bernath, A.M.

Elective brain irradiation (EBI) in a dosage of 3000 rad (midplane) in 2 weeks (nominal standard dose (NSD) = 1314 ret) has proven highly effective in preventing initial brain relapse in small cell lung carcinoma. However, the optimal radiation dose for EBI is unknown. 55 patients (31 with regional disease, 24 with extensive disease) without brain metastases were treated with a 4 drug chemotherapy program, (lomustine (CCNU), methotrexate, cyclophosphamide, vincristine) plus radiotherapy (R.T.), 3000 rad in 2 weeks to the primary chest lesion and were randomized to EBI or a control group. The EBI consisted of 2400 rad whole brain,more » midplane, in 8 fractions, 10 days (NSD = 1130 ret) given at the same time as the R.T. to the primary (3 weeks post-initial chemotherapy). Though all 54 evaluable patients received CCNU 50 mg/M/sup 2/q. 6 weeks, there were 5 initial brain relapses among 31 control patients (16%) vs none in the 23 EBI patients. The time at risk for recurrence was similar in the two groups, i.e. 31 weeks median in the EBI and 32 weeks in the no-EBI patients. Brain relapses occurred in 2/17 with limited disease and 3/14 with extensive disease. It appears that 2400 rad in 8 fractions is as effective for EBI as larger doses. Toxicity was limited to alopecia. Survival was not significantly affected by EBI, though there is a suggestion of improvement in the regional group.« less

The antinociceptive effect of intrathecal administration of epibatidine with clonidine or neostigmine in the formalin test in rats.

PubMed

Hama, A T; Lloyd, G K; Menzaghi, F

2001-03-01

The analgesic effect of intrathecal injection of epibatidine, clonidine and neostigmine, compounds that elevate ACh, was examined in the formalin test, a model of post-injury central sensitization in the rat. The compounds were injected alone and in combination. Intrathecal injection of epibatidine alone did not alter pain behaviors, compared to vehicle-treated rats. Intrathecal injection of clonidine dose-dependently reduced tonic pain behaviors (ED(50)+/-95% confidence limits=6.7+/-4.8 microg). The combination of clonidine and epibatidine (C:E), in the ratio of 26:1, dose-dependently reduced tonic pain behaviors; and the ED(50) of C:E was 1.1+/-0.98 microg a significant 6-fold leftward shift of the dose response curve, compared with clonidine alone. The antinociceptive effect of C:E (26:1) was attenuated by pre-treatment with the nAChR antagonist mecamylamine. Neostigmine dose-dependently reduced tonic pain behaviors (ED(50)=1.5+/-1.3 microg). The combination of neostigmine and epibatidine, in a ratio of 8:1, significantly shifted the dose response curve 4-fold to the left (ED(50)=0.4+/-0.3 microg). The effect is mediated in part by the activation of the nAChR and possibly by the enhanced release of ACh. These data demonstrate significant enhancement of the antinociceptive effects of spinally delivered analgesics by a nAChR agonist, suggesting that this class of compounds may have utility as adjuvants when combined with conventional therapeutics.

Current situations and discussions in Japan in relation to the new occupational equivalent dose limit for the lens of the eye.

PubMed

Yokoyama, Sumi; Hamada, Nobuyuki; Hayashida, Toshiyuki; Tsujimura, Norio; Tatsuzaki, Hideo; Kurosawa, Tadahiro; Nabatame, Kuniaki; Ohguchi, Hiroyuki; Ohno, Kazuko; Yamauchi-Kawaura, Chiyo; Iimoto, Takeshi; Ichiji, Takeshi; Hotta, Yutaka; Iwai, Satoshi; Akahane, Keiichi

2017-09-25

Since the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens of the eye in 2011, there have been extensive discussions in various countries. This paper reviews the current situation in radiation protection of the ocular lens and the discussions on the potential impact of the new lens dose limit in Japan. Topics include historical changes to the lens dose limit, the current situation with occupational lens exposures (e.g., in medical workers, nuclear workers, and Fukushima nuclear power plant workers) and measurements, and the current status of biological studies and epidemiological studies on radiation cataracts. Our focus is on the situation in Japan, but we believe such information sharing will be useful in many other countries.

A phase 1 study of eribulin mesylate (E7389), a novel microtubule-targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314).

PubMed

Schafer, Eric S; Rau, Rachel E; Berg, Stacey; Liu, Xiaowei; Minard, Charles G; D'Adamo, David; Scott, Rachael; Reyderman, Larisa; Martinez, Gresel; Devarajan, Sandhya; Reid, Joel M; Fox, Elizabeth; Weigel, Brenda J; Blaney, Susan M

2018-05-02

Eribulin mesylate is a novel anticancer agent that inhibits microtubule growth, without effects on shortening, and promotes nonproductive tubulin aggregate formation. We performed a phase 1 trial to determine the dose-limiting toxicities (DLTs), maximum tolerated or recommended phase 2 dose (MTD/RP2D), and pharmacokinetics (PK) of eribulin in children with refractory or recurrent solid (excluding central nervous system) tumors. Eribulin was administered intravenously on days 1 and 8 in 21-day cycles. Three dose levels (1.1, 1.4, and 1.8 mg/m 2 /dose) were evaluated using the rolling six design with additional patients enrolled into a PK expansion cohort at the MTD. PK samples were obtained following the day 1, cycle 1 dose. Twenty-three patients, ages 3-17 (median 14) years were enrolled; 20 were evaluable for toxicity. DLTs occurred in 0/6 and 1/6 subjects at the 1.1 and 1.4 mg/m 2 /dose, respectively. One subject at the 1.4 mg/m 2 /dose had grade 4 neutropenia and grade 3 fatigue. At the 1.8 mg/m 2 /dose, 2/5 subjects experienced dose-limiting (grade 4) neutropenia. Grade 3/4 non-DLTs included lymphopenia and hypokalemia, while low-grade toxicities included anorexia and nausea. No episodes of grade > 2 corrected QT interval prolongation or peripheral neuropathy were reported. Eribulin pharmacokinetic parameters were highly variable; the median elimination half-life was 39.6 (range 24.2-96.4) hr. A partial response was observed in one patient (Ewing sarcoma). Eribulin was well tolerated in children with refractory or recurrent solid tumors with neutropenia identified as the primary DLT. The RP2D of eribulin is 1.4 mg/m 2 /dose on days 1 and 8 of a 21-day cycle. © 2018 Wiley Periodicals, Inc.

Dose estimation to eye lens of industrial gamma radiography workers using the Monte Carlo method.

PubMed

de Lima, Alexandre Roza; Hunt, John Graham; Da Silva, Francisco Cesar Augusto

2017-12-01

The ICRP Statement on Tissue Reactions (2011), based on epidemiological evidence, recommended a reduction for the eye lens equivalent dose limit from 150 to 20 mSv per year. This paper presents mainly the dose estimations received by industrial gamma radiography workers, during planned or accidental exposure to the eye lens, Hp(10) and effective dose. A Brazilian Visual Monte Carlo Dose Calculation program was used and two relevant scenarios were considered. For the planned exposure situation, twelve radiographic exposures per day for 250 days per year, which leads to a direct exposure of 10 h per year, were considered. The simulation was carried out using a 192 Ir source with 1.0 TBq of activity; a source/operator distance between 5 and 10 m and placed at heights of 0.02 m, 1 m and 2 m, and an exposure time of 12 s. Using a standard height of 1 m, the eye lens doses were estimated as being between 16.3 and 60.3 mGy per year. For the accidental exposure situation, the same radionuclide and activity were used, but in this case the doses were calculated with and without a collimator. The heights above ground considered were 1.0 m, 1.5 m and 2.0 m; the source/operator distance was 40 cm, and the exposure time 74 s. The eye lens doses at 1.5 m were 12.3 and 0.28 mGy without and with a collimator, respectively. The conclusions were that: (1) the estimated doses show that the 20 mSv annual limit for eye lens equivalent dose can directly impact industrial gamma radiography activities, mainly in industries with high number of radiographic exposures per year; (2) the risk of lens opacity has a low probability for a single accident, but depending on the number of accidental exposures and the dose levels found in planned exposures, the threshold dose can easily be exceeded during the professional career of an industrial radiography operator, and; (3) in a first approximation, Hp(10) can be used to estimate the equivalent dose to the eye lens.

Out-of-field doses from pediatric craniospinal irradiations using 3D-CRT, IMRT, helical tomotherapy and electron-based therapy

NASA Astrophysics Data System (ADS)

De Saint-Hubert, Marijke; Verellen, Dirk; Poels, Kenneth; Crijns, Wouter; Magliona, Federica; Depuydt, Tom; Vanhavere, Filip; Struelens, Lara

2017-07-01

Medulloblastoma treatment involves irradiation of the entire central nervous system, i.e. craniospinal irradiation (CSI). This is associated with the significant exposure of large volumes of healthy tissue and there is growing concern regarding treatment-associated side effects. The current study compares out-of-field organ doses in children receiving CSI through 3D-conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT) and an electron-based technique, and includes radiation doses resulting from imaging performed during treatment. An extensive phantom study is performed, using an anthropomorphic phantom corresponding to a five year old child, in which organ absorbed doses are measured using thermoluminescent detectors. Additionally, the study evaluates and explores tools for calculating out-of-field patient doses using the treatment planning system (TPS) and analytical models. In our study, 3D-CRT resulted in very high doses to a limited number of organs, while it was able to spare organs such as the lungs and breast when compared to IMRT and HT. Both IMRT and HT spread the dose over more organs and were able to spare the heart, thyroid, bladder, uterus and testes when compared to 3D-CRT. The electron-based technique considerably decreased the out-of-field doses in deep-seated organs but could not avoid nearby out-of-field organs such as the lungs, ribs, adrenals, kidneys and uterus. The daily imaging dose is small compared to the treatment dose burden. The TPS error for out-of-field doses was most pronounced for organs further away from the target; nevertheless, no systematic underestimation was observed for any of the studied TPS systems. Finally, analytical modeling was most optimal for 3D-CRT although the number of organs that could be modeled was limited. To conclude, none of the techniques studied was capable of sparing all organs from out-of-field doses. Nevertheless, the electron-based technique showed the most promise for out-of-field organ dose reduction during CSI when compared to photon techniques.

Transcriptomic Dose-Response Analysis for Mode of Action ...

EPA Pesticide Factsheets

Microarray and RNA-seq technologies can play an important role in assessing the health risks associated with environmental exposures. The utility of gene expression data to predict hazard has been well documented. Early toxicogenomics studies used relatively high, single doses with minimal replication. Thus, they were not useful in understanding health risks at environmentally-relevant doses. Until the past decade, application of toxicogenomics in dose response assessment and determination of chemical mode of action has been limited. New transcriptomic biomarkers have evolved to detect chemical hazards in multiple tissues together with pathway methods to study biological effects across the full dose response range and critical time course. Comprehensive low dose datasets are now available and with the use of transcriptomic benchmark dose estimation techniques within a mode of action framework, the ability to incorporate informative genomic data into human health risk assessment has substantially improved. The key advantage to applying transcriptomic technology to risk assessment is both the sensitivity and comprehensive examination of direct and indirect molecular changes that lead to adverse outcomes. Book Chapter with topic on future application of toxicogenomics technologies for MoA and risk assessment