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

PubMed

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

2018-03-16

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

WE-D-BRE-01: A Sr-90 Irradiation Device for the Study of Cutaneous Radiation Injury

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

Dorand, JE; Bourland, JD; Burnett, LR

2014-06-15

Purpose: To determine dosimetric character for a custom-built Sr-90 beta irradiator designed for the study of Cutaneous Radiation Injury (CRI) in a porcine animal model. In the event of a radiological accident or terrorist event, Sr-90, a fission by-product, will likely be produced. CRI is a main concern due to the low energy and superficial penetration in tissue of beta particles from Sr-90. Seven 100 mCi plaque Sr-90 radiation sources within a custom-built irradiation device create a 40 mm diameter region of radiation-induced skin injury as part of a larger project to study the efficacy of a topical keratin-based productmore » in CRI healing. Methods: A custom-built mobile irradiation device was designed and implemented for in vivo irradiations. Gafchromic™ EBT3 radiochromic film and a PTW Markus chamber type 23343 were utilized for dosimetric characterization of the beta fluence at the surface produced by this device. Films were used to assess 2-dimensional dose distribution and percent depth dose characteristics of the radiation field. Ion chamber measurements provided dose rate data within the field. Results: The radiation field produced by the irradiation device is homogeneous with high uniformity (∼5%) and symmetry (∼3%) with a steep dose fall-off with depth from the surface. Dose rates were determined to be 3.8 Gy/min and 3.3 Gy/min for film and ion chamber measurements, respectively. A dose rate of 3.4 Gy/min was used to calculate irradiation times for in vivo irradiations. Conclusion: The custom-built irradiation device enables the use of seven Sr-90 beta sources in an array to deliver a 40 mm diameter area of homogeneous skin dose with a dose rate that is useful for research purposes and clinically relevant for the induction of CRI. Doses of 36 and 42 Gy successfully produce Grade III CRI and are used in the study of the efficacy of KeraStat™. This project has been funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under Contract No. HHSO100201200007C.« less

Effect of multiple short highly energetic X-ray pulses on the synthesis of endoglucanase by a mutant strain of Trichoderma reesei-M7.

PubMed

Gemishev, Orlin; Zapryanov, Stanislav; Blagoev, Alexander; Markova, Maya; Savov, Valentin

2014-09-03

Bioconversion of cellulose-containing substrate to glucose represents an important area of modern biotechnology. Enzymes for the degradation of the polysaccharide part of biomass have been produced, mostly by fungi belonging to genus Trichoderma . Studies were carried out with the mutant strain Trichoderma reesei- M7, a cellulase producer. Spores of the enzyme producer were irradiated with different doses of characteristic X-ray radiation from metallic tungsten (mainly the W Kα1 and Kα2 lines) with a high dose rate. The latter is a specific property of the dense plasma focus (DPF) device, which has pulsed operation and thus gives short and highly energetic pulses of multiple types of rays and particles. In this case, we focused our study on the influence of hard X-rays. The doses of X-rays absorbed by the spores varied in the range of approximately 5-11,000 mSv measured with thermoluminescent dosimeters (TLD). The influence of the applied doses in combination with exceptionally high dose rates (in the order of tens of millisieverts per microsecond) on the activity of the produced endoglucanase, amount of biomass and extra-cellular protein, was studied in batch cultivation conditions. In the dose range of 200-1200 mSv, some enhancement of endoglucanase activity was obtained: around 18%-32%, despite the drop of the biomass amount, compared with the untreated material.

Effect of multiple short highly energetic X-ray pulses on the synthesis of endoglucanase by a mutant strain of Trichoderma reesei-M7

PubMed Central

Gemishev, Orlin; Zapryanov, Stanislav; Blagoev, Alexander; Markova, Maya; Savov, Valentin

2014-01-01

Bioconversion of cellulose-containing substrate to glucose represents an important area of modern biotechnology. Enzymes for the degradation of the polysaccharide part of biomass have been produced, mostly by fungi belonging to genus Trichoderma. Studies were carried out with the mutant strain Trichoderma reesei-M7, a cellulase producer. Spores of the enzyme producer were irradiated with different doses of characteristic X-ray radiation from metallic tungsten (mainly the W Kα1 and Kα2 lines) with a high dose rate. The latter is a specific property of the dense plasma focus (DPF) device, which has pulsed operation and thus gives short and highly energetic pulses of multiple types of rays and particles. In this case, we focused our study on the influence of hard X-rays. The doses of X-rays absorbed by the spores varied in the range of approximately 5–11,000 mSv measured with thermoluminescent dosimeters (TLD). The influence of the applied doses in combination with exceptionally high dose rates (in the order of tens of millisieverts per microsecond) on the activity of the produced endoglucanase, amount of biomass and extra-cellular protein, was studied in batch cultivation conditions. In the dose range of 200–1200 mSv, some enhancement of endoglucanase activity was obtained: around 18%–32%, despite the drop of the biomass amount, compared with the untreated material. PMID:26019569

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

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

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

2004-03-31

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

Benchmark studies of induced radioactivity produced in LHC materials, Part II: Remanent dose rates.

PubMed

Brugger, M; Khater, H; Mayer, S; Prinz, A; Roesler, S; Ulrici, L; Vincke, H

2005-01-01

A new method to estimate remanent dose rates, to be used with the Monte Carlo code FLUKA, was benchmarked against measurements from an experiment that was performed at the CERN-EU high-energy reference field facility. An extensive collection of samples of different materials were placed downstream of, and laterally to, a copper target, intercepting a positively charged mixed hadron beam with a momentum of 120 GeV c(-1). Emphasis was put on the reduction of uncertainties by taking measures such as careful monitoring of the irradiation parameters, using different instruments to measure dose rates, adopting detailed elemental analyses of the irradiated materials and making detailed simulations of the irradiation experiment. The measured and calculated dose rates are in good agreement.

Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.

PubMed

Cone, Katherine; Lanpher, Janell; Kinens, Abigail; Richard, Philomena; Couture, Sarah; Brackin, Rebecca; Payne, Emily; Harrington, Kylee; Rice, Kenner C; Stevenson, Glenn W

2018-05-01

Although delta/mu receptor interactions vary as a function of behavioral endpoint, there have been no assessments of these interactions using assays of pain-depressed responding. This is the first report of delta/mu interactions using an assay of pain-depressed behavior. A mult-cycle FR10 operant schedule was utilized in the presence of (nociception) and in the absence of (rate suppression) a lactic acid inflammatory pain-like manipulation. SNC80 and methadone were used as selective/high efficacy delta and mu agonists, respectively. Both SNC80 and methadone alone produced a dose-dependent restoration of pain-depressed responding and dose-dependent response rate suppression. Three fixed ratio mixtures, based on the relative potencies of the drugs in the nociception assay, also produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that all three mixtures produced supra-additive antinociceptive effects and simply additive sedation effects. The therapeutic index (TI) inversely varied as a function of amount of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI, and larger amounts produced a lower TI. Compared to literature using standard pain-elicited assays, the orderly relationship between SNC80 and TI reported here may be a unique function of assessing pain-depressed behavior.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2004-07-01

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

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

DTIC Science & Technology

1986-06-17

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

Direct Measurement of Perchlorate Exposure Biomarkers in a Highly Exposed Population: A Pilot Study

PubMed Central

Wong, Michelle; Copan, Lori; Olmedo, Luis; Patton, Sharyle; Haas, Robert; Atencio, Ryan; Xu, Juhua; Valentin-Blasini, Liza

2011-01-01

Exposure to perchlorate is ubiquitous in the United States and has been found to be widespread in food and drinking water. People living in the lower Colorado River region may have perchlorate exposure because of perchlorate in ground water and locally-grown produce. Relatively high doses of perchlorate can inhibit iodine uptake and impair thyroid function, and thus could impair neurological development in utero. We examined human exposures to perchlorate in the Imperial Valley among individuals consuming locally grown produce and compared perchlorate exposure doses to state and federal reference doses. We collected 24-hour urine specimen from a convenience sample of 31 individuals and measured urinary excretion rates of perchlorate, thiocyanate, nitrate, and iodide. In addition, drinking water and local produce were also sampled for perchlorate. All but two of the water samples tested negative for perchlorate. Perchlorate levels in 79 produce samples ranged from non-detect to 1816 ppb. Estimated perchlorate doses ranged from 0.02 to 0.51 µg/kg of body weight/day. Perchlorate dose increased with the number of servings of dairy products consumed and with estimated perchlorate levels in produce consumed. The geometric mean perchlorate dose was 70% higher than for the NHANES reference population. Our sample of 31 Imperial Valley residents had higher perchlorate dose levels compared with national reference ranges. Although none of our exposure estimates exceeded the U. S. EPA reference dose, three participants exceeded the acceptable daily dose as defined by bench mark dose methods used by the California Office of Environmental Health Hazard Assessment. PMID:21394205

Selective enhancement of fentanyl-induced antinociception by the delta agonist SNC162 but not by ketamine in rhesus monkeys: Further evidence supportive of delta agonists as candidate adjuncts to mu opioid analgesics.

PubMed

Banks, Matthew L; Folk, John E; Rice, Kenner C; Negus, S Stevens

2010-12-01

Mu-opioid receptor agonists such as fentanyl are effective analgesics, but their clinical use is limited by untoward effects. Adjunct medications may improve the effectiveness and/or safety of opioid analgesics. This study compared interactions between fentanyl and either the noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine or the delta-opioid receptor agonist SNC162 [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-phenyl)methyl]-N,N-diethylbenzamide] in two behavioral assays in rhesus monkeys. An assay of thermal nociception evaluated tail-withdrawal latencies from water heated to 50 and 54°C. An assay of schedule-controlled responding evaluated response rates maintained under a fixed-ratio 30 schedule of food presentation. Effects of each drug alone and of three mixtures of ketamine+fentanyl (22:1, 65:1, 195:1 ketamine/fentanyl) or SNC162+fentanyl (59:1, 176:1, 528:1 SNC162/fentanyl) were evaluated in each assay. All drugs and mixtures dose-dependently decreased rates of food-maintained responding, and drug proportions in the mixtures were based on relative potencies in this assay. Ketamine and SNC162 were inactive in the assay of thermal antinociception, but fentanyl and all mixtures produced dose-dependent antinociception. Drug interactions were evaluated using dose-addition and dose-ratio analysis. Dose-addition analysis revealed that interactions for all ketamine/fentanyl mixtures were additive in both assays. SNC162/fentanyl interactions were usually additive, but one mixture (176:1) produced synergistic antinociception at 50°C. Dose-ratio analysis indicated that ketamine failed to improve the relative potency of fentanyl to produce antinociception vs. rate suppression, whereas two SNC162/fentanyl mixtures (59:1 and 176:1) increased the relative potency of fentanyl to produce antinociception. These results suggest that delta agonists may produce more selective enhancement than ketamine of mu agonist-induced antinociception. Copyright © 2010 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-10-01

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

GABAB-receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra.

PubMed

Engberg, G; Kling-Petersen, T; Nissbrandt, H

1993-11-01

Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABAB-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABAB-receptor agonist baclofen (1-16 mg/kg) was associated with a dose-dependent regularization of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularization of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GABAA-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3-10 min) did neither promote nor prevent the regularization of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABAB-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst firing activity on these neurons.

A centrally mediated prolonged hypotension produced by oxotremorine or pilocarpine

PubMed Central

Dage, R.C.

1979-01-01

1 Oxotremorine, methyloxotremorine, pilocarpine or arecoline were given intravenously to anaesthetized cats, dogs or rats, and intraperitoneally to conscious normotensive and spontaneously hypertensive rats, pretreated with doses of methylatropine that completely blocked peripheral muscarinic receptors, to ascertain their effects on blood pressure and heart rate. 2 Oxotremorine but not methyloxotremorine produced a prolonged hypotension in cats and dogs but not in rats. Heart rate was not changed. Pilocarpine, although less potent, produced an identical effect, whereas the effect of arecoline was short by comparison. The hypotensive effect of these drugs was reversed by atropine. 3 In dogs, oxotremorine produced a prolonged hypotension with no change in heart rate or cardiac output. 4 A decrease in spontaneous sympathetic nerve activity accompanied the hypotension in cats. Both effects were reversed by atropine but could be reinvoked by large doses of oxotremorine. 5 The oxotremorine-induced hypotension in cats was not altered by decerebration but was abolished by high cervical spinal section. 6 The results indicate that the prolonged hypotension elicited by oxotremorine is mediated by an action at muscarinic receptors in the brain stem resulting in a decrease in sympathetic nerve activity and peripheral resistance but not heart rate or cardiac output. PMID:760887

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

PubMed

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

2002-01-01

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

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

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

Solar Variability and the Near-Earth Environment: Mining Enhanced Low Dose Rate Sensitivity Data From the Microelectronics and Photonics Test Bed Space Experiment

NASA Technical Reports Server (NTRS)

Turflinger, T.; Schmeichel, W.; Krieg, J.; Titus, J.; Campbell, A.; Reeves, M.; Marshall (P.); Hardage, Donna (Technical Monitor)

2004-01-01

This effort is a detailed analysis of existing microelectronics and photonics test bed satellite data from one experiment, the bipolar test board, looking to improve our understanding of the enhanced low dose rate sensitivity (ELDRS) phenomenon. Over the past several years, extensive total dose irradiations of bipolar devices have demonstrated that many of these devices exhibited ELDRS. In sensitive bipolar transistors, ELDRS produced enhanced degradation of base current, resulting in enhanced gain degradation at dose rates <0.1 rd(Si)/s compared to similar transistors irradiated at dose rates >1 rd(Si)/s. This Technical Publication provides updated information about the test devices, the in-flight experiment, and both flight-and ground-based observations. Flight data are presented for the past 5 yr of the mission. These data are compared to ground-based data taken on devices from the same date code lots. Information about temperature fluctuations, power shutdowns, and other variables encountered during the space flight are documented.

Treatment of aplastic anaemia with lower-dose anti-thymocyte globulin produces similar response rates and survival as per standard dose anti-thymocyte globulin schedules.

PubMed

Scott, A; Morris, K; Butler, J; Mills, A K; Kennedy, G A

2016-10-01

Aplastic anaemia (AA) is a rare acquired bone marrow failure syndrome resulting from the immune-mediated destruction of haemopoietic stem cells. For adults in whom first-line haemopoietic progenitor cell transplantation is not feasible, combination anti-thymocyte globulin (ATGAM) plus cyclosporine A is standard therapy; however, there are minimal data available regarding the optimal ATGAM dosage in terms of efficacy and survival. Our institutions have historically used different dosing protocols of ATGAM in the treatment of AA. We aimed to review the outcome of AA patients treated with these protocols and compare them to the published literature. We conducted a retrospective study of 31 adults who received first-line ATGAM for AA and compared response rates and survival between cohorts who received standard (40 mg/kg/day D1-4) versus lower-dose (15 mg/kg/day D1-5) ATGAM schedules. There were similar rates of response (64 vs 71%, P = 1.0), relapse (33 vs 33%, P = 1.0), transformation (14 vs 24%, P = 0.66) or infection (43 vs 47%, P = 1.0), respectively, between standard and lower-dose cohorts. At a median follow up of 24 months, there was no statistical difference between standard and lower-dose cohorts in either event-free (42.2 vs 64.7%, P = 0.91) or overall survival (73.1 vs 88.2%, P = 0.75). Our experience suggests that lower-dose ATGAM at 15 mg/kg/day D1-5 as treatment of AA produces similar responses and outcomes as per standard-dose ATGAM schedules. Prospective trials comparing ATGAM dose schedules in AA are warranted. © 2016 Royal Australasian College of Physicians.

Some cosmic radiation dose measurements aboard flights connecting Zagreb Airport.

PubMed

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

2008-02-01

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

Six steps to a successful dose-reduction strategy

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

Bennett, M.

1995-03-01

The increased importance of demonstrating achievement of the ALARA principle has helped produce a proliferation of dose-reduction ideas. Across a company there may be many dose-reduction items being pursued in a variety of areas. However, companies have a limited amount of resource and, therefore, to ensure funding is directed to those items which will produce the most benefit and that all areas apply a common policy, requires the presence of a dose-reduction strategy. Six steps were identified in formulating the dose-reduction strategy for Rolls-Royce and Associates (RRA): (1) collating the ideas; (2) quantitatively evaluating them on a common basis; (3)more » prioritizing the ideas in terms of cost benefit, (4) implementation of the highest priority items; (5) monitoring their success; (6) periodically reviewing the strategy. Inherent in producing the dose-reduction strategy has been a comprehensive dose database and the RRA-developed dose management computer code DOMAIN, which allows prediction of dose rates and dose. The database enabled high task dose items to be identified, assisted in evaluating dose benefits, and monitored dose trends once items had been implemented. The DOMAIN code was used both in quantifying some of the project dose benefits and its results, such as dose contours, used in some of the dose-reduction items themselves. In all, over fifty dose-reduction items were evaluated in the strategy process and the items which will give greatest benefit are being implemented. The strategy has been successful in giving renewed impetus and direction to dose-reduction management.« less

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

PubMed

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

2016-02-01

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

Enhanced renal prostaglandin production in the dog. I. Effects on renal function.

PubMed

Tannenbaum, J; Splawinski, J A; Oates, J A; Nies, A S

1975-01-01

The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 and F2alpha.PGE2given at 0.01-0.3 mug/kg min--1 produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rage increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0-30.0 mug/kg min--1 similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2 and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2alpha had essentially no effects at infusion rates of 0.03-1.0 mug/kg min--1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11,14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2 were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.

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

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

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

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

Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

PubMed Central

Carter, Lawrence P.; Griffiths, Roland R.; Mintzer, Miriam Z.

2009-01-01

Rationale Illicit gamma-hydroxybutyrate (GHB) has received attention as a “date rape drug” that produces robust amnesia; however, there is little experimental evidence in support of GHB’s amnestic effects. Objectives This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers. Materials and methods Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined. Results Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate. Conclusions Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers. PMID:19543883

Optically Stimulated Luminescent Dosimetry for High Dose Rate Brachytherapy

PubMed Central

Tien, Christopher Jason; Ebeling, Robert; Hiatt, Jessica R.; Curran, Bruce; Sternick, Edward

2012-01-01

Purpose: The objective was to determine whether optically stimulated luminescent dosimeters (OSLDs) were appropriate for in vivo measurements in high dose rate brachytherapy. In order to make this distinction, three dosimetric characteristics were tested: dose linearity, dose rate dependence, and angular dependence. The Landauer nanoDot™ OSLDs were chosen due to their popularity and their availability commercially. Methods: To test the dose linearity, each OSLD was placed at a constant location and the dwell time was varied. Next, in order to test the dose rate dependence, each OSLD was placed at different OLSD-to-source distances and the dwell time was held constant. A curved geometry was created using a circular Accuboost® applicator in order to test angular dependence. Results: The OSLD response remained linear for high doses and was independent of dose rate. For doses up to 600 cGy, the linear coefficient of determination was 0.9988 with a response of 725 counts per cGy. The angular dependence was significant only in “edge-on” scenarios. Conclusion: OSLDs are conveniently read out using commercially available readers. OSLDs can be re-read and serve as a permanent record for clinical records or be annealed using conventional fluorescent light. Lastly, OSLDs are produced commercially for $5 each. Due to these convenient features, in conjunction with the dosimetric performance, OSLDs should be considered a clinically feasible and attractive tool for in vivo HDR brachytherapy measurements. PMID:22888476

Central α- and β-adrenoceptors modifying arterial blood pressure and heart rate in conscious cats

PubMed Central

Day, M.D.; Roach, A.G.

1974-01-01

1 In conscious unrestrained cats noradrenaline, α-methylnoradrenaline and clonidine, infused into the lateral cerebral ventricles (i.c.v.) caused dose-related falls in blood pressure and heart rate; both effects were abolished after i.c.v. phentolamine. 2 In 12 out of 20 cats, i.c.v. isoprenaline and salbutamol when given caused dose-related pressor responses and tachycardias. These effects were abolished after i.c.v. β-adrenoceptor blocking drugs but were unaffected by α-adrenoceptor blocking agents. 3 In 5 out of 20 cats, i.c.v. isoprenaline regularly produced dose-related falls in blood pressure with associated tachycardias; both effects were abolished after i.c.v. β-adrenoceptor blocking agents. 4 Intracerebroventricular dopamine produced cardiovascular responses which were qualitatively similar to those produced by i.c.v. isoprenaline. 5 Intracerebroventricular adrenaline produced complex responses in untreated animals but typical α-effects were obtained after prior i.c.v. treatment with a β-adrenoceptor blocking agent and typical β-effects after i.c.v. pretreatment with an α-adrenoceptor blocking agent. 6 The cardiovascular changes produced by i.c.v. β-adrenoceptor agonists were abolished after systemic administration of hexamethonium or bethanidine. 7 The results are discussed in the light of the mode of action of β-adrenoceptor stimulants and β-adrenoceptor blocking agents in the treatment of hypertension. PMID:4451747

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

Radiation dosimeter

DOEpatents

Fox, Richard J.

1983-01-01

A radiation detector readout circuit is provided which produces a radiation dose-rate readout from a detector even though the detector output may be highly energy dependent. A linear charge amplifier including an output charge pump circuit amplifies the charge signal pulses from the detector and pumps the charge into a charge storage capacitor. The discharge rate of the capacitor through a resistor is controlled to provide a time-dependent voltage which when integrated provides an output proportional to the dose-rate of radiation detected by the detector. This output may be converted to digital form for readout on a digital display.

Radiation dosimeter

DOEpatents

Fox, R.J.

1981-09-01

A radiation detector readout circuit is provided which produces a radiation dose-rate readout from a detector even through the detector output may be highly energy dependent. A linear charge amplifier including an output charge pump circuit amplifies the charge signal pulses from the detector and pumps the charge into a charge storage capacitor. The discharge rate of the capacitor through a resistor is controlled to provide a time-dependent voltage which when integrated provides an output proportional to the dose-rate of radiation detected by the detector. This output may be converted to digital form for readout on a digital display.

Safety pharmacology of acute MDMA administration in healthy subjects.

PubMed

Vizeli, Patrick; Liechti, Matthias E

2017-05-01

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is being investigated in MDMA-assisted psychotherapy. The present study characterized the safety pharmacology of single-dose administrations of MDMA (75 or 125 mg) using data from nine double-blind, placebo-controlled, crossover studies performed in the same laboratory in a total of 166 healthy subjects. The duration of the subjective effects was 4.2 ± 1.3 h (range: 1.4-8.2 h). The 125 mg dose of MDMA produced greater 'good drug effect' ratings than 75 mg. MDMA produced moderate and transient 'bad drug effect' ratings, which were greater in women than in men. MDMA increased systolic blood pressure to >160 mmHg, heart rate >100 beats/min, and body temperature >38°C in 33%, 29% and 19% of the subjects, respectively. These proportions of subjects with hypertension (>160 mmHg), tachycardia, and body temperature >38°C were all significantly greater after 125 mg MDMA compared with the 75 mg dose. Acute and subacute adverse effects of MDMA as assessed by the List of Complaints were dose-dependent and more frequent in females. MDMA did not affect liver or kidney function at EOS 29 ± 22 days after use. No serious adverse events occurred. In conclusion, MDMA produced predominantly acute positive subjective drug effects. Bad subjective drug effects and other adverse effects were significantly more common in women. MDMA administration was overall safe in physically and psychiatrically healthy subjects and in a medical setting. However, the risks of MDMA are likely higher in patients with cardiovascular disease and remain to be investigated in patients with psychiatric disorders.

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; Jesse, Robert; MacLean, Katherine A; Barrett, Frederick S; Cosimano, Mary P; Klinedinst, Maggie A

2018-01-01

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level ("standard") support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282.

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors

PubMed Central

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; Jesse, Robert; MacLean, Katherine A; Barrett, Frederick S; Cosimano, Mary P; Klinedinst, Maggie A

2017-01-01

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level (“standard”) support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282 PMID:29020861

Terrestrial Gamma Radiation Dose Rate of West Sarawak

NASA Astrophysics Data System (ADS)

Izham, A.; Ramli, A. T.; Saridan Wan Hassan, W. M.; Idris, H. N.; Basri, N. A.

2017-10-01

A study of terrestrial gamma radiation (TGR) dose rate was conducted in west of Sarawak, covering Kuching, Samarahan, Serian, Sri Aman, and Betong divisions to construct a baseline TGR dose rate level data of the areas. The total area covered was 20,259.2 km2, where in-situ measurements of TGR dose rate were taken using NaI(Tl) scintillation detector Ludlum 19 micro R meter NaI(Tl) approximately 1 meter above ground level. Twenty-nine soil samples were taken across the 5 divisions covering 26 pairings of 9 geological formations and 7 soil types. A hyperpure Germanium detector was then used to find the samples' 238U, 232Th, and 40K radionuclides concentrations producing a correction factor Cf = 0.544. A total of239 measured data were corrected with Cf resulting in a mean Dm of 47 ± 1 nGy h-1, with a range between 5 nGy h-1 - 103 nGy h-1. A multiple regression analysis was conducted between geological means and soil types means against the corrected TGR dose rate Dm, generating Dg,s= 0.847Dg+ 0.637Ds- 22.313 prediction model with a normalized Beta equation of Dg,s= 0.605Dg+ 0.395Ds. The model has an 84.6% acceptance of Whitney- Mann test null hypothesis when tested against the corrected TGR dose rates.

Dose rate estimation around a 60Co gamma-ray irradiation source by means of 115mIn photoactivation.

PubMed

Murataka, Ayanori; Endo, Satoru; Kojima, Yasuaki; Shizuma, Kiyoshi

2010-01-01

Photoactivation of nuclear isomer (115m)In with a halflife of 4.48 h occurs by (60)Co gamma-ray irradiation. This is because the resonance gamma-ray absorption occurs at 1078 keV level for stable (115)In, and that energy gamma-rays are produced by Compton scattering of (60)Co primary gamma-rays. In this work, photoactivation of (115m)In was applied to estimate the dose rate distribution around a (60)Co irradiation source utilizing a standard dose rate taken by alanine dosimeter. The (115m)In photoactivation was measured at 10 to 160 cm from the (60)Co source. The derived dose rate distribution shows a good agreement with both alanine dosimeter data and Monte Carlo simulation. It is found that angular distribution of the dose rate along a circumference at radius 2.8 cm from the central axis shows +/- 10% periodical variation reflecting the radioactive strength of the source rods, but less periodic distribution at radius 10 and 20 cm. The (115m)In photoactivation along the vertical direction in the central irradiation port strongly depends on the height and radius as indicated by Monte Carlo simulation. It is demonstrated that (115m)In photoactivation is a convenient method to estimate the dose rate distribution around a (60)Co source.

SU-E-T-495: Neutron Induced Electronics Failure Rate Analysis for a Single Room Proton Accelerator

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

Knutson, N; DeWees, T; Klein, E

2014-06-01

Purpose: To determine the failure rate as a function of neutron dose of the range modulator's servo motor controller system (SMCS) while shielded with Borated Polyethylene (BPE) and unshielded in a single room proton accelerator. Methods: Two experimental setups were constructed using two servo motor controllers and two motors. Each SMCS was then placed 30 cm from the end of the plugged proton accelerator applicator. The motor was then turned on and observed from outside of the vault while being irradiated to known neutron doses determined from bubble detector measurements. Anytime the motor deviated from the programmed motion a failuremore » was recorded along with the delivered dose. The experiment was repeated using 9 cm of BPE shielding surrounding the SMCS. Results: Ten SMCS failures were recorded in each experiment. The dose per monitor unit for the unshielded SMCS was 0.0211 mSv/MU and 0.0144 mSv/MU for the shielded SMCS. The mean dose to produce a failure for the unshielded SMCS was 63.5 ± 58.3 mSv versus 17.0 ±12.2 mSv for the shielded. The mean number of MUs between failures were 2297 ± 1891 MU for the unshielded SMCS and 2122 ± 1523 MU for the shielded. A Wilcoxon Signed Ranked test showed the dose between failures were significantly different (P value = 0.044) while the number of MUs between failures were not (P value = 1.000). Statistical analysis determined a SMCS neutron dose of 5.3 mSv produces a 5% chance of failure. Depending on the workload and location of the SMCS, this failure rate could impede clinical workflow. Conclusion: BPE shielding was shown to not reduce the average failure of the SMCS and relocation of the system outside of the accelerator vault was required to lower the failure rate enough to avoid impeding clinical work flow.« less

Safety of Oral Dronabinol During Opioid Withdrawal in Humans

PubMed Central

Jicha, Crystal J.; Lofwall, Michelle R.; Nuzzo, Paul A.; Babalonis, Shanna; Elayi, Samy Claude; Walsh, Sharon L.

2015-01-01

Background Opioid dependence remains a significant public health problem worldwide with only three FDA-approved treatments, all targeting the mu-opioid receptor. Dronabinol, a cannabinoid (CB) 1 receptor agonist, is currently under investigation as a novel opioid withdrawal treatment. This study reports on safety outcomes of dronabinol among adults in opioid withdrawal. Methods Twelve adults physically dependent on short-acting opioids participated in this 5-week within-subject, randomized, double blind, placebo-controlled inpatient study. Volunteers were maintained on oral oxycodone 30mg qid. Double-blind placebo substitutions occurred for 21 hours before each of 7 experimental sessions in order to produce opioid withdrawal. A single oral test dose was administered each session (placebo, oxycodone 30 and 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Heart rate, blood pressure, respiratory outcomes and pupil diameter were assessed repeatedly. Results Dronabinol 40mg produced sustained sinus tachycardia accompanied by anxiety and panic necessitating dose reduction to 30mg. Sinus tachycardia and anxiety also occurred in one volunteer after dronabinol 20mg. Compared to placebo, dronabinol 20 and 30mg produced significant increases in heart rate beginning 1 hour after drug administration that lasted approximately two hours (p<0.05). Dronabinol 5 and 10mg produced placebo-like effects. Oxycodone produced prototypic mu-opioid agonist effects (e.g., miosis). Conclusion Dronabinol 20mg and higher increased heart rate among healthy adults at rest who were in a state of opioid withdrawal, raising concern about its safety. These results have important implications for future dosing strategies and may limit the utility of dronabinol as a treatment for opioid withdrawal. PMID:26483357

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-12-01

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

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

PubMed

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

2016-12-01

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

The Influence of Nicotine Dose and Nicotine Dose Expectancy on the Cognitive and Subjective Effects of Cigarette Smoking

PubMed Central

Juliano, Laura M.; Fucito, Lisa M.; Harrell, Paul T.

2013-01-01

This study investigated the independent and interactive effects of nicotine dose and nicotine dose expectancy on smoking outcomes using a 2 (given nicotine vs. placebo) × 2 (told nicotine vs. placebo) Balanced Placebo Design (BPD). Smokers (N = 148) completed the Rapid Visual Information Processing Task (RVIP) and measures of smoking urge, mood, and cigarette ratings (e.g., satisfying) after smoking a nicotine or placebo cigarette crossed with instructions that the cigarette contained either nicotine or no nicotine. Nicotine cigarettes (0.6 mg nicotine) produced better sustained attention performance than placebos as indicated by RVIP reaction time, hits, and sensitivity (A′). Nicotine cigarettes also produced better mood and greater rewarding subjective effects of the cigarettes on 11 of 11 dimensions compared to placebos. Nicotine instructions resulted in fewer RVIP false alarms, better mood, and greater rewarding subjective effects of the cigarettes on 9 of 11 dimensions compared to placebo instructions. Nicotine dose by nicotine dose expectancy interactions were also observed for urge and tension-anxiety, such that the dose expectancy manipulation produced differential effects only among those who smoked placebo cigarettes. In contrast a significant interaction for self-reported vigor-activity demonstrated that the dose expectancy manipulation produced effects only among those who smoked nicotine cigarettes. This study provides additional evidence that nicotine improves cognitive performance, and provides initial evidence that denicotinized cigarettes smoked under the guise that they contain nicotine influence cognitive performance, albeit with less robust effects than nicotine. These data may inform the development of expectancy-based interventions for tobacco dependence. PMID:21463067

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2015-03-01

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

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

PubMed

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

2013-08-30

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

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

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

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

PubMed

Aryal, P; Molloy, J

2012-06-01

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

Extravasation of a therapeutic dose of 131I-metaiodobenzylguanidine: prevention, dosimetry, and mitigation.

PubMed

Bonta, Dacian V; Halkar, Raghuveer K; Alazraki, Naomi

2011-09-01

After the extravasation of a therapeutic dose of (131)I-metaiodobenzylguanidine that produced a radiation burn to a patient's forearm, we instituted a catheter placement verification protocol. Before therapy infusion, proper placement is verified by administering 37 MBq of (99m)Tc-pertechnetate through the catheter, and monitoring activity at the administration site and on the contralateral extremity. A dosimetric model describing both high-rate and low-rate dose components was developed and predicted that the basal epidermal layer received a radiation dose consistent with the observed moist desquamation radiation skin toxicity. No extravasation incidents have occurred since the verification procedure was instituted. To protect against radiation injury from extravasation of therapeutic radionuclides, test administration of a small (99m)Tc dose with probe monitoring of comparable sites in both upper extremities appears to be an effective preventive measure.

Microdosemeter instrument (MIDN) for assessing risk in space.

PubMed

Pisacane, V L; Dolecek, Q E; Malak, H; Cucinotta, F A; Zaider, M; Rosenfeld, A B; Rusek, A; Sivertz, M; Dicello, J F

2011-02-01

Radiation in space generally produces higher dose rates than that on the Earth's surface, and contributions from primary galactic and solar events increase with altitude within the magnetosphere. Presently, no personnel monitor is available to astronauts for real-time monitoring of dose, radiation quality and regulatory risk. This group is developing a prototypic instrument for use in an unknown, time-varying radiation field. This microdosemeter-dosemeter nucleon instrument is for use in a spacesuit, spacecraft, remote rover and other applications. It provides absorbed dose, dose rate and dose equivalent in real time so that action can be taken to reduce exposure. Such a system has applications in health physics, anti-terrorism and radiation-hardening of electronics as well. The space system is described and results of ground-based studies are presented and compared with predictions of transport codes. An early prototype in 2007 was successfully launched, the only solid-state microdosemeter to have flown in space.

THE DEPRESSANT EFFECT OF CONTINUOUS COBALT-60 RADIATION ON THE SECONDARY TETANUS ANTITOXIN RESPONSE IN MICE

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

Stoner, R.D.; Hale, W.M.

1958-05-01

The radiosensitivity of the secondary tetanus antitoxin response in mice was demonstrated after rather low doses of continuous gamma -radiation given at a dose rate of 4 rep/hr. Accumulated doses of 48 to 288 rep depressed antitoxin formation. Comparable doses of acute gamma radiation did not depress antitoxin production. Acute doses of 350 to 650 rep sharply depressed the secondary antibody response, however. Extended periods of continuous gamma -radiation from 10 to 28 days to accumulated doses of 960 to 2688 rep markedly depressed the secondary antibody response. An accumulated dose of 2688 rep was needed to depress antitoxin formationmore » to the level observed after an acute dose of 650 rep. When the secondary stimulus of fluid tetanus toxoid was given prior to 10 days of continuous exposure to an accumulated dose of 860 rep, the secondary antibody respense was not depressed. Irradiated mice recovered the ability to produce a normal secondary antitoxin response during the second week after an accumulated dose of 1248 rep. The secondary antitoxin response was depressed in mice given long-continued gamma -radiation at a dose rate of 1 rep/hr. (auth)« less

Dosimetric characterizations of GZP6 60Co high dose rate brachytherapy sources: application of superimposition method

PubMed Central

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Mowlavi, Ali Asghar; Meigooni, Ali Soleimani

2012-01-01

Background Dosimetric characteristics of a high dose rate (HDR) GZP6 Co-60 brachytherapy source have been evaluated following American Association of Physicists in MedicineTask Group 43U1 (AAPM TG-43U1) recommendations for their clinical applications. Materials and methods MCNP-4C and MCNPX Monte Carlo codes were utilized to calculate dose rate constant, two dimensional (2D) dose distribution, radial dose function and 2D anisotropy function of the source. These parameters of this source are compared with the available data for Ralstron 60Co and microSelectron192Ir sources. Besides, a superimposition method was developed to extend the obtained results for the GZP6 source No. 3 to other GZP6 sources. Results The simulated value for dose rate constant for GZP6 source was 1.104±0.03 cGyh-1U-1. The graphical and tabulated radial dose function and 2D anisotropy function of this source are presented here. The results of these investigations show that the dosimetric parameters of GZP6 source are comparable to those for the Ralstron source. While dose rate constant for the two 60Co sources are similar to that for the microSelectron192Ir source, there are differences between radial dose function and anisotropy functions. Radial dose function of the 192Ir source is less steep than both 60Co source models. In addition, the 60Co sources are showing more isotropic dose distribution than the 192Ir source. Conclusions The superimposition method is applicable to produce dose distributions for other source arrangements from the dose distribution of a single source. The calculated dosimetric quantities of this new source can be introduced as input data to the GZP6 treatment planning system (TPS) and to validate the performance of the TPS. PMID:23077455

Gamma irradiator dose mapping simulation using the MCNP code and benchmarking with dosimetry.

PubMed

Sohrabpour, M; Hassanzadeh, M; Shahriari, M; Sharifzadeh, M

2002-10-01

The Monte Carlo transport code, MCNP, has been applied in simulating dose rate distribution in the IR-136 gamma irradiator system. Isodose curves, cumulative dose values, and system design data such as throughputs, over-dose-ratios, and efficiencies have been simulated as functions of product density. Simulated isodose curves, and cumulative dose values were compared with dosimetry values obtained using polymethyle-methacrylate, Fricke, ethanol-chlorobenzene, and potassium dichromate dosimeters. The produced system design data were also found to agree quite favorably with those of the system manufacturer's data. MCNP has thus been found to be an effective transport code for handling of various dose mapping excercises for gamma irradiators.

[Radioecological studies of freshwater mollusks in the Chernobyl accident exclusion zone].

PubMed

Gudkov, D I; Nazarov, A B; Dziubenko, E V; Kaglian, A E; Klenus, V G

2009-01-01

Species-specificity and dynamics of 90Sr, 137Cs and some transuranic elements accumulation in bivalve and gastropod freshwater molluscs of the Chernobyl exclusion zone during 1997-2008 was analyzed. The results of radiation dose and chromosome aberration rate estimation and the analysis of hemolymph composition of freshwater snail (Lymnaea stagnalis L.) was produced. The absorbed dose rate was registered in the range of 0.3-85.0 microGy/h. In closed water bodies the heightened chromosome aberration rate (up to 27%) in embryo tissues, and also the change of haematological indexes for the adult individuals of snails was registered.

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

NASA Astrophysics Data System (ADS)

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

2015-11-01

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

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

PubMed

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

2007-01-01

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

Analysis of dose rates received around the storage pool for irradiated control rods in a BWR nuclear power plant.

PubMed

Ródenas, J; Abarca, A; Gallardo, S

2011-08-01

BWR control rods are activated by neutron reactions in the reactor. The dose produced by this activity can affect workers in the area surrounding the storage pool, where activated rods are stored. Monte Carlo (MC) models for neutron activation and dose assessment around the storage pool have been developed and validated. In this work, the MC models are applied to verify the expected reduction of dose when the irradiated control rod is hanged in an inverted position into the pool. 2010 Elsevier Ltd. All rights reserved.

Role of gamma-aminobutyric acid type A (GABAA) receptor subtypes in acute benzodiazepine physical dependence-like effects: evidence from squirrel monkeys responding under a schedule of food presentation

PubMed Central

Fischer, Bradford D.; Teixeira, Laura P.; van Linn, Michael L.; Namjoshi, Ojas A.; Cook, James M.; Rowlett, James K.

2013-01-01

Rationale Assays of schedule-controlled responding can be used to characterize the pharmacology of benzodiazepines and other GABAA receptor modulators, and are sensitive to changes in drug effects that are related to physical dependence. Objective The present study used this approach to investigate the role of GABAA receptor subtypes in mediating dependence-like effects following benzodiazepine administration. Methods Squirrel monkeys (n=6) were trained on a fixed-ratio schedule of food reinforcement. Initially, the response rate-decreasing effects of chlordiazepoxide (0.1–10 mg/kg; nonselective GABAA receptor agonist), zolpidem (0.032–1.0 mg/kg; α1 subunit-containing GABAA subtype-preferring agonist) and HZ-166 (0.1–10 mg/kg; functionally selective α2 and α3 subunit-containing GABAA receptor agonist) were assessed. Next, acute dependence-like effects following single injections of chlordiazepoxide, zolpidem and HZ-166 were assessed with flumazenil (0.1–3.2 mg/kg; nonselective GABAA receptor antagonist). Finally, acute dependence-like effects following zolpidem administration were assessed with βCCt and 3-PBC (0.1–3.2 mg/kg and 0.32–10 mg/kg, respectively; α1 subunit-containing GABAA receptor antagonists). Results Chlordiazepoxide, zolpidem and HZ-166 produced dose- and time-dependent decreases in response rates, whereas flumazenil, βCCt and 3-PBC were ineffective. After the drug effects waned, flumazenil produced dose-dependent decreases in response rates following administration of 10 mg/kg chlordiazepoxide and 1.0 mg/kg zolpidem, but not following any dose of HZ-166. Further, both βCCt and 3-PBC produced dose-dependent decreases in response rates when administered after 1.0 mg/kg zolpidem. Conclusions These data raise the possibility that α1 subunit-containing GABAA receptors play a major role in physical dependence-related behaviors following a single injection of a benzodiazepine. PMID:23354533

Role of gamma-aminobutyric acid type A (GABAA) receptor subtypes in acute benzodiazepine physical dependence-like effects: evidence from squirrel monkeys responding under a schedule of food presentation.

PubMed

Fischer, Bradford D; Teixeira, Laura P; van Linn, Michael L; Namjoshi, Ojas A; Cook, James M; Rowlett, James K

2013-05-01

Assays of schedule-controlled responding can be used to characterize the pharmacology of benzodiazepines and other GABAA receptor modulators, and are sensitive to changes in drug effects that are related to physical dependence. The present study used this approach to investigate the role of GABAA receptor subtypes in mediating dependence-like effects following benzodiazepine administration. Squirrel monkeys (n = 6) were trained on a fixed-ratio schedule of food reinforcement. Initially, the response rate-decreasing effects of chlordiazepoxide (0.1-10 mg/kg; nonselective GABAA receptor agonist), zolpidem (0.032-1.0 mg/kg; α1 subunit-containing GABAA subtype-preferring agonist), and HZ-166 (0.1-10 mg/kg; functionally selective α2 and α3 subunit-containing GABAA receptor agonist) were assessed. Next, acute dependence-like effects following single injections of chlordiazepoxide, zolpidem, and HZ-166 were assessed with flumazenil (0.1-3.2 mg/kg; nonselective GABAA receptor antagonist). Finally, acute dependence-like effects following zolpidem administration were assessed with βCCt and 3-PBC (0.1-3.2 mg/kg and 0.32-10 mg/kg, respectively; α1 subunit-containing GABAA receptor antagonists). Chlordiazepoxide, zolpidem, and HZ-166 produced dose- and time-dependent decreases in response rates, whereas flumazenil, βCCT, and 3-PBC were ineffective. After the drug effects waned, flumazenil produced dose-dependent decreases in response rates following administration of 10 mg/kg chlordiazepoxide and 1.0 mg/kg zolpidem, but not following any dose of HZ-166. Further, both βCCT and 3-PBC produced dose-dependent decreases in response rates when administered after 1.0 mg/kg zolpidem. These data raise the possibility that α1 subunit-containing GABAA receptors play a major role in physical dependence-related behaviors following a single injection of a benzodiazepine.

Validating Fricke dosimetry for the measurement of absorbed dose to water for HDR 192Ir brachytherapy: a comparison between primary standards of the LCR, Brazil, and the NRC, Canada.

PubMed

Salata, Camila; David, Mariano Gazineu; de Almeida, Carlos Eduardo; El Gamal, Islam; Cojocaru, Claudiu; Mainegra-Hing, Ernesto; McEwen, Malcom

2018-04-05

Two Fricke-based absorbed dose to water standards for HDR Ir-192 dosimetry, developed independently by the LCR in Brazil and the NRC in Canada have been compared. The agreement in the determination of the dose rate from a HDR Ir-192 source at 1 cm in a water phantom was found to be within the k  =  1 combined measurement uncertainties of the two standards: D NRC /D LCR   =  1.011, standard uncertainty  =  2.2%. The dose-based standards also agreed within the uncertainties with the manufacturer's stated dose rate value, which is traceable to a national standard of air kerma. A number of possible influence quantities were investigated, including the specific method for producing the ferrous-sulphate Fricke solution, the geometry of the holder, and the Monte Carlo code used to determine correction factors. The comparison highlighted the lack of data on the determination of G(Fe 3+ ) in this energy range and the possibilities for further development of the holders used to contain the Fricke solution. The comparison also confirmed the suitability of Fricke dosimetry for Ir-192 primary standard dose rate determinations at therapy dose levels.

Validating Fricke dosimetry for the measurement of absorbed dose to water for HDR 192Ir brachytherapy: a comparison between primary standards of the LCR, Brazil, and the NRC, Canada

NASA Astrophysics Data System (ADS)

Salata, Camila; Gazineu David, Mariano; de Almeida, Carlos Eduardo; El Gamal, Islam; Cojocaru, Claudiu; Mainegra-Hing, Ernesto; McEwen, Malcom

2018-04-01

Two Fricke-based absorbed dose to water standards for HDR Ir-192 dosimetry, developed independently by the LCR in Brazil and the NRC in Canada have been compared. The agreement in the determination of the dose rate from a HDR Ir-192 source at 1 cm in a water phantom was found to be within the k  =  1 combined measurement uncertainties of the two standards: D NRC/D LCR  =  1.011, standard uncertainty  =  2.2%. The dose-based standards also agreed within the uncertainties with the manufacturer’s stated dose rate value, which is traceable to a national standard of air kerma. A number of possible influence quantities were investigated, including the specific method for producing the ferrous-sulphate Fricke solution, the geometry of the holder, and the Monte Carlo code used to determine correction factors. The comparison highlighted the lack of data on the determination of G(Fe3+) in this energy range and the possibilities for further development of the holders used to contain the Fricke solution. The comparison also confirmed the suitability of Fricke dosimetry for Ir-192 primary standard dose rate determinations at therapy dose levels.

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

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

Measurements of the dose due to cosmic rays in aircraft

NASA Astrophysics Data System (ADS)

Vuković, B.; Lisjak, I.; Radolić, V.; Vekić, B.; Planinić, J.

2006-06-01

When the primary particles from space, mainly protons, enter the atmosphere, they produce interactions with air nuclei, and cosmic-ray showers are induced. The radiation field at aircraft altitude is complex, with different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The cosmic radiation dose aboard A320 and ATR 42 aircraft was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter; radon concentration in the atmosphere was measured with the Alpha Guard radon detector. The estimated occupational effective dose for the aircraft crew (A320) working 500 h per year was 1.64 mSv. Another experiment was performed by the flights Zagreb-Paris-Buenos Aires and reversely, when one measured cosmic radiation dose; for 26.7 h of flight, the TLD dosimeter registered the total dose of 75 μSv and the average dose rate was 2.7 μSv/h. In the same month, February 2005, a traveling to Japan (24 h flight: Zagreb-Frankfurt-Tokyo and reversely) and the TLD-100 measurement showed the average dose rate of 2.4 μSv/h.

Dronabinol and marijuana in HIV-positive marijuana smokers. Caloric intake, mood, and sleep.

PubMed

Haney, Margaret; Gunderson, Erik W; Rabkin, Judith; Hart, Carl L; Vosburg, Suzanne K; Comer, Sandra D; Foltin, Richard W

2007-08-15

Individuals with HIV constitute the largest group using cannabinoids for medicinal reasons; yet, no studies have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol maintenance in HIV-positive marijuana smokers. This placebo-controlled within-subjects study evaluated marijuana and dronabinol across a range of behaviors: eating topography, mood, cognitive performance, physiologic measures, and sleep. HIV-positive marijuana smokers (n = 10) completed 2 16-day inpatient phases. Each dronabinol (5 and 10 mg) and marijuana (2.0% and 3.9% Delta9-tetrahydrocannabinol [THC]) dose was administered 4 times daily for 4 days, but only 1 drug was active per day, thereby maintaining double-blind dosing. Four days of placebo washout separated each active cannabinoid condition. As compared with placebo, marijuana and dronabinol dose dependently increased daily caloric intake and body weight in HIV-positive marijuana smokers. All cannabinoid conditions produced significant intoxication, except for low-dose dronabinol (5 mg); the intoxication was rated positively (eg, "good drug effect") with little evidence of discomfort and no impairment of cognitive performance. Effects of marijuana and dronabinol were comparable, except that only marijuana (3.9% THC) improved ratings of sleep. These data suggest that for HIV-positive marijuana smokers, both dronabinol (at doses 8 times current recommendations) and marijuana were well tolerated and produced substantial and comparable increases in food intake.

Design and characterization of a new high-dose-rate brachytherapy Valencia applicator for larger skin lesions

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

Candela-Juan, C., E-mail: ccanjuan@gmail.com; Niatsetski, Y.; Laarse, R. van der

Purpose: The aims of this study were (i) to design a new high-dose-rate (HDR) brachytherapy applicator for treating surface lesions with planning target volumes larger than 3 cm in diameter and up to 5 cm in size, using the microSelectron-HDR or Flexitron afterloader (Elekta Brachytherapy) with a {sup 192}Ir source; (ii) to calculate by means of the Monte Carlo (MC) method the dose distribution for the new applicator when it is placed against a water phantom; and (iii) to validate experimentally the dose distributions in water. Methods: The PENELOPE2008 MC code was used to optimize dwell positions and dwell times.more » Next, the dose distribution in a water phantom and the leakage dose distribution around the applicator were calculated. Finally, MC data were validated experimentally for a {sup 192}Ir mHDR-v2 source by measuring (i) dose distributions with radiochromic EBT3 films (ISP); (ii) percentage depth–dose (PDD) curve with the parallel-plate ionization chamber Advanced Markus (PTW); and (iii) absolute dose rate with EBT3 films and the PinPoint T31016 (PTW) ionization chamber. Results: The new applicator is made of tungsten alloy (Densimet) and consists of a set of interchangeable collimators. Three catheters are used to allocate the source at prefixed dwell positions with preset weights to produce a homogenous dose distribution at the typical prescription depth of 3 mm in water. The same plan is used for all available collimators. PDD, absolute dose rate per unit of air kerma strength, and off-axis profiles in a cylindrical water phantom are reported. These data can be used for treatment planning. Leakage around the applicator was also scored. The dose distributions, PDD, and absolute dose rate calculated agree within experimental uncertainties with the doses measured: differences of MC data with chamber measurements are up to 0.8% and with radiochromic films are up to 3.5%. Conclusions: The new applicator and the dosimetric data provided here will be a valuable tool in clinical practice, making treatment of large skin lesions simpler, faster, and safer. Also the dose to surrounding healthy tissues is minimal.« less

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

PubMed Central

Schuller, Bradley W.; Binns, Peter J.; Riley, Kent J.; Ma, Ling; Hawthorne, M. Frederick; Coderre, Jeffrey A.

2006-01-01

The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received whole-body epithermal neutron irradiation at a dose rate of 0.57 ± 0.04 Gy·min−1. An additional dose was selectively targeted to endothelial cells from the short-ranged (5–9 μm) particles released from neutron capture reactions in 10B confined to the blood by incorporation into liposomes 70–90 nm in diameter. Different liposome formulations produced 45 ± 7 or 118 ± 12 μg/g 10B in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 ± 0.09 or 1.90 ± 0.16 Gy·min−1, respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2- to 3-fold increased doses to the microvasculature, relative to the nonspecific whole-body neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 ± 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome. PMID:16505359

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

NASA Astrophysics Data System (ADS)

Schuller, Bradley W.; Binns, Peter J.; Riley, Kent J.; Ma, Ling; Hawthorne, M. Frederick; Coderre, Jeffrey A.

2006-03-01

The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received whole-body epithermal neutron irradiation at a dose rate of 0.57 ± 0.04 Gy·min-1. An additional dose was selectively targeted to endothelial cells from the short-ranged (5-9 μm) particles released from neutron capture reactions in 10B confined to the blood by incorporation into liposomes 70-90 nm in diameter. Different liposome formulations produced 45 ± 7 or 118 ± 12 μg/g 10B in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 ± 0.09 or 1.90 ± 0.16 Gy·min-1, respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2- to 3-fold increased doses to the microvasculature, relative to the nonspecific whole-body neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 ± 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome. gastrointestinal syndrome | boron | liposomes | neutron capture

Hormonal priming, induction of ovulation and in-vitro fertilization of the endangered Wyoming toad (Bufo baxteri)

PubMed Central

Browne, Robert K; Seratt, Jessica; Vance, Carrie; Kouba, Andrew

2006-01-01

The endangered Wyoming toad (Bufo baxteri) is the subject of an extensive captive breeding and reintroduction program. Wyoming toads in captivity rarely ovulate spontaneously and hormonal induction is used to ovulate females or to stimulate spermiation in males. With hormonal induction, ovulation is unreliable and egg numbers are low. The sequential administration of anovulatory doses of hormones (priming) has increased egg numbers and quality in both anurans and fish. Consequently, we tested the efficacy of a combination of human Chorionic Gonadotrophin (hCG) and Luteinizing Hormone Releasing Hormone analogue (LHRHa) administered as one dose, or two or three sequential doses to Bufo baxteri on egg numbers, fertilization and early embryo development. Spawning toads deposited eggs into Simplified Amphibian Ringers (SAR) solution to enable controlled in-vitro fertilization (IVF) with sperm from hormonally induced male toads. Unprimed females receiving a single mixed normally ovulatory dose of 500 IU hCG plus 4 micrograms of LHRHa produced no eggs. Whereas females primed with this dose and an anovulatory dose (100 IU hCG and 0.8 micrograms of LHRHa) of the same hormones, or primed only with an anovulatory dose, spawned after then receiving an ovulatory dose. Higher total egg numbers were produced with two primings than with one priming. Moreover, two primings produced significantly more eggs from each individual female than one priming. The cleavage rate of eggs was not found to differ between one or two primings. Nevertheless, embryo development with eggs from two primings gave a significantly greater percentage neurulation and swim-up than those from one priming. Of the male toads receiving a single dose of 300 IU hCG, 80% produced spermic urine with the greatest sperm concentration 7 hours post-administration (PA). However, peak sperm motility (95%) was achieved at 5 hours PA and remained relatively constant until declining 20 hours PA. In conclusion, Bufo baxteri egg numbers and quality benefited from sequential priming with LHRHa and hCG whereas spermic urine for IVF was produced from males with a single dose of hCG. The power of assisted reproduction technology in the conservation of endangered amphibians is shown by the release of nearly 2000 tadpoles produced by IVF during this study. PMID:16790071

SU-F-J-133: Adaptive Radiation Therapy with a Four-Dimensional Dose Calculation Algorithm That Optimizes Dose Distribution Considering Breathing Motion

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

Ali, I; Algan, O; Ahmad, S

Purpose: To model patient motion and produce four-dimensional (4D) optimized dose distributions that consider motion-artifacts in the dose calculation during the treatment planning process. Methods: An algorithm for dose calculation is developed where patient motion is considered in dose calculation at the stage of the treatment planning. First, optimal dose distributions are calculated for the stationary target volume where the dose distributions are optimized considering intensity-modulated radiation therapy (IMRT). Second, a convolution-kernel is produced from the best-fitting curve which matches the motion trajectory of the patient. Third, the motion kernel is deconvolved with the initial dose distribution optimized for themore » stationary target to produce a dose distribution that is optimized in four-dimensions. This algorithm is tested with measured doses using a mobile phantom that moves with controlled motion patterns. Results: A motion-optimized dose distribution is obtained from the initial dose distribution of the stationary target by deconvolution with the motion-kernel of the mobile target. This motion-optimized dose distribution is equivalent to that optimized for the stationary target using IMRT. The motion-optimized and measured dose distributions are tested with the gamma index with a passing rate of >95% considering 3% dose-difference and 3mm distance-to-agreement. If the dose delivery per beam takes place over several respiratory cycles, then the spread-out of the dose distributions is only dependent on the motion amplitude and not affected by motion frequency and phase. This algorithm is limited to motion amplitudes that are smaller than the length of the target along the direction of motion. Conclusion: An algorithm is developed to optimize dose in 4D. Besides IMRT that provides optimal dose coverage for a stationary target, it extends dose optimization to 4D considering target motion. This algorithm provides alternative to motion management techniques such as beam-gating or breath-holding and has potential applications in adaptive radiation therapy.« less

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

PubMed

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

2017-07-01

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

Peripheral opioid analgesia in teeth with symptomatic inflamed pulps.

PubMed Central

Uhle, R. A.; Reader, A.; Nist, R.; Weaver, J.; Beck, M.; Meyers, W. J.

1997-01-01

The purpose of this study was to investigate the ability of low-dose fentanyl to produce analgesia when administered via the periodontal ligament injection in teeth with symptomatic, inflamed pulps. All subjects presented for emergency treatment with moderate to severe pain and had a posterior tooth with a clinical diagnosis of irreversible pulpitis. Twenty subjects randomly received either 10 micrograms fentanyl citrate or saline placebo via the periodontal ligament injection in a double-blind manner. The subjects rated their pain prior to injection and rated pain intensity and pain half gone for 59 min postinjection. Low-dose fentanyl delivered via the periodontal ligament injection in inflamed teeth provided significantly greater analgesia than the saline placebo (P < 0.05). Since the dose of fentanyl used was less than the dose required to provide analgesia by a central mechanism, the results of this study may be consistent with a peripheral opioid mechanism of action. PMID:9481968

Skyshine photon doses from 6 and 10 MV medical linear accelerators.

PubMed

de Paiva, Eduardo; da Rosa, Luiz A R

2012-01-05

The skyshine radiation phenomenon consists of the scattering of primary photon beams in the atmosphere above the roof of a medical linear accelerator facility, generating an additional dose at ground level in the vicinity of the treatment room. Thus, with respect to radioprotection, this situation plays an important role when the roof is designed with little shielding and there are buildings next to the radiotherapy treatment room. In literature, there are few reported skyshine-measured doses and these contain poor agreement with empirical calculations. In this work, we carried out measurements of skyshine photon dose rates produced from eight different 6 and 10 MV medical accelerators. Each measurement was performed outside the room facility, with the beam positioned in the upward direction, at a horizontal distance from the target and for a 40 cm × 40 cm maximum photon field size at the accelerator isocenter. Measured dose-equivalent rates results were compared with calculations obtained by an empirical expression, and differences between them deviated in one or more order of magnitude.

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

PubMed

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

2012-12-05

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

“Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs

PubMed Central

Barrett, Frederick S.; Schlienz, Nicolas J.; Lembeck, Natalie; Waqas, Muhammad; Vandrey, Ryan

2018-01-01

Abstract Introduction: Cannabis has been historically classified as a hallucinogen. However, subjective cannabis effects do not typically include hallucinogen-like effects. Empirical reports of hallucinogen-like effects produced by cannabis in controlled settings, particularly among healthy research volunteers, are rare and have mostly occurred after administration of purified Δ-9 tetrahydrocannabinol (THC) rather than whole plant cannabis. Methods: The case of a healthy 30-year-old male who experienced auditory and visual hallucinations in a controlled laboratory study after inhaling vaporized cannabis that contained 25 mg THC (case dose) is presented. Ratings on the Hallucinogen Rating Scale (HRS) following the case dose are compared with HRS ratings obtained from the participant after other doses of cannabis and with archival HRS data from laboratory studies involving acute doses of cannabis, psilocybin, dextromethorphan (DXM), and salvinorin A. Results: Scores on the Volition subscale of the HRS were greater for the case dose than for the maximum dose administered in any other comparison study. Scores on the Intensity and Perception subscales were greater for the case dose than for the maximum dose of cannabis, psilocybin, or salvinorin A. Scores on the Somaesthesia subscale were greater for the case dose than for the maximum dose of DXM, salvinorin A, or cannabis. Scores on the Affect and Cognition subscales for the case dose were significantly lower than for the maximum doses of psilocybin and DXM. Conclusion: Acute cannabis exposure in a healthy adult male resulted in self-reported hallucinations that rated high in magnitude on several subscales of the HRS. However, the hallucinatory experience in this case was qualitatively different than that typically experienced by participants receiving classic and atypical hallucinogens, suggesting that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action. This type of adverse event needs to be considered in the clinical use of cannabis. PMID:29682608

MO-FG-BRA-05: Dosimetric and Radiobiological Validation of Respiratory Gating in Conventional and Hypofractionated Radiotherapy of the Lung: Effect of Dose, Dose Rate, Gating Window and Breathing Pattern

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

Cervino, L; Soultan, D; Pettersson, N

2016-06-15

Purpose: to evaluate the dosimetric and radiobiological consequences from having different gating windows, dose rates, and breathing patterns in gated VMAT lung radiotherapy. Methods: A novel 3D-printed moving phantom with central high and peripheral low tracer uptake regions was 4D FDG-PET/CT-scanned using ideal, patient-specific regular, and irregular breathing patterns. A scan of the stationary phantom was obtained as a reference. Target volumes corresponding to different uptake regions were delineated. Simultaneous integrated boost (SIB) 6 MV VMAT plans were produced for conventional and hypofractionated radiotherapy, using 30–70 and 100% cycle gating scenarios. Prescribed doses were 200 cGy with SIB to 240more » cGy to high uptake volume for conventional, and 800 with SIB to 900 cGy for hypofractionated plans. Dose rates of 600 MU/min (conventional and hypofractionated) and flattening filter free 1400 MU/min (hypofractionated) were used. Ion chamber measurements were performed to verify delivered doses. Vials with A549 cells placed in locations matching ion chamber measurements were irradiated using the same plans to measure clonogenic survival. Differences in survival for the different doses, dose rates, gating windows, and breathing patterns were analyzed. Results: Ion chamber measurements agreed within 3% of the planned dose, for all locations, breathing patterns and gating windows. Cell survival depended on dose alone, and not on gating window, breathing pattern, MU rate, or delivery time. The surviving fraction varied from approximately 40% at 2Gy to 1% for 9 Gy and was within statistical uncertainty relative to that observed for the stationary phantom. Conclusions: Use of gated VMAT in PET-driven SIB radiotherapy was validated using ion chamber measurements and cell survival assays for conventional and hypofractionated radiotherapy.« less

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

PubMed

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

2017-11-01

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

Human exposure to large solar particle events in space

NASA Technical Reports Server (NTRS)

Townsend, L. W.; Wilson, J. W.; Shinn, J. L.; Curtis, S. B.

1992-01-01

Whenever energetic solar protons produced by solar particle events traverse bulk matter, they undergo various nuclear and atomic collision processes which significantly alter the physical characteristics and biologically important properties of their transported radiation fields. These physical interactions and their effect on the resulting radiation field within matter are described within the context of a recently developed deterministic, coupled neutron-proton space radiation transport computer code (BRYNTRN). Using this computer code, estimates of human exposure in interplanetary space, behind nominal (2 g/sq cm) and storm shelter (20 g/sq cm) thicknesses of aluminum shielding, are made for the large solar proton event of August 1972. Included in these calculations are estimates of cumulative exposures to the skin, ocular lens, and bone marrow as a function of time during the event. Risk assessment in terms of absorbed dose and dose equivalent is discussed for these organs. Also presented are estimates of organ exposures for hypothetical, worst-case flare scenarios. The rate of dose equivalent accumulation places this situation in an interesting region of dose rate between the very low values of usual concern in terrestrial radiation environments and the high-dose-rate values prevalent in radiation therapy.

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation

NASA Astrophysics Data System (ADS)

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

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

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

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Danish A.I. field data with sexed semen.

PubMed

Borchersen, S; Peacock, M

2009-01-01

The objective of this study was to compare conception rates, non-return rates and sex ratios of sexed and conventional semen from the same sires in commercial dairy herds in Denmark. The semen was produced from three bulls from each of the three major dairy breeds in Denmark: Holstein, Jersey and Danish Red Dairy Breed (nine bulls total), in order to answer questions on breeds differences in field results. AI was performed by trained technicians using a minimum of 150 doses of sorted sperm and 50 control doses from each bull. During the trial, a total of 2087 doses were used in 63 herds. The trial showed that the conception rate using sorted semen was 5% points lower than with conventional doses for Danish Reds, 7% points for Jerseys, and 12% points for Holsteins. Translating this into non-return rate revealed differences of 10-20% points among bulls. These differences are thought to be a good indicator of what to expect from commercial use of sexed semen. The sex ratios varied from 89% to 93% female calves among breeds, which on average is consistent with the theoretical average sex ratio of 93% females considering the low number of inseminations.

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

PubMed

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

2005-07-01

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

Evaluation Of Shielding Efficacy Of A Ferrite Containing Ceramic Material

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

Verst, C.

2015-10-12

The shielding evaluation of the ferrite based Mitsuishi ceramic material has produced for several radiation sources and possible shielding sizes comparative dose attenuation measurements and simulated projections. High resolution gamma spectroscopy provided uncollided and scattered photon spectra at three energies, confirming theoretical estimates of the ceramic’s mass attenuation coefficient, μ/ρ. High level irradiation experiments were performed using Co-60, Cs-137, and Cf-252 sources to measure penetrating dose rates through steel, lead, concrete, and the provided ceramic slabs. The results were used to validate the radiation transport code MCNP6 which was then used to generate dose rate attenuation curves as a functionmore » of shielding material, thickness, and mass for photons and neutrons ranging in energy from 200 keV to 2 MeV.« less

Dose response characteristics of polymethacrylic acid gel (PMAAG) for a polymerization-based dosimeter using NMR.

PubMed

Iskandar, S M; Elias, S; Jumiah, H; Asri, M T M; Masrianis, A; Ab Rahman, M Z; Taiman, K; Abdul Rashid, M Y

2004-05-01

The radiation-response characteristics of polymetharylic acid gel dosimeter prepared with different concentrations of monomer and cross-linker is described in these studies. The dosimeters were prepared under the hypoxic condition in a glove box and were then irradiated with gamma-rays produced by Co-60 radionuclide that was generated at 1.25MeV energy. The irradiation took place at different doses ranged from 0Gy to 19Gy. Due to the radiation activities, chain-reaction polymerisation processes had taken place in the formation of polymethacrylic acid (PMAA) gel, which cause the dose response mechanism increased in the NMR relaxation rates of protons. It has been observed that for higher concentration of monomer and cross-linker, the polymerization rate was increased.

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

PubMed

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

2018-06-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-07-01

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

A retrospective study of artificial insemination of 251 mares using chilled and fixed time frozen-thawed semen.

PubMed

Crowe, C A M; Ravenhill, P J; Hepburn, R J; Shepherd, C H

2008-09-01

Historically, artificial insemination (AI) using frozen semen has been perceived to have poorer success rates and be more labour intensive than using chilled semen. A retrospective study was therefore conducted to compare the conception rate achieved by AI between chilled and frozen semen, using fixed time insemination protocols over 2 breeding seasons. Artificial insemination using chilled semen produces a higher conception rate than that achieved with frozen semen. Mares (n = 251) were inseminated with either chilled (n = 112) or frozen (n = 139) semen in the 2006 and 2007 northern hemisphere breeding season. Per rectum ultrasonography of the mare's reproductive tract determined the timing of insemination, and deslorelin acetate was used to induce ovulation. Chilled semen insemination was performed using a single preovulatory dose delivered into the uterine body. Frozen semen was administered as 2 doses (pre- and post ovulation) using a deep uterine insemination technique. Pregnancy was detected ultrasonographically at 15 days post insemination. Conception rates were compared using a Chi-squared test. Insemination with frozen semen produced a significantly (P = 0.022) higher seasonal conception rate (82.0%) than that achieved with chilled semen (69.6%). Insemination with frozen semen can achieve conception rates equal to those with chilled semen, enabling the mare owner a greater selection of stallions.

The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs.

PubMed

Tamura, Jun; Ishizuka, Tomohito; Fukui, Sho; Oyama, Norihiko; Kawase, Kodai; Miyoshi, Kenjiro; Sano, Tadashi; Pasloske, Kirby; Yamashita, Kazuto

2015-03-01

The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone.

The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs

PubMed Central

TAMURA, Jun; ISHIZUKA, Tomohito; FUKUI, Sho; OYAMA, Norihiko; KAWASE, Kodai; MIYOSHI, Kenjiro; SANO, Tadashi; PASLOSKE, Kirby; YAMASHITA, Kazuto

2014-01-01

The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone. PMID:25428797

Evaluation of a Proposed Biodegradable 188Re Source for Brachytherapy Application

PubMed Central

Khorshidi, Abdollah; Ahmadinejad, Marjan; Hamed Hosseini, S.

2015-01-01

Abstract This study aimed to evaluate dosimetric characteristics based on Monte Carlo (MC) simulations for a proposed beta emitter bioglass 188Re seed for internal radiotherapy applications. The bioactive glass seed has been developed using the sol-gel technique. The simulations were performed for the seed using MC radiation transport code to investigate the dosimetric factors recommended by the AAPM Task Group 60 (TG-60). Dose distributions due to the beta and photon radiation were predicted at different radial distances surrounding the source. The dose rate in water at the reference point was calculated to be 7.43 ± 0.5 cGy/h/μCi. The dosimetric factors consisting of the reference point dose rate, D(r0,θ0), the radial dose function, g(r), the 2-dimensional anisotropy function, F(r,θ), the 1-dimensional anisotropy function, φan(r), and the R90 quantity were estimated and compared with several available beta-emitting sources. The element 188Re incorporated in bioactive glasses produced by the sol-gel technique provides a suitable solution for producing new materials for seed implants applied to brachytherapy applications in prostate and liver cancers treatment. Dose distribution of 188Re seed was greater isotropic than other commercially attainable encapsulated seeds, since it has no end weld to attenuate radiation. The beta radiation-emitting 188Re source provides high doses of local radiation to the tumor tissue and the short range of the beta particles limit damage to the adjacent normal tissue. PMID:26181543

Cancer radiotherapy based on femtosecond IR laser-beam filamentation yielding ultra-high dose rates and zero entrance dose.

PubMed

Meesat, Ridthee; Belmouaddine, Hakim; Allard, Jean-François; Tanguay-Renaud, Catherine; Lemay, Rosalie; Brastaviceanu, Tiberius; Tremblay, Luc; Paquette, Benoit; Wagner, J Richard; Jay-Gerin, Jean-Paul; Lepage, Martin; Huels, Michael A; Houde, Daniel

2012-09-18

Since the invention of cancer radiotherapy, its primary goal has been to maximize lethal radiation doses to the tumor volume while keeping the dose to surrounding healthy tissues at zero. Sadly, conventional radiation sources (γ or X rays, electrons) used for decades, including multiple or modulated beams, inevitably deposit the majority of their dose in front or behind the tumor, thus damaging healthy tissue and causing secondary cancers years after treatment. Even the most recent pioneering advances in costly proton or carbon ion therapies can not completely avoid dose buildup in front of the tumor volume. Here we show that this ultimate goal of radiotherapy is yet within our reach: Using intense ultra-short infrared laser pulses we can now deposit a very large energy dose at unprecedented microscopic dose rates (up to 10(11) Gy/s) deep inside an adjustable, well-controlled macroscopic volume, without any dose deposit in front or behind the target volume. Our infrared laser pulses produce high density avalanches of low energy electrons via laser filamentation, a phenomenon that results in a spatial energy density and temporal dose rate that both exceed by orders of magnitude any values previously reported even for the most intense clinical radiotherapy systems. Moreover, we show that (i) the type of final damage and its mechanisms in aqueous media, at the molecular and biomolecular level, is comparable to that of conventional ionizing radiation, and (ii) at the tumor tissue level in an animal cancer model, the laser irradiation method shows clear therapeutic benefits.

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

PubMed Central

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

2005-01-01

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

Lung dosimetry for inhaled long-lived radionuclides and radon progeny.

PubMed

Hussain, M; Winkler-Heil, R; Hofmann, W

2011-05-01

The current version of the stochastic lung dosimetry model IDEAL-DOSE considers deposition in the whole tracheobronchial (TB) and alveolar airway system, while clearance is restricted to TB airways. For the investigation of doses produced by inhaled long-lived radionuclides (LLR) together with short-lived radon progeny, alveolar clearance has to be considered. Thus, present dose calculations are based on the average transport rates proposed for the revision of the ICRP human respiratory tract model. The results obtained indicate that LLR cleared from the alveolar region can deliver up to two to six times higher doses to the TB region when compared with the doses from directly deposited particles. Comparison of LLR doses with those of short-lived radon progeny indicates that LLR in uranium mines can deliver up to 5 % of the doses predicted for the short-lived radon daughters.

Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding

PubMed Central

Siemian, Justin N.; Li, Jiuzhou; Zhang, Yanan; Li, Jun-Xu

2015-01-01

Rationale Recent evidence suggests that imidazoline I2 receptor ligands are suitable for combination therapy with opioids. Quantitative analysis of I2 receptor ligands combined with non-opioid drugs is necessary for justification of alternative pain therapies. Objective This study systematically examined the anti-hyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen. Methods Von Frey and Hargreaves tests were used to examine the anti-hyperalgesic effects of drugs in complete Freund’s adjuvant (CFA)-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to assess the rate-suppressing effects of study drugs. Dose-addition and isobolographic analyses were used to assess drug-drug interactions for all assays. Results 2-BFI (3.2–17.8 mg/kg, i.p.), phenyzoline (17.8–100 mg/kg, i.p.), and acetaminophen (56–178 mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and acetaminophen produced infra-additive to additive interactions while phenyzoline and acetaminophen produced additive to supra-additive interactions. The same drug combinations suppressed response rate in a supra-additive manner. Conclusions Quantitative analysis of the anti-hyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen. PMID:26613734

Sensitive Detection of Radiation-Induced Medulloblastomas after Acute or Protracted Gamma-Ray Exposures in Ptch1 Heterozygous Mice Using a Radiation-Specific Molecular Signature.

PubMed

Tsuruoka, Chizuru; Blyth, Benjamin J; Morioka, Takamitsu; Kaminishi, Mutsumi; Shinagawa, Mayumi; Shimada, Yoshiya; Kakinuma, Shizuko

2016-10-01

Recently reported studies have led to a heightened awareness of the risks of cancer induced by diagnostic radiological imaging, and in particular, the risk of brain cancer after childhood CT scans. One feature of Ptch1 +/- mice is their sensitivity to radiation-induced medulloblastomas (an embryonic cerebellar tumor) during a narrow window of time centered on the days around birth. Little is known about the dynamics of how dose protraction interacts with such narrow windows of sensitivity in individual tissues. Using medulloblastomas from irradiated Ptch1 +/- mice with a hybrid C3H × C57BL/6 F1 genetic background, we previously showed that the alleles retained on chromosome 13 (which harbors the Ptch1 gene) reveal two major mechanisms of loss of the wild-type allele. The loss of parental alleles from the telomere extending up to or past the Ptch1 locus by recombination (spontaneous type) accounts for almost all medulloblastomas in nonirradiated mice, while tumors in irradiated mice often exhibited interstitial deletions, which start downstream of the wild-type Ptch1 and extend up varying lengths towards the centromere (radiation type). In this study, Ptch1 +/- mice were exposed to an acute dose of either 100 or 500 mGy gamma rays in utero or postnatally, or the same radiation doses protracted over a four-day period, and were monitored for medulloblastoma development. The results showed dose- and age-dependent radiation-induced type tumors. Furthermore, the size of the radiation-induced deletion differed with the dose rate. The results of this work suggest that tumor latency may be related to the size of the deletion. In this study, 500 mGy exposure produced radiation-induced type tumors at all ages and dose rates, while 100 mGy exposure did not significantly produce radiation-induced type tumors. The radiation signature allows for unique mechanistic insight into the action of radiation to induce DNA lesions with known causal relationship to a specific tumor type, particularly for doses and dose rates that are relevant to both diagnostic and accidental radiological exposures.

SU-E-T-413: Examining Acquisition Rate for Using MatriXX Ion Chamber Array to Measure HDR Brachytherapy Treatments

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

Wagar, M; Bhagwat, M; O’Farrell, D

2015-06-15

Purpose: There are unique obstacles to implementing the MatriXX ionchamber array as a QA tool in Brachytherapy given that the device is designed for use in the MV energy range. One of the challenges we investigate is the affect of acquisition rates on dose measurement accuracy for HDR treatment plans. Methods: A treatment plan was optimized in Oncentra Brachy TPS to deliver a planar dose to a 5×5cm region at 10mm depth. The applicator was affixed to the surface of the MatriXX array. The plan was delivered multiple times using a Nucleatron HDR afterloader with a 2.9Ci Ir192 source. Formore » each measurement the sampling rate of the MatriXX movie mode was varied (30ms and 500ms). This experiment was repeated with identical parameters, following a source exchange, with an 11.2Ci Ir192 source. Finally, a single snap measurement was acquired. Analysis was preformed to evaluate the fidelity of the dose delivery for each iteration of the experiment. Evaluation was based on the comparison between the measured and TPS predicted dose. Results: Higher sample rates induce a greater discrepancy between the predicted and measured dose. Delivering the plan using a lower activity source also produced greater discrepancy in the measurement due to the increased delivery time. Analyzing the single snap measurement showed little difference from the 500ms integral dose measurement. Conclusion: The advantage of using movie mode for HDR treatment delivery QA is the ability for real time source tracking in addition to dose measurement. Our analysis indicates that 500ms is an optimal frame rate.« less

Space Radiation Effects and Hardness Assurance for Linear Integrated Circuits

NASA Technical Reports Server (NTRS)

Johnston, A. H.

2000-01-01

New effects that complicate the application of linear devices in space are discussed, including enhanced damage at low dose rate and proton damage, which cause permanent degradation. Transients produced by protons and heavy ions are also discussed.

In vitro production of sheep embryos using laparoscopic folliculocentesis: alternative gonadotrophin treatments for stimulation of oocyte donors.

PubMed

Baldassarre, H; Furnus, C C; De Matos, D G; Pessi, H

1996-02-01

Three different gonadotrophin regimens for the stimulation of donors for laparoscopic folliculocentesis were tested in a total of 142 ewes. The recovered oocytes were subjected to in vitro maturation, fertilization, and culture (IVM/IVF/IVC) for 7 d using standard procedures for sheep. The estrous cycles of all ewes were synchronized using intravaginal sponges containing 60 mg of medroxyprogesterone acetate (MPA) inserted for 14 d. In Experiment 1, all ewes were superovulated with a total dose of 125 IU FSH and 125 IU LH. One-half of the ewes received the gonadotrophin treatment in 4 decreasing doses at 12-h intervals starting 48 h before follicle aspiration (Control), while the other half received the total dose in a single injection at -24 h before collection (Oneshot). There were no significant differences between treatments for recovery rate (81.6 +/- 5.3 vs 77.4 +/- 10.3), cleavage rate (60.6 +/- 20.8 vs 61.4 +/- 23.4), or normal development to the blastocyst stage (20.8 +/- 18.2 vs 13.1 +/- 10.3). However, a higher percentage of ewes produced at least 1 normal blastocyst in the Control group (56.4 vs 31.6%; P < 0.05). In Experiment 2, the control regimen was repeated in half of the ewes, while the remainder were treated with half of the FSH total dose plus 500 IU eCG in a single injection at -24 h before oocyte collection (Oneshot-eCG). The recovery rate (80.9 +/- 5.6 vs 73.3 +/- 15.3), cleavage rate (76.8 +/-19.9 vs 79.7 +/- 22.6), normal development to blastocysts (19.2 +/- 15.3 vs 23.3 +/- 10.7), and percentage of ewes producing at least 1 normal blastocyst (55.9 vs 51.6%) did not differ between treatments. The large variability observed between ewes in the production of normal blastocysts is comparable to that observed with standard MOET procedures, in which a proportion of donors fail to produce good embryos. With the in vitro procedures described here, we were able to produce normal embryos from more than half of the treated ewes, indicating that the technology is useful for the multiplication of genetically valuable animals affected by temporary or irreversible infertility.

Biological Effects of Nuclear Explosions (BENE) Domain Guide

DTIC Science & Technology

2012-09-01

DATE (DD-MM-YYYY) 2. REPORT TYPE 3. DATES COVERED (From – To) Technical Report October 2004-April 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER...greatly increased in the nearby region because increasing amounts of contaminated earth and debris are sucked up into the radioactive cloud. In the case...or a denial scenario involving radioisotopes will be non-uniform exposure with various doses and dose rates producing very large variations in

Digital radiography can reduce scoliosis x-ray exposure

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

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

1990-09-01

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

Subjective and Cardiovascular Effects of Intravenous Methamphetamine during Perindopril Maintenance: A Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study.

PubMed

Verrico, Christopher D; Haile, Colin N; De La Garza, Richard; Grasing, Kenneth; Kosten, Thomas R; Newton, Thomas F

2016-07-01

Our pilot study suggested that the angiotensin-converting enzyme inhibitor perindopril might reduce some subjective effects produced by i.v. methamphetamine. We characterized the impact of a wider range of perindopril doses on methamphetamine-induced effects in a larger group of non-treatment-seeking, methamphetamine-using volunteers. Before treatment, participants received 30mg methamphetamine. After 5 to 7 days of perindopril treatment (0, 4, 8, or 16mg/d), participants received 15 and 30mg of methamphetamine on alternate days. Before and after treatment, participants rated subjective effects and cardiovascular measures were collected. Prior to treatment with perindopril, there were no significant differences between treatment groups on maximum or peak subjective ratings or on peak cardiovascular effects. Following perindopril treatment, there were significant main effects of treatment on peak subjective ratings of "anxious" and "stimulated"; compared to placebo treatment, treatment with 8mg perindopril significantly reduced peak ratings of both anxious (P=.0009) and stimulated (P=.0070). There were no significant posttreatment differences between groups on peak cardiovascular effects. Moderate doses of perindopril (8mg) significantly reduced peak subjective ratings of anxious and stimulated as well as attenuated many other subjective effects produced by methamphetamine, likely by inhibiting angiotensin II synthesis. Angiotensin II is known to facilitate the effects of norepinephrine, which contributes to methamphetamine's subjective effects. The lack of a classic dose-response function likely results from either nonspecific effects of perindopril or from between-group differences that were not accounted for in the current study (i.e., genetic variations and/or caffeine use). The current findings suggest that while angiotensin-converting enzyme inhibitors can reduce some effects produced by methamphetamine, more consistent treatment effects might be achieved by targeting components of the renin-angiotensin system that are downstream of angiotensin-converting enzyme. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Dimethyl Sulfoxide (DMSO) Produces Widespread Apoptosis in the Developing Central Nervous System

PubMed Central

Hanslick, Jennifer L.; Lau, Karen; Noguchi, Kevin K.; Olney, John W.; Zorumski, Charles F.; Mennerick, Steven; Farber, Nuri B.

2009-01-01

Dimethyl sulfoxide (DMSO) is a solvent that is routinely used as a cryopreservative in allogous bone marrow and organ transplantion. We exposed C57Bl/6 mice of varying postnatal ages (P0–P30) to DMSO in order to study whether DMSO could produce apoptotic degeneration in the developing CNS. DMSO produced widespread apoptosis in the developing mouse brain at all ages tested. Damage was greatest at P7. Significant elevations above the background rate of apoptosis occurred at the lowest dose tested, 0.3 ml/kg. In an in vitro rat hippocampal culture preparation, DMSO produced neuronal loss at concentrations of 0.5% and 1.0%. The ability of DMSO to damage neurons in dissociated cultures indicates that the toxicity likely results from a direct cellular effect. Because children, who undergo bone marrow transplantation, are routinely exposed to DMSO at doses higher than 0.3 ml/kg, there is concern that DMSO might be producing similar damage in human children. PMID:19100327

Proton radiography and proton computed tomography based on time-resolved dose measurements

NASA Astrophysics Data System (ADS)

Testa, Mauro; Verburg, Joost M.; Rose, Mark; Min, Chul Hee; Tang, Shikui; Hassane Bentefour, El; Paganetti, Harald; Lu, Hsiao-Ming

2013-11-01

We present a proof of principle study of proton radiography and proton computed tomography (pCT) based on time-resolved dose measurements. We used a prototype, two-dimensional, diode-array detector capable of fast dose rate measurements, to acquire proton radiographic images expressed directly in water equivalent path length (WEPL). The technique is based on the time dependence of the dose distribution delivered by a proton beam traversing a range modulator wheel in passive scattering proton therapy systems. The dose rate produced in the medium by such a system is periodic and has a unique pattern in time at each point along the beam path and thus encodes the WEPL. By measuring the time dose pattern at the point of interest, the WEPL to this point can be decoded. If one measures the time-dose patterns at points on a plane behind the patient for a beam with sufficient energy to penetrate the patient, the obtained 2D distribution of the WEPL forms an image. The technique requires only a 2D dosimeter array and it uses only the clinical beam for a fraction of second with negligible dose to patient. We first evaluated the accuracy of the technique in determining the WEPL for static phantoms aiming at beam range verification of the brain fields of medulloblastoma patients. Accurate beam ranges for these fields can significantly reduce the dose to the cranial skin of the patient and thus the risk of permanent alopecia. Second, we investigated the potential features of the technique for real-time imaging of a moving phantom. Real-time tumor tracking by proton radiography could provide more accurate validations of tumor motion models due to the more sensitive dependence of proton beam on tissue density compared to x-rays. Our radiographic technique is rapid (˜100 ms) and simultaneous over the whole field, it can image mobile tumors without the problem of interplay effect inherently challenging for methods based on pencil beams. Third, we present the reconstructed pCT images of a cylindrical phantom containing inserts of different materials. As for all conventional pCT systems, the method illustrated in this work produces tomographic images that are potentially more accurate than x-ray CT in providing maps of proton relative stopping power (RSP) in the patient without the need for converting x-ray Hounsfield units to proton RSP. All phantom tests produced reasonable results, given the currently limited spatial and time resolution of the prototype detector. The dose required to produce one radiographic image, with the current settings, is ˜0.7 cGy. Finally, we discuss a series of techniques to improve the resolution and accuracy of radiographic and tomographic images for the future development of a full-scale detector.

Sulfide toxicity: Mechanical ventilation and hypotension determine survival rate and brain necrosis

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

Baldelli, R.J.; Green, F.H.Y.; Auer, R.N.

1993-09-01

Occupational exposure to hydrogen sulfide is one of the leading causes of sudden death in the workplace, especially in the oil and gas industry. High-dose exposure causes immediate neurogenic apnea and death; lower doses cause [open quotes]knockdown[close quotes] (transient loss of consciousness, with apnea). Because permanent neurological sequelae have been reported, the authors sought to determine whether sulfide can directly kill central nervous system neurons. Ventilated and unventilated rats were studied to allow administration of higher doses of sulfide and to facilitate physiological monitoring. It was extremely difficult to produce cerebral necrosis with sulfide. Only one of eight surviving unventilatedmore » rats given high-dose sulfide (a dose that was lethal in [ge]50% of animals) showed cerebral necrosis. Mechanical ventilation shifted the dose that was lethal in 50% of the animals to 190 mg/kg from 94 mg/kg in the unventilated rats. Sulfide was found to potently depress blood pressure. Cerebral necrosis was absent in the ventilated rats (n = 11), except in one rat that showed profound and sustained hypotension to [le]35 Torr. Electroencephalogram activity ceased during exposure but recovered when the animals regained consciousness. The authors conclude that very-high-dose sulfide is incapable of producing cerebral necrosis by a direct histotoxic effect. 32 refs., 5 figs.« less

Sub-second pencil beam dose calculation on GPU for adaptive proton therapy.

PubMed

da Silva, Joakim; Ansorge, Richard; Jena, Rajesh

2015-06-21

Although proton therapy delivered using scanned pencil beams has the potential to produce better dose conformity than conventional radiotherapy, the created dose distributions are more sensitive to anatomical changes and patient motion. Therefore, the introduction of adaptive treatment techniques where the dose can be monitored as it is being delivered is highly desirable. We present a GPU-based dose calculation engine relying on the widely used pencil beam algorithm, developed for on-line dose calculation. The calculation engine was implemented from scratch, with each step of the algorithm parallelized and adapted to run efficiently on the GPU architecture. To ensure fast calculation, it employs several application-specific modifications and simplifications, and a fast scatter-based implementation of the computationally expensive kernel superposition step. The calculation time for a skull base treatment plan using two beam directions was 0.22 s on an Nvidia Tesla K40 GPU, whereas a test case of a cubic target in water from the literature took 0.14 s to calculate. The accuracy of the patient dose distributions was assessed by calculating the γ-index with respect to a gold standard Monte Carlo simulation. The passing rates were 99.2% and 96.7%, respectively, for the 3%/3 mm and 2%/2 mm criteria, matching those produced by a clinical treatment planning system.

The optimization of fermentation conditions for producing cellulase of Bacillus amyloliquefaciens and its application to goose feed

PubMed Central

Ye, Miao; Sun, Linghong; Yang, Ru; Qi, KeZong

2017-01-01

The proper culture conditions for producing cellulase of Bacillus amyloliquefaciens S1, isolated from the cecum of goose was optimized by single-factor experiment combined with orthogonal test. The properties of the cellulase were investigated by DNS method. The appropriate doses of B. amyloliquefaciens S1 were obtained by adding them to goose feed. It indicated that the suitable culture conditions of producing cellulase were the culture temperature of 37°C, the initial pH of 7.0, the incubation time of 72 h and the loaded liquid volume of 75 ml per 250 ml. The effects of each factor on producing cellulase by B. amyloliquefaciens S1 were as follows: initial pH > incubation time = culture temperature > loaded liquid volume. The optimum reaction temperature and pH were 50°C and 7.0, respectively. This enzyme is a kind of neutral cellulase that possesses resistance to heat and acidity. It showed high activity to absorbent cotton, soya bean meal and filter paper. By adding different doses of B. amyloliquefaciens S1 to the goose feed, it was found that the egg production, average egg weight, fertilization rate and the hatching rate were promoted both in experiment 1 (1.5 g kg−1) and experiment 2 (3 g kg−1). Also the difference of egg production, fertilization rate and hatching rate between experiment 1 and control group was obvious (p < 0.05), and the average egg weight was significantly increased in experiment 2 (p < 0.05). PMID:29134097

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

PubMed

Kum, Oyeon

2018-06-01

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

Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts.

PubMed

Broome, E J; Brown, D L; Mitchel, R E J

2002-08-01

The dose response for adaption to radiation at low doses was compared in normal human fibroblasts (AG1522) exposed to either (60)Co gamma rays or (3)H beta particles. Cells were grown in culture to confluence and exposed at either 37 degrees C or 0 degrees C to (3)H beta-particle or (60)Co gamma-ray adapting doses ranging from 0.1 mGy to 500 mGy. These cells, and unexposed control cells, were allowed to adapt during a fixed 3-h, 37 degrees C incubation prior to a 4-Gy challenge dose of (60)Co gamma rays. Adaption was assessed by measuring micronucleus frequency in cytokinesis-blocked, binucleate cells. No adaption was detected in cells exposed to (60)Co gamma radiation at 37 degrees C after a dose of 0.1 mGy given at a low dose rate or to 500 mGy given at a high dose rate. However, low-dose-rate exposure (1-3 mGy/min) to any dose between 1 and 500 mGy from either radiation, delivered at either temperature, caused cells to adapt and reduced the micronucleus frequency that resulted from the subsequent 4-Gy exposure. Within this dose range, the magnitude of the reduction was the same, regardless of the dose or radiation type. These results demonstrate that doses as low as (on average) about one track per cell (1 mGy) produce the same maximum adaptive response as do doses that deposit many tracks per cell, and that the two radiations were not different in this regard. Exposure at a temperature where metabolic processes, including DNA repair, were inactive (0 degrees C) did not alter the result, indicating that the adaptive response is not sensitive to changes in the accumulation of DNA damage within this range. The results also show that the RBE for low doses of tritium beta-particle radiation is 1, using adaption as the end point.

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-01-01

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

A fast and simple dose-calibrator-based quality control test for the radionuclidic purity of cyclotron-produced (99m)Tc.

PubMed

Tanguay, J; Hou, X; Esquinas, P; Vuckovic, M; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2015-11-07

Cyclotron production of 99mTc through the (100)Mo(p,2n)99mTc reaction channel is actively being investigated as an alternative to reactor-based (99)Mo generation by nuclear fission of (235)U. Like most radioisotope production methods, cyclotron production of 99mTc will result in creation of unwanted impurities, including Tc and non-Tc isotopes. It is important to measure the amounts of these impurities for release of cyclotron-produced 99mTc (CPTc) for clinical use. Detection of radioactive impurities will rely on measurements of their gamma (γ) emissions. Gamma spectroscopy is not suitable for this purpose because the overwhelming presence of 99mTc and the count-rate limitations of γ spectroscopy systems preclude fast and accurate measurement of small amounts of impurities. In this article we describe a simple and fast method for measuring γ emission rates from radioactive impurities in CPTc. The proposed method is similar to that used to identify (99)Mo breakthrough in generator-produced 99mTc: one dose calibrator (DC) reading of a CPTc source placed in a lead shield is followed by a second reading of the same source in air. Our experimental and theoretical analysis show that the ratio of DC readings in lead to those in air are linearly related to γ emission rates from impurities per MBq of 99mTc over a large range of clinically-relevant production conditions. We show that estimates of the γ emission rates from Tc impurities per MBq of 99mTc can be used to estimate increases in radiation dose (relative to pure 99mTc) to patients injected with CPTc-based radiopharmaceuticals. This enables establishing dosimetry-based clinical-release criteria that can be tested using commercially-available dose calibrators. We show that our approach is highly sensitive to the presence of 93gTc, 93mTc, 94gTc, 94mTc, 95mTc, 95gTc, and 96gTc, in addition to a number of non-Tc impurities.

A fast and simple dose-calibrator-based quality control test for the radionuclidic purity of cyclotron-produced 99mTc

NASA Astrophysics Data System (ADS)

Tanguay, J.; Hou, X.; Esquinas, P.; Vuckovic, M.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2015-11-01

Cyclotron production of {{}99\\text{m}} Tc through the 100Mo(p,2n){{}99\\text{m}} Tc reaction channel is actively being investigated as an alternative to reactor-based 99Mo generation by nuclear fission of 235U. Like most radioisotope production methods, cyclotron production of {{}99\\text{m}} Tc will result in creation of unwanted impurities, including Tc and non-Tc isotopes. It is important to measure the amounts of these impurities for release of cyclotron-produced {{}99\\text{m}} Tc (CPTc) for clinical use. Detection of radioactive impurities will rely on measurements of their gamma (γ) emissions. Gamma spectroscopy is not suitable for this purpose because the overwhelming presence of {{}99\\text{m}} Tc and the count-rate limitations of γ spectroscopy systems preclude fast and accurate measurement of small amounts of impurities. In this article we describe a simple and fast method for measuring γ emission rates from radioactive impurities in CPTc. The proposed method is similar to that used to identify 99Mo breakthrough in generator-produced {{}99\\text{m}} Tc: one dose calibrator (DC) reading of a CPTc source placed in a lead shield is followed by a second reading of the same source in air. Our experimental and theoretical analysis show that the ratio of DC readings in lead to those in air are linearly related to γ emission rates from impurities per MBq of {{}99\\text{m}} Tc over a large range of clinically-relevant production conditions. We show that estimates of the γ emission rates from Tc impurities per MBq of {{}99\\text{m}} Tc can be used to estimate increases in radiation dose (relative to pure {{}99\\text{m}} Tc) to patients injected with CPTc-based radiopharmaceuticals. This enables establishing dosimetry-based clinical-release criteria that can be tested using commercially-available dose calibrators. We show that our approach is highly sensitive to the presence of {{}93\\text{g}} Tc, {{}93\\text{m}} Tc, {{}94\\text{g}} Tc, {{}94\\text{m}} Tc, {{}95\\text{m}} Tc, {{}95\\text{g}} Tc, and {{}96\\text{g}} Tc, in addition to a number of non-Tc impurities.

Effects of GA3 Pregerminative Treatment on Gentiana lutea L. var. aurantiaca Germination and Seedlings Morphology

PubMed Central

González-López, Óscar; Casquero, Pedro A.

2014-01-01

Gentiana lutea L. is widely used in bitter beverages and in medicine; Gentianae Radix is the pharmaceutical name of the root of G. lutea. These uses have generated a high demand. The wild populations of Gentiana lutea var. aurantiaca (M. Laínz) M. Laínz have been decimated; it is necessary to establish guidelines for its cultivation. Gentian as most alpine species has dormant seeds. Dormancy can be removed by cold and by means of a gibberellic acid (GA3) treatment. However, cold treatments produce low germination percentages and GA3 treatments may produce off-type seedlings. So, the objective was to determine, for the first time, the presowing treatments that allow high germination rate and good seedling morphology. The best pregerminative doses of GA3 to break seed dormancy were 100, 500, and 1000 ppm, while the best doses to optimize the seedling habit were 50 and 100 ppm. This study provides, for the first time, a 100 ppm GA3 dose that led to a high germination rate and good seedling morphology, as the starting point for gentian regular cultivation. PMID:25105167

Effects of GA3 pregerminative treatment on Gentiana lutea L. var. aurantiaca germination and seedlings morphology.

PubMed

González-López, Óscar; Casquero, Pedro A

2014-01-01

Gentiana lutea L. is widely used in bitter beverages and in medicine; Gentianae Radix is the pharmaceutical name of the root of G. lutea. These uses have generated a high demand. The wild populations of Gentiana lutea var. aurantiaca (M. Laínz) M. Laínz have been decimated; it is necessary to establish guidelines for its cultivation. Gentian as most alpine species has dormant seeds. Dormancy can be removed by cold and by means of a gibberellic acid (GA3) treatment. However, cold treatments produce low germination percentages and GA3 treatments may produce off-type seedlings. So, the objective was to determine, for the first time, the presowing treatments that allow high germination rate and good seedling morphology. The best pregerminative doses of GA3 to break seed dormancy were 100, 500, and 1000 ppm, while the best doses to optimize the seedling habit were 50 and 100 ppm. This study provides, for the first time, a 100 ppm GA3 dose that led to a high germination rate and good seedling morphology, as the starting point for gentian regular cultivation.

Calorimetry of electron beams and the calibration of dosimeters at high doses

NASA Astrophysics Data System (ADS)

Humphreys, J. C.; McLaughlin, W. L.

Graphite or metal calorimeters are used to make absolute dosimetric measurements of high-energy electron beams. These calibrated beams are then used to calibrate several types of dosimeters for high-dose applications such as medical-product sterilization, polymer modification, food processing, or electronic-device hardness testing. The electron beams are produced either as continuous high-power beams at approximately 4.5 MeV by d.c. type accelerators or in the energy range of approximately 8 to 50 MeV using pulsed microwave linear accelerators (linacs). The continuous beams are generally magnetically scanned to produce a broad, uniform radiation environment for the processing of materials of extended lateral dimensions. The higher-energy pulsed beams may also be scanned for processing applications or may be used in an unscanned, tightly-focused mode to produce maximum absorbed dose rates such as may be required for electronic-device radiation hardness testing. The calorimeters are used over an absorbed dose range of 10 2 to 10 4 Gy. Intercomparison studies are reported between National Institute of Standards and Technology (NIST) and UK National Physical Laboratory (NPL) graphite disk calorimeters at high doses, using the NPL 10-MeV linac, and agreement was found within 1.5%. It was also shown that the electron-beam responses of radiochromic film dosimeters and alanine pellet dosimeters can be accurately calibrated by comparison with calorimeter readings.

Ceruletide intravenous dose-response study by a simplified scintigraphic technique

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

Krishnamurthy, G.T.; Turner, F.E.; Mangham, D.

1985-04-01

The intravenous dose response of a ceruletide diethylamine (ceruletide) was established by a simplified scintigraphic technique where multiple graded doses were given sequentially on a single occasion. The gallbladder volume was presented nongeometrically by /sup 99m/Tc-IDA counts. The mean latent period, ejection period, and ejection rate were similar for all four groups of subjects given 1-20 ng/kg of ceruletide. The ejection fractions were similar to the values when the identical dose of ceruletide was administered sequentially either before or after another dose. A dose of 5 ng/kg produced the most physiologic type of emptying. Intravenous doses of 10 ng/kg andmore » larger caused adverse reactions in 42% of the total doses in the form of abdominal pain, nausea, systolic and diastolic hypotension, or bradycardia. It is concluded that the dose response of a cholecystokininlike agent (ceruletide) can be established reliably by a scintigraphic technique where multiple graded doses are given on a single occasion.« less

Spinal action of neurokinins producing cardiovascular responses in the conscious freely moving rat: evidence for a NK-1 receptor mechanism.

PubMed

Hasséssian, H; Drapeau, G; Couture, R

1988-12-01

This study was initiated to characterize the receptors which mediate the cardiovascular responses elicited by the intrathecal (i.th.) administration of neurokinins (NK) in the conscious freely moving rat. The dose response profile for substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) was determined over 0.065-65 nmol doses of the peptides. After i.th. administration at the T8-T10 thoracic level, only SP elicited a dose dependent pressor response. However, all NK elicited a dose dependent increase in heart rate (HR), and the following rank order of potency was observed: SP greater than NKA greater than NKB. SP (6.5 nmol) produced cardiovascular responses markedly greater than an equimolar dose of any of the seven SP fragments which were studied. The C-terminal sequences SP (4-11), [pGlu5]SP (5-11), [pGlu6]SP (6-11), and SP (7-11), as a group were slightly more potent than the N-terminal fragments, SP (1-4), SP (1-7) and SP (1-9) which were almost inactive. The NK-1 receptor selective agonists [Pro9, Met(O2)11]SP and [beta-Ala4, Sar9, Met(O2)11]SP (4-11), produced pressor and positive chronotropic responses equal to or greater in intensity than SP. With up to 6.5 nmol of the NK-2 receptor selective agonist [Nle10]NKA (4-10), no dose dependent cardiovascular response was produced and the NK-3 receptor selective agonist senktide (succinyl-[Asp6, MePhe8]SP (6-11], produced neither a cardiac nor pressor response when 6.5 nmol was administered. These results are consistent with the hypothesis that, receptors of the NK-1 subtype mediate the cardiovascular responses evoked by the spinal action of NK.

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

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

Lee, E; Meyer, J

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

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

PubMed

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

2000-02-01

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

Neutron-Irradiated Samples as Test Materials for MPEX

DOE PAGES

Ellis, Ronald James; Rapp, Juergen

2015-10-09

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

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

PubMed

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

2002-01-01

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

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.

The space radiation environment

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

Robbins, D E

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

Effect of Cytotoxic Therapy on Sexuality and Gonadal Function

DTIC Science & Technology

1981-01-01

have produced toxicities involving multiple organ and testosterone levels fall. systems. Drug induced azoospermia and amenor- In women FSH stimulates ...Additionally, several men complained that Summary although their libido was satisfactory, orgasm The dose of a cytotoxic agent that produces was not...some of the men enced irritability and some became physically PATIENTS LIBIDO RATING: MALES 10 9 8 SEXUAL ACTIVITY 5 Fig. 1. Correlation of WEEKLY 4

Immobilization of grizzly bears (Ursus arctos) with dexmedetomidine, tiletamine, and zolazepam.

PubMed

Teisberg, Justin E; Farley, Sean D; Nelson, O Lynne; Hilderbrand, Grant V; Madel, Michael J; Owen, Patricia A; Erlenbach, Joy A; Robbins, Charles T

2014-01-01

Safe and effective immobilization of grizzly bears (Ursus arctos) is essential for research and management. Fast induction of anesthesia, maintenance of healthy vital rates, and predictable recoveries are priorities. From September 2010 to May 2012, we investigated these attributes in captive and wild grizzly bears anesthetized with a combination of a reversible α2 agonist (dexmedetomidine [dexM], the dextrorotatory enantiomer of medetomidine) and a nonreversible N-methyl-d-aspartate (NMDA) agonist and tranquilizer (tiletamine and zolazepam [TZ], respectively). A smaller-than-expected dose of the combination (1.23 mg tiletamine, 1.23 mg zolazepam, and 6.04 µg dexmedetomidine per kg bear) produced reliable, fast ataxia (3.7 ± 0.5 min, x̄±SE) and workable anesthesia (8.1 ± 0.6 min) in captive adult grizzly bears. For wild bears darted from a helicopter, a dose of 2.06 mg tiletamine, 2.06 mg zolazepam, and 10.1 µg dexmedetomidine/kg produced ataxia in 2.5 ± 0.3 min and anesthesia in 5.5 ± 1.0 min. Contrary to published accounts of bear anesthesia with medetomidine, tiletamine, and zolazepam, this combination did not cause hypoxemia or hypoventilation, although mild bradycardia (<50 beats per min) occurred in most bears during the active season. With captive bears, effective dose rates during hibernation were approximately half those during the active season. The time to first signs of recovery after the initial injection of dexMTZ was influenced by heart rate (P<0.001) and drug dose (P<0.001). Intravenous (IV) injection of the reversal agent, atipamezole, significantly decreased recovery time (i.e., standing on all four feet and reacting to the surrounding environment) relative to intramuscular injection. Recovery times (25 ± 8 min) following IV injections of the recommended dose of atipamezole (10 µg/µg of dexmedetomidine) and half that dose (5 µg/µg) did not differ. However, we recommend use of the full dose based on the appearance of a more complete recovery. Field trials confirmed that the dexMTZ + atipamezole protocol is safe, reliable, and predictable when administered to wild grizzly bears, especially during helicopter capture operations.

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

PubMed

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

2013-01-15

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

Is Slow-Onset Long-Acting Monoamine Transport Blockade to Cocaine as Methadone is to Heroin? Implication for Anti-Addiction Medications

PubMed Central

Peng, Xiao-Qing; Xi, Zheng-Xiong; Li, Xia; Spiller, Krista; Li, Jie; Chun, Lauren; Wu, Kuo-Ming; Froimowitz, Mark; Gardner, Eliot L

2010-01-01

The success of methadone in treating opiate addiction has suggested that long-acting agonist therapies may be similarly useful for treating cocaine addiction. Here, we examined this hypothesis, using the slow-onset long-acting monoamine reuptake inhibitor 31,345, a trans-aminotetralin analog, in a variety of addiction-related animal models, and compared it with methadone's effects on heroin's actions in the same animal models. Systemic administration of 31,345 produced long-lasting enhancement of electrical brain-stimulation reward (BSR) and extracellular nucleus accumbens (NAc) dopamine (DA). Pretreatment with 31,345 augmented cocaine-enhanced BSR, prolonged cocaine-enhanced NAc DA, and produced a long-term (24-48 h) reduction in cocaine self-administration rate without obvious extinction pattern, suggesting an additive effect of 31,345 with cocaine. In contrast, methadone pretreatment not only dose-dependently inhibited heroin self-administration with an extinction pattern but also dose-dependently inhibited heroin-enhanced BSR and NAc DA, suggesting functional antagonism by methadone of heroin's actions. In addition, 31,345 appears to possess significant abuse liability, as it produces dose-dependent enhancement of BSR and NAc DA, maintains a low rate of self-administration behavior, and dose-dependently reinstates drug-seeking behavior. In contrast, methadone only partially maintains self-administration with an extinction pattern, and fails to induce reinstatement of drug-seeking behavior. These findings suggest that 31,345 is a cocaine-like slow-onset long-acting monoamine transporter inhibitor that may act as an agonist therapy for cocaine addiction. However, its pattern of action appears to be significantly different from that of methadone. Ideal agonist substitutes for cocaine should fully emulate methadone's actions, that is, functionally antagonizing cocaine's action while blocking monoamine transporters to augment synaptic DA. PMID:20827272

SU-F-T-15: Evaluation of 192Ir, 60Co and 169Yb Sources for High Dose Rate Prostate Brachytherapy Inverse Planning Using An Interior Point Constraint Generation Algorithm

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

Mok Tsze Chung, E; Aleman, D; Safigholi, H

Purpose: The effectiveness of using a combination of three sources, {sup 60}Co, {sup 192}Ir and {sup 169}Yb, is analyzed. Different combinations are compared against a single {sup 192}Ir source on prostate cancer cases. A novel inverse planning interior point algorithm is developed in-house to generate the treatment plans. Methods: Thirteen prostate cancer patients are separated into two groups: Group A includes eight patients with the prostate as target volume, while group B consists of four patients with a boost nodule inside the prostate that is assigned 150% of the prescription dose. The mean target volume is 35.7±9.3cc and 30.6±8.5cc formore » groups A and B, respectively. All patients are treated with each source individually, then with paired sources, and finally with all three sources. To compare the results, boost volume V150 and D90, urethra Dmax and D10, and rectum Dmax and V80 are evaluated. For fair comparison, all plans are normalized to a uniform V100=100. Results: Overall, double- and triple-source plans were better than single-source plans. The triple-source plans resulted in an average decrease of 21.7% and 1.5% in urethra Dmax and D10, respectively, and 8.0% and 0.8% in rectum Dmax and V80, respectively, for group A. For group B, boost volume V150 and D90 increased by 4.7% and 3.0%, respectively, while keeping similar dose delivered to the urethra and rectum. {sup 60}Co and {sup 192}Ir produced better plans than their counterparts in the double-source category, whereas {sup 60}Co produced more favorable results than the remaining individual sources. Conclusion: This study demonstrates the potential advantage of using a combination of two or three sources, reflected in dose reduction to organs-at-risk and more conformal dose to the target. three sources, reflected in dose reduction to organs-at-risk and more conformal dose to the target. Our results show that {sup 60}Co, {sup 192}Ir and {sup 169}Yb produce the best plans when used simultaneously and can thus be an alternative to {sup 192}Ir-only in high-dose-rate prostate brachytherapy.« less

High dose rate brachytherapy for oral cancer

PubMed Central

YamazakI, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

2013-01-01

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. PMID:23179377

High dose rate brachytherapy for oral cancer.

PubMed

Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

2013-01-01

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

Atmospheric Ionizing Radiation (AIR) ER-2 Preflight Analysis

NASA Technical Reports Server (NTRS)

Tai, Hsiang; Wilson, John W.; Maiden, D. L.

1998-01-01

Atmospheric ionizing radiation (AIR) produces chemically active radicals in biological tissues that alter the cell function or result in cell death. The AIR ER-2 flight measurements will enable scientists to study the radiation risk associated with the high-altitude operation of a commercial supersonic transport. The ER-2 radiation measurement flights will follow predetermined, carefully chosen courses to provide an appropriate database matrix which will enable the evaluation of predictive modeling techniques. Explicit scientific results such as dose rate, dose equivalent rate, magnetic cutoff, neutron flux, and air ionization rate associated with those flights are predicted by using the AIR model. Through these flight experiments, we will further increase our knowledge and understanding of the AIR environment and our ability to assess the risk from the associated hazard.

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

PubMed

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

2000-02-01

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

Effects of low to moderate acute doses of pramipexole on impulsivity and cognition in healthy volunteers.

PubMed

Hamidovic, Ajna; Kang, Un Jung; de Wit, Harriet

2008-02-01

The neurotransmitter dopamine is integrally involved in the rewarding effects of drugs, and it has also been thought to mediate impulsive behaviors in animal models. Most of the studies of drug effects on impulsive behaviors in humans have involved drugs with complex actions on different transmitter systems and different receptor subtypes. The present study was designed to characterize the effect of single doses of pramipexole, a D2/D3 agonist, on measures of cognitive and impulsive behavior, as well as on mood in healthy volunteers. Healthy men and women (N = 10) received placebo and 2 doses of pramipexole, 0.25 and 0.50 mg, in a within-subject, double-blinded study. Outcome measures included changes in cognitive performance, assessed by the Automated Neuropsychological Assessment Metrics, several behavioral measures related to impulsive behavior, including the Balloon Analogue Risk Task, Delay Discounting Task, Go/No-Go Task, Card Perseveration Task, and subjective ratings of mood assessed by Addiction Research Center Inventory, Profile of Mood States, and Drug Effects Questionnaire. Pramipexole decreased positive ratings of mood (euphoria, intellectual efficiency, and energy) and increased both subjectively reported sedation and behavioral sedation indicated by impaired cognitive performance on several measures of the Automated Neuropsychological Assessment Metrics. Single low to medium doses of this drug did not produce a decrease in impulsive responding on behavioral measures included in this study. The sedative-like effects observed in this study may reflect presynaptic actions of the drug. Higher doses with postsynaptic actions may be needed to produce either behavioral or subjective stimulant-like effects.

Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats.

PubMed

Wiley, Jenny L; Lefever, Timothy W; Marusich, Julie A; Craft, Rebecca M

2017-03-01

Women report greater sensitivity to the subjective effects of Δ 9 -tetrahydrocannabinol (THC). Similarly, female rodents tend to be more sensitive to some pharmacological effects of THC and synthetic cannabinoids. This study examined sex differences in discriminative stimulus and response rate effects of THC and synthetic cannabinoids in rats. A cumulative dosing THC discrimination procedure was utilized to evaluate sex differences in the discriminative stimulus effects of THC and three synthetic cannabinoids: CP47,497, WIN55,212-2, and JWH-018. Sex differences in the effects of these four compounds and a degradant of A-834735 on response rates also were assessed in a food-reinforced discrete dosing procedure. Females required a lower training dose than males for acquisition of the discrimination. Further, THC was more potent at producing rimonabant-reversible discriminative stimulus and response rate effects in females. While synthetic cannabinoids were more potent in producing THC-like effects than was THC in female rats, greater discrepancies were observed in male rats. Similar sensitivity to the response rate-decreasing effects induced by most, but not all (A-834735 degradant), synthetic cannabinoids was seen in both sexes. This study represents one of the first direct comparisons of sex differences in THC discrimination. Females were more sensitive to THC's effects, which may be related, in part, to sex differences in THC metabolism. Synthetic cannabinoids were more potent than THC in both sexes, but were considerably more so in male than in female rats. Future research should emphasize further characterization of sex differences in cannabinoid pharmacology. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats*

PubMed Central

Wiley, Jenny L.; Lefever, Timothy W.; Marusich, Julie A.; Craft, Rebecca M.

2017-01-01

Background Women report greater sensitivity to the subjective effects of Δ9-tetrahydrocannabinol (THC). Similarly, female rodents tend to be more sensitive to some pharmacological effects of THC and synthetic cannabinoids. This study examined sex differences in discriminative stimulus and response rate effects of THC and synthetic cannabinoids in rats. Methods A cumulative dosing THC discrimination procedure was utilized to evaluate sex differences in the discriminative stimulus effects of THC and three synthetic cannabinoids: CP47,497, WIN55,212-2, and JWH-018. Sex differences in the effects of these four compounds and a degradant of A-834735 on response rates also were assessed in a food-reinforced discrete dosing procedure. Results Females required a lower training dose than males for acquisition of the discrimination. Further, THC was more potent at producing rimonabant-reversible discriminative stimulus and response rate effects in females. While synthetic cannabinoids were more potent in producing THC-like effects than was THC in female rats, greater discrepancies were observed in male rats. Similar sensitivity to the response rate-decreasing effects induced by most, but not all (A-834735 degradant), synthetic cannabinoids was seen in both sexes. Conclusions This study represents one of the first direct comparisons of sex differences in THC discrimination. Females were more sensitive to THC’s effects, which may be related, in part, to sex differences in THC metabolism. Synthetic cannabinoids were more potent than THC in both sexes, but were considerably more so in male than in female rats. Future research should emphasize further characterization of sex differences in cannabinoid pharmacology. PMID:28130989

Moxonidine and cognitive function: interactions with moclobemide and lorazepam.

PubMed

Wesnes, K; Simpson, P M; Jansson, B; Grahnén, A; Weimann, H J; Küppers, H

1997-01-01

Moxonidine represents a new generation of centrally acting antihypertensive drugs. It binds to I1-imidazoline receptors and exerts its antihypertensive activity through a reduction in systemic vascular resistance, while cardiac output remains unchanged or even increases slightly. Moxonidine is prescribed for the treatment of mild to moderate hypertension. Typical doses are 0.4 to 2.0 mg given as one dose in the morning or as divided doses in the morning and evening. The effects of moxonidine 0.4 mg once daily in combination with moclobemide or lorazepam were investigated in two, double-blind, randomised, placebo-controlled, two-way crossover studies in a total of 48 healthy volunteers. Safety assessments were made in each study and included pre- and post-study measurement of blood pressure, heart rate, ECG, haematology, blood biochemistry, and urinalysis, and recording of adverse events. In the first study, moxonidine alone was found to produce small but statistically significant impairments of vigilance detection speed at 4 h and 6 h. Lowering of subjective alertness was also observed. Repeat dosing with moxonidine produced an impairment of memory scanning performance. These findings were not reproduced in the second study, in which moxonidine alone produced an improvement in immediate word recall at 4 h and 6 h. No interactions were observed when moxonidine was co-administered with moclobemide. Moxonidine, when co-administered with lorazepam, produced interactions with three tasks requiring high levels of attention: choice, simple reaction time and digit vigilance performance; memory tasks; immediate word recall, delayed word recall accuracy; and visual tracking. A total of 47 adverse events were reported in study 1. Moxonidine produced a slight decrease of systolic and diastolic blood pressure. In study 2, a total of 55 adverse events were reported. In both trials, the most frequently reported events were tiredness and dryness of mouth, the latter occurring only under the moxonidine treatment. There were no clinically relevant changes observed in blood pressure, pulse rate, and laboratory tests in either study, nor was there any evidence of any interaction between moxonidine and either moclobemide or lorazepam. Moxonidine was found to be safe and well tolerated in healthy volunteers. However, the impairments on attentional tasks were greater when moxonidine was co-administered with lorazepam 1 mg. These effects should be considered when moxonidine is codosed with lorazepam, although they were smaller than would have been produced by a single dose of lorazepam 2 mg.

Relationship between cocaine-induced subjective effects and dopamine transporter occupancy

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

Volkow, N.D.; Fischman, M.; Wang, G.J.

The ability of cocaine to occupy the dopamine transporter has been linked to its reinforcing properties. However, such a relationship has not been demonstrated in humans. Methods: Positron Emission Tomography and [C-11]cocaine were used to estimate dopamine transporter occupancies after different doses of cocaine in 18 active cocaine abusers. The ratio of the distribution volume of [C-11]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd +1 and is insensitive to changes in cerebral blood flow, was our measure of dopamine transporter availability. In parallel subjective effects were measured to assess the relationship between dopamine transporter occupancy and cocainesmore » behavioral effects. Intravenous cocaine produced a significant dose,-dependent blockade of dopamine transporters: 73 % for 0.6 mg/kg; 601/6 for 0.3 mg/kg; 48 % for 0.1 mg/kg iv and 40 % for 0.05 mg/kg. In addition, dopamine transporter occupancies were significantly correlated with cocaine plasma concentration (r = 0.55 p < 0.001). Cocaine also produced dose-dependent increases in self-reported ratings of {open_quotes}high{close_quotes} which were significantly correlated with the levels of dopamine transporter blockade. Discussion: These results provide the first documentation in humans that dopamine transporter occupancy is associated with cocaine induced subjective effects. They also suggest that dopamine transporter occupancies equal to or greater than 60% are required to produce significant effects on ratings of {open_quotes}high{close_quotes}.« less

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Trovafloxacin in Combination with Vancomycin against Penicillin-Resistant Pneumococci in the Rabbit Meningitis Model

PubMed Central

Rodoni, Dina; Hänni, Fränzi; Gerber, Cynthia M.; Cottagnoud, Marianne; Neftel, Klaus; Täuber, Martin G.; Cottagnoud, Philippe

1999-01-01

Trovafloxacin, a new fluoroquinolone, produced bactericidal activity (−0.33 ± 0.13 Δlog10 CFU/ml · h; intravenously [i.v.] administered dose, 15 mg/kg) comparable to that of vancomycin (−0.39 ± 0.18 Δlog10 CFU/ml · h; i.v. administered dose, 20 mg/kg) in the treatment of experimental meningitis in rabbits due to a pneumococcal strain highly resistant to penicillin (MIC of penicillin G, 4 μg/ml). The combination of both drugs significantly increased (P < 0.05) the killing rate (−0.60 ± 0.23 Δlog10 CFU/ml · h) compared to that produced by either monotherapy. These results were also confirmed in vitro. PMID:10103211

Sub-second pencil beam dose calculation on GPU for adaptive proton therapy

NASA Astrophysics Data System (ADS)

da Silva, Joakim; Ansorge, Richard; Jena, Rajesh

2015-06-01

Although proton therapy delivered using scanned pencil beams has the potential to produce better dose conformity than conventional radiotherapy, the created dose distributions are more sensitive to anatomical changes and patient motion. Therefore, the introduction of adaptive treatment techniques where the dose can be monitored as it is being delivered is highly desirable. We present a GPU-based dose calculation engine relying on the widely used pencil beam algorithm, developed for on-line dose calculation. The calculation engine was implemented from scratch, with each step of the algorithm parallelized and adapted to run efficiently on the GPU architecture. To ensure fast calculation, it employs several application-specific modifications and simplifications, and a fast scatter-based implementation of the computationally expensive kernel superposition step. The calculation time for a skull base treatment plan using two beam directions was 0.22 s on an Nvidia Tesla K40 GPU, whereas a test case of a cubic target in water from the literature took 0.14 s to calculate. The accuracy of the patient dose distributions was assessed by calculating the γ-index with respect to a gold standard Monte Carlo simulation. The passing rates were 99.2% and 96.7%, respectively, for the 3%/3 mm and 2%/2 mm criteria, matching those produced by a clinical treatment planning system.

Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations

PubMed Central

Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J

2014-01-01

Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 108, 2 × 109 and 2 × 1010 colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 109 CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 1010 CFU). The challenge dose, 2 × 1010 CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains. PMID:24028276

Estimating neutron dose equivalent rates from heavy ion reactions around 10 MeV amu(-1) using the PHITS code.

PubMed

Iwamoto, Yosuke; Ronningen, R M; Niita, Koji

2010-04-01

It has been sometimes necessary for personnel to work in areas where low-energy heavy ions interact with targets or with beam transport equipment and thereby produce significant levels of radiation. Methods to predict doses and to assist shielding design are desirable. The Particle and Heavy Ion Transport code System (PHITS) has been typically used to predict radiation levels around high-energy (above 100 MeV amu(-1)) heavy ion accelerator facilities. However, predictions by PHITS of radiation levels around low-energy (around 10 MeV amu(-1)) heavy ion facilities to our knowledge have not yet been investigated. The influence of the "switching time" in PHITS calculations of low-energy heavy ion reactions, defined as the time when the JAERI Quantum Molecular Dynamics model (JQMD) calculation stops and the Generalized Evaporation Model (GEM) calculation begins, was studied using neutron energy spectra from 6.25 MeV amu(-1) and 10 MeV amu(-1) (12)C ions and 10 MeV amu(-1) (16)O ions incident on a copper target. Using a value of 100 fm c(-1) for the switching time, calculated neutron energy spectra obtained agree well with the experimental data. PHITS was then used with the switching time of 100 fm c(-1) to simulate an experimental study by Ohnesorge et al. by calculating neutron dose equivalent rates produced by 3 MeV amu(-1) to 16 MeV amu(-1) (12)C, (14)N, (16)O, and (20)Ne beams incident on iron, nickel and copper targets. The calculated neutron dose equivalent rates agree very well with the data and follow a general pattern which appears to be insensitive to the heavy ion species but is sensitive to the target material.

Influence of 12C6+ ion irradiation on mutant avermitilis

NASA Astrophysics Data System (ADS)

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

2012-11-01

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

FACTORS AFFECTING THE USE OF CAF2:MN THERMOLUMINESCENT DOSIMETERS FOR LOW-LEVEL ENVIRONMENTAL RADIATION MONITORING

EPA Science Inventory

An investigation was made of factors affecting the use of commercially-produced CaF2:Mn thermoluminescent dosimeters for low level environmental radiation monitoring. Calibration factors and self-dosing rates were quantified for 150 thermoluminescent dosimeters. Laboratory studie...

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

PubMed

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

2004-01-01

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

Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans

PubMed Central

Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Elayi, Samy Claude; Walsh, Sharon L.

2016-01-01

Background The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal. Methods Twelve opioid dependent adults participated in this 5-week, inpatient, double-blind, randomized, placebo-controlled study. Volunteers were maintained on double-blind oxycodone (30mg oral, four times/day) and participated in a training session followed by 7 experimental sessions, each testing a single oral test dose (placebo, oxycodone 30 and 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Placebo was substituted for oxycodone maintenance doses for 21 hours before each session in order to produce measurable opioid withdrawal. Outcomes included observer- and participant-ratings of opioid agonist, opioid withdrawal and psychomotor/cognitive performance. Results Oxycodone produced prototypic opioid agonist effects (i.e., suppressing withdrawal and increasing subjective effects indicative of abuse liability). Dronabinol 5 and 10mg produced effects most similar to placebo, while the 20 and 30mg doses produced modest signals of withdrawal suppression that were accompanied by dose-related increases in high, sedation, bad effects, feelings of heart racing, and tachycardia. Dronabinol was not liked more than placebo, showed some impairment in cognitive performance, and was identified as marijuana with increasing dose. Conclusion CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal. PMID:27234658

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

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

Damilakis, J; Perisinakis, K; Solomou, G

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

Brachytherapy dosimetry of 125I and 103Pd sources using an updated cross section library for the MCNP Monte Carlo transport code.

PubMed

Bohm, Tim D; DeLuca, Paul M; DeWerd, Larry A

2003-04-01

Permanent implantation of low energy (20-40 keV) photon emitting radioactive seeds to treat prostate cancer is an important treatment option for patients. In order to produce accurate implant brachytherapy treatment plans, the dosimetry of a single source must be well characterized. Monte Carlo based transport calculations can be used for source characterization, but must have up to date cross section libraries to produce accurate dosimetry results. This work benchmarks the MCNP code and its photon cross section library for low energy photon brachytherapy applications. In particular, we calculate the emitted photon spectrum, air kerma, depth dose in water, and radial dose function for both 125I and 103Pd based seeds and compare to other published results. Our results show that MCNP's cross section library differs from recent data primarily in the photoelectric cross section for low energies and low atomic number materials. In water, differences as large as 10% in the photoelectric cross section and 6% in the total cross section occur at 125I and 103Pd photon energies. This leads to differences in the dose rate constant of 3% and 5%, and differences as large as 18% and 20% in the radial dose function for the 125I and 103Pd based seeds, respectively. Using a partially updated photon library, calculations of the dose rate constant and radial dose function agree with other published results. Further, the use of the updated photon library allows us to verify air kerma and depth dose in water calculations performed using MCNP's perturbation feature to simulate updated cross sections. We conclude that in order to most effectively use MCNP for low energy photon brachytherapy applications, we must update its cross section library. Following this update, the MCNP code system will be a very effective tool for low energy photon brachytherapy dosimetry applications.

Numerical simulation of the radiation environment on Martian surface

NASA Astrophysics Data System (ADS)

Zhao, L.

2015-12-01

The radiation environment on the Martian surface is significantly different from that on earth. Existing observation and studies reveal that the radiation environment on the Martian surface is highly variable regarding to both short- and long-term time scales. For example, its dose rate presents diurnal and seasonal variations associated with atmospheric pressure changes. Moreover, dose rate is also strongly influenced by the modulation from GCR flux. Numerical simulation and theoretical explanations are required to understand the mechanisms behind these features, and to predict the time variation of radiation environment on the Martian surface if aircraft is supposed to land on it in near future. The high energy galactic cosmic rays (GCRs) which are ubiquitous throughout the solar system are highly penetrating and extremely difficult to shield against beyond the Earth's protective atmosphere and magnetosphere. The goal of this article is to evaluate the long term radiation risk on the Martian surface. Therefore, we need to develop a realistic time-dependent GCR model, which will be integrated with Geant4 transport code subsequently to reproduce the observed variation of surface dose rate associated with the changing heliospheric conditions. In general, the propagation of cosmic rays in the interplanetary medium can be described by a Fokker-Planck equation (or Parker equation). In last decade,we witnessed a fast development of GCR transport models within the heliosphere based on accurate gas-dynamic and MHD backgrounds from global models of the heliosphere. The global MHD simulation produces a more realistic pattern of the 3-D heliospheric structure, as well as the interface between the solar system and the surrounding interstellar space. As a consequence, integrating plasma background obtained from global-dependent 3-D MHD simulation and stochastic Parker transport simulation, we expect to produce an accurate global physical-based GCR modulation model. Combined with the Geant4 transport code, this GCR model will provide valuable insight into the long-term dose rates variation on the Martian surface.

Parabolic quantitative structure-activity relationships and photodynamic therapy: application of a three-compartment model with clearance to the in vivo quantitative structure-activity relationships of a congeneric series of pyropheophorbide derivatives used as photosensitizers for photodynamic therapy.

PubMed

Potter, W R; Henderson, B W; Bellnier, D A; Pandey, R K; Vaughan, L A; Weishaupt, K R; Dougherty, T J

1999-11-01

An open three-compartment pharmacokinetic model was applied to the in vivo quantitative structure-activity relationship (QSAR) data of a homologous series of pyropheophorbide photosensitizers for photodynamic therapy (PDT). The physical model was a lipid compartment sandwiched between two identical aqueous compartments. The first compartment was assumed to clear irreversibly at a rate K0. The measured octanol-water partition coefficients, P(i) (where i is the number of carbons in the alkyl chain) and the clearance rate K0 determined the clearance kinetics of the drugs. Solving the coupled differential equations of the three-compartment model produced clearance kinetics for each of the sensitizers in each of the compartments. The third compartment was found to contain the target of PDT. This series of compounds is quite lipophilic. Therefore these drugs are found mainly in the second compartment. The drug level in the third compartment represents a small fraction of the tissue level and is thus not accessible to direct measurement by extraction. The second compartment of the model accurately predicted the clearance from the serum of mice of the hexyl ether of pyropheophorbide a, one member of this series of compounds. The diffusion and clearance rate constants were those found by fitting the pharmacokinetics of the third compartment to the QSAR data. This result validated the magnitude and mechanistic significance of the rate constants used to model the QSAR data. The PDT response to dose theory was applied to the kinetic behavior of the target compartment drug concentration. This produced a pharmacokinetic-based function connecting PDT response to dose as a function of time postinjection. This mechanistic dose-response function was fitted to published, single time point QSAR data for the pheophorbides. As a result, the PDT target threshold dose together with the predicted QSAR as a function of time postinjection was found.

Remediation of incomplete nitrification and capacity increase of biofilters at different drinking water treatment plants through copper dosing.

PubMed

Wagner, Florian B; Nielsen, Peter Borch; Boe-Hansen, Rasmus; Albrechtsen, Hans-Jørgen

2018-04-01

Drinking water treatment plants based on groundwater may suffer from incomplete ammonium removal, which deteriorates drinking water quality and constrains water utilities in the operation of their plants. Ammonium is normally removed through nitrification in biological granular media filters, and recent studies have demonstrated that dosing of copper can stimulate the removal of ammonium. Here, we investigated if copper dosing could generically improve ammonium removal of biofilters, at treatment plants with different characteristics. Copper was dosed at ≤1.5 μg Cu/L to biofilters at 10 groundwater treatment plants, all of which had displayed several years of incomplete nitrification. Plants exceeded the Danish national water quality standard of 0.05 mg NH 4 + /L by a factor of 2-12. Within only 2-3 weeks of dosing, ammonium removal rates increased significantly (up to 150%). Nitrification was fully established, with ammonium effluent concentrations of <0.01 mg NH 4 + -N/L at most plants, regardless of the differences in raw water chemistry, ammonium loading rates, filter design and operation, or treatment plant configuration. However, for filters without primary filtration, it took longer time to reach complete ammonium removal than for filters receiving prefiltered water, likely due to sorption of copper to iron oxides, at plants without prefiltration. With complete ammonium removal, we subjected two plants to short-term loading rate upshifts, to examine the filters' ability to cope with loading rate variations. After 2 months of dosing and an average loading rate of 1.0 g NH 4 + -N/m 3 filter material/h, the loading rate was upshifted by 50%. Yet, a filter managed to completely remove all the influent ammonium, showing that with copper dosing the filter had extra capacity to remove ammonium even beyond its normal loading rates. Depth sampling revealed that the ammonium removal rate of the filter's upper 10 cm increased more than 7-fold from 0.67 to 4.90 g NH 4 + -N/m 3 /h, and that nitrite produced from increased ammonium oxidation was completely oxidized further to nitrate. Hence, no problems with nitrite accumulation or breakthrough occurred. Overall, copper dosing generically enhanced nitrification efficiency and allowed a range of quite different plants to meet water quality standards, even at increased loading rates. The capacity increase is highly relevant in practice, as it makes filters more robust towards sudden ammonium loading rate variations. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2011-12-01

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

Radiation effects program

NASA Astrophysics Data System (ADS)

1985-09-01

No existing LINAC Based Beam Heating facility comes within a factor of ten of the needs of a high heating rate thermodynamic properties research facility. The facility could be built at the Naval Research Lab. for a cost in the neighborhood of 2 million dollars. The 10 MeV electron beam would not produce any serious radioactivity but would provide unprecedented beam power for such other applications as food processing, sewer treatment, materials curing, radiation hardness assurance, etc. One can always achieve lower current densities by scattering the beam and moving the device under test further away from the scatterer. In this case one must rely on the TLD readings to indicate the dose rate at the point of interest. For general utility with the beam covering about four TLD's fairly evenly one can claim that the NRL LINAC can produce a maximum dose rate of about 6 x 10 to the 10th power rads (Si) per second for a pulse length of 1.5 microseconds, and about 1.4 x 10 to the 11th power rads (Si) per second in a 50 nanosecond pulse. In both cases the beam area is about 0.4 square centimeters.

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

NASA Astrophysics Data System (ADS)

Shen, Ming-Yi

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

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

PubMed

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

2001-02-01

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

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

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Richardson, Richard B.

2015-07-01

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

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

PubMed

El-Jaby, Samy; Richardson, Richard B

2015-07-01

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

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

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

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

2012-02-01

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

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

PubMed

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

2016-10-01

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

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

PubMed

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

2017-02-01

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

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

NASA Astrophysics Data System (ADS)

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

2013-11-01

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

Effects of intrathecal or intracerebroventricular administration of nonsteroidal anti-inflammatory drugs on a C-fiber reflex in rats.

PubMed

Bustamante, D; Paeile, C; Willer, J C; Le Bars, D

1997-06-01

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 times threshold), and recruitment curves were built by varying the stimulus intensity from 0 to 7 times threshold. The intrathecal (i.t.) but not i.c.v. administration of aspirin, indomethacin, ketoprofen and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex. In contrast, saline was ineffective. Regardless of the route of administration, the drugs never produced disturbances in heart rate and/or acid-base equilibrium. When a constant level of stimulation was used, 500 microg of aspirin i.t. induced a blockade of the reflex immediately after the injection, followed by a partial recovery. Indomethacin produced a stable depression, which reached 80 to 90% with an i.t. dose of 500 microg. Ketoprofen and lysine clonixinate produced a more stable effect; the highest doses (500 microg) produced a steady-state depression of approximately 50% for approximately 30 min. When the recruitment curves were built with a range of nociceptive stimulus intensities, all of the drugs except for indomethacin produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without major modifications in the thresholds; indomethacin also induced a significant dose-related increase in the threshold. The orders of potency for both stimulation paradigms with the i.t. route were the same, namely aspirin > indomethacin > lysine clonixinate > or = ketoprofen. It is concluded that nonsteroidal anti-inflammatory drugs elicit significant antinociceptive effects at a spinal level, which do not depend on the existence of a hyperalgesic or inflammatory state. Such effects were not seen after injections within the lateral ventricle.

Developmental toxicity of CdTe QDs in zebrafish embryos and larvae

NASA Astrophysics Data System (ADS)

Duan, Junchao; Yu, Yongbo; Li, Yang; Yu, Yang; Li, Yanbo; Huang, Peili; Zhou, Xianqing; Peng, Shuangqing; Sun, Zhiwei

2013-07-01

Quantum dots (QDs) have widely been used in biomedical and biotechnological applications. However, few studies focus on the assessing toxicity of QDs exposure in vivo. In this study, zebrafish embryos were treated with CdTe QDs (4 nm) during 4-96 h post-fertilization (hpf). Mortality, hatching rate, malformation, heart rate, and QDs uptake were detected. We also measured the larval behavior to analyze whether QDs had persistent effects on larvae locomotor activity at 144 hpf. The results showed that as the exposure dosages increased, the hatching rate and heart rate of zebrafish embryos were decreased, while the mortality increased. Exposure to QDs caused embryonic malformations, including head malformation, pericardial edema, yolk sac edema, bent spine, and yolk not depleted. QDs fluorescence was mainly localized in the intestines region. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lowest dose (2.5 nM QDs) produced substantial hyperactivity while the higher doses groups (5, 10, and 20 nM QDs) elicited remarkably hypoactivity in dark periods. In summary, the data of this article indicated that QDs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior.

Absorbed dose calculations in a brachytherapy pelvic phantom using the Monte Carlo method

PubMed Central

Rodríguez, Miguel L.; deAlmeida, Carlos E.

2002-01-01

Monte Carlo calculations of the absorbed dose at various points of a brachytherapy anthropomorphic phantom are presented. The phantom walls and internal structures are made of polymethylmethacrylate and its external shape was taken from a female Alderson phantom. A complete Fletcher‐Green type applicator with the uterine tandem was fixed at the bottom of the phantom reproducing a typical geometrical configuration as that attained in a gynecological brachytherapy treatment. The dose rate produced by an array of five 137Cs CDC‐J type sources placed in the applicator colpostats and the uterine tandem was evaluated by Monte Carlo simulations using the code penelope at three points: point A, the rectum, and the bladder. The influence of the applicator in the dose rate was evaluated by comparing Monte Carlo simulations of the sources alone and the sources inserted in the applicator. Differences up to 56% in the dose may be observed for the two cases in the planes including the rectum and bladder. The results show a reduction of the dose of 15.6%, 14.0%, and 5.6% in the rectum, bladder, and point A respectively, when the applicator wall and shieldings are considered. PACS number(s): 87.53Jw, 87.53.Wz, 87.53.Vb, 87.66.Xa PMID:12383048

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

PubMed

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

2017-01-01

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

Acute effects of caffeine on several operant behaviors in rhesus monkeys.

PubMed

Buffalo, E A; Gillam, M P; Allen, R R; Paule, M G

1993-11-01

The acute effects of 1,3-trimethylxanthine (caffeine) were assessed using an operant test battery (OTB) of complex food-reinforced tasks that are thought to depend upon relatively specific brain functions, such as motivation to work for food (progressive ratio, PR), learning (incremental repeated acquisition, IRA), color and position discrimination (conditioned position responding, CPR), time estimation (temporal response differentiation, TRD), and short-term memory and attention (delayed matching-to-sample, DMTS). Endpoints included response rates (RR), accuracies (ACC), and percent task completed (PTC). Caffeine sulfate (0.175-20.0 mg/kg, IV), given 15 min pretesting, produced significant dose-dependent decreases in TRD percent task completed and accuracy at doses > or = 5.6 mg/kg. Caffeine produced no systematic effects on either DMTS or PR responding, but low doses tended to enhance performance in both IRA and CPR tasks. Thus, in monkeys, performance of an operant task designed to model time estimation is more sensitive to the disruptive effects of caffeine than is performance of the other tasks in the OTB.

Discriminative-Stimulus, Subject-rated and Physiological Effects of Methamphetamine in Humans Pretreated with Aripiprazole

PubMed Central

Sevak, Rajkumar J.; Vansickel, Andrea R.; Stoops, William W.; Glaser, Paul E. A.; Hays, Lon R.; Rush, Craig R.

2013-01-01

Methamphetamine is thought to produce its behavioral effects by releasing dopamine (DA), serotonin (5-HT) and norepinephrine. Results from animal studies support this notion, while results from human laboratory studies have not consistently demonstrated the importance of monoamine systems in the behavioral effects of methamphetamine. Human laboratory procedures of drug-discrimination are well suited to assess neuropharmacological mechanisms of the training drug by studying pharmacological manipulation. In this human laboratory study, six participants with a history of recreational stimulant use learned to discriminate 10 mg oral methamphetamine. After acquiring the discrimination (i.e., ≥80% correct responding on 4 consecutive sessions), the effects of a range of doses of methamphetamine (0, 2.5, 5, 10 and 15 mg), alone and in combination with 0 and 20 mg aripiprazole (a partial agonist at D2 and 5-HT1A receptors), were assessed. Methamphetamine alone functioned as a discriminative stimulus, produced prototypical stimulant-like subject-rated drug effects (e.g., increased ratings of Good Effects, Talkative-Friendly, and Willing to Pay For) and elevated cardiovascular indices. These effects were generally a function of dose. Aripiprazole alone did not occasion methamphetamine-appropriate responding or produce subject-rated effects, but modestly impaired performance. Administration of aripiprazole significantly attenuated the discriminative-stimulus and cardiovascular effects of methamphetamine, as well as some of the subject-rated drug effects. These results indicate that monoamine systems likely play a role in the behavioral effects of methamphetamine in humans. Moreover, given the concordance between past results with d-amphetamine and the present findings, d-amphetamine can likely serve as a model for the pharmacological effects of methamphetamine. PMID:21694622

Estrus synchronization in sheep with synthetic progestagens.

PubMed

Awel, Hayatu; Eshetu, Lisanework; Tadesse, Gebrehiwot; Birhanu, Alemselam; Khar, S K

2009-10-01

Sixteen female sheep of Degua breed were assigned to receive either the full dose of norgestomet ear implant and injectable solution containing norgestomet and estradiol valerate (n = 8) or half the dose (n = 8). The ear implants were removed in both groups on day 12. All ewes received an intramuscular administration of 500 IU PMSG at implant withdrawal. Synchronized ewes were individually hand mated twice at 48 and 60 hours after implant removal. One ewe in each group however refused mating on both occasions. Pregnancy diagnosis was conducted by bimanual external palpation 90 to 100 days post mating. The conception rates (3/7, 42.85%) and (5/7, 71.42%) were recorded in the two treatment groups, respectively. All eight ewes lambed between 145 to 153 days post mating. In group I ewes carried only singletons (prolificity rate 1.0) whereas in group II two ewes delivered twins, producing 7 lambs with prolificity rate of 1.4 (N.S). From this preliminary investigation it appears that the lower dose of norgestomet ear implants offers better option for estrus synchronization accompanied by higher fertility.

Influence of injected interstitials on the void swelling in two structural variants of 304L stainless steel induced by self-ion irradiation at 500 °C

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

Sun, C.; Garner, F. A.; Shao, L.

The two variants of AISI 304L stainless steel (SS) with different grain size distributions were ion irradiated at 500 °C to a peak dose of ~60 dpa. In the coarse-grained annealed variant, a peak swelling of ~12% was observed closer to the specimen surface rather than at the depth of peak displacement damage. The forward shift in depth between peak swelling and peak dose is proposed to be a consequence of suppression of void nucleation by injected interstitials. The swelling behavior in the front portion of the ion range mirrors that of neutron-induced swelling in this steel, exhibiting significant curvaturemore » with increasing dose as the swelling rate approaches the terminal swelling rate of 1%/dpa. Furthermore, an ultrafine grain variant of this steel produced by severely plastic deformation exhibits a similar suppression of void nucleation in the injected interstitial region, but also shows a significantly extended transient regime, not reaching the terminal swelling rate by 60 dpa.« less

Influence of injected interstitials on the void swelling in two structural variants of 304L stainless steel induced by self-ion irradiation at 500 °C

DOE PAGES

Sun, C.; Garner, F. A.; Shao, L.; ...

2017-03-28

The two variants of AISI 304L stainless steel (SS) with different grain size distributions were ion irradiated at 500 °C to a peak dose of ~60 dpa. In the coarse-grained annealed variant, a peak swelling of ~12% was observed closer to the specimen surface rather than at the depth of peak displacement damage. The forward shift in depth between peak swelling and peak dose is proposed to be a consequence of suppression of void nucleation by injected interstitials. The swelling behavior in the front portion of the ion range mirrors that of neutron-induced swelling in this steel, exhibiting significant curvaturemore » with increasing dose as the swelling rate approaches the terminal swelling rate of 1%/dpa. Furthermore, an ultrafine grain variant of this steel produced by severely plastic deformation exhibits a similar suppression of void nucleation in the injected interstitial region, but also shows a significantly extended transient regime, not reaching the terminal swelling rate by 60 dpa.« less

Monte Carlo simulation of a compact microbeam radiotherapy system based on carbon nanotube field emission technology.

PubMed

Schreiber, Eric C; Chang, Sha X

2012-08-01

Microbeam radiation therapy (MRT) is an experimental radiotherapy technique that has shown potent antitumor effects with minimal damage to normal tissue in animal studies. This unique form of radiation is currently only produced in a few large synchrotron accelerator research facilities in the world. To promote widespread translational research on this promising treatment technology we have proposed and are in the initial development stages of a compact MRT system that is based on carbon nanotube field emission x-ray technology. We report on a Monte Carlo based feasibility study of the compact MRT system design. Monte Carlo calculations were performed using EGSnrc-based codes. The proposed small animal research MRT device design includes carbon nanotube cathodes shaped to match the corresponding MRT collimator apertures, a common reflection anode with filter, and a MRT collimator. Each collimator aperture is sized to deliver a beam width ranging from 30 to 200 μm at 18.6 cm source-to-axis distance. Design parameters studied with Monte Carlo include electron energy, cathode design, anode angle, filtration, and collimator design. Calculations were performed for single and multibeam configurations. Increasing the energy from 100 kVp to 160 kVp increased the photon fluence through the collimator by a factor of 1.7. Both energies produced a largely uniform fluence along the long dimension of the microbeam, with 5% decreases in intensity near the edges. The isocentric dose rate for 160 kVp was calculated to be 700 Gy∕min∕A in the center of a 3 cm diameter target. Scatter contributions resulting from collimator size were found to produce only small (<7%) changes in the dose rate for field widths greater than 50 μm. Dose vs depth was weakly dependent on filtration material. The peak-to-valley ratio varied from 10 to 100 as the separation between adjacent microbeams varies from 150 to 1000 μm. Monte Carlo simulations demonstrate that the proposed compact MRT system design is capable of delivering a sufficient dose rate and peak-to-valley ratio for small animal MRT studies.

Cardiovascular effects of Nemopilema nomurai (Scyphozoa: Rhizostomeae) jellyfish venom in rats.

PubMed

Kim, Euikyung; Lee, Seunghwan; Kim, Jong-Shu; Yoon, Won Duk; Lim, Donghyun; Hart, Andrew J; Hodgson, Wayne C

2006-12-15

Over the past few years, populations of the giant jellyfish Nemopilema nomurai (Scyphozoa: Rhizostomeae) have increased dramatically in the waters of China, Korea, and Japan without any definitive reason. This has resulted in severe damage to fisheries in the areas. During a pilot study, we observed that the venom of N. nomurai produced a functional cardiac depression in mice. However, the mechanism of action was not examined. In the present study, we investigated the cardiovascular effects of nematocyst-derived venom from N. nomurai in anesthetized rats. Venom (0.1-2.4 mg protein/kg, i.v.) produced dose-dependent hypotension (65+/-12% of initial at a cumulative dose of 3 mg/kg) and bradycardia (80+/-5% of initial at a cumulative dose of 3 mg/kg). At the highest dose, this was characterized by a transient decrease in blood pressure (phase 1) followed by a return to basal level and then a slower decrease in blood pressure (phase 2). Venom also produced a decrease in rate and force of contraction in the rat isolated atria. Interestingly, venom induced a contraction of isolated aortic rings which was blocked by felodipine but not by prazosin, suggesting the contraction is mediated by calcium channel activation. These results suggest that the negative inotropic and chronotropic effects of the venom of N. nomurai may be due to a direct effect on the heart.

Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys.

PubMed

Moerke, Megan J; Banks, Matthew L; Cheng, Kejun; Rice, Kenner C; Negus, S Stevens

2017-12-01

Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice. Adult male rhesus monkeys with double-lumen intravenous catheters responded for concurrently available food pellets and cocaine injections (0-0.1mg/kg/injection) during daily sessions. Cocaine choice and overall reinforcement rates were evaluated during 7-day treatments with saline or test drugs. During saline treatment, cocaine maintained a dose-dependent increase in cocaine-vs.-food choice. The mu-opioid receptor agonist morphine (0.032-0.32mg/kg/h) dose-dependently increased cocaine choice and decreased rates of reinforcement. A dose of the mu-selective opioid receptor antagonist naltrexone (0.0032mg/kg/h) that completely blocked morphine effects had no effect on cocaine choice when it was administered alone, but it enhanced the effectiveness of a threshold dose of 0.032mg/kg/h amphetamine to decrease cocaine choice without also enhancing nonselective behavioral disruption by this dose of amphetamine. Conversely, the kappa-selective opioid antagonist norbinalorphimine did not enhance amphetamine effects on cocaine choice. These results suggest that amphetamine maintenance produces mu opioid-receptor mediated effects that oppose its anti-cocaine effects. Co-administration of naltrexone may selectively enhance amphetamine potency to decrease cocaine choice without increasing amphetamine potency to produce general behavioral disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

WE-E-BRE-03: Biological Validation of a Novel High-Throughput Irradiator for Predictive Radiation Sensitivity Bioassays

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

Fowler, TL; Martin, JA; Shepard, AJ

2014-06-15

Purpose: The large dose-response variation in both tumor and normal cells between individual patients has led to the recent implementation of predictive bioassays of patient-specific radiation sensitivity in order to personalize radiation therapy. This exciting new clinical paradigm has led us to develop a novel high-throughput, variable dose-rate irradiator to accompany these efforts. Here we present the biological validation of this irradiator through the use of human cells as a relative dosimeter assessed by two metrics, DNA double-strand break repair pathway modulation and intercellular reactive oxygen species production. Methods: Immortalized human tonsilar epithelial cells were cultured in 96-well micro titermore » plates and irradiated in groups of eight wells to absorbed doses of 0, 0.5, 1, 2, 4, and 8 Gy. High-throughput immunofluorescent microscopy was used to detect γH2AX, a DNA double-strand break repair mechanism recruiter. The same analysis was performed with the cells stained with CM-H2DCFDA that produces a fluorescent adduct when exposed to reactive oxygen species during the irradiation cycle. Results: Irradiations of the immortalized human tonsilar epithelial cells at absorbed doses of 0, 0.5, 1, 2, 4, and 8 Gy produced excellent linearity in γH2AX and CM-H2DCFDA with R2 values of 0.9939 and 0.9595 respectively. Single cell gel electrophoresis experimentation for the detection of physical DNA double-strand breaks in ongoing. Conclusions: This work indicates significant potential for our high-throughput variable dose rate irradiator for patient-specific predictive radiation sensitivity bioassays. This irradiator provides a powerful tool by increasing the efficiency and number of assay techniques available to help personalize radiation therapy.« less

SU-F-T-513: Dosimetric Validation of Spatially Fractionated Radiotherapy Using Gel Dosimetry

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

Papanikolaou, P; Watts, L; Kirby, N

2016-06-15

Purpose: Spatially fractionated radiation therapy, also known as GRID therapy, is used to treat large solid tumors by irradiating the target to a single dose of 10–20Gy through spatially distributed beamlets. We have investigated the use of a 3D gel for dosimetric characterization of GRID therapy. Methods: GRID therapy is an external beam analog of volumetric brachytherapy, whereby we produce a distribution of hot and cold dose columns inside the tumor volume. Such distribution can be produced with a block or by using a checker-like pattern with MLC. We have studied both types of GRID delivery. A cube shaped acrylicmore » phantom was filled with polymer gel and served as a 3D dosimeter. The phantom was scanned and the CT images were used to produce two plans in Pinnacle, one with the grid block and one with the MLC defined grid. A 6MV beam was used for the plan with a prescription of 1500cGy at dmax. The irradiated phantom was scanned in a 3T MRI scanner. Results: 3D dose maps were derived from the MR scans of the gel dosimeter and were found to be in good agreement with the predicted dose distribution from the RTP system. Gamma analysis showed a passing rate of 93% for 5% dose and 2mm DTA scoring criteria. Both relative and absolute dose profiles are in good agreement, except in the peripheral beamlets where the gel measured slightly higher dose, possibly because of the changing head scatter conditions that the RTP is not fully accounting for. Our results have also been benchmarked against ionization chamber measurements. Conclusion: We have investigated the use of a polymer gel for the 3D dosimetric characterization and evaluation of GRID therapy. Our results demonstrated that the planning system can predict fairly accurately the dose distribution for GRID type therapy.« less

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

Rahman, Nur Aira Abd, E-mail: nur-aira@nm.gov.my; Lombigit, Lojius; Abdullah, Nor Arymaswati

This paper presents the design of new digital radiation survey meter with LND7121 Geiger Muller tube detector and Atmega328P microcontroller. Development of the survey meter prototype is carried out on Arduino Uno platform. 16-bit Timer1 on the microcontroller is utilized as external pulse counter to produce count per second or CPS measurement. Conversion from CPS to dose rate technique is also performed by Arduino to display results in micro Sievert per hour (μSvhr{sup −1}). Conversion factor (CF) value for conversion of CPM to μSvhr{sup −1} determined from manufacturer data sheet is compared with CF obtained from calibration procedure. The surveymore » meter measurement results are found to be linear for dose rates below 3500 µSv/hr.« less

Arduino based radiation survey meter

NASA Astrophysics Data System (ADS)

Rahman, Nur Aira Abd; Lombigit, Lojius; Abdullah, Nor Arymaswati; Azman, Azraf; Dolah, Taufik; Muzakkir, Amir; Jaafar, Zainudin; Mohamad, Glam Hadzir Patai; Ramli, Abd Aziz Mhd; Zain, Rasif Mohd; Said, Fazila; Khalid, Mohd Ashhar; Taat, Muhamad Zahidee

2016-01-01

This paper presents the design of new digital radiation survey meter with LND7121 Geiger Muller tube detector and Atmega328P microcontroller. Development of the survey meter prototype is carried out on Arduino Uno platform. 16-bit Timer1 on the microcontroller is utilized as external pulse counter to produce count per second or CPS measurement. Conversion from CPS to dose rate technique is also performed by Arduino to display results in micro Sievert per hour (μSvhr-1). Conversion factor (CF) value for conversion of CPM to μSvhr-1 determined from manufacturer data sheet is compared with CF obtained from calibration procedure. The survey meter measurement results are found to be linear for dose rates below 3500 µSv/hr.

Neuroleptics and learning: effects of haloperidol, molindone, mesoridazine and thioridazine on the behavior of pigeons under a repeated acquisition procedure.

PubMed

Poling, A; Cleary, J; Berens, K; Thompson, T

1990-12-01

The purpose of the present study was to examine the effects of haloperidol (0.3-10 mg/kg), molindone (0.3-5.6 mg/kg), mesoridazine (0.3-10) and thioridazine (0.3-25 mg/kg) on the behavior of pigeons exposed to a repeated acquisition procedure. At sufficiently high doses, each of these neuroleptics increased error rates (interfered with learning) and reduced rate of responding. When the drugs were compared on the basis of absolute doses administered, haloperidol disrupted behavior at doses considerably lower than the other drugs. If, however, chlorpromazine equivalent doses were examined, haloperidol was the least disruptive of the four drugs. Comparing the degree of behavioral disruption produced by the four drugs with their relative neuroreceptor affinities for dopamine D-2, cholinergic muscarinic, histamine H1, alpha-1 adrenergic and alpha-2 adrenergic receptors suggests that behavioral disruption cannot be attributed in any simple way to dopamine or acetylcholine receptor blockade. The relationship between the behavioral effects of neuroleptics and their simple neuropharmacological actions must be considered as highly tentative.

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

PubMed

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

2012-01-01

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

Skyshine photon doses from 6 and 10 MV medical linear accelerators

PubMed Central

da Rosa, Luiz A. R.

2012-01-01

The skyshine radiation phenomenon consists of the scattering of primary photon beams in the atmosphere above the roof of a medical linear accelerator facility, generating an additional dose at ground level in the vicinity of the treatment room. Thus, with respect to radioprotection, this situation plays an important role when the roof is designed with little shielding and there are buildings next to the radiotherapy treatment room. In literature, there are few reported skyshine‐measured doses and these contain poor agreement with empirical calculations. In this work, we carried out measurements of skyshine photon dose rates produced from eight different 6 and 10 MV medical accelerators. Each measurement was performed outside the room facility, with the beam positioned in the upward direction, at a horizontal distance from the target and for a 40 cm×40 cm maximum photon field size at the accelerator isocenter. Measured dose‐equivalent rates results were compared with calculations obtained by an empirical expression, and differences between them deviated in one or more order of magnitude. PACS numbers: 87.53.‐j, 87.53.Bn PMID:22231219

Shielding synchrotron light sources: Advantages of circular shield walls tunnels

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

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

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

Shielding synchrotron light sources: Advantages of circular shield walls tunnels

DOE PAGES

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

2016-04-26

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

Behavioural profile of exendin-4/naltrexone dose combinations in male rats during tests of palatable food consumption.

PubMed

Wright, F L; Rodgers, R J

2014-09-01

The glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 potently suppresses food intake in animals and humans. However, little is known about the behavioural specificity of this effect either when administered alone or when co-administered with another anorectic agent. The present study characterises the effects of exendin-4, both alone and in combination with naltrexone, on behaviours displayed by male rats during tests with palatable mash. Experiment 1 examined the dose-response effects of exendin-4 (0.025-2.5 μg/kg, IP), while experiment 2 profiled the effects of low-dose combinations of the peptide (0.025 and 0.25 μg/kg) and naltrexone (0.1 mg/kg). In experiment 1, exendin-4 dose dependently suppressed food intake as well as the frequency and rate of eating. However, these effects were accompanied by dose-dependent reductions in all active behaviours and, at 2.5 μg/kg, a large increase in resting and disruption of the behavioural satiety sequence (BSS). In experiment 2, while exendin-4 (0.25 μg/kg) and naltrexone each produced a significant reduction in intake and feeding behaviour (plus an acceleration in the BSS), co-treatment failed to produce stronger effects than those seen in response to either compound alone. Similarities between the behavioural signature of exendin-4 and that previously reported for the emetic agent lithium chloride would suggest that exendin-4 anorexia is related to the aversive effects of the peptide. Furthermore, as low-dose combinations of the peptide with naltrexone failed to produce an additive/synergistic anorectic effect, this particular co-treatment strategy would not appear to have therapeutic significance.

Mealtime glucose regulation with nateglinide in healthy volunteers: comparison with repaglinide and placebo.

PubMed

Kalbag, J B; Walter, Y H; Nedelman, J R; McLeod, J F

2001-01-01

This study was designed to compare the pharmacodynamic effects of single doses of nateglinide (A-4166), repaglinide, and placebo on mealtime insulin secretion and glycemic control in healthy subjects. Fifteen healthy volunteers participated in this open-label five-period crossover study. They received single 10-min preprandial doses of 120 mg nateglinide, 0.5 or 2 mg repaglinide, or placebo or 1 min preprandially of 2 mg repaglinide. Subjects received each dose only once, 48 h apart. Pharmacodynamic and pharmacokinetic assessments were performed from 0 to 12 h postdose. Nateglinide induced insulin secretion more rapidly than 2 and 0.5 mg repaglinide and placebo (10 min preprandial), with mean rates of insulin rise of 2.3, 1.3, 1.15, and 0.8 microU x ml(-1) x min(-1), respectively, over the 0- to 30-min postmeal interval. After peaking, insulin concentrations decreased rapidly in the nateglinide-treated group and were similar to placebo within 2 h postdose. After 2 mg repaglinide, peak insulin concentrations were delayed and returned to baseline more slowly than with nateglinide treatment. Nateglinide treatment produced lower average plasma glucose concentrations in the 0- to 2-h postdose interval than either dose of repaglinide and placebo (P < 0.05 vs. 0.5 mg repaglinide and placebo). Plasma glucose concentrations returned more rapidly to predose levels with nateglinide treatment than with either dose of repaglinide. Treatment with repaglinide produced a sustained hypoglycemic effect up to 6 h postdose. In this single-dose study in nondiabetic volunteers, nateglinide provided a more rapid and shorter-lived stimulation of insulin secretion than repaglinide, resulting in lower meal-related glucose excursions. If similar results are observed in diabetes, nateglinide may produce a more physiological insulin secretory response with the potential for a reduced risk of postabsorptive hypoglycemia.

[Neutron Dosimetry System Using CR-39 for High-energy X-ray Radiation Therapy].

PubMed

Yabuta, Kazutoshi; Monzen, Hajime; Tamura, Masaya; Tsuruta, Takao; Itou, Tetsuo; Nohtomi, Akihiro; Nishimura, Yasumasa

2014-01-01

Neutrons are produced during radiation treatment by megavolt X-ray energies. However, it is difficult to measure neutron dose especially just during the irradiation. Therefore, we have developed a system for measuring neutrons with the solid state track detector CR-39, which is free from the influence of the X-ray beams. The energy spectrum of the neutrons was estimated by a Monte Carlo simulation method, and the estimated neutron dose was corrected by the contribution ratio of each energy. Pit formation rates of CR-39 ranged from 2.3 x 10(-3) to 8.2 x 10(-3) for each detector studied. According to the estimated neutron energy spectrum, the energy values for calibration were 144 keV and 515keV, and the contribution ratios were approximately 40:60 for 10 MV photons and 20:70 for photons over 15 MV. Neutron doses measured in the center of a high-energy X-ray field were 0.045 mSv/Gy for a 10 MV linear accelerator and 0.85 mSv/Gy for a 20 MV linear accelerator. We successfully developed the new neutron dose measurement system using the solid track detector, CR-39. This on-time neutron measurement system allows users to measure neutron doses produced in the radiation treatment room more easily.

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

NASA Astrophysics Data System (ADS)

Heredia, Athena Yvonne

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

The Efficacy and Safety of the Novel Peripheral Analgesic Isovaline as an Adjuvant to Propofol for General Anesthesia and Conscious Sedation: A Proof-of-Principle Study in Mice.

PubMed

Whitehead, Ryan A; Schwarz, Stephan K W; Asiri, Yahya I; Fung, Timothy; Puil, Ernest; MacLeod, Bernard A

2015-12-01

The combination of propofol and an opioid analgesic is widely used for procedural sedation, as well as total IV anesthesia. However, opioids produce respiratory depression, a primary cause of death due to these agents. We recently reported on the antinociceptive actions of isovaline, a small nonbiogenic amino acid that does not readily cross the blood-brain barrier and acts on peripheral γ-aminobutyric acid type B receptors. Here, we explored the possibility that isovaline may be an effective and safe alternative to opioids as an adjunct to propofol for producing anesthesia. With approval from our Animal Care Committee, we conducted an in vivo study in adult female CD-1 mice using Dixon's "up-and-down" method for dose assessment. Animals received intraperitoneal saline, propofol, isovaline, fentanyl, or coadministration of propofol with isovaline or fentanyl. We assessed hypnosis by a loss of righting reflex and immobility by an absence of motor response to tail clip application. General anesthesia was defined as the presence of both hypnosis and immobility. We assessed conscious sedation as a decrease in time on a rotarod. The maximal dose without respiratory rates of <4 per minute, apnea, or death was defined as the maximal tolerated dose. Either isovaline or fentanyl coadministered with propofol at its half-maximal effective dose (ED50) for hypnosis produced general anesthesia (isovaline ED50, 96 mg/kg [95% confidence interval {CI}, 88-124 mg/kg]; fentanyl ED50, 0.12 mg/kg [95% CI, 0.08-3.5 mg/kg]). Propofol produced hypnosis (ED50, 124 mg/kg [95% CI, 84-3520 mg/kg]) but did not block responses to tail clip application. Neither isovaline nor fentanyl produced hypnosis at doses which produced immobility (isovaline ED50, 350 mg/kg [95% CI, 286-1120 mg/kg]; fentanyl ED50, 0.35 mg/kg [95% CI, 0.23-0.51 mg/kg]). Isovaline at its analgesic ED50, coadministered with a subhypnotic dose of propofol (40 mg/kg), did not exacerbate propofol-induced deficits in rotarod performance. The median maximal tolerated dose of fentanyl coadministered with the hypnotic ED50 of propofol was 11 mg/kg (95% CI, 8-18 mg/kg). Isovaline at a maximal deliverable (soluble) dose of 5000 mg/kg produced no apparent respiratory depression or other adverse effects. The novel analgesic, isovaline, coadministered with propofol, produced general anesthesia and conscious sedation in mice. The margin of safety for propofol-isovaline was considerably higher than that for propofol-fentanyl. This study's results show that propofol-based sedation and general anesthesia can be effectively and safely produced by replacing the conventional opioid component with a brain-impermeant peripherally acting γ-aminobutyric acid type B receptor agonist. The results provide proof of the principle of combining a peripheral analgesic with a centrally acting hypnotic to produce general anesthesia. This principle suggests a novel approach to clinical general anesthesia and conscious sedation.

Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations.

PubMed

Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J

2014-06-01

Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 10(8) , 2 × 10(9) and 2 × 10(10) colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 10(9) CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 10(10) CFU). The challenge dose, 2 × 10(10) CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains. © 2013 The Authors. APMIS published by John Wiley & Sons Ltd.

Phase 2 trial of bortezomib in combination with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with bortezomib, rituximab, methotrexate, and cytarabine for untreated mantle cell lymphoma.

PubMed

Romaguera, Jorge E; Wang, Michael; Feng, Lei; Fayad, Luis E; Hagemeister, Frederick; McLaughlin, Peter; Rodriguez, M Alma; Fanale, Michelle; Orlowski, Robert; Kwak, Larry W; Neelapu, Sattva; Oki, Yasuhiro; Pro, Barbara; Younes, Anas; Samaniego, Felipe; Fowler, Nathan; Hartig, Kimberly; Valentinetti, Marisa; Smith, Judy; Ford, Peggy; Naig, Adam; Medeiros, L Jeffrey; Kantarjian, Hagop M; Goy, Andre

2018-05-03

Although the outcomes of patients with mantle cell lymphoma (MCL) have improved, there is still no cure. Bortezomib has a 33% response rate in relapsed/refractory MCL and has shown additive and/or synergistic effects in preclinical trials with known effective agents. This is a report of a prospective phase 2 trial of bortezomib added to rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (BzR-hyperCVAD)/rituximab, high-dose methotrexate, and high-dose cytarabine (BzR-MA) for 95 patients with newly diagnosed MCL. The overall and complete response rates were 100% and 82%, respectively. Hematologic toxicity was high but expected and did not lead to an increased incidence of neutropenic fever or dose reductions in comparison with a similar reported regimen without bortezomib. After a median follow-up of 44 months, the median overall survival had not been reached, and the time to treatment failure (TTF) was 55 months, which is not different from that of historical controls. BzR-hyperCVAD/BzR-MA at the dose and schedule studied produced high rates of response and a TTF similar to that of historical reports without bortezomib. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Alternative Reinforcer Response Cost Impacts Cocaine Choice in Humans

PubMed Central

Stoops, William W.; Lile, Joshua A.; Glaser, Paul E.A.; Hays, Lon R.; Rush, Craig R.

2011-01-01

Cocaine use disorders are an unrelenting public health concern. Behavioral treatments reduce cocaine use by providing non-drug alternative reinforcers. The purpose of this human laboratory experiment was to determine how response cost for non-drug alternative reinforcers influenced cocaine choice. Seven cocaine-using, non-treatment-seeking subjects completed a crossover, double-blind protocol in which they first sampled doses of intranasal cocaine (5, 10, 20 or 30 mg) and completed a battery of subject-rated and physiological measures. Subjects then made eight discrete choices between the sampled dose and an alternative reinforce (US$0.25). The response cost to earn a cocaine dose was always a fixed ratio (FR) of 100 responses. The response cost for the alternative reinforcer varied across sessions (FR1, FR10, FR100, FR1000). Dose-related increases were observed for cocaine choice. Subjects made fewer drug choices when the FR requirements for the alternative reinforcers were lower than that for drug relative to when the FR requirements were equal to or higher than that for drug. Intranasal cocaine also produced prototypical stimulant-like subject-rated and physiological effects (e.g., increased ratings of Like Drug; elevated blood pressure). These data demonstrate that making alternative reinforcers easier to earn reduces cocaine self-administration, which has implications for treatment efforts. PMID:22015480

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

PubMed Central

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

2014-01-01

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

Simulation of irradiation exposure of electronic devices due to heavy ion therapy with Monte Carlo Code MCNP6

NASA Astrophysics Data System (ADS)

Lapins, Janis; Guilliard, Nicole; Bernnat, Wolfgang; Buck, Arnulf

2017-09-01

During heavy ion irradiation therapy the patient has to be located exactly at the right position to make sure that the Bragg peak occurs in the tumour. The patient has to be moved in the range of millimetres to scan the ill tissue. For that reason a special table was developed which allows exact positioning. The electronic control can be located outside the surgery. But that has some disadvantage for the construction. To keep the system compact it would be much more comfortable to put the electronic control inside the surgery. As a lot of high energetic secondary particles are produced during the therapy causing a high dose in the room it is important to find positions with low dose rates. Therefore, investigations are needed where the electronic devices should be located to obtain a minimum of radiation, help to prevent the failure of sensitive devices. The dose rate was calculated for carbon ions with different initial energy and protons over the entire therapy room with Monte Carlo particle tracking using MCNP6. The types of secondary particles were identified and the dose rate for a thin silicon layer and an electronic mixture material was determined. In addition, the shielding effect of several selected material layers was calculated using MCNP6.

Global real-time dose measurements using the Automated Radiation Measurements for Aerospace Safety (ARMAS) system

NASA Astrophysics Data System (ADS)

Tobiska, W. Kent; Bouwer, D.; Smart, D.; Shea, M.; Bailey, J.; Didkovsky, L.; Judge, K.; Garrett, H.; Atwell, W.; Gersey, B.; Wilkins, R.; Rice, D.; Schunk, R.; Bell, D.; Mertens, C.; Xu, X.; Wiltberger, M.; Wiley, S.; Teets, E.; Jones, B.; Hong, S.; Yoon, K.

2016-11-01

The Automated Radiation Measurements for Aerospace Safety (ARMAS) program has successfully deployed a fleet of six instruments measuring the ambient radiation environment at commercial aircraft altitudes. ARMAS transmits real-time data to the ground and provides quality, tissue-relevant ambient dose equivalent rates with 5 min latency for dose rates on 213 flights up to 17.3 km (56,700 ft). We show five cases from different aircraft; the source particles are dominated by galactic cosmic rays but include particle fluxes for minor radiation periods and geomagnetically disturbed conditions. The measurements from 2013 to 2016 do not cover a period of time to quantify galactic cosmic rays' dependence on solar cycle variation and their effect on aviation radiation. However, we report on small radiation "clouds" in specific magnetic latitude regions and note that active geomagnetic, variable space weather conditions may sufficiently modify the magnetospheric magnetic field that can enhance the radiation environment, particularly at high altitudes and middle to high latitudes. When there is no significant space weather, high-latitude flights produce a dose rate analogous to a chest X-ray every 12.5 h, every 25 h for midlatitudes, and every 100 h for equatorial latitudes at typical commercial flight altitudes of 37,000 ft ( 11 km). The dose rate doubles every 2 km altitude increase, suggesting a radiation event management strategy for pilots or air traffic control; i.e., where event-driven radiation regions can be identified, they can be treated like volcanic ash clouds to achieve radiation safety goals with slightly lower flight altitudes or more equatorial flight paths.

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.

External dose assessment in the Ukraine following the Chernobyl accident

NASA Astrophysics Data System (ADS)

Frazier, Remi Jordan Lesartre

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

Effects of organophosphorus anticholinesterase compounds on brain glucose and energy metabolism. Final summary report, 1 October 1981-29 February 1984

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

Medina, M.A.; Miller, A.L.

1984-09-01

The effects of Soman and paraoxon on cerebral metabolic rate (CMRg) and the levels of various metabolites in rate brain were investigated. In non-convulsing animals, 0.8 of the paraoxon LD50 and 0.5 of the Soman LD50 tended to lower CMRg. A higher dose of Soman, 0.8-0.95 of the LD50, resulted in convulsive seizures in some but not all of the animals. In convulsing rats the CMRg and lactate levels were elevated primarily in the cortex and thalamus/basal ganglia. Decreased ATP and glucose levels with an elevated CMRg and lactate concentration was observed in the cortex, suggesting that Soman may bemore » uncoupling oxidative phosphorylation. Pretreatment with atropine prevented the behavioral manifestations and the elevated CMRg but not the hyperglycemia produced by an 0.8 LD50 dose of Soman. These results suggest that Soman-induced convulsions are similar to those produced by other central nervous system (CNS) excitatory agents in that only certain brain regions are affected. The use of atropine to block the CNS disturbances produced by Soman appears to be effective also does not result in the extensive depression of CMRg observed with TAB, a mixture of trimedoxime, atropine and benactyzine.« less

Reinforcing Doses of Intravenous Cocaine Produce Only Modest Dopamine Uptake Inhibition.

PubMed

Brodnik, Zachary D; Ferris, Mark J; Jones, Sara R; España, Rodrigo A

2017-02-15

The reinforcing efficacy of cocaine is thought to stem from inhibition of the dopamine transporter (DAT) and subsequent increases in extracellular dopamine concentrations in the brain. In humans, this hypothesis has generally been supported by positron emission tomography imaging studies where the percent of DATs occupied by cocaine is used as a measure of cocaine activity in the brain. Interpretation of these studies, however, often relies on the assumption that measures of DAT occupancy directly correspond with functional DAT blockade. In the current studies, we used in vivo and in vitro fast scan cyclic voltammetry in mice to measure dopamine uptake inhibition following varying doses of cocaine as well as two high affinity DAT inhibitors. We then compared dopamine clearance rates following these drug treatments to dopamine clearance obtained from DAT knockout mice as a proxy for complete DAT blockade. We found that administration of abused doses of cocaine resulted in approximately 2% of maximal DAT blockade. Overall, our data indicate that abused doses of cocaine produce a relatively modest degree of DA uptake inhibition, and suggest that the relationship between DAT occupancy and functional blockade of the DAT is more complex than originally posited.

DOSE AND GAMMA-RAY SPECTRA FROM NEUTRON-INDUCED RADIOACTIVITY IN MEDICAL LINEAR ACCELERATORS FOLLOWING HIGH-ENERGY TOTAL BODY IRRADIATION.

PubMed

Keehan, S; Taylor, M L; Smith, R L; Dunn, L; Kron, T; Franich, R D

2016-12-01

Production of radioisotopes in medical linear accelerators (linacs) is of concern when the beam energy exceeds the threshold for the photonuclear interaction. Staff and patients may receive a radiation dose as a result of the induced radioactivity in the linac. Gamma-ray spectroscopy was used to identify the isotopes produced following the delivery of 18 MV photon beams from a Varian 21EX and an Elekta Synergy. The prominent radioisotopes produced include 187 W, 63 Zn, 56 Mn, 24 Na and 28 Al in both linac models. The dose rate was measured at the beam exit window (12.6 µSv in the first 10 min) following 18 MV total body irradiation (TBI) beams. For a throughput of 24 TBI patients per year, staff members are estimated to receive an annual dose of up to 750 μSv at the patient location. This can be further reduced to 65 μSv by closing the jaws before re-entering the treatment bunker. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effect of acetyl strophanthidin on the hearts of normal dogs.

PubMed

Hayes, A H; McShane, W P; Sidell, F R

1970-05-01

1. The ED50 of acetyl strophanthidin for producing ventricular arrhythmias in normal dogs was 54.5 mug/kg intravenously.2. Doses up to and including those which caused ventricular tachycardia did not produce either atrial arrhythmias or significant aberration of A-V conduction.3. Although the classic digitalis-induced rate and e.c.g. waveform changes may appear after administration of acetyl strophanthidin, their presence or absence have no value in predicting the subsequent development of ventricular arrhythmias.

Interactions between scopolamine and muscarinic cholinergic agonists or cholinesterase inhibitors on spatial alternation performance in rats.

PubMed

Shannon, H E; Bemis, K G; Hendrix, J C; Ward, J S

1990-12-01

The effects on working memory of the muscarinic cholinergic agonists oxotremorine, arecoline, RS86 and pilocarpine, and the cholinesterase inhibitors physostigmine and tetrahydroaminoacadine were investigated in male F344 rats. Working memory was assessed by behavior maintained under a spatial alternation schedule of food presentation in which the interval between trials was varied from 2 to 32 sec. Under control conditions the percentage of correct responses decreased as the retention interval was varied from 2 to 32 sec. Administered alone the cholinergic agonists oxotremorine (0.01-0.1 mg/kg), arecoline (3-30 mg/kg), RS86 (0.3-3 mg/kg) and pilocarpine (0.3-3.0 mg/kg), and the cholinesterase inhibitors physostigmine (0.01-0.1 mg/kg) and tetrahydroaminoacridine (0.3-3.0 mg/kg) either had no effect on or produced dose-related deficits in working memory and decreases in response rates. The muscarinic antagonist scopolamine (0.1 mg/kg) produced retention interval-dependent decreases in the percentage of correct responding and rates of responding. The cholinergic agonists and tetrahydroaminoacridine failed to reverse the effects of scopolamine. However, physostigmine produced a dose-dependent reversal of the working-memory deficits and response-rate decreasing effects of scopolamine. The present results are consistent with the interpretation that drugs which primarily enhance M2 muscarinic cholinergic transmission are ineffective in enhancing working memory or in reversing scopolamine-induced deficits in working memory.

Pharmacodynamic Profile of Tramadol in Humans: Influence of Naltrexone Pretreatment

PubMed Central

Stoops, William W.; Lofwall, Michelle R.; Nuzzo, Paul A.; Craig, Lori B.; Siegel, Anthony J.; Walsh, Sharon L.

2012-01-01

Rationale Tramadol is a prescription analgesic that activates mu opioid and monoamine receptor systems. Tramadol is thought to have limited abuse potential compared to mu opioid agonists, but laboratory data indicate that it shares some of their pharmacodynamic effects. Objectives This study evaluated the effect of mu opioid receptor blockade with naltrexone on the pharmacodynamic action of tramadol in humans. Methods This inpatient, double-blind, randomized, within-subject study examined the effects of oral placebo, tramadol (87.5, 175 and 350 mg) and hydromorphone (4 and 16 mg; positive control) after 1 hr pretreatment with oral naltrexone (0 and 50 mg). Ten recreational opioid users completed the study. Pharmacodynamic effects were measured before and for 7 hr after initial drug administration. Results Lower doses of tramadol and hydromorphone were generally placebo-like. Hydromorphone (16 mg) produced prototypic mu opioid agonist-like effects that were blocked by naltrexone. Tramadol (350 mg) produced miosis and increased ratings of “Good Effects” and “Liking ,” but also increased ratings of “Bad Effects.” Naltrexone reversed tramadol-induced physiological effects and mydriasis emerged, but unlike results with hydromorphone, naltrexone only partially attenuated tramadol’s positive subjective effects and actually enhanced several unpleasant subjective ratings. Conclusions Naltrexone can be used to disentangle the mixed neuropharmacological actions of tramadol. High dose tramadol produces a mixed profile of effects. These data suggest that both mu and non-mu opioid actions play a role in tramadol’s subjective profile of action. PMID:22623016

Qualification tests for {sup 192}Ir sealed sources

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

Iancso, Georgeta, E-mail: georgetaiancso@yahoo.com; Iliescu, Elena, E-mail: georgetaiancso@yahoo.com; Iancu, Rodica, E-mail: georgetaiancso@yahoo.com

This paper describes the results of qualification tests for {sup 192}Ir sealed sources, available in Testing and Nuclear Expertise Laboratory of National Institute for Physics and Nuclear Engineering 'Horia Hulubei' (I.F.I.N.-HH), Romania. These sources had to be produced in I.F.I.N.-HH and were tested in order to obtain the authorization from The National Commission for Nuclear Activities Control (CNCAN). The sources are used for gammagraphy procedures or in gammadefectoscopy equipments. Tests, measurement methods and equipments used, comply with CNCAN, AIEA and International Quality Standards and regulations. The qualification tests are: 1. Radiological tests and measurements: dose equivalent rate at 1 m;more » tightness; dose equivalent rate at the surface of the transport and storage container; external unfixed contamination of the container surface. 2. Mechanical and climatic tests: thermal shock; external pressure; mechanic shock; vibrations; boring; thermal conditions for storage and transportation. Passing all tests, it was obtained the Radiological Security Authorization for producing the {sup 192}Ir sealed sources. Now IFIN-HH can meet many demands for this sealed sources, as the only manufacturer in Romania.« less

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

PubMed Central

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

2012-01-01

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

Verification of the Accountability Method as a Means to Classify Radioactive Wastes Processed Using THOR Fluidized Bed Steam Reforming at the Studsvik Processing Facility in Erwin, Tennessee, USA - 13087

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

Olander, Jonathan; Myers, Corey

2013-07-01

Studsviks' Processing Facility Erwin (SPFE) has been treating Low-Level Radioactive Waste using its patented THOR process for over 13 years. Studsvik has been mixing and processing wastes of the same waste classification but different chemical and isotopic characteristics for the full extent of this period as a general matter of operations. Studsvik utilizes the accountability method to track the movement of radionuclides from acceptance of waste, through processing, and finally in the classification of waste for disposal. Recently the NRC has proposed to revise the 1995 Branch Technical Position on Concentration Averaging and Encapsulation (1995 BTP on CA) with additionalmore » clarification (draft BTP on CA). The draft BTP on CA has paved the way for large scale blending of higher activity and lower activity waste to produce a single waste for the purpose of classification. With the onset of blending in the waste treatment industry, there is concern from the public and state regulators as to the robustness of the accountability method and the ability of processors to prevent the inclusion of hot spots in waste. To address these concerns and verify the accountability method as applied by the SPFE, as well as the SPFE's ability to control waste package classification, testing of actual waste packages was performed. Testing consisted of a comprehensive dose rate survey of a container of processed waste. Separately, the waste package was modeled chemically and radiologically. Comparing the observed and theoretical data demonstrated that actual dose rates were lower than, but consistent with, modeled dose rates. Moreover, the distribution of radioactivity confirms that the SPFE can produce a radiologically homogeneous waste form. The results of the study demonstrate: 1) the accountability method as applied by the SPFE is valid and produces expected results; 2) the SPFE can produce a radiologically homogeneous waste; and 3) the SPFE can effectively control the waste package classification. (authors)« less

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

PubMed

Hillman, D J; Green, S W

1994-10-01

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

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg.

PubMed

Abadelah, Mohamad; Chrystyn, Henry; Bagherisadeghi, Golshan; Abdalla, Gaballa; Larhrib, Hassan

2018-01-01

Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.

Environmental Fate and Biological Consequences of Chemicals Related to Air Force Activities

DTIC Science & Technology

1982-09-01

milliliters of a 10% solution over a 78.5-square centimeter surface. Sample treated cores were tested under laboratory conditions and in field studies and using...natural weather conditions for comparative tests. No Sig- nificant differences were noted between field and laboratory conditions . Biological...JP-4- and JP-5-dosed cores initially show a stressed condition as indicated by an increased rate in CO2 produc- tion followed by a rate of CO2

The extreme solar cosmic ray particle event on 20 January 2005 and its influence on the radiation dose rate at aircraft altitude.

PubMed

Bütikofer, R; Flückiger, E O; Desorgher, L; Moser, M R

2008-03-01

In January 2005 toward the end of solar activity cycle 23 the Sun was very active. Between 15 and 20 January 2005, the solar active region NOAA AR 10720 produced five powerful solar flares. In association with this major solar activity several pronounced variations in the ground-level cosmic ray intensity were observed. The fifth of these flares (X7.1) produced energetic solar cosmic rays that caused a giant increase in the count rates of the ground-based cosmic ray detectors (neutron monitors). At southern polar neutron monitor stations the increase of the count rate reached several thousand percent. From the recordings of the worldwide network of neutron monitors, we determined the characteristics of the solar particle flux near Earth. In the initial phase of the event, the solar cosmic ray flux near Earth was extremely anisotropic. The energy spectrum of the solar cosmic rays was fairly soft during the main and the decay phase. We investigated also the flux of different secondary particle species in the atmosphere and the radiation dosage at flight altitude. Our analysis shows a maximum increment of the effective dose rate due to solar cosmic rays in the south polar region around 70 degrees S and 130 degrees E at flight altitude of almost three orders of magnitude.

Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice.

PubMed

Moerke, Megan J; de Moura, Fernando B; Koek, Wouter; McMahon, Lance R

2016-09-05

Some drugs that are positive allosteric nAChR modulators in vitro, desformylflustrabromine (dFBr), PNU-120596 and LY 2087101, have not been fully characterized in vivo. These drugs were examined for their capacity to share or modify the hypothermic and discriminative stimulus effects of nicotine (1mg/kg s.c.) in male C57Bl/6J mice. Nicotine, dFBr, and PNU-120596 produced significant hypothermia, whereas LY 2087101 (up to 100mg/kg) did not. Nicotine dose-dependently increased nicotine-appropriate responding and decreased response rate; the respective ED50 values were 0.56mg/kg and 0.91mg/kg. The modulators produced no more than 38% nicotine-appropriate responding up to doses that disrupted operant responding. Rank order potency was the same for hypothermia and rate-decreasing effects: nicotine>dFBr>PNU-120596=LY 2087101. Mecamylamine and the α4β2 nAChR antagonist dihydro-β-erythroidine, but not the α7 antagonist methyllycaconitine, antagonized the hypothermic effects of nicotine. In contrast, mecamylamine did not antagonize the hypothermic effects of the modulators. The combined discriminative stimulus effects of DFBr and nicotine were synergistic, whereas the combined hypothermic effects of nicotine with either dFBr or PNU-120596 were infra-additive. PNU-120596 did not modify the nicotine discriminative stimulus, and LY 2087101 did not significantly modify either effect of nicotine. Positive modulation of nicotine at nAChRs by PNU-120596 and LY 2087101 in vitro does not appear to confer enhancement of the nAChR-mediated hypothermic or discriminative stimulus effects of nicotine. However, dFBr appears to be a positive allosteric modulator of some behavioral effects of nicotine at doses of dFBr smaller than the doses producing unwanted effects (e.g. hypothermia) through non-nAChR mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice

PubMed Central

Moerke, Megan J.; de Moura, Fernando B.; Koek, Wouter; McMahon, Lance R.

2016-01-01

Some drugs that are positive allosteric nAChR modulators in vitro, desformylflustrabromine (dFBr), PNU-120596 and LY 2087101, have not been fully characterized in vivo. These drugs were examined for their capacity to share or modify the hypothermic and discriminative stimulus effects of nicotine (1 mg/kg s.c.) in male C57Bl/6J mice. Nicotine, dFBr, and PNU-120596 produced significant hypothermia, whereas LY 2087101 (up to 100 mg/kg) did not. Nicotine dose-dependently increased nicotine-appropriate responding and decreased response rate; the respective ED50 values were 0.56 mg/kg and 0.91 mg/kg. The modulators produced no more than 38% nicotine-appropriate responding up to doses that disrupted operant responding. Rank order potency was the same for hypothermia and rate-decreasing effects: nicotine>dFBr>PNU-120596=LY 2087101. Mecamylamine and the α4β2 nAChR antagonist dihydro-β-erythroidine, but not the α7 antagonist methyllycaconitine, antagonized the hypothermic effects of nicotine. In contrast, mecamylamine did not antagonize the hypothermic effects of the modulators. The combined discriminative stimulus effects of DFBr and nicotine were synergistic, whereas the combined hypothermic effects of nicotine with either dFBr or PNU-120596 were infra-additive. PNU-120596 did not modify the nicotine discriminative stimulus, and LY 2087101 did not significantly modify either effect of nicotine. Positive modulation of nicotine at nAChRs by PNU-120596 and LY 2087101 in vitro does not appear to confer enhancement of the nAChR-mediated hypothermic or discriminative stimulus effects of nicotine. However, dFBr appears to be a positive allosteric modulator of some behavioral effects of nicotine at doses of dFBr smaller than the doses producing unwanted effects (e.g. hypothermia) through non-nAChR mechanisms. PMID:27238974

Atomic bomb health benefits.

PubMed

Luckey, T D

2008-01-01

Media reports of deaths and devastation produced by atomic bombs convinced people around the world that all ionizing radiation is harmful. This concentrated attention on fear of miniscule doses of radiation. Soon the linear no threshold (LNT) paradigm was converted into laws. Scientifically valid information about the health benefits from low dose irradiation was ignored. Here are studies which show increased health in Japanese survivors of atomic bombs. Parameters include decreased mutation, leukemia and solid tissue cancer mortality rates, and increased average lifespan. Each study exhibits a threshold that repudiates the LNT dogma. The average threshold for acute exposures to atomic bombs is about 100 cSv. Conclusions from these studies of atomic bomb survivors are: One burst of low dose irradiation elicits a lifetime of improved health.Improved health from low dose irradiation negates the LNT paradigm.Effective triage should include radiation hormesis for survivor treatment.

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

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

Pak, Daniel; Vineberg, Karen; Feng, Felix

2012-08-01

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

The radiation environment on the surface of Mars - Numerical calculations of the galactic component with GEANT4/PLANETOCOSMICS.

PubMed

Matthiä, Daniel; Berger, Thomas

2017-08-01

Galactic cosmic radiation and secondary particles produced in the interaction with the atmosphere lead to a complex radiation field on the Martian surface. A workshop ("1st Mars Space Radiation Modeling Workshop") organized by the MSL-RAD science team was held in June 2016 in Boulder with the goal to compare models capable to predict this radiation field with each other and measurements from the RAD instrument onboard the curiosity rover taken between November 15, 2015 and January 15, 2016. In this work the results of PLANETOCOSMICS/GEANT4 contributed to the workshop are presented. Calculated secondary particle spectra on the Martian surface are investigated and the radiation field's directionality of the different particles in dependence on the energy is discussed. Omnidirectional particle fluxes are used in combination with fluence to dose conversion factors to calculate absorbed dose rates and dose equivalent rates in a slab of tissue. Copyright © 2017. Published by Elsevier Ltd.

Subjective and physiological effects after controlled Sativex and oral THC administration.

PubMed

Karschner, E L; Darwin, W D; McMahon, R P; Liu, F; Wright, S; Goodwin, R S; Huestis, M A

2011-03-01

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses.

Subjective and Physiological Effects After Controlled Sativex and Oral THC Administration

PubMed Central

Karschner, EL; Darwin, WD; McMahon, RP; Liu, F; Wright, S; Goodwin, RS; Huestis, MA

2013-01-01

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and “good drug effects” with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses. PMID:21289620

Acute d-amphetamine pretreatment does not alter stimulant self-administration in humans.

PubMed

Stoops, William W; Vansickel, Andrea R; Lile, Joshua A; Rush, Craig R

2007-05-01

Recent clinical research indicates that d-amphetamine is effective in treating cocaine and methamphetamine dependence. There is concern, however, with the use of d-amphetamine as a pharmacotherapy because acute administration of d-amphetamine decreases inhibition in cocaine-using individuals and may increase drug-taking behavior. The purpose of the present experiment was to determine whether acute d-amphetamine pretreatment would alter the reinforcing, subject-rated, and cardiovascular effects of d-amphetamine. To this end, 7 human volunteers first sampled doses of oral d-amphetamine (0, 8, and 16 mg). These doses engender moderate drug taking and were selected to avoid a ceiling or floor effect. Volunteers were then allowed to self-administer these sampled doses using a modified progressive-ratio procedure in two sessions in which they received pretreatment with either 0 or 15 mg oral d-amphetamine 2 h prior to completing the modified progressive-ratio procedure. d-Amphetamine produced prototypical stimulant-like effects (e.g., increased ratings of stimulated, elevated blood pressure) and maintained responding on the modified progressive-ratio schedule. Pretreatment with 15 mg oral d-amphetamine also produced prototypical stimulant-like effects, but failed to alter break points for d-amphetamine on the modified progressive-ratio procedure relative to placebo pretreatment. These results indicate that acute d-amphetamine pretreatment does not increase stimulant self-administration.

Research trends with food irradiation in Japan (in Japanese)

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

Sato, T.

Potatoes and onions are irradiated to prevent their germination for 8 months after harvest. Twenty-seven tons of potatoes were exposed to /sup 60/Co gamma irradiation at a dose rate of 7 x 10/sup 4/ R/hr. Potatoes irradiated with a dose of 7 to 15 Krads were stored for 8 months at room temperature, and were suitable market produce. Sapporo yellow onions, produced in Hokkaido and which passed the year-end for storage, were mainly studied. It was possible to prevent germination of the onions if irradiated at a dose of 3 to 10 Krads within the dormant period. Concerning rice, itmore » was suggested that prevention of the main harmful insects of rice, such as rice weevil, Sordidus zeamais and Sordidus oryzal, was possible by sterilization and inactivation through irradiation at a dose of 15 Krads. The sterilization dose for harmful insects of wheat was 5 to 7 Krads. Theoff flavor in the wheat was recognized immediately after irradiation at a dose of 20 Krads, but after three months wheat did not show off flavor even with 50 Krads irradiation. As a result, the volume of bread was larger in irradiated bread rather than in nonirradiated bread. Vienna sausage without preservatives was irradiated in 500 Krads under the condition of being kept in cold storage at 10 deg C. Its decomposition was delayed one week. The proper dose for boiled fishpaste was determined to be 300 Krads, and its preservation period was prolonged from 7 to 10 days to 21 days by irradiation. In mandarin oranges, off flavor was caused by a dose level of 50 Krads of /sup 60/Co gamma radiation. Therefore, irradiation of mandarin oranges has to depend on electron irnadiation, but problems remain regarding the irradiation technique. In a study of the safety of irradiated food, potato irradiation was permitted by the Ministry of Health and Welfare at a dose of 15 Knads in August of 1972. Lastly, the condition of potato irradiation in the producing and consuming districts and economic problems are discussed. (JA)« less

Mu/Kappa Opioid Interactions in Rhesus Monkeys: Implications for Analgesia and Abuse Liability

PubMed Central

Negus, S. Stevens; Katrina Schrode, KA; Stevenson, Glenn W.

2008-01-01

Mu opioid receptor agonists are clinically valuable as analgesics; however, their use is limited by high abuse liability. Kappa opioid agonists also produce antinociception, but they do not produce mu agonist-like abuse-related effects, suggesting that they may enhance the antinociceptive effects and/or attenuate the abuse-related effects of mu agonists. To evaluate this hypothesis, the present study examined interactions between the mu agonist fentanyl and the kappa agonist U69,593 in three behavioral assays in rhesus monkeys. In an assay of schedule-controlled responding, monkeys responded under a fixed-ratio 30 (FR 30) schedule of food presentation. Fentanyl and U69,593 each produced rate-decreasing effects when administered alone, and mixtures of 0.22:1, 0.65:1 and 1.96:1 U69,593/fentanyl usually produced subadditive effects. In an assay of thermal nociception, tail withdrawal latencies were measured from water heated to 50°C. Fentanyl and U69,593 each produced dose-dependent antinociception, and effects were additive for all mixtures. In an assay of drug self-administration, rhesus monkeys responded for i.v. drug injection, and both dose and FR values were manipulated. Fentanyl maintained self-administration, whereas U69,593 did not. Addition of U69,593 to fentanyl produced a proportion-dependent decrease in both rates of fentanyl self-administration and behavioral economic measures of the reinforcing efficacy of fentanyl. Taken together, these results suggest that simultaneous activation of mu and kappa receptors, either with a mixture of selective drugs or with a single drug that targets both receptors, may reduce abuse liability without reducing analgesic effects relative to selective mu agonists administered alone. PMID:18837635

Radiological Shielding Design for the Neutron High-Resolution Backscattering Spectrometer EMU at the OPAL Reactor

NASA Astrophysics Data System (ADS)

Ersez, Tunay; Esposto, Fernando; Souza, Nicolas R. de

2017-09-01

The shielding for the neutron high-resolution backscattering spectrometer (EMU) located at the OPAL reactor (ANSTO) was designed using the Monte Carlo code MCNP 5-1.60. The proposed shielding design has produced compact shielding assemblies, such as the neutron pre-monochromator bunker with sliding cylindrical block shields to accommodate a range of neutron take-off angles, and in the experimental area - shielding of neutron focusing guides, choppers, flight tube, backscattering monochromator, and additional shielding elements inside the Scattering Tank. These shielding assemblies meet safety and engineering requirements and cost constraints. The neutron dose rates around the EMU instrument were reduced to < 0.5 µSv/h and the gamma dose rates to a safe working level of ≤ 3 µSv/h.

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

PubMed

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

2015-10-01

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

Compact Tissue-equivalent Proportional Counter for Deep Space Human Missions

PubMed Central

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

2015-01-01

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

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

PubMed

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

2017-06-01

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

Effect of mixed pinning landscapes produced by 6 MeV oxygen irradiation on the resulting critical current densities Jc in 1.3 μm thick GdBa2Cu3O7-d coated conductors grown by co-evaporation

NASA Astrophysics Data System (ADS)

Haberkorn, N.; Suárez, S.; Pérez, P. D.; Troiani, H.; Granell, P.; Golmar, F.; Lee, Jae-Hun; Moon, S. H.

2017-11-01

We report the influence of crystalline defects introduced by 6 MeV 16O3+ irradiation on the critical current densities Jc and flux creep rates in 1.3 μm thick GdBa2Cu3O7-δ coated conductor produced by co-evaporation. Pristine films with pinning produced mainly by random nanoparticles with diameter close to 50 nm were irradiated with doses between 2 × 1013 cm-2 and 4 × 1014 cm-2. The irradiations were performed with the ion beam perpendicular to the surface of the samples. The Jc and the flux creep rates were analyzed for two magnetic field configurations: magnetic field applied parallel (H║c) and at 45° (H║45°) to the c-axis. The results show that at temperatures below 40 K the in-field Jc dependences can be significantly improved by irradiation. For doses of 1 × 1014 cm-2 the Jc values at μ0H = 5 T are doubled without affecting significantly the Jc at small fields. Analyzing the flux creep rates as function of the temperature in both magnetic field configurations, it can be observed that the irradiation suppresses the peak associated with double-kink relaxation and increases the flux creep rates at intermediate and high temperatures. Under 0.5 T, the flux relaxation for H‖c and H||45° in pristine films presents characteristic glassy exponents μ = 1.63 and μ = 1.45, respectively. For samples irradiated with 1 × 1014 cm-2, these values drop to μ = 1.45 and μ = 1.24, respectively

Optimization for high-dose-rate brachytherapy of cervical cancer with adaptive simulated annealing and gradient descent.

PubMed

Yao, Rui; Templeton, Alistair K; Liao, Yixiang; Turian, Julius V; Kiel, Krystyna D; Chu, James C H

2014-01-01

To validate an in-house optimization program that uses adaptive simulated annealing (ASA) and gradient descent (GD) algorithms and investigate features of physical dose and generalized equivalent uniform dose (gEUD)-based objective functions in high-dose-rate (HDR) brachytherapy for cervical cancer. Eight Syed/Neblett template-based cervical cancer HDR interstitial brachytherapy cases were used for this study. Brachytherapy treatment plans were first generated using inverse planning simulated annealing (IPSA). Using the same dwell positions designated in IPSA, plans were then optimized with both physical dose and gEUD-based objective functions, using both ASA and GD algorithms. Comparisons were made between plans both qualitatively and based on dose-volume parameters, evaluating each optimization method and objective function. A hybrid objective function was also designed and implemented in the in-house program. The ASA plans are higher on bladder V75% and D2cc (p=0.034) and lower on rectum V75% and D2cc (p=0.034) than the IPSA plans. The ASA and GD plans are not significantly different. The gEUD-based plans have higher homogeneity index (p=0.034), lower overdose index (p=0.005), and lower rectum gEUD and normal tissue complication probability (p=0.005) than the physical dose-based plans. The hybrid function can produce a plan with dosimetric parameters between the physical dose-based and gEUD-based plans. The optimized plans with the same objective value and dose-volume histogram could have different dose distributions. Our optimization program based on ASA and GD algorithms is flexible on objective functions, optimization parameters, and can generate optimized plans comparable with IPSA. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Incorporating information from the U.S. Department of Energy low-dose program into regulatory decision-making: three policy integration challenges.

PubMed

Locke, Paul A

2009-11-01

The U.S. Department of Energy (U.S. DOE) sponsors a research program aimed at gaining a better understanding of how low-dose radiation affects cellular functioning and progression toward disease. There have been calls to incorporate into regulatory decision-making the scientific information that this program has produced. After a discussion of the evolution of radiation protection law and the weight-of-evidence approach that agencies employ, this paper offers some preliminary thoughts about how to approach this complex and important policy question. Three implementation challenges are identified and discussed. The first implementation challenge involves explaining low-dose effects in a systems biology model. The second challenge arises when issues of population susceptibility are juxtaposed against molecular and mechanistic studies, such as those that make up much of the U.S. DOE low-dose program. The third challenge concerns integrating the results of radiation epidemiology, especially epidemiologic studies among cohorts that are exposed to low dose and low-dose rate radiation, with the results of U.S. DOE low-dose studies.

Down-regulation of tryptamine binding sites following chronic molindone administration. A comparison with responses of dopamine and 5-hydroxytryptamine receptors.

PubMed

Nguyen, T V; Juorio, A V

1989-10-01

The present study assessed changes of tryptamine, dopamine D2, 5-HT1 and 5-HT2 binding sites in rat brain following chronic treatment with low (5 mg/kg/day) and high (40 mg/kg/day) doses of molindone, a clinically effective psychotropic drug. The high-dose molindone treatment produced a decrease in the number of tryptamine binding sites while both high and low doses caused an increase in the number of dopamine D2 binding sites in the striatum. No significant changes were observed in either 5-HT1 or 5-HT2 binding sites in the cerebral cortex. Competition binding experiments showed that molindone was a potent inhibitor at dopamine D2 but less effective at tryptamine, 5-HT1 and 5-HT2 binding sites. The inhibition activity of molindone towards type A monoamine oxidase produced a significant increase in endogenous tryptamine accumulation rate which was much higher than that of dopamine and 5-HT. These findings suggest that the reduction in the number of tryptamine binding sites produced by chronic molindone administration is related to monoamine oxidase inhibition and that the increase in the number of dopamine D2 binding sites is correlated to receptor blocking activity of the drug.

Fenoterol delivery by Respimat soft mist inhaler versus CFC metered dose inhaler: cumulative dose-response study in asthma patients.

PubMed

Vincken, Walter; Dewberry, Helen; Moonen, Diane

2003-09-01

Respimat (RMT) soft mist inhaler (SMI) is a novel, propellant-free alternative to chlorofluorocarbon metered-dose inhalers (CFC-MDIs). The aim of this study was to evaluate the safety and establish the equipotent dose of fenoterol delivered by RMT SMI vs. a conventional MDI. Double-blind, randomized, crossover, comparative study between fenoterol inhaled via RMT (either 50 microg/actuation, RMT50; or 100 microg/actuation. RMT100) and MDI (100 microg/actuation; MDI100). A total of 41 asthma patients received cumulative doses of fenoterol 600 microg (RMT50) or 1200 microg (RMT100 and MDI100) on 3 test days. The bronchodilator response (forced expiratory volume in 1 second [FEV1]) was considered therapeutically equivalent (i.e., noninferior) if the 95% confidence intervals for the difference in their mean changes from baseline were within limits of +/- 0.15L. Systemic exposure was evaluated from plasma fenoterol levels. Adverse events (AEs) were recorded. RMT50 and RMT100 produced noninferior bronchodilatation to MDI100 from 30minutes after the first dose. RMT50 showed equivalent safety and tolerability to MDI100, whereas RMT100 produced a higher incidence of AEs, a significantly greater plasma potassium reduction and a significant increase in pulse rate. Fenoterol plasma levels were twice as high with RMT100 as with RMT50 or MDI100. CONCLUSIONS; The nominal dose of fenoterol administered via RMT SMI can be at least halved to achieve equivalent efficacy, safety, and tolerability to a MDI.

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

PubMed

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

2015-08-01

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

Uranyl sulfate irradiations at the Van de Graaff: A means to combat uranyl peroxide precipitation

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

Youker, Amanda J.; Kalensky, Michael; Quigley, Kevin J.

As part of an effort to support SHINE Medical Technologies in developing a process to produce Mo-99 by neutron-induced fission, a series of irradiation experiments was performed with a 3 MeV Van de Graaff accelerator to generate high radiation doses in 0.5–2 mL uranyl sulfate solutions. The purpose was to determine what conditions result in uranyl peroxide precipitation and what can be done to prevent its formation. The effects of temperature, dose rate, uranium concentration, and the addition of known catalysts for the destruction of peroxide were determined.

Two dose Augmentin treatment of acute gonorrhoea in men.

PubMed Central

Lim, K B; Rajan, V S; Giam, Y C; Lui, E O; Sng, E H; Yeo, K L

1984-01-01

We studied 192 men with acute gonococcal urethritis, 97 of whom received two oral doses of Augmentin (amoxycillin 3 g and clavulanic acid 250 mg) separated by a four hour interval; the remaining 95 received 2 g kanamycin in a single intramuscular injection. Of the patients treated with Augmentin, 93 (95.9%) were cured, which was significantly more than the 83 (87.4%) patients treated with kanamycin. Augmentin was equally effective in the treatment of penicillinase producing Neisseria gonorrhoeae (PPNG) and non-PPNG infections, the cure rates for which were 96.6% and 95.6% respectively. PMID:6428699

Setup and Calibration of SLAC's Peripheral Monitoring Stations

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

Cooper, C.

2004-09-03

The goals of this project were to troubleshoot, repair, calibrate, and establish documentation regarding SLAC's (Stanford Linear Accelerator Center's) PMS (Peripheral Monitoring Station) system. The PMS system consists of seven PMSs that continuously monitor skyshine (neutron and photon) radiation levels in SLAC's environment. Each PMS consists of a boron trifluoride (BF{sub 3}) neutron detector (model RS-P1-0802-104 or NW-G-20-12) and a Geiger Moeller (GM) gamma ray detector (model TGM N107 or LND 719) together with their respective electronics. Electronics for each detector are housed in Nuclear Instrument Modules (NIMs) and are plugged into a NIM bin in the station. All communicationmore » lines from the stations to the Main Control Center (MCC) were tested prior to troubleshooting. To test communication with MCC, a pulse generator (Systron Donner model 100C) was connected to each channel in the PMS and data at MCC was checked for consistency. If MCC displayed no data, the communication cables to MCC or the CAMAC (Computer Automated Measurement and Control) crates were in need of repair. If MCC did display data, then it was known that the communication lines were intact. All electronics from each station were brought into the lab for troubleshooting. Troubleshooting usually consisted of connecting an oscilloscope or scaler (Ortec model 871 or 775) at different points in the circuit of each detector to record simulated pulses produced by a pulse generator; the input and output pulses were compared to establish the location of any problems in the circuit. Once any problems were isolated, repairs were done accordingly. The detectors and electronics were then calibrated in the field using radioactive sources. Calibration is a process that determines the response of the detector. Detector response is defined as the ratio of the number of counts per minute interpreted by the detector to the amount of dose equivalent rate (in mrem per hour, either calculated or measured). Detector response for both detectors is dependent upon the energy of the incident radiation; this trend had to be accounted for in the calibration of the BF{sub 3} detector. Energy dependence did not have to be taken into consideration when calibrating the GM detectors since GM detector response is only dependent on radiation energy below 100 keV; SLAC only produces a spectrum of gamma radiation above 100 keV. For the GM detector, calibration consisted of bringing a {sup 137}Cs source and a NIST-calibrated RADCAL Radiation Monitor Controller (model 9010) out to the field; the absolute dose rate was determined by the RADCAL device while simultaneously irradiating the GM detector to obtain a scaler reading corresponding to counts per minute. Detector response was then calculated. Calibration of the BF{sub 3} detector was done using NIST certified neutron sources of known emission rates and energies. Five neutron sources ({sup 238}PuBe, {sup 238}PuB, {sup 238}PuF4, {sup 238}PuLi and {sup 252}Cf) with different energies were used to account for the energy dependence of the response. The actual neutron dose rate was calculated by date-correcting NIST source data and considering the direct dose rate and scattered dose rate. Once the total dose rate (sum of the direct and scattered dose rates) was known, the response vs. energy curve was plotted. The first station calibrated (PMS6) was calibrated with these five neutron sources; all subsequent stations were calibrated with one neutron source and the energy dependence was assumed to be the same.« less

Cortisol Release in Response to UVB Exposure in Xiphophorus Fish

PubMed Central

Contreras, Adam J.; Boswell, Mikki; Downs, Kevin P.; Pasquali, Amanda; Walter, Ronald B.

2014-01-01

Xiphophorus fishes are comprised of 26 known species. Interspecies hybridization between select species has been utilized to produce experimental models to study melanoma development. Xiphophorus melanoma induction protocols utilize ultraviolet light (UVB) to induce DNA damage and associated downstream tumorigenesis. However, the impact of induced stress caused by the UVB treatment of the experimental animals undergoing tumor induction protocols has not been assessed. Stress is an adaptive physiological response to excessive or unpredictable environmental stimuli. The stress response in fishes may be measured by assay of cortisol released into the water. Here, we present results from investigations of stress response during experimental treatment and UVB exposure in X. maculatus Jp 163 B, X. couchianus, and F1 interspecies hybrids produced from the mating X. maculatus Jp 163 B x X. couchianus. Overall, cortisol release rates for males and females after UVB exposure showed no statistical differences. At lower UVB doses (8 and 16 kJ/m2), X. couchianus exhibited 2 fold higher levels of DNA damage then either X. maculatus or the F1 hybrid. However, based on cortisol release rates, none of the fish types tested induced a primary stress response at the UVB lower doses (8 and 16 kJ/m2). In contrast, at a very high UVB dose (32 kJ/m2) both X. maculatus and the F1 hybrid showed a 5 fold increase in cortisol release rate. To determine the effect of pigmentation on UVB induced stress, wild type and albino X. hellerii were exposed to UVB (32 kJ/m2). Albino X. hellerii exhibited 3.7 fold increase in cortisol release while wild type X. hellerii did not exhibit a significant cortisol response to UVB. Overall, the data suggest the rather low UVB doses often employed in tumour induction protocols do not induce a primary stress response in Xiphophorus fishes. PMID:24625568

A comparison of menotropin, highly-purified menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection

PubMed Central

Esteves, Sandro C; Schertz, Joan C; Verza, Sidney; Schneider, Danielle T; Zabaglia, Silval FC

2009-01-01

Background Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency. Methods A retrospective analysis of 865 consecutive intracytoplasmic sperm injection (ICSI) cycles of controlled ovarian hyperstimulation (COH) compared the clinical efficacy of three gonadotropins (menotropin [hMG; n = 299], highly-purified hMG [HP-hMG; n = 330] and follitropin alfa [r-hFSH; n = 236]) for ovarian stimulation after pituitary down-regulation. The endpoints were live birth rates and total doses of gonadotropin per cycle and per pregnancy. Results Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin used, which was introduced sequentially (hMG, then HP-hMG, and finally r-hFSH). Live birth rates were not significantly different for hMG (24.4%), HP-hMG (32.4%) and r-hFSH (30.1%; p = 0.09) groups. Total dose of gonadotropin per cycle was significantly higher in the hMG (2685 +/- 720 IU) and HP-hMG (2903 +/- 867 IU) groups compared with the r-hFSH-group (2268 +/- 747 IU; p < 0.001). Total dose of gonadotropin required to achieve clinical pregnancy was 15.7% and 11.0% higher for the hMG and HP-hMG groups, respectively, compared with the r-hFSH group, and for live births, the differences observed were 45.3% and 19.8%, respectively. Conclusion Although similar live birth rates were achieved, markedly lower doses of r-hFSH were required compared with hMG or HP-hMG. PMID:19828024

[Myocardial electrogenesis in laboratory rats under conditions of acute nitrite intoxication].

PubMed

Shumilova, T E; Shereshkov, V I; Ianvareva, I N; Nozdrachev, A D

2010-01-01

In anesthetized male rats the arterial blood pressure in femoral artery and electrocardiogram in standard leads were recorded uninterruptedly for 1-1.5 h under conditions of acute nitrite intoxication produced by a subcutaneous injection of water solution of sodium nitrite (donor of nitric oxide) at concentrations of 10, 30, and 50 mg/kg body mass. Results of the study have shown dose-dependent changes of arterial pressure as well as of time and amplitude characteristics of electrocardiogram under effect of NaNO2. At the threshold hypoxic dose, an increase of amplitude of R and S waves was observed by the 30-45th min, while at the maximal NaNO2 dose, amplitude of all waves rose by the 15th min of intoxication. High nitric doses often caused an increase of the ST segment above the isoelectric line and a rise of the amplitude of the T wave, on which a notch appeared in some cases. The change of the ECG time parameters was expressed in the dose-dependent development of bradycardia for the first 4-7 min; its level correlated with the progressively decreasing arterial pressure in the beginning (the 2-4th min) of nitrite intoxication. Variation analysis of heart rate spectral characteristics by Baevskii has revealed a rise of the total spectral power of pulse oscillations. Under effect of nitrite, in the spectrum of cardiointervals, quent recovery of the normal ECG spectrum in the end of the experimental period. The maximal nitrite dose produced more pronounced shifts of the heart rate spectrum towards the LF and VLF diapasons that were not restored for 1 h of experiment. Transitory processes of readjustment of the cardiac rhythm had discrete character. The nitrite dose of 50 mg/kg body mass increased the RR-interval after 4-7 min with amplitude steps of 3-5 imp/s and the time constant of 20-40 s. The revealed ECG changes had the reflex (enhancement of parasympathetic tonus) and metabolic (the hypoxic and histotoxic damage of myocardium) nature.

Measurements and PHITS Monte Carlo Estimations of Residual Activities Induced by the 181 MeV Proton Beam in the Injection Area at J-PARC RCS Ring

NASA Astrophysics Data System (ADS)

Yamakawa, Emi; Yoshimoto, Masahiro; Kinsho, Michikazu

At the injection area of the RCS ring in the J-PARC, residual gamma dose at the rectangular ceramic ducts, especially immediately downstream of the charge-exchanged foil, has increased with the output beam power. In order to investigate the cause of high residual activities, residual gamma dose and radioactive sources produced at the exterior surface of the ducts have been measured by a GM survey meter and a handy type of Germanium (Ge) semiconductor detector in the case of 181 MeV injected proton beam energy. With these measurements, it is revealed that the radioactive sources produced by nuclear reactions cause the high activities at the injection area. For a better understanding of phenomena in the injection area, various simulations have been done with the PHITS Monte Carlo code. The distribution of radioactive sources and residual gamma dose rate obtained by the calculations are consistent with the measurement results. With this consistency, secondary neutrons and protons derived from nuclear reactions at the charge-exchanged foil are the dominant cause to high residual gamma dose at the ceramic ducts in the injection area. These measurements and calculations are unique approaches to reveal the cause of high residual dose around the foil. This study is essential for the future of high-intensity proton accelerators using a stripping foil.

Toxicity of hydroxyurea in rats and dogs.

PubMed

Morton, Daniel; Reed, Lori; Huang, Wenhu; Marcek, John M; Austin-LaFrance, Robert; Northcott, Carrie A; Schelling, Scott H; Enerson, Bradley E; Tomlinson, Lindsay

2015-06-01

The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascular, and gastrointestinal toxicity with steep dose response curves. In rats dosed for 10 days, 50 mg/kg/day was tolerated; 500 mg/kg/day produced decreased body weight gain; decreased circulating leukocytes, erythrocytes, and platelets; decreased cellularity of thymus, lymph nodes, and bone marrow; and epithelial degeneration and/or dysplasia of the stomach and small intestine; 1,500 mg/kg/day resulted in deaths on day 5. In dogs, a single dose at ≥ 250 mg/kg caused prostration leading to unscheduled euthanasia. Dogs administered 50 mg/kg/day for 1 month had decreased circulating leukocytes, erythrocytes, and platelets; increased bone marrow cellularity with decreased maturing granulocytes; increased creatinine kinase activity; and increased iron pigment in bone marrow and hepatic sinusoidal cells. In telemetered dogs, doses ≥ 15 mg/kg decreased systolic blood pressure (BP); 50 mg/kg increased diastolic BP, heart rate, and change in blood pressure over time (+dP/dt), and decreased QT and PR intervals and maximum left ventricular systolic and end diastolic pressures with measures returning to control levels within 24 hr. © 2014 by The Author(s).

The interaction of natural background gamma radiation with depleted uranium micro-particles in the human body.

PubMed

Pattison, John E

2013-03-01

In this study, some characteristics of the photo-electrons produced when natural background gamma radiation interacts with micron-sized depleted uranium (DU) particles in the human body have been estimated using Monte Carlo simulations. In addition, an estimate has been made of the likelihood of radiological health effects occurring due to such an exposure. Upon exposure to naturally occurring background gamma radiation, DU particles in the body will produce an enhancement of the dose to the tissue in the immediate vicinity of the particles due to the photo-electric absorption of the radiation in the particle. In this study, the photo-electrons produced by a 10 μm-size particle embedded in tissue at the centre of the human torso have been investigated. The mean energies of the photo-electrons in the DU particle and in the two consecutive immediately surrounding 2 μm-wide tissue shells around the particle were found to be 38, 49 and 50 keV, respectively, with corresponding ranges of 1.3, 38 and 39 μm, respectively. The total photo-electron fluence-rates in the two consecutive 2 μm-wide tissue layers were found to be 14% and 7% of the fluence-rate in the DU particle, respectively. The estimated dose enhancement due to one 10 μm-sized DU particle in 1 cm(3) of tissue was less than 2 in 10 million of the dose received by the tissue without a particle being present. The increase in risk of death from cancer due to this effect is consequently insignificant.

Transmutation and activation of reduced activation ferritic martensitic steel in molten salt cooled fusion power plants

NASA Astrophysics Data System (ADS)

Cheng, E. T.

2004-08-01

Neutron activation analysis was conducted for the reduced activation ferritic/martensitic (RAFM) steel used in flibe molten-salt cooled fusion blankets. After 22.4 MW yr/m 2 of neutron exposure, the RAFM steel first wall in a molten salt blanket with 40% lithium-6 enrichment in lithium was found to be within 1 mSv/h in contact dose rate after 100 yr of cooling. The contact dose rate drops to 30 and 20 μSv/h or less, respectively, when the cooling times are 300 and 500 yr after discharge. The RAFM steel discharged from the high-temperature shield component would be allowed for hands-on recycling after 100 yr of cooling, when the contact dose rate is 10 μSv/h or less. The most significant changes found in the RAFM steel first wall due to nuclear transmutation, are 10% decrease in W and 10% increase in Ti. Additionally, there are minor elements produced: Mn - <1.2%, V - <0.26%, Re - <0.2%, Ta - <0.08%, and Os - <0.1%, all in weight percent. The gaseous elements generated are H and He, and the, respectively, accumulated quantities are about 260 and 190 wppm.

Repeated chlorpromazine administration increases a behavioural response of rats to 5-hydroxytryptamine receptor stimulation.

PubMed Central

Green, A R

1977-01-01

1 The hyperactivity syndrome produced in rats by administration of tranylcypromine (20 mg/kg i.p.) followed 30 min later by L-tryptophan (50 mg/kg i.p.) is generally considered to be due to increased 5-hydroxytryptamine (5-HT) functional activity. It is inhibited by chlorpromazine (30 mg/kg i.p.) injected 60 min before the tranylcypromine. However, chlorpromazine injection for 4 days either at a dose of 30 mg/kg once daily or 5 mg/kg twice daily results in an enhanced hyperactivity response to tranylcypromine and L-tryptophan administration 24 h after the final dose of chlorpromazine. 2 One injection of chlorpromazine (30 mg/kg) did not produce enhancement 24 h later and the inhibition of the tranylcypromine/L-tryptophan hyperactivity observed after acute chlorpromazine injection was seen if the rats were given tranylcypromine and L-tryptophan 1 h after the fourth chlorpromazine (30 mg/kg) dose. 3 Chlorpromazine (30 mg/kg) once daily or 5 mg/kg twice daily for 4 days resulted in rats displaying enhanced behavioral responses to the suggested 5-HT agonist 5-methoxy N,N-dimethyltryptamine (2 mg/kg) on day 5. 4 Chlorpromazine (30 mg/kg) once daily for 4 days produces a slight increase in brain 5-hydroxytryptamine (5-HT) concentration on day 5, but no difference in the rate of brain 5-HT synthesis or the rate of 5-HT accumulation after tranylcypromine and L-tryptophan administration. 5. There is some evidence that chlorpromazine blocks 5-HT receptors. It has also been observed that several other neuroleptic drugs do not produce enhanced 5-HT responses after repeated administration. It is suggested therefore that the enhanced behavioural response to 5-HT receptor stimulation following repeated chlorpromazine administration may be because this drug blocks 5-HT receptors. PMID:264797

Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.

PubMed Central

Bauer, K G; Kaik, B; Sertl, K; Kaik, G A

1993-01-01

1. The airway and tremor response and cardiovascular and hypokalaemic effects of single and cumulative doses of fenoterol given by dry powder capsules (DPC) and by metered dose inhaler (MDI) were studied in asthmatics in two randomized, crossover trials. 2. Single doses of fenoterol DPC and MDI (0.2 mg, 0.4 mg), investigated in 24 subjects, produced similar, dose-dependent increases in FEV1. Fenoterol DPC caused less tremor response and less hypokalaemic effects than fenoterol MDI. 3. Cumulative doses of fenoterol DPC and MDI (0.2, 0.6, 1.4, 3.0, 6.2 mg), investigated in 12 subjects, produced a comparable bronchodilatation (mean maximum increase in FEV1 was 0.53 +/- 0.06/0.52 +/- 0.081 for DPC/MDI) and a similar, dose-dependent rise in heart rate (35 +/- 3.81/41 +/- 2.25 beats min(-1)). The rise in tremor and the fall in plasma potassium were smaller after DPC than after MDI. The mean maximum changes were 51.58 +/- 6.41/95.83 +/- 6.75 cm s(-2) for tremor and -0.68 +/- 0.09/-0.96 +/- 0.10 mmol l(-1) for potassium. 4. Our findings may result from a difference in the pharmacokinetics of the dry powder and the aerosol formulation, particularly differences in distribution and absorption. 5. In conclusion, fenoterol DPC used in low therapeutic doses (0.2,0.4 mg), is preferable to the MDI. Fenoterol DPC used as rescue medication in high cumulative doses, do not suggest a greater safety margin than the MDI and the same restrictions should be considered for the fenoterol dry powder formulation as suggested for the MDI. PMID:12959305

Microchemical and microstructural evolution of AISI 304 stainless steel irradiated in EBR-II at PWR-relevant dpa rates

NASA Astrophysics Data System (ADS)

Dong, Y.; Sencer, B. H.; Garner, F. A.; Marquis, E. A.

2015-12-01

AISI 304 stainless steel was irradiated at 416 °C and 450 °C at a 4.4 × 10-9 and 3.05 × 10-7 dpa/s to ∼0.4 and ∼28 dpa, respectively, in the reflector of the EBR-II fast reactor. Both unirradiated and irradiated conditions were examined using standard and scanning transmission electron microscopy, energy dispersive spectroscopy, and atom probe tomography on very small specimens produced by focused ion beam milling. These results are compared with previous electron microscopy examination of 3 mm disks from essentially the same material. By comparing a very low dose specimen with a much higher dose specimen, both derived from a single reactor assembly, it has been demonstrated that the coupled microstructural and microchemical evolution of dislocation loops and other sinks begins very early, with elemental segregation producing at these sinks what appears to be measurable precursors to fully formed precipitates found at higher doses. The nature of these sinks and their possible precursors are examined in detail.

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

NASA Astrophysics Data System (ADS)

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

1995-01-01

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

SU-E-T-238: Monte Carlo Estimation of Cerenkov Dose for Photo-Dynamic Radiotherapy

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

Chibani, O; Price, R; Ma, C

Purpose: Estimation of Cerenkov dose from high-energy megavoltage photon and electron beams in tissue and its impact on the radiosensitization using Protoporphyrine IX (PpIX) for tumor targeting enhancement in radiotherapy. Methods: The GEPTS Monte Carlo code is used to generate dose distributions from 18MV Varian photon beam and generic high-energy (45-MV) photon and (45-MeV) electron beams in a voxel-based tissueequivalent phantom. In addition to calculating the ionization dose, the code scores Cerenkov energy released in the wavelength range 375–425 nm corresponding to the pick of the PpIX absorption spectrum (Fig. 1) using the Frank-Tamm formula. Results: The simulations shows thatmore » the produced Cerenkov dose suitable for activating PpIX is 4000 to 5500 times lower than the overall radiation dose for all considered beams (18MV, 45 MV and 45 MeV). These results were contradictory to the recent experimental studies by Axelsson et al. (Med. Phys. 38 (2011) p 4127), where Cerenkov dose was reported to be only two orders of magnitude lower than the radiation dose. Note that our simulation results can be corroborated by a simple model where the Frank and Tamm formula is applied for electrons with 2 MeV/cm stopping power generating Cerenkov photons in the 375–425 nm range and assuming these photons have less than 1mm penetration in tissue. Conclusion: The Cerenkov dose generated by high-energy photon and electron beams may produce minimal clinical effect in comparison with the photon fluence (or dose) commonly used for photo-dynamic therapy. At the present time, it is unclear whether Cerenkov radiation is a significant contributor to the recently observed tumor regression for patients receiving radiotherapy and PpIX versus patients receiving radiotherapy only. The ongoing study will include animal experimentation and investigation of dose rate effects on PpIX response.« less

Effect of transfusional iron intake on response to chelation therapy in beta-thalassemia major.

PubMed

Cohen, Alan R; Glimm, Ekkehard; Porter, John B

2008-01-15

The success of chelation therapy in controlling iron overload in patients with thalassemia major is highly variable and may partly depend on the rate of transfusional iron loading. Using data from the 1-year phase III study of deferasirox, including volumes of transfused red blood cells and changes in liver iron concentration (LIC) in 541 patients, the effect of iron loading on achieving neutral or negative iron balance was assessed in patients receiving different doses of deferasirox and the comparator deferoxamine. After dose adjustment, reductions in LIC after 1 year of deferasirox or deferoxamine therapy correlated with transfusional iron intake. At a deferasirox dose of 20 mg/kg per day, neutral or negative iron balance was achieved in 46% and 75% of patients with the highest and lowest transfusional iron intake, respectively; 30 mg/kg per day produced successful control of iron stores in 96% of patients with a low rate of transfusional iron intake. Splenectomized patients had lower transfusional iron intake and greater reductions in iron stores than patients with intact spleens. Transfusional iron intake should be monitored on an ongoing basis in thalassemia major patients, and the rate of transfusional iron loading should be considered when choosing the appropriate dose of an iron-chelating agent. This study is registered at http://clinicaltrials.gov as NCT00061750.

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

PubMed Central

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

2018-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2013-11-01

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

Amphetamine self-administration in light and moderate drinkers.

PubMed

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

2011-03-01

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

Radiation-quality dependent cellular response in mutation induction in normal human cells.

PubMed

Suzuki, Masao; Tsuruoka, Chizuru; Uchihori, Yukio; Kitamura, Hisashi; Liu, Cui Hua

2009-09-01

We studied cellular responses in normal human fibroblasts induced with low-dose (rate) or low-fluence irradiations of different radiation types, such as gamma rays, neutrons and high linear energy transfer (LET) heavy ions. The cells were pretreated with low-dose (rate) or low-fluence irradiations (approximately 1 mGy/7-8 h) of 137Cs gamma rays, 241Am-Be neutrons, helium, carbon and iron ions before irradiations with an X-ray challenging dose (1.5 Gy). Helium (LET = 2.3 keV/microm), carbon (LET = 13.3 keV/microm) and iron (LET = 200 keV/microm) ions were produced by the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. No difference in cell-killing effect, measured by a colony forming assay, was observed among the pretreatment with different radiation types. In mutation induction, which was detected in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus to measure 6-thioguanine resistant clones, there was no difference in mutation frequency induced by the X-ray challenging dose between unpretreated and gamma-ray pretreated cells. In the case of the pretreatment of heavy ions, X-ray-induced mutation was around 1.8 times higher in helium-ion pretreated and 4.0 times higher in carbon-ion pretreated cells than in unpretreated cells (X-ray challenging dose alone). However, the mutation frequency in cells pretreated with iron ions was the same level as either unpretreated or gamma-ray pretreated cells. In contrast, it was reduced at 0.15 times in cells pretreated with neutrons when compared to unpretreated cells. The results show that cellular responses caused by the influence of hprt mutation induced in cells pretreated with low-dose-rate or low-fluence irradiations of different radiation types were radiation-quality dependent manner.

Performance characteristics of the MIT fission converter based epithermal neutron beam.

PubMed

Riley, K J; Binns, P J; Harling, O K

2003-04-07

A pre-clinical characterization of the first fission converter based epithermal neutron beam (FCB) designed for boron neutron capture therapy (BNCT) has been performed. Calculated design parameters describing the physical performance of the aluminium and Teflon filtered beam were confirmed from neutron fluence and absorbed dose rate measurements performed with activation foils and paired ionization chambers. The facility currently provides an epithermal neutron flux of 4.6 x 10(9) n cm(-2) s(-1) in-air at the patient position that makes it the most intense BNCT source in the world. This epithermal neutron flux is accompanied by very low specific photon and fast neutron absorbed doses of 3.5 +/- 0.5 and 1.4 +/- 0.2 x 10(-13) Gy cm2, respectively. A therapeutic dose rate of 1.7 RBE Gy min(-1) is achievable at the advantage depth of 97 mm when boronated phenylalanine (BPA) is used as the delivery agent, giving an average therapeutic ratio of 5.7. In clinical trials of normal tissue tolerance when using the FCB, the effective prescribed dose is due principally to neutron interactions with the nonselectively absorbed BPA present in brain. If an advanced compound is considered, the dose to brain would instead be predominately from the photon kerma induced by thermal neutron capture in hydrogen and advantage parameters of 0.88 Gy min(-1), 121 mm and 10.8 would be realized for the therapeutic dose rate, advantage depth and therapeutic ratio, respectively. This study confirms the success of a new approach to producing a high intensity, high purity epithermal neutron source that attains near optimal physical performance and which is well suited to exploit the next generation of boron delivery agents.

EXOMARS IRAS (DOSE) radiation measurements.

NASA Astrophysics Data System (ADS)

Federico, C.; Di Lellis, A. M.; Fonte, S.; Pauselli, C.; Reitz, G.; Beaujean, R.

The characterization and the study of the radiations on their interaction with organic matter is of great interest in view of the human exploration on Mars. The Ionizing RAdiation Sensor (IRAS) selected in the frame of the ExoMars/Pasteur ESA mission is a lightweight particle spectrometer combining various techniques of radiation detection in space. It characterizes the first time the radiation environment on the Mars surface, and provide dose and dose equivalent rates as precursor information absolutely necessary to develop ways to mitigate the radiation risks for future human exploration on Mars. The Martian radiation levels are much higher than those found on Earth and they are relatively low for space. Measurements on the surface will show if they are similar or not to those seen in orbit (modified by the presence of ``albedo'' neutrons produced in the regolith and by the thin Martian atmosphere). IRAS consists of a telescope based on segmented silicon detectors of about 40\\userk\\milli\\metre\\user;k diameter and 300\\user;k\\micro\\metre\\user;k thickness, a segmented organic scintillator, and of a thermoluminescence dosimeter. The telescope will continuously monitor temporal variation of the particle count rate, the dose rate, particle and LET (Linear Energy Transfer) spectra. Tissue equivalent BC430 scintillator material will be used to measure the neutron dose. Neutrons are selected by a criteria requiring no signal in the anti-coincidence. Last, the passive thermoluminescence dosimeter, based on LiF:Mg detectors, regardless the on board operation timing, will measure the total dose accumulated during the exposure period and due to beta and gamma radiation, with a responsivity very close to that of a human tissue.

Adaptation and validation of a commercial head phantom for cranial radiosurgery dosimetry end-to-end audit.

PubMed

Dimitriadis, Alexis; Palmer, Antony L; Thomas, Russell A S; Nisbet, Andrew; Clark, Catharine H

2017-06-01

To adapt and validate an anthropomorphic head phantom for use in a cranial radiosurgery audit. Two bespoke inserts were produced for the phantom: one for providing the target and organ at risk for delineation and the other for performing dose measurements. The inserts were tested to assess their positional accuracy. A basic treatment plan dose verification with an ionization chamber was performed to establish a baseline accuracy for the phantom and beam model. The phantom and inserts were then used to perform dose verification measurements of a radiosurgery plan. The dose was measured with alanine pellets, EBT extended dose film and a plastic scintillation detector (PSD). Both inserts showed reproducible positioning (±0.5 mm) and good positional agreement between them (±0.6 mm). The basic treatment plan measurements showed agreement to the treatment planning system (TPS) within 0.5%. Repeated film measurements showed consistent gamma passing rates with good agreement to the TPS. For 2%-2 mm global gamma, the mean passing rate was 96.7% and the variation in passing rates did not exceed 2.1%. The alanine pellets and PSD showed good agreement with the TPS (-0.1% and 0.3% dose difference in the target) and good agreement with each other (within 1%). The adaptations to the phantom showed acceptable accuracies. The presence of alanine and PSD do not affect film measurements significantly, enabling simultaneous measurements by all three detectors. Advances in knowledge: A novel method for thorough end-to-end test of radiosurgery, with capability to incorporate all steps of the clinical pathway in a time-efficient and reproducible manner, suitable for a national audit.

Atomic Bomb Health Benefits

PubMed Central

Luckey, T. D.

2008-01-01

Media reports of deaths and devastation produced by atomic bombs convinced people around the world that all ionizing radiation is harmful. This concentrated attention on fear of miniscule doses of radiation. Soon the linear no threshold (LNT) paradigm was converted into laws. Scientifically valid information about the health benefits from low dose irradiation was ignored. Here are studies which show increased health in Japanese survivors of atomic bombs. Parameters include decreased mutation, leukemia and solid tissue cancer mortality rates, and increased average lifespan. Each study exhibits a threshold that repudiates the LNT dogma. The average threshold for acute exposures to atomic bombs is about 100 cSv. Conclusions from these studies of atomic bomb survivors are: One burst of low dose irradiation elicits a lifetime of improved health.Improved health from low dose irradiation negates the LNT paradigm.Effective triage should include radiation hormesis for survivor treatment. PMID:19088902

Feasibility study on an integrated AEC-grid device for the optimization of image quality and exposure dose in mammography

NASA Astrophysics Data System (ADS)

Kim, Kyo-Tae; Yun, Ryang-Young; Han, Moo-Jae; Heo, Ye-Ji; Song, Yong-Keun; Heo, Sung-Wook; Oh, Kyeong-Min; Park, Sung-Kwang

2017-10-01

Currently, in the radiation diagnosis field, mammography is used for the early detection of breast cancer. In addition, studies are being conducted on a grid to produce high-quality images. Although the grid ratio of the grid, which affects the scattering removal rate, must be increased to improve image quality, it increases the total exposure dose. While the use of automatic exposure control is recommended to minimize this problem, existing mammography equipment, unlike general radiography equipment, is mounted on the back of a detector. Therefore, the device is greatly affected by the detector and supporting device, and it is difficult to control the exposure dose. Accordingly, in this research, an integrated AEC-grid device that simultaneously performs AEC and grid functions was used to minimize the unnecessary exposure dose while removing scattering, thereby realizing superior image quality.

A 3-lever discrimination procedure reveals differences in the subjective effects of low and high doses of MDMA.

PubMed

Harper, David N; Langen, Anna-Lena; Schenk, Susan

2014-01-01

Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors. A three-lever drug discrimination paradigm was used. Rats were trained to respond on different levers following saline, AMPH (0.5mg/kg, IP) or MDMA (1.5mg/kg, IP) injections. Generalization curves were generated for a range of different doses of both drugs and the effect of the D1-like antagonist, SCH23390 on the discriminative stimulus effects of different doses of MDMA was determined. Rats accurately discriminated MDMA, AMPH and saline. Low doses of MDMA produced almost exclusive responding on the MDMA lever but at doses of 3.0mg/kg MDMA or higher, responding shifted to the AMPH lever. The AMPH response produced by higher doses of MDMA was attenuated by pretreatment with SCH23390. The data suggest that low doses and higher doses of MDMA produce distinct discriminative stimuli. The shift to AMPH-like responding following administration of higher doses of MDMA, and the decrease in this response following administration of SCH23390 suggests a dopaminergic component to the subjective experience of MDMA at higher doses. Copyright © 2013 Elsevier Inc. All rights reserved.

The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

PubMed Central

Heikel, T. A. J.; Lathe, G. H.

1970-01-01

1. The effect of oestrogens and progestogens and their 17α-ethinyl derivatives on bile flow, maximum rate of bilirubin secretion, serum and liver bilirubin has been studied. 2. Both 17α-ethinyl substituted oestrogens and progestogens greatly reduced the basal bile flow. The parent compounds, oestradiol-17β and 19-nortestosterone had little or no effect. 3. A much larger dose of progestogens (40 mg/kg) than oestrogens (5 mg/kg) was needed. 4. Between 12 and 48 h were required for 17α-ethinyloestradiol to produce the effect. 5. Bilirubin maximum secretion rate (Tm) was little affected, the only significant reduction being produced by the 3-methyl ether of 17α-ethinyloestradiol (mestranol). 6. Rises in serum conjugated bilirubin following infusion of bilirubin were produced by 17α-ethinyloestradiol and mestranol but not by the progestogens. PMID:5441412

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

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

2016-06-01

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

An assessment of a 3D EPID-based dosimetry system using conventional two- and three-dimensional detectors for VMAT.

PubMed

Stevens, S; Dvorak, P; Spevacek, V; Pilarova, K; Bray-Parry, M; Gesner, J; Richmond, A

2018-01-01

To provide a 3D dosimetric evaluation of a commercial portal dosimetry system using 2D/3D detectors under ideal conditions using VMAT. A 2D ion chamber array, radiochromic film and gel dosimeter were utilised to provide a dosimetric evaluation of transit phantom and pre-treatment 'fluence' EPID back-projected dose distributions for a standard VMAT plan. In-house 2D and 3D gamma methods compared pass statistics relative to each dosimeter and TPS dose distributions. Fluence mode and transit EPID dose distributions back-projected onto phantom geometry produced 2D gamma pass rates in excess of 97% relative to other tested detectors and exported TPS dose planes when a 3%, 3 mm global gamma criterion was applied. Use of a gel dosimeter within a glass vial allowed comparison of measured 3D dose distributions versus EPID 3D dose and TPS calculated distributions. 3D gamma comparisons between modalities at 3%, 3 mm gave pass rates in excess of 92%. Use of fluence mode was indicative of transit results under ideal conditions with slightly reduced dose definition. 3D EPID back projected dose distributions were validated against detectors in both 2D and 3D. Cross validation of transit dose delivered to a patient is limited due to reasons of practicality and the tests presented are recommended as a guideline for 3D EPID dosimetry commissioning; allowing direct comparison between detector, TPS, fluence and transit modes. The results indicate achievable gamma scores for a complex VMAT plan in a homogenous phantom geometry and contributes to growing experience of 3D EPID dosimetry. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

1990-05-01

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

Effects of peptide YY and neuropeptide Y on gastric emptying in man.

PubMed

Allen, J M; Fitzpatrick, M L; Yeats, J C; Darcy, K; Adrian, T E; Bloom, S R

1984-01-01

Neuropeptide Y (NPY) and peptide YY (PYY) are two structurally related peptides. PYY has been identified within endocrine cells and NPY within nerves of the gastrointestinal tract. Infusion of PYY at a low dose at a nominal rate of 2 pmol/kg/min resulted in an increment of 59.2 +/- 7.1 pmol/1 in plasma concentration and a significant delay in gastric emptying of glucose. Infusion of NPY at the same rate produced similar plasma concentrations (52.5 +/- 1.1 pmol/1) and had no significant effect on the rate of gastric emptying.

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

PubMed

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

2018-06-01

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

Efficacy trial of Vi polysaccharide vaccine against typhoid fever in south-western China.

PubMed Central

Yang, H. H.; Wu, C. G.; Xie, G. Z.; Gu, Q. W.; Wang, B. R.; Wang, L. Y.; Wang, H. F.; Ding, Z. S.; Yang, Y.; Tan, W. S.; Wang, W. Y.; Wang, X. C.; Qin, M.; Wang, J. H.; Tang, H. A.; Jiang, X. M.; Li, Y. H.; Wang, M. L.; Zhang, S. L.; Li, G. L.

2001-01-01

OBJECTIVE: To test the efficacy of locally produced Vi vaccine over a time period of longer than one year. METHODS: A double-blinded, randomized field trial was performed in Guangxi Zhuang Autonomous Region in south-western China, using 30 micrograms doses of locally produced Vi. Enrolled subjects were 3-50 years of age, although the majority (92%) were school-aged children, who have the highest rate of typhoid fever in this setting. A total of 131,271 people were systematically allocated a single dose of 30 micrograms of Vi polysaccharide or saline placebo. The study population was followed for 19 months, with passive surveillance conducted in the Ministry of Health and the Regional Health and Anti-epidemic Centre (HAEC). Clinically suspected cases of typhoid fever were confirmed by blood culture, or by serological reaction with O-antigen (Widal tests). FINDINGS: After 19 months, there were 23 culture-confirmed cases of typhoid fever in the placebo group versus 7 cases in the Vi group (Protective efficacy (PE) = 69%; 95% CI = 28%, 87%). Most of the isolates were from school-aged children: 22 cases in the placebo group versus 6 in the Vi group (PE = 72%; 95% CI = 32%, 82%). No serious post-injection reactions were observed. The locally produced Vi polysaccharide vaccine showed levels of protective efficacy similar to those for Vi vaccine produced in industrial countries. CONCLUSION: The slightly higher dose of vaccine did not seem to alter efficacy significantly in China. PMID:11477965

Meal frequency of pre-exercise carbohydrate feedings.

PubMed

Chryssanthopoulos, C; Petridou, A; Maridaki, M; Mougios, V

2008-04-01

This study compared the effect of single and multiple carbohydrate feedings before exercise on biochemical and physiological responses during exercise. Eight males performed 3 runs for 1 h at 70 % VO(2max) after consuming a meal containing 2.5 g carbohydrate per kg body mass in a single dose 3 h before exercise (SF), the same meal in 5 equal doses at 3, 2.5, 2, 1.5, and 1 h before exercise (MF), or a liquid placebo 3 h before exercise (P). RER and carbohydrate oxidation rates were higher in SF and MF compared to P trials, but there was no difference between SF and MF trials. Pre-exercise insulin was 2.0- and 3.4- fold higher in SF and MF, respectively, compared to P, and 1.7-fold higher in MF compared to SF. Glycerol and NEFA were higher in P compared to SF and MF trials before and at the end of exercise. In conclusion, a carbohydrate meal containing 2.5 g . kg(-1) ingested in doses over 3 h before running produced higher hyperinsulinemia pre-exercise than that produced when the meal was consumed in a single dose. Nevertheless, estimated carbohydrate utilization and adipose tissue lipolysis during exercise after multiple feedings seemed to be as high as after a single feeding.

Combined effects of methamphetamine and zolpidem on performance and mood during simulated night shift work.

PubMed

Hart, Carl L; Haney, Margaret; Nasser, Jennifer; Foltin, Richard W

2005-07-01

Individuals who work irregular or rotating shifts often use stimulants and sedatives to offset shift-change-related mood and performance decrements. During this simulated shift work study the acute effects of the stimulant, methamphetamine were examined, and the effects of the hypnotic, zolpidem, and the combination were assessed during the shift after drug administration. Eight volunteers completed this 21-day, within-participant, residential laboratory study during which they received a single oral methamphetamine dose (0 or 10 mg) 1 h after waking, i.e., before task performance, and a single oral zolpidem dose (0 or 10 mg) 1 h before bedtime under 2 shift conditions: day shift and night shift. When participants received placebo at both dosing times, performance on some psychomotor tasks (e.g., the digit-symbol substitution task) and on some measures of mood (e.g., ratings of "Energetic") were disrupted during the night shift, relative to the day shift. Methamphetamine alone eliminated virtually all shift-related disruptions, while zolpidem alone and the drug combination produced few effects. These data indicate that shift changes produce performance impairments and mood alterations that are improved by a single low to moderate dose of methamphetamine. Zolpidem, given alone or in combination with methamphetamine, did not alleviate most shift-change mood and performance effects.

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

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

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

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

2012-12-01

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

Impact of Radiation Biology on Fundamental Insights in Biology

DOE R&D Accomplishments Database

Setlow, Richard B.

1982-07-27

Research supported by OHER [Office of Health and Environmental Research] and its predecessors has as one of its major goals an understanding of the effects of radiation at low doses and dose rates on biological systems, so as to predict their effects on humans. It is not possible to measure such effects directly. They must be predicted from basic knowledge on how radiation affects cellular components such as DNA and membranes and how cells react to such changes. What is the probability of radiation producing human mutations and what are the probabilities of radiation producing cancer? The end results of such studies are radiation exposure standards for workers and for the general population. An extension of these goals is setting standards for exposure to chemicals involved in various energy technologies. This latter problem is much more difficult because chemical dosimetry is a primitive state compared to radiation dosimetry.

Brachytherapy treatment simulation of strontium-90 and ruthenium-106 plaques on small size posterior uveal melanoma using MCNPX code

NASA Astrophysics Data System (ADS)

Barbosa, N. A.; da Rosa, L. A. R.; Facure, A.; Braz, D.

2014-02-01

Concave eye applicators with 90Sr/90Y and 106Ru/106Rh beta-ray sources are usually used in brachytherapy for the treatment of superficial intraocular tumors as uveal melanoma with thickness up to 5 mm. The aim of this work consisted in using the Monte Carlo code MCNPX to calculate the 3D dose distribution on a mathematical model of the human eye, considering 90Sr/90Y and 160Ru/160Rh beta-ray eye applicators, in order to treat a posterior uveal melanoma with a thickness 3.8 mm from the choroid surface. Mathematical models were developed for the two ophthalmic applicators, CGD produced by BEBIG Company and SIA.6 produced by the Amersham Company, with activities 1 mCi and 4.23 mCi respectively. They have a concave form. These applicators' mathematical models were attached to the eye model and the dose distributions were calculated using the MCNPX *F8 tally. The average doses rates were determined in all regions of the eye model. The *F8 tally results showed that the deposited energy due to the applicator with the radionuclide 106Ru/106Rh is higher in all eye regions, including tumor. However the average dose rate in the tumor region is higher for the applicator with 90Sr/90Y, due to its high activity. Due to the dosimetric characteristics of these applicators, the PDD value for 3 mm water is 73% for the 106Ru/106Rh applicator and 60% for 90Sr/90Y applicator. For a better choice of the applicator type and radionuclide it is important to know the thickness of the tumor and its location.

Evoked changes in cardiovascular function in rats by infusion of levosimendan, OR-1896 [(R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide], OR-1855 [(R)-6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one], dobutamine, and milrinone: comparative effects on peripheral resistance, cardiac output, dP/dt, pulse rate, and blood pressure.

PubMed

Segreti, Jason A; Marsh, Kennan C; Polakowski, James S; Fryer, Ryan M

2008-04-01

Levosimendan enhances cardiac contractility primarily via Ca(2+) sensitization, and it induces vasodilation through the activation of ATP-sensitive potassium channels and large conductance Ca(2+)-activated K(+) channels. However, the concentration-dependent hemodynamic effects of levosimendan and its metabolites (R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide (OR-1896) and (R)-6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (OR-1855) have not been well defined. Thus, levosimendan (0.03, 0.10, 0.30, and 1.0 mumol/kg/30 min; n = 6) was infused as four escalating 30-min i.v. doses targeting therapeutic to supratherapeutic concentrations of levosimendan (C(max), approximately 62.6 ng/ml); metabolites were infused at one-half log-unit lower doses and responses compared to dobutamine (beta(1)-agonist) and milrinone (phosphodiesterase 3 inhibitor). Peak concentrations of levosimendan, OR-1896, and OR-1855 at the end of the high dose were 323 +/- 14, 83 +/- 2, and 6 +/- 2 ng/ml, respectively (OR-1855 rapidly metabolized to OR-1896; peak = 82 +/- 3 ng/ml). Levosimendan and OR-1896 produced dose-dependent reductions in blood pressure and peripheral resistance with a rank potency, based on ED(15) values, of OR-1896 (0.03 mumol/kg) > OR-1855 > levosimendan > milrinone (0.24 mumol/kg); an ED(15) for dobutamine could not be defined. Only dobutamine produced increases in pulse pressure (30 +/- 5%) and rate-pressure product (34 +/- 4%). All of the compounds, with the exception of OR-1855, elicited dose-dependent increases in dP/dt with a rank potency, based on ED(50) values, of dobutamine (0.03 mumol/kg) > levosimendan > OR-1896 > milrinone (0.09 mumol/kg), although only levosimendan produced sustained increases in cardiac output (9 +/- 4%). Thus, levosimendan and OR-1896 are hemodynamically active at sub- to supratherapeutic concentrations (whereas the effects of OR-1855 in the rat are thought to be predominantly mediated by conversion to OR-1896) and produce direct inotropic effects and also direct relaxation of the peripheral vasculature, which clearly differentiates them from dobutamine, which does not elicit K(+) channel activation, suggesting a more balanced effect on the cardiac-contractile state and K(+) channel-mediated changes in vascular resistance.

Hollow-Fiber Pharmacodynamic Studies and Mathematical Modeling To Predict the Efficacy of Amoxicillin for Anthrax Postexposure Prophylaxis in Pregnant Women and Children

PubMed Central

VanScoy, Brian; Liu, Weiguo; Kulawy, Robert; Drusano, G. L.

2013-01-01

Amoxicillin is considered an option for postexposure prophylaxis of Bacillus anthracis in pregnant and postpartum women who are breastfeeding and in children because of the potential toxicities of ciprofloxacin and doxycycline to the fetus and child. The amoxicillin regimen that effectively kills B. anthracis and prevents resistance is unknown. Fourteen-day dose range and dose fractionation studies were conducted in in vitro pharmacodynamic models to identify the exposure intensity and pharmacodynamic index of amoxicillin that are linked with optimized killing of B. anthracis and resistance prevention. Studies with dicloxacillin, a drug resistant to B. anthracis beta-lactamase, evaluated the role of beta-lactamase production in the pharmacodynamic indices for B. anthracis killing and resistance prevention. Dose fractionation studies showed that trough/MIC and not time above MIC was the index for amoxicillin that was linked to successful outcome through resistance prevention. Failure of amoxicillin regimens was due to inducible or stable high level expression of beta-lactamases. Studies with dicloxacillin demonstrated that a time above MIC of ≥94% was linked with treatment success when B. anthracis beta-lactamase activity was negated. Recursive partitioning analysis showed that amoxicillin regimens that produced peak concentrations of <10.99 μg/ml and troughs of >1.75 μg/ml provided a 100% success rate. Other amoxicillin peak and trough values produced success rates of 28 to 67%. For postpartum and pregnant women and children, Monte Carlo simulations predicted success rates for amoxicillin at 1 g every 8 h (q8h) of 53, 33, and 44% (30 mg/kg q8h), respectively. We conclude that amoxicillin is suboptimal for postexposure prophylaxis of B. anthracis in pregnant and postpartum women and in children. PMID:24041894

Fractionated gemtuzumab ozogamicin and standard dose cytarabine produced prolonged second remissions in patients over the age of 55 years with acute myeloid leukemia in late first relapse.

PubMed

Pilorge, Sylvain; Rigaudeau, Sophie; Rabian, Florence; Sarkozy, Clémentine; Taksin, Anne L; Farhat, Hassan; Merabet, Fathia; Ghez, Stéphanie; Raggueneau, Victoria; Terré, Christine; Garcia, Isabelle; Renneville, Aline; Preudhomme, Claude; Castaigne, Sylvie; Rousselot, Philippe

2014-04-01

Gemtuzumab ozogamicin (fGO), a humanized anti-CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥ 6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m², days 1, 4, 7) with standard-dose cytarabine (200 mg/m² /day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty-four patients (median age 68 years) received fGO with cytarabine. Median follow-up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two-year overall survival (OS) was 51% (95% CI: 28-69) and 2 years relapse-free survival (RFS) was 51% (95%CI: 25-72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse. Copyright © 2013 Wiley Periodicals, Inc.

[Epidemiologic and therapeutic study on gonococcal infections--clinical efficacy of cefetamet pivoxil].

PubMed

Nishimura, M; Kumamoto, Y; Hirose, T; Hayashi, K; Tsukamoto, T; Gohro, T; Ikegaki, S; Kamito, H; Inoke, T; Henmi, I

1990-07-01

We studied the epidemiology of 109 cases of gonococcal infections (105 males with urethritis and 4 females with cervicitis), together with the basic and clinical effects of cefetamet pivoxil in the cases. The peak of age distribution of the male patients was in the younger half of their twenties, and all of the 4 female cases were between 20 and 39 years old. The major source of infections in the males younger than 25 years old was their girl friends or so-called pick-up friends, and that of the males older than 25 years old workers serving at an amusement center, for example, bars and so-called special massage parlor, which accounted for about three fourths of the male cases between 35 and 44 years old. The distribution of the MIC (inoculum size; 10(6) CFU/ml) of Cefetamet against beta-lactamase non penicillinase producing Neisseria gonorrhoeae (non-PPNG) ranged from 0.025 to 0.1 microgram/ml and that against beta-lactamase producing Neisseria gonorrhoeae ranged from 0.025 to 0.05 microgram/ml. The isolation rate of PPNG was 10.2% (9/88). In male patients with gonococcal urethritis, the efficacy rate was 100% on days 3 and 7 for 1,000 mg single dose and 7-day treatment and 500 mg single dose treatment. One of the cases treated with 250 mg single dose therapy was unchanged at 3, but the efficacy rate of the remaining cases was 100% at day 7. Complicated urethritis with C. trachomatis was noticed in 25.7% (5/105) of the male urethritis and in 25.0% (1/4) of the female cervicitis cases. The only side effect was diarrhea observed in 1 of the 124 case (0.8%).

Effects of denopamine (TA-064), a new positive inotropic agent, on myocardial oxygen consumption and left ventricular dimension in anesthetized dogs.

PubMed

Ikeo, T; Nagao, T

1985-10-01

We compared the effects of denopamine (TA-064) and isoproterenol on hemodynamics, myocardial oxygen consumption and the left ventricular (LV) dimension in halothane-N2O anesthetized dogs. Denopamine (0.25-1 micrograms/kg/min, i.v., infusion X 15 min) produced a maximum increase in LV dp/dtmax by 64% of the control, without affecting aortic pressure significantly. Doses of isoproterenol (0.01-0.04 micrograms/kg/min, i.v., infusion X 15 min) were selected to produce a positive inotropic action similar to that of denopamine. Denopamine produced significantly less increasing effects in heart rate, cardiac output and myocardial oxygen consumption and had more reducing effects in LV internal diameter than isoproterenol, while isoproterenol tended to produce a more potent increase in coronary blood flow, but a smaller decrease in LV end-diastolic pressure than denopamine. PQ interval was similarly reduced. Denopamine caused no substantial increase in myocardial oxygen consumption at a lower dose, at which LV dp/dtmax was significantly increased. A weak effect of denopamine on myocardial oxygen consumption may result partly from a weak positive chronotropic effect and partly from a reduction of preload and cardiac size.

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment

PubMed Central

Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

2015-01-01

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device. PMID:26171983

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.

PubMed

Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

2015-07-14

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

Monte Carlo Investigation on the Effect of Heterogeneities on Strut Adjusted Volume Implant (SAVI) Dosimetry

NASA Astrophysics Data System (ADS)

Koontz, Craig

Breast cancer is the most prevalent cancer for women with more than 225,000 new cases diagnosed in the United States in 2012 (ACS, 2012). With the high prevalence, comes an increased emphasis on researching new techniques to treat this disease. Accelerated partial breast irradiation (APBI) has been used as an alternative to whole breast irradiation (WBI) in order to treat occult disease after lumpectomy. Similar recurrence rates have been found using ABPI after lumpectomy as with mastectomy alone, but with the added benefit of improved cosmetic and psychological results. Intracavitary brachytherapy devices have been used to deliver the APBI prescription. However, inability to produce asymmetric dose distributions in order to avoid overdosing skin and chest wall has been an issue with these devices. Multi-lumen devices were introduced to overcome this problem. Of these, the Strut-Adjusted Volume Implant (SAVI) has demonstrated the greatest ability to produce an asymmetric dose distribution, which would have greater ability to avoid skin and chest wall dose, and thus allow more women to receive this type of treatment. However, SAVI treatments come with inherent heterogeneities including variable backscatter due to the proximity to the tissue-air and tissue-lung interfaces and variable contents within the cavity created by the SAVI. The dose calculation protocol based on TG-43 does not account for heterogeneities and thus will not produce accurate dosimetry; however Acuros, a model-based dose calculation algorithm manufactured by Varian Medical Systems, claims to accurately account for heterogeneities. Monte Carlo simulation can calculate the dosimetry with high accuracy. In this thesis, a model of the SAVI will be created for Monte Carlo, specifically using MCNP code, in order to explore the affects of heterogeneities on the dose distribution. This data will be compared to TG-43 and Acuros calculated dosimetry to explore their accuracy.

Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents.

PubMed

Gatch, Michael B; Dolan, Sean B; Forster, Michael J

2017-08-01

There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe), and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±)-3,4-methylenedioxymethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information. 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (≥80%) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74-78% drug-appropriate responding in DOM-trained and MDMA-trained rats at doses that suppressed responding. 5-MeO-DALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25I-NBOMe, fully substituted for DOM, whereas only 25B-NBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.

Planning Guidance for Response to a Nuclear Detonation

DTIC Science & Technology

2009-01-16

Radiation and Fallout One of the primary outputs from a nuclear explosion is radiation . Intense... on the jet streams and have a low-level global impact. Radiation Injuries and Fallout Health Impacts A nuclear explosion will produce dangerous... radiation dose rates based on the quantity of visible fallout. Therefore, visible fallout may possibly be used as an indicator of a direct radiation

Dopaminergic Actions of D-Amphetamine on Schedule-Induced Polydipsia in Rats

ERIC Educational Resources Information Center

Pellon, Ricardo; Ruiz, Ana; Rodriguez, Cilia; Flores, Pilar

2007-01-01

Schedule-induced polydipsia in rats was developed by means of a fixed-time 60-s schedule of food presentation. The acute administration of d-amphetamine sulfate (0.1-3.0 mg/kg) produced a dose-dependent decrease in the rate of licking. D-Amphetamine shifted to the left the temporal distribution of adjunctive drinking within interfood intervals.…

Treatment Sequencing for Childhood ADHD: A Multiple-Randomization Study of Adaptive Medication and Behavioral Interventions.

PubMed

Pelham, William E; Fabiano, Gregory A; Waxmonsky, James G; Greiner, Andrew R; Gnagy, Elizabeth M; Pelham, William E; Coxe, Stefany; Verley, Jessica; Bhatia, Ira; Hart, Katie; Karch, Kathryn; Konijnendijk, Evelien; Tresco, Katy; Nahum-Shani, Inbal; Murphy, Susan A

2016-01-01

Behavioral and pharmacological treatments for children with attention deficit/hyperactivity disorder (ADHD) were evaluated to address whether endpoint outcomes are better depending on which treatment is initiated first and, in case of insufficient response to initial treatment, whether increasing dose of initial treatment or adding the other treatment modality is superior. Children with ADHD (ages 5-12, N = 146, 76% male) were treated for 1 school year. Children were randomized to initiate treatment with low doses of either (a) behavioral parent training (8 group sessions) and brief teacher consultation to establish a Daily Report Card or (b) extended-release methylphenidate (equivalent to .15 mg/kg/dose bid). After 8 weeks or at later monthly intervals as necessary, insufficient responders were rerandomized to secondary interventions that either increased the dose/intensity of the initial treatment or added the other treatment modality, with adaptive adjustments monthly as needed to these secondary treatments. The group beginning with behavioral treatment displayed significantly lower rates of observed classroom rule violations (the primary outcome) at study endpoint and tended to have fewer out-of-class disciplinary events. Further, adding medication secondary to initial behavior modification resulted in better outcomes on the primary outcomes and parent/teacher ratings of oppositional behavior than adding behavior modification to initial medication. Normalization rates on teacher and parent ratings were generally high. Parents who began treatment with behavioral parent training had substantially better attendance than those assigned to receive training following medication. Beginning treatment with behavioral intervention produced better outcomes overall than beginning treatment with medication.

Development and Validation of a New Fallout Transport Method Using Variable Spectral Winds

NASA Astrophysics Data System (ADS)

Hopkins, Arthur Thomas

A new method has been developed to incorporate variable winds into fallout transport calculations. The method uses spectral coefficients derived by the National Meteorological Center. Wind vector components are computed with the coefficients along the trajectories of falling particles. Spectral winds are used in the two-step method to compute dose rate on the ground, downwind of a nuclear cloud. First, the hotline is located by computing trajectories of particles from an initial, stabilized cloud, through spectral winds, to the ground. The connection of particle landing points is the hotline. Second, dose rate on and around the hotline is computed by analytically smearing the falling cloud's activity along the ground. The feasibility of using specgtral winds for fallout particle transport was validated by computing Mount St. Helens ashfall locations and comparing calculations to fallout data. In addition, an ashfall equation was derived for computing volcanic ash mass/area on the ground. Ashfall data and the ashfall equation were used to back-calculate an aggregated particle size distribution for the Mount St. Helens eruption cloud. Further validation was performed by comparing computed and actual trajectories of a high explosive dust cloud (DIRECT COURSE). Using an error propagation formula, it was determined that uncertainties in spectral wind components produce less than four percent of the total dose rate variance. In summary, this research demonstrated the feasibility of using spectral coefficients for fallout transport calculations, developed a two-step smearing model to treat variable winds, and showed that uncertainties in spectral winds do not contribute significantly to the error in computed dose rate.

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

PubMed Central

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

2011-01-01

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

Analysis of fission and activation radionuclides produced by a uranium-fueled nuclear detonation and identification of the top dose-producing radionuclides.

PubMed

Kraus, Terry; Foster, Kevin

2014-08-01

The radiological assessment of the nuclear fallout (i.e., fission and neutron-activation radionuclides) from a nuclear detonation is complicated by the large number of fallout radionuclides. This paper provides the initial isotopic source term inventory of the fallout from a uranium-fueled nuclear detonation and identifies the significant and insignificant radiological dose producing radionuclides over 11 dose integration time periods (time phases) of interest. A primary goal of this work is to produce a set of consistent, time phase-dependent lists of the top dose-producing radionuclides that can be used to prepare radiological assessment calculations and data products (e.g., maps of areas that exceed protective action guidelines) in support of public and worker protection decisions. The ranked lists of top dose-producing radionuclides enable assessors to perform atmospheric dispersion modeling and radiological dose assessment modeling more quickly by using relatively short lists of radionuclides without significantly compromising the accuracy of the modeling and the dose projections. This paper also provides a superset-list of the top dose-producing fallout radionuclides from a uranium-fueled nuclear detonation that can be used to perform radiological assessments over any desired time phase. Furthermore, this paper provides information that may be useful to monitoring and sampling and laboratory analysis personnel to help understand which radionuclides are of primary concern. Finally, this paper may be useful to public protection decision makers because it shows the importance of quickly initiating public protection actions to minimize the radiological dose from fallout.

Characteristics of fiber-optic radiation sensor for passive scattering proton beams

NASA Astrophysics Data System (ADS)

Son, J.; Kim, M.; Jeong, J.; Lim, Y.; Lee, S. B.; Shin, D.; Yoon, M.

2017-11-01

The aims of this study were to investigate the characteristics of a fiber-optic radiation sensor (FORS) that detects the fluorescence light produced by proton beam and to verify its effectiveness in proton therapy quality assurance (QA). Various characteristics of the FORS were investigated, such as the linearity of its relationships to the sensitive length of fiber for the proton beams of intermediate ranges (165.46 and 178.37 MeV) and to the measured dose, as well as its dose rate dependence. In addition, patient specific precription dose QA was conducted for five patients actually undergoing proton therapy and the results were compared with the doses measured using an ion chamber. The results show that the signal of the FORS is linearly related to the sensitive length of fiber and to the irradiated dose in the range from 1 to 500 cGy. The QA results obtained using the FORS system showed good agreement with the corresponding ion chamber results, with an average difference of 0.40% and a standard deviation of 0.35%. The FORS was dose-rate independent for proton currents up to 5 Gy/min. The profiles of various proton beams obtained using an array of FORS, which were measured as an application of the developed dosimetric system, closely agreed with the profiles acquired using EBT3 film. In summary, the experimental results of FORS demonstrated its effectiveness for use in various proton therapy QA tests.

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

PubMed

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

2012-01-01

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

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

PubMed

Heishman, S J; Henningfield, J E

2000-10-01

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

Tailored on demand anti-coagulant dosing: an in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms.

PubMed

Arafat, Basel; Qinna, Nidal; Cieszynska, Milena; Forbes, Robert T; Alhnan, Mohamed A

2018-04-16

Coumarin therapy has been associated with high levels of inter- and intra-individual variation in the required dose to reach a therapeutic anticoagulation outcome. Therefore, a dynamic system that is able to achieve accurate delivery of a warfarin dose is of significant importance. Here we assess, the ability of 3D printing to fabricate and deliver tailored individualised precision dosing using an in-vitro model. Sodium warfarin loaded filaments were compounded using hot melt extrusion (HME) and further fabricated via fused deposition modelling (FDM) 3D printing to produce capsular-ovoid-shaped dosage forms loaded at 200 and 400 µg dose. The solid dosage forms and comparator warfarin aqueous solutions were administered by oral gavage to Sprague-Dawley rats. In vitro, warfarin release was faster at pH 1.2 in comparison to pH 2. A novel UV imaging approach indicated that the erosion of the methacrylate matrix was at a rate of 16.4 and 15.2 µm/min for horizontal and vertical planes respectively. In vivo, 3D printed forms were as proportionately effective as their comparative solution form in doubling plasma exposure following a doubling of warfarin dose (184% versus 192% respectively). The 3D printed ovoids showed a lower C max of warfarin (1.51 and 3.33 mg/mL versus 2.5 and 6.44 mg/mL) and a longer T max (6 and 3.7 versus 4 and 1.5 h) in comparison to liquid formulation. This work demonstrates for the first time in vivo, the potential of FDM 3D printing to produce a tailored specific dosage form and to accurately titrate coumarin dose response to an individual patient. Copyright © 2018. Published by Elsevier B.V.

Evaluation of equivalent dose from neutrons and activation products from a 15-MV X-ray LINAC

PubMed Central

Israngkul-Na-Ayuthaya, Isra; Suriyapee, Sivalee; Pengvanich, Phongpheath

2015-01-01

A high-energy photon beam that is more than 10 MV can produce neutron contamination. Neutrons are generated by the [γ,n] reactions with a high-Z target material. The equivalent neutron dose and gamma dose from activation products have been estimated in a LINAC equipped with a 15-MV photon beam. A Monte Carlo simulation code was employed for neutron and photon dosimetry due to mixed beam. The neutron dose was also experimentally measured using the Optically Stimulated Luminescence (OSL) under various conditions to compare with the simulation. The activation products were measured by gamma spectrometer system. The average neutron energy was calculated to be 0.25 MeV. The equivalent neutron dose at the isocenter obtained from OSL measurement and MC calculation was 5.39 and 3.44 mSv/Gy, respectively. A gamma dose rate of 4.14 µSv/h was observed as a result of activations by neutron inside the treatment machine. The gamma spectrum analysis showed 28Al, 24Na, 54Mn and 60Co. The results confirm that neutrons and gamma rays are generated, and gamma rays remain inside the treatment room after the termination of X-ray irradiation. The source of neutrons is the product of the [γ,n] reactions in the machine head, whereas gamma rays are produced from the [n,γ] reactions (i.e. neutron activation) with materials inside the treatment room. The most activated nuclide is 28Al, which has a half life of 2.245 min. In practice, it is recommended that staff should wait for a few minutes (several 28Al half-lives) before entering the treatment room after the treatment finishes to minimize the dose received. PMID:26265661

Nitrosamine-induced carcinogenesis. The alkylation of N-7 of guanine of nucleic acids of the rat by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate

PubMed Central

Swann, P. F.; Magee, P. N.

1971-01-01

1. The extent of ethylation of N-7 of guanine in the nucleic acids of rat tissue in vivo by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate was measured. 2. All compounds produced measurable amounts of 7-ethyl-guanine. 3. A single dose of diethylnitrosamine or N-ethyl-N-nitrosourea produced tumours of the kidney in the rat. Three doses of ethyl methanesulphonate produced kidney tumours, but a single dose did not. 4. A single dose of diethylnitrosamine produced twice as much ethylation of N-7 of guanine in DNA of kidney as did N-ethyl-N-nitrosourea. A single dose of both compounds induced kidney tumours, although of a different histological type. 5. A single dose of ethyl methanesulphonate produced ten times as much ethylation of N-7 of guanine in kidney DNA as did N-ethyl-N-nitrosourea without producing tumours. 6. The relevance of these findings to the hypothesis that alkylation of a cellular component is the mechanism of induction of tumours by nitroso compounds is discussed. PMID:5145908

TU-FG-201-06: Remote Dosimetric Auditing for Clinical Trials Using EPID Dosimetry: A Pilot Study

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

Miri, N; Legge, K; Greer, P

2016-06-15

Purpose: To perform a pilot study for remote dosimetric credentialing of intensity modulated radiation therapy (IMRT) based clinical trials. The study introduces a novel, time efficient and inexpensive dosimetry audit method for multi-center credentialing. The method employs electronic portal imaging device (EPID) to reconstruct delivered dose inside a virtual flat/cylindrical water phantom. Methods: Five centers, including different accelerator types and treatment planning systems (TPS), were asked to download two CT data sets of a Head and Neck (H&N) and Postprostatectomy (P-P) patients to produce benchmark plans. These were then transferred to virtual flat and cylindrical phantom data sets that weremore » also provided. In-air EPID images of the plans were then acquired, and the data sent to the central site for analysis. At the central site, these were converted to DICOM format, all images were used to reconstruct 2D and 3D dose distributions inside respectively the flat and cylindrical phantoms using inhouse EPID to dose conversion software. 2D dose was calculated for individual fields and 3D dose for the combined fields. The results were compared to corresponding TPS doses. Three gamma criteria were used, 3%3mm-3%/2mm–2%/2mm with a 10% dose threshold, to compare the calculated and prescribed dose. Results: All centers had a high pass rate for the criteria of 3%/3 mm. For 2D dose, the average of centers mean pass rate was 99.6% (SD: 0.3%) and 99.8% (SD: 0.3%) for respectively H&N and PP patients. For 3D dose, 3D gamma was used to compare the model dose with TPS combined dose. The mean pass rate was 97.7% (SD: 2.8%) and 98.3% (SD: 1.6%). Conclusion: Successful performance of the method for the pilot centers establishes the method for dosimetric multi-center credentialing. The results are promising and show a high level of gamma agreement and, the procedure is efficient, consistent and inexpensive. Funding has been provided from Department of Radiation Oncology, TROG Cancer Research and the University of Newcastle. Narges Miri is a recipient of a University of Newcastle postgraduate scholarship.« less

Effects of radioactive hot particles on pig skin

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

Kaurin, D.G.; Baum, J.W.; Schaefer, C.W.

1997-06-01

The purpose of these studies was to determine the incidence and severity of lesions resulting from very localized deposition of dose to skin from small (< 0.5 mm) discrete radioactive particles as produced in the work environments of nuclear reactors. Hanford mini-pigs were exposed, both on a slightly off the skin, to localized replicate doses from 0.31 to 64 Gy (averaged over 1 cm{sup 2} at 70 {mu}m depth unless noted otherwise) using Sc-46, Yb-175, Tm-170, and fissioned UC{sub 2} isotopes having maximum beta-particle energies from about 0.3 to 3 MeV. Erythema and scabs (indicating ulceration) were scored for upmore » to 71 days post-irradiation. The responses followed normal cumulative probability distributions, and therefore, no true threshold could be defined. Hence, 10 and 50% scab incidence rates were deduced using probit analyses. The lowest dose which produced 10% incidence was about 1 Gy for Yb-175 (0.5 MeV maximum energy) beta particle exposures, and about 3 to 9 Gy for other isotopes. The histopathology of lesions was determined at several doses. Single exposures to doses as large as 1,790 Gy were also given, and results were observed for up to 144 days post-exposure. Severity of detriment was estimated by analyzing the results in terms of lesion diameter, persistence, and infection. Over 1,100 sites were exposed. Only two exposed sites became infected after doses near 5000 Gy; the lesions healed quickly on treatment. 105 refs., 145 figs., 47 tabs.« less

Brachytherapy for cervix cancer: low-dose rate or high-dose rate brachytherapy – a meta-analysis of clinical trials

PubMed Central

Viani, Gustavo A; Manta, Gustavo B; Stefano, Eduardo J; de Fendi, Ligia I

2009-01-01

Background The literature supporting high-dose rate brachytherapy (HDR) in the treatment of cervical carcinoma derives primarily from retrospective series. However, controversy still persists regarding the efficacy and safety of HDR brachytherapy compared to low-dose rate (LDR) brachytherapy, in particular, due to inadequate tumor coverage for stage III patients. Whether LDR or HDR brachytherapy produces better results for these patients in terms of survival rate, local control rate and the treatment complications remain controversial. Methods A meta-analysis of RCT was performed comparing LDR to HDR brachytherapy for cervix cancer treated for radiotherapy alone. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, as well as abstracts published in the annual proceedings were systematically searched. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We used "recommend" for strong recommendations, and "suggest" for weak recommendations. Results Pooled results from five randomized trials (2,065 patients) of HDR brachytherapy in cervix cancer showed no significant increase of mortality (p = 0.52), local recurrence (p = 0.68), or late complications (rectal; p = 0.7, bladder; p = 0.95 or small intestine; p = 0.06) rates as compared to LDR brachytherapy. In the subgroup analysis no difference was observed for overall mortality and local recurrence in patients with clinical stages I, II and III. The quality of evidence was low for mortality and local recurrence in patients with clinical stage I, and moderate for other clinical stages. Conclusion Our meta-analysis shows that there are no differences between HDR and LDR for overall survival, local recurrence and late complications for clinical stages I, II and III. By means of the GRADE system, we recommend the use of HDR for all clinical stages of cervix cancer. PMID:19344527

Main Sources and Doses of Space Radiation during Mars Missions and Total Radiation Risk for Cosmonauts

NASA Astrophysics Data System (ADS)

Mitrikas, Victor; Aleksandr, Shafirkin; Shurshakov, Vyacheslav

This work contains calculation data of generalized doses and dose equivalents in critical organs and tissues of cosmonauts produces by galactic cosmic rays (GCR), solar cosmic rays (SCR) and the Earth’s radiation belts (ERB) that will impact crewmembers during a flight to Mars, while staying in the landing module and on the Martian surface, and during the return to Earth. Also calculated total radiation risk values during whole life of cosmonauts after the flight are presented. Radiation risk (RR) calculations are performed on the basis of a radiobiological model of radiation damage to living organisms, while taking into account reparation processes acting during continuous long-term exposure at various dose rates and under acute recurrent radiation impact. The calculations of RR are performed for crewmembers of various ages implementing a flight to Mars over 2 - 3 years in maximum and minimum of the solar cycle. The total carcinogenic and non-carcinogenic RR and possible life-span shortening are estimated on the basis of a model of the radiation death probability for mammals. This model takes into account the decrease in compensatory reserve of an organism as well as the increase in mortality rate and descent of the subsequent lifetime of the cosmonaut. The analyzed dose distributions in the shielding and body areas are applied to making model calculations of tissue equivalent spherical and anthropomorphic phantoms.

Alternative Reinforcer Response Cost Impacts Methamphetamine Choice in Humans

PubMed Central

Bennett, J. Adam; Stoops, William W.; Rush, Craig R.

2012-01-01

Methamphetamine use disorders are a persistent public health concern. Behavioral treatments have demonstrated that providing access to non-drug alternative reinforcers reduces methamphetamine use. The purpose of this human laboratory experiment was to determine how changes in response cost for non-drug alternative reinforcers influenced methamphetamine choice. Seven subjects with past year histories of recreational stimulant use completed a placebo-controlled, crossover, double-blind protocol in which they first sampled doses of oral methamphetamine (0, 8 or 16 mg) and completed a battery of subject-rated and physiological measures. During subsequent sessions, subjects then made eight discrete choices between 1/8th of the sampled dose and an alternative reinforcer ($0.25). The response cost to earn a methamphetamine dose was always 500 responses (FR500). The response cost for the alternative reinforcer varied across sessions (FR500, FR1000, FR2000, FR3000). Methamphetamine functioned as a positive reinforcer and produced prototypical stimulant-like effects (e.g., elevated blood pressure, increased ratings of “Stimulated”). Choice for doses over money was sensitive to changes in response cost for alternative reinforcers in that more doses were taken at higher FR values than at lower FR values. Placebo choices changed as a function of alternative reinforcer response cost to a greater degree than active methamphetamine choices. These findings suggest that manipulating the effort necessary to earn alternative reinforcers could impact methamphetamine use. PMID:23046851

The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

PubMed

Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

2017-07-01

To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

Collaboration of local government and experts responding to increase in environmental radiation level due to the nuclear disaster: focusing on their activities and latest radiological discussion.

PubMed

Iimoto, T; Nunokawa, J; Fujii, H; Takashima, R; Hashimoto, M; Fukuhara, T; Yajima, T; Matsuzawa, H; Kurosawa, K; Yanagawa, Y; Someya, S

2015-11-01

Activities were introduced in Kashiwa city in the Tokyo metropolitan area to correspond to the elevated environmental radiation level after the disaster of the Fukushima Daiichi nuclear power plant. These were based on a strong cooperation between local governments and experts. Ambient dose rate and radioactivity of foodstuff produced inside of the city have been monitored. Representative ambient dose rates around living environments have almost already become their original levels of the pre-accident because of the decontamination activity, natural washout and effective half-lives of radioactivity. The internal annual dose due to radioactive cesium under the policy of 'Local Production for Local Consumption' is estimated as extremely low comparing the variation range due to natural radioactivity. Systematic survey around a retention basin has been started. All of these latest monitoring data would be one of the core information for the policy making as well as a cost-benefit discussion and risk communication. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Recommended treatment for urinary tract infection in pregnancy.

PubMed

Vercaigne, L M; Zhanel, G G

1994-02-01

To establish and recommend a therapeutic regimen for the treatment of urinary tract infection (UTI) in pregnancy based on the published studies. An English-language literature search employing MEDLINE, Index Medicus, and bibliographic reviews of the references obtained were searched (key terms: urinary tract infection, UTI, pregnancy, bacteriuria). All identified human studies dealing with bacteriuria or UTI in pregnancy were analyzed. Limited data are available regarding the appropriate antibiotic management of UTI in pregnancy. Single-dose cure rates with amoxicillin are approximately 80 percent. Trimethoprim/sulfamethoxazole provides cure rates of greater than 80 percent. Cephalosporins and nitrofurantoin produce variable results. We recommend separating pregnant subjects with UTI into two groups. Those with asymptomatic bacteriuria can be treated with a single dose of an antimicrobial to which the organism is susceptible. For those with symptomatic UTI, we recommend amoxicillin 500 mg tid for three days. Urine cultures should be repeated seven days following therapy to assess cure or failure. Well-designed studies need to be performed, comparing single-dose and three-day therapy for UTI in pregnancy.

Single dosing comparison of the relative cardiac beta 1/beta 2 activity of inhaled fenoterol and salbutamol in normal subjects.

PubMed Central

Newnham, D M; Wheeldon, N M; Lipworth, B J; McDevitt, D G

1993-01-01

BACKGROUND--The aim of the present study was to compare the dose related effects of fenoterol and salbutamol on cardiac beta 1 and beta 2 receptors using the beta 1 selective antagonist atenolol, in order to dissect out relative beta 1/beta 2 mediated responses. METHODS--Fourteen normal volunteers were randomised to receive pretreatment with either atenolol 25 mg or placebo, followed by inhaled fenoterol or salbutamol in equal doses by weight (cumulative doses of 1 mg and 4 mg). Measurements were made 30 minutes after inhaling each dose of beta 2 agonist. Values (mean and 95% CI) were expressed as a change from baseline. RESULTS--At 4 mg fenoterol produced equivalent falls in serum potassium and increases in tremor to salbutamol. The mean (95% CI) increase in heart rate (beats/min) with fenoterol at 4 mg after placebo was 47 (41-53) and after atenolol was 34 (28-40), with values for salbutamol being 46 (40-52) after placebo and 30 (24-36) after atenolol. The inotropic response (stroke distance) after atenolol at the 4 mg dose was 5.0 (3.9-6.1) cm for fenoterol and 4.7 (3.5-5.9) cm for salbutamol. There were no significant differences in heart rate or stroke distance response between the two drugs after either placebo or atenolol. Furthermore, ECG effects (Q-Tc and T wave) of fenoterol and salbutamol were comparable at both doses. CONCLUSIONS--These results show that there is no difference in the respective chronotropic or inotropic activities of fenoterol and salbutamol on cardiac beta 1 or beta 2 receptors when given at higher than conventional doses. PMID:8102213

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

The in vivo pharmacological profile of a 5-HT1 receptor agonist, CP-122,288, a selective inhibitor of neurogenic inflammation.

PubMed

Gupta, P; Brown, D; Butler, P; Ellis, P; Grayson, K L; Land, G C; Macor, J E; Robson, S F; Wythes, M J; Shepperson, N B

1995-11-01

1. The aim of the present study was to investigate the in vivo pharmacological profile of CP-122,288, an indole-derivative with a conformationally restricted N-methylpyrrolidinyl basic side chain in the C-3 position. This C-3 substituent structurally differentiates CP-122,288 from the 5-HT1D receptor agonist sumatriptan, which possesses an N,N-dimethylaminoethyl group. [Formula: see text] 2. When administered prior to electrical stimulation of the trigeminal ganglion, CP-122,288 (0.3-300 ng kg-1, i.v.) produced a dose-related inhibition of plasma protein extravasation in rat dura mater (minimum effective dose, MED, 3 ng kg-1 i.v., P < 0.05; maximal inhibition of plasma extravasation at 30 ng kg-1 i.v., P < 0.01). Sumatriptan produced a similar inhibition of plasma leakage in the dura, but at much higher dose levels (MED, 100 micrograms kg-1 i.v., P < 0.05). Thus, CP-122,288 is of the order of 10(4) fold more potent than sumatriptan. 3. At all doses tested, CP-122,288 did not inhibit plasma protein extravasation measured in extracranial tissues such as the lower lip, eyelid, and conjunctiva. 4. In a separate series of studies in the anaesthetized rat, CP-122,288 (0.003-3 micrograms kg-1 i.v.) produced no change in either heart rate or mean arterial blood pressure, thus demonstrating that doses of CP-122,288 which inhibit plasma protein leakage in rat dura, are devoid of hemodynamic effects. 5. Following a 5 min period of electrical stimulation of the trigeminal ganglion, a 20 min period of sustained neurogenically-driven plasma extravasation, occurring in the absence of electrical stimulation, was initiated. By administration of the compound 5 min after completing the phase of electrical stimulation, this protocol permitted the evaluation of the activity of CP-122,288 on an ongoing and established inflammatory event. CP-122,288 (30 and 300 ng kg-1, i.v., P < 0.01 and P < 0.05, respectively) produced a complete inhibition of plasma protein leakage which was consistent with its effects when administered prior to trigeminal ganglion stimulation. 6. In the anaesthetized dog, CP-122,288 and sumatriptan, at 1-300 micrograms kg-1, i.v., produced a dose-dependent reduction in carotid arterial blood flow and coronary arterial diameter. These data demonstrate that sumatriptan inhibits neurogenic inflammation in the rat (MED, 100 micrograms kg-1, i.v.), and produces vasoconstriction in the dog, over a similar dose-range. Interestingly, doses of CP-122,288 that inhibit neurogenic inflammation in rat dura mater (0.3-300 ng kg-1) were demonstrated to be devoid of vasoconstrictor activity in either the carotid or coronary vascular beds of dog. 7. These data demonstrate that in the rat, CP-122,288 is a highly potent and selective inhibitor of neurogenic inflammation in intracranial tissues, at doses which are devoid of vasoconstrictor activity in dog. Potentially, CP-122,288 may be of use for the acute treatment of migraine, without the risk of cardiovascular side-effects.

[Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

PubMed

Sokić, D; Janković, S M

1994-01-01

Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

Effect of piracetam, a nootropic agent, on rat brain monoamines and prostaglandins.

PubMed

Bhattacharya, S K; Upadhyay, S N; Jaiswal, A K; Bhattacharya, S

1989-03-01

Piracetam is the prototype of a new class of psychotropic drugs, the nootropic agents, which are claimed to selectively improve the higher telencephalic integrative activities. The effect of piracetam on rat brain monoamines and prostaglandins (PGs) was assessed so as to garner information on its mode of action. Two doses of the drug were used, a lower dose (20 mg/kg ip) and a higher dose (100 mg/kg, ip), the latter being known to exert a facilitatory effect on learning and memory. Piracetam produced a dose-related effect on rat brain serotonin (5HT) and noradrenaline (NA), with the lower dose inducing a decrease in 5HT levels and an increase in NA concentrations. The higher dose of piracetam produced the opposite effect. Dopamine (DA) levels were not significantly affected. The lower dose of the drug attenuated 5HT turnover and augmented that of NA, whereas the higher dose of piracetam produced the reverse effects, in clorgyline treated rats. The lower dose of piracetam produced a slight and statistically insignificant increase in rat brain PGE2 and PGF2 alpha. However, the higher dose of the drug produced marked increase in the levels of both the PGs. The observed biochemical effects may provide a basis for the nootropic effect of piracetam. However, they may also be due to the GA-BA-mimetic action of the drug, particularly those observed with the lower dose of piracetam.

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

PubMed

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

2016-04-01

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

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

PubMed Central

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

2016-01-01

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

Dosimetric intercomparison of permanent Ho-166 seed's implants and HDR Ir-192 brachytherapy in breast cancer.

PubMed

de Campos, Tarcisio Passos Ribeiro; Nogueira, Luciana Batista; Trindade, Bruno; Cuperschmid, Ethel Mizrahy

2016-01-01

To provide a comparative dosimetric analysis of permanent implants of Ho(166)-seeds and temporary HDR Ir(192)-brachytherapy through computational simulation. Brachytherapy with Ir(192)-HDR or LDR based on temporary wires or permanent radioactive seed implants can be used as dose reinforcement for breast radiation therapy. Permanent breast implants have not been a practical clinical routine; although, I(125) and Pd(103)-seeds have already been reported. Biodegradable Ho(166)-ceramic-seeds have been addressed recently. Simulations of implants of nine Ho(166)-seeds and equivalent with HDR Ir(192)-brachytherapy were elaborated in MCNP5, shaped in a computational multivoxel simulator which reproduced a female thorax phantom. Spatial dose rate distributions and dose-volume histograms were generated. Protocol's analysis involving exposure time, seed's activities and dose were performed. Permanent Ho(166)-seed implants presented a maximum dose rate per unit of contained activity (MDR) of 1.1601 μGy h(-1) Bq(-1); and, a normalized MDR in standard points (8 mm, equidistant to 03-seeds - SP1, 10 mm - SP2) of 1.0% (SP1) and 0.5% (SP2), respectively. Ir(192)-brachytherapy presented MDR of 4.3945 × 10(-3) μGy h(-1) Bq(-1); and, 30% (SP1), and 20% (SP2). Therefore, seed's implant activities of 333 MBq (Ho(166)) and 259 GBq (Ir(192)) produced prescribed doses of 58 Gy (SP1; 5d) and 56 Gy (SP1, 5 fractions, 6 min), respectively. Breast Ho(166)-implants of 37-111 MBq are attractive due to the high dose rate near 6-10 mm from seeds, equivalent to Ir(192)-brachytherapy of 259 GBq (3 fractions, 6 min) providing similar dose in standard points at a week; however, with spatial dose distribution better confined. The seed positioning can be adjusted for controlling the breast tumor, in stages I and II, in flat and deep tumors, without any breast volumetric limitation.

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

PubMed

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

2010-03-01

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

Application of a computational decision model to examine acute drug effects on human risk taking.

PubMed

Lane, Scott D; Yechiam, Eldad; Busemeyer, Jerome R

2006-05-01

In 3 previous experiments, high doses of alcohol, marijuana, and alprazolam acutely increased risky decision making by adult humans in a 2-choice (risky vs. nonrisky) laboratory task. In this study, a computational modeling analysis known as the expectancy valence model (J. R. Busemeyer & J. C. Stout, 2002) was applied to individual-participant data from these studies, for the highest administered dose of all 3 drugs and corresponding placebo doses, to determine changes in decision-making processes that may be uniquely engendered by each drug. The model includes 3 parameters: responsiveness to rewards and losses (valence or motivation); the rate of updating expectancies about the value of risky alternatives (learning/memory); and the consistency with which trial-by-trial choices match expected outcomes (sensitivity). Parameter estimates revealed 3 key outcomes: Alcohol increased responsiveness to risky rewards and decreased responsiveness to risky losses (motivation) but did not alter expectancy updating (learning/memory); both marijuana and alprazolam produced increases in risk taking that were related to learning/memory but not motivation; and alcohol and marijuana (but not alprazolam) produced more random response patterns that were less consistently related to expected outcomes on the 2 choices. No significant main effects of gender or dose by gender interactions were obtained, but 2 dose by gender interactions approached significance. These outcomes underscore the utility of using a computational modeling approach to deconstruct decision-making processes and thus better understand drug effects on risky decision making in humans.

The role of the dopaminergic projections in MFB self-stimulation.

PubMed

Gallistel, C R

1986-11-01

Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.

The role of the dopaminergic projections in MFB self-stimulation.

PubMed

Gallistel, C R

1986-06-01

Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.

Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

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

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

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

Optimisation techniques in vaginal cuff brachytherapy.

PubMed

Tuncel, N; Garipagaoglu, M; Kizildag, A U; Andic, F; Toy, A

2009-11-01

The aim of this study was to explore whether an in-house dosimetry protocol and optimisation method are able to produce a homogeneous dose distribution in the target volume, and how often optimisation is required in vaginal cuff brachytherapy. Treatment planning was carried out for 109 fractions in 33 patients who underwent high dose rate iridium-192 (Ir(192)) brachytherapy using Fletcher ovoids. Dose prescription and normalisation were performed to catheter-oriented lateral dose points (dps) within a range of 90-110% of the prescribed dose. The in-house vaginal apex point (Vk), alternative vaginal apex point (Vk'), International Commission on Radiation Units and Measurements (ICRU) rectal point (Rg) and bladder point (Bl) doses were calculated. Time-position optimisations were made considering dps, Vk and Rg doses. Keeping the Vk dose higher than 95% and the Rg dose less than 85% of the prescribed dose was intended. Target dose homogeneity, optimisation frequency and the relationship between prescribed dose, Vk, Vk', Rg and ovoid diameter were investigated. The mean target dose was 99+/-7.4% of the prescription dose. Optimisation was required in 92 out of 109 (83%) fractions. Ovoid diameter had a significant effect on Rg (p = 0.002), Vk (p = 0.018), Vk' (p = 0.034), minimum dps (p = 0.021) and maximum dps (p<0.001). Rg, Vk and Vk' doses with 2.5 cm diameter ovoids were significantly higher than with 2 cm and 1.5 cm ovoids. Catheter-oriented dose point normalisation provided a homogeneous dose distribution with a 99+/-7.4% mean dose within the target volume, requiring time-position optimisation.

76 FR 35672 - Revised Effectiveness Determination; Sunscreen Drug Products for Over-the-Counter Human Use

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

... are given ultraviolet (UV) radiation doses produced by a solar simulator (i.e., a UV lamp). Under... increasingly higher UV doses produced by the solar simulator. However, because the solar simulator can produce far higher UV radiation doses than a consumer would ever receive even under the most severe sun...

Testing of selected pharmacological agents for capturing waterfowl [Annual Progress Report

USGS Publications Warehouse

Cline, D.R.

1970-01-01

The response of game-farm mallards (Frost strain) to seven pharmacological immobilizing agents was evaluated in Phase I of a planned four-phase study. A limited amount of testing was also done with wild mallards. Single dosages were administered to determine the mean effective dose (ED50) and mean lethal dose (LD50), The therapeutic index, or safety factor (LD50/ED50), and palatability were also established. Optimum dosage rates of compounds administered orally on baits were not considered in this phase of the study. Compounds were-administered by intubation and calculated in terms of mg/kg. All except one compound produced narcosis within 5 minutes at the effective dose rate.Immobilization periods for the seven compounds ranged from 7-24 minutes, and recovery periods from 1.0-6.5 hours. Such wide variations in actions of the compounds can be attributed to a compound's rate of absorption, the ease with which it passes the blood-brain barrier, its solubility in tissues, and its rate of metabolism in the liver and kidneys. Length of both the immobilization and recovery periods were extended when dosages were increased. There was no delayed mortality among survivors with any of the seven compounds at either the ED50 or LD50. Females were generally more sensitive to the anesthetizing agents than males. The ED50 for wild mallards was substantially higher than that for the experimental game-farm birds for the two compounds on which this was tested.Tribromoethanol (Avertin of Winthrop Laboratories) satisfied all test criteria an Phase I and will be subjected to more intensive investigation in ensuing tests. Thiopental sodium (Pentothal of Amdal Company) and pentobarbital sodium (Nembutal of Abbott Laboratories) were judged to be marginal. Although their therapeutic indexes were good (5.00), recovery periods were prolonged and toxic convulsions occurred at medium to high dose rates as the LD50 was approached.Alpha-chloralose (Fisher Scientific) proved least promising of the seven compounds, mainly because of its unacceptable therapeutic index (2.25) and because it possesses prolonged induction and recovery periods. Two new experimental drugs, methoxymol and metomidate (Pitman-Moore), appeared effective and safe when administered by intubation but produced a taste aversion when added to bait. Rejection because of taste was also a problem with secobarbital (Seconal of Elanco Products), and its therapeutic index of 2.75 was unacceptable. Monitoring of heart and respiratory rates, and body temperature by telemetry showed promise as a technique for determining physiological response to drug action.

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

PubMed Central

Pasternack, Jordan B.; Howell, Roger W.

2012-01-01

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

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

PubMed

Pasternack, Jordan B; Howell, Roger W

2013-02-01

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

Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study.

PubMed

Tanaka, Yoshiya; Takeuchi, Tsutomu; Yamanaka, Hisashi; Nakamura, Hiroyuki; Toyoizumi, Shigeyuki; Zwillich, Samuel

2015-07-01

To evaluate oral tofacitinib versus placebo for treatment of active rheumatoid arthritis in Japanese patients with inadequate response to disease-modifying antirheumatic drugs. In this double-blind, placebo-controlled, randomized, parallel-group, 12-week, phase 2 study (clinicaltrials.gov NCT00687193), 317 patients received tofacitinib: 1, 3, 5, 10, or 15 mg as monotherapy or placebo twice daily (BID). response rate by American College of Rheumatology (ACR) ≥ 20% improvement criteria (ACR20) at week 12. ACR20 response rates: 37.7% (20/53), 67.9% (36/53), 73.1% (38/52), 84.9% (45/53), and 90.7% (49/54) with tofacitinib: 1, 3, 5, 10, and 15 mg BID, respectively, versus 15.4% (8/52) with placebo (p < 0.01; all doses). Dose-dependent ACR20 responses with tofacitinib versus placebo occurred from week 2 onward (p < 0.05). Changes from baseline in 28-joint disease activity score using erythrocyte sedimentation rate improved with tofacitinib versus placebo from week 4 (p < 0.01; all doses). Six tofacitinib patients experienced treatment-related serious adverse events (AEs). Most common treatment-emergent AEs: nasopharyngitis (10% vs 12%) and hyperlipidemia (5% vs 0%). Serum creatinine, hemoglobin, and total-, low-, and high-density lipoprotein-cholesterol levels increased with tofacitinib. Tofacitinib produced dose-dependent ACR20 responses and reduced disease activity. The safety profile was consistent with that reported from global monotherapy trials.

Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study

PubMed Central

Tanaka, Yoshiya; Takeuchi, Tsutomu; Yamanaka, Hisashi; Nakamura, Hiroyuki; Toyoizumi, Shigeyuki; Zwillich, Samuel

2015-01-01

Abstract Objectives. To evaluate oral tofacitinib versus placebo for treatment of active rheumatoid arthritis in Japanese patients with inadequate response to disease-modifying antirheumatic drugs. Methods. In this double-blind, placebo-controlled, randomized, parallel-group, 12-week, phase 2 study (clinicaltrials.gov NCT00687193), 317 patients received tofacitinib: 1, 3, 5, 10, or 15 mg as monotherapy or placebo twice daily (BID). Primary endpoint: response rate by American College of Rheumatology (ACR) ≥ 20% improvement criteria (ACR20) at week 12. Results. ACR20 response rates: 37.7% (20/53), 67.9% (36/53), 73.1% (38/52), 84.9% (45/53), and 90.7% (49/54) with tofacitinib: 1, 3, 5, 10, and 15 mg BID, respectively, versus 15.4% (8/52) with placebo (p < 0.01; all doses). Dose-dependent ACR20 responses with tofacitinib versus placebo occurred from week 2 onward (p < 0.05). Changes from baseline in 28-joint disease activity score using erythrocyte sedimentation rate improved with tofacitinib versus placebo from week 4 (p < 0.01; all doses). Six tofacitinib patients experienced treatment-related serious adverse events (AEs). Most common treatment-emergent AEs: nasopharyngitis (10% vs 12%) and hyperlipidemia (5% vs 0%). Serum creatinine, hemoglobin, and total-, low-, and high-density lipoprotein-cholesterol levels increased with tofacitinib. Conclusions. Tofacitinib produced dose-dependent ACR20 responses and reduced disease activity. The safety profile was consistent with that reported from global monotherapy trials. PMID:25496464

The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific.

PubMed

Elmes, N J; Nasveld, P E; Kitchener, S J; Kocisko, D A; Edstein, M D

2008-11-01

Tafenoquine is being developed for radical cure and post-exposure prophylaxis of Plasmodium vivax malaria. In an open-label study, 1512 Australian Defence Force personnel received one of three tafenoquine 3 d regimens [400 mg once daily (od), 200 mg twice daily (bid), 200 mg od] or daily primaquine (22.5 mg) plus doxycycline (100 mg) over 14 d in Bougainville and in Timor-Leste for post-exposure prophylaxis. The relapse rate of subjects treated in Bougainville with tafenoquine (n=173) was 1.2% (200 mg bid x 3 d) and 2.3% (400 mg od x 3 d), while primaquine plus doxycycline (n=175) was 3.4%. For subjects treated in Timor-Leste with tafenoquine (n=636), the relapse rate was 4.9% (200 mg od x 3 d), 5.3% (200 mg bid x 3 d) and 11.0% (400 mg od x 3d), while primaquine plus doxycycline (n=289) was 10.0%. The most frequent adverse events reported across all groups were nausea, abdominal distress and diarrhoea. There was a dose-dependent reduction in adverse events with a reduced dose of tafenoquine, with the lowest dose (total 600 mg over 3 d) producing rates of adverse events equivalent to that of primaquine plus doxycycline. The much shorter dosing regimen of tafenoquine should increase compliance, which is often suboptimal with primaquine after leaving an endemic area. [Australian New Zealand Clinical Trials Registry Number 12607000588493].

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

PubMed

Hannoun-Lévi, J-M; Peiffert, D

2014-10-01

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

Excess processing of oxidative damaged bases causes hypersensitivity to oxidative stress and low dose rate irradiation.

PubMed

Yoshikawa, Y; Yamasaki, A; Takatori, K; Suzuki, M; Kobayashi, J; Takao, M; Zhang-Akiyama, Q-M

2015-10-01

Ionizing radiations such as X-ray and γ-ray can directly or indirectly produce clustered or multiple damages in DNA. Previous studies have reported that overexpression of DNA glycosylases in Escherichia coli (E. coli) and human lymphoblast cells caused increased sensitivity to γ-ray and X-ray irradiation. However, the effects and the mechanisms of other radiation, such as low dose rate radiation, heavy-ion beams, or hydrogen peroxide (H2O2), are still poorly understood. In the present study, we constructed a stable HeLaS3 cell line overexpressing human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) protein. We determined the survival of HeLaS3 and HeLaS3/hOGG1 cells exposed to UV, heavy-ion beams, γ-rays, and H2O2. The results showed that HeLaS3 cells overexpressing hOGG1 were more sensitive to γ-rays, OH(•), and H2O2, but not to UV or heavy-ion beams, than control HeLaS3. We further determined the levels of 8-oxoG foci and of chromosomal double-strand breaks (DSBs) by detecting γ-H2AX foci formation in DNA. The results demonstrated that both γ-rays and H2O2 induced 8-oxoguanine (8-oxoG) foci formation in HeLaS3 cells. hOGG1-overexpressing cells had increased amounts of γ-H2AX foci and decreased amounts of 8-oxoG foci compared with HeLaS3 control cells. These results suggest that excess hOGG1 removes the oxidatively damaged 8-oxoG in DNA more efficiently and therefore generates more DSBs. Micronucleus formation also supported this conclusion. Low dose-rate γ-ray effects were also investigated. We first found that overexpression of hOGG1 also caused increased sensitivity to low dose rate γ-ray irradiation. The rate of micronucleus formation supported the notion that low dose rate irradiation increased genome instability.

Assessing dose rate distributions in VMAT plans

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

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

NASA Technical Reports Server (NTRS)

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

2018-01-01

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

High-dose melphalan and autologous stem cell transplantation for AL amyloidosis: recent trends in treatment-related mortality and 1-year survival at a single institution

PubMed Central

Seldin, D. C.; Andrea, N.; Berenbaum, I.; Berk, J. L.; Connors, L.; Dember, L. M.; Doros, G.; Fennessey, S.; Finn, K.; Girnius, S.; Lerner, A.; Libbey, C.; Meier-Ewert, H. K.; O’Connell, R.; O’Hara, C.; Quillen, K.; Ruberg, F. L.; Sam, F.; Segal, A.; Shelton, A.; Skinner, M.; Sloan, J. M.; Wiesman, J. F.; Sanchorawala, V.

2017-01-01

Treatment with high-dose melphalan chemotherapy supported by hematopoietic rescue with autologous stem cells produces high rates of hematologic responses and improvement in survival and organ function for patients with AL amyloidosis. Ongoing clinical trials explore pre-transplant induction regimens, post-transplant consolidation or maintenance approaches, and compare transplant to non-transplant regimens. To put these studies into context, we reviewed our recent experience with transplant for AL amyloidosis in the Amyloid Treatment and Research Program at Boston Medical Center and Boston University School of Medicine. Over the past 10 years, there was a steady reduction in rates of treatment-related mortality and improvement in 1-year survival, now approximately 5% and 90%, respectively, based upon an intention-to-treat analysis. Median overall survival of patients treated with this approach at our center exceeds 7.5 years. PMID:21838459

Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans.

PubMed

Strassman, R J; Qualls, C R; Berg, L M

1996-05-01

Tolerance of the behavioral effects of the short-acting, endogenous hallucinogen, N,N-dimethyltryptamine (DMT) is seen inconsistently in animals, and has not been produced in humans. The nature and time course of responses to repetitive, closely spaced administrations of an hallucinogenic dose of DMT were characterized. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate, or saline placebo, four times, at 30 min intervals, on 2 separate days, in a randomized, double-blind, design. Tolerance to "psychedelic" subjective effects did not occur according to either clinical interview or Hallucinogen Rating Scale scores. Adrenocorticotropic hormone (ACTH), prolactin, cortisol, and heart rate responses decreased with repeated DMT administration, although blood pressure did not. These data demonstrate the unique properties of DMT relative to other hallucinogens and underscore the differential regulation of the multiple processes mediating the effects of DMT.

Mapping the space radiation environment in LEO orbit by the SATRAM Timepix payload on board the Proba-V satellite

NASA Astrophysics Data System (ADS)

Granja, Carlos; Polansky, Stepan

2016-07-01

Detailed spatial- and time-correlated maps of the space radiation environment in Low Earth Orbit (LEO) are produced by the spacecraft payload SATRAM operating in open space on board the Proba-V satellite from the European Space Agency (ESA). Equipped with the hybrid semiconductor pixel detector Timepix, the compact radiation monitor payload provides the composition and spectral characterization of the mixed radiation field with quantum-counting and imaging dosimetry sensitivity, energetic charged particle tracking, directionality and energy loss response in wide dynamic range in terms of particle types, dose rates and particle fluxes. With a polar orbit (sun synchronous, 98° inclination) at the altitude of 820 km the payload samples the space radiation field at LEO covering basically the whole planet. First results of long-period data evaluation in the form of time-and spatially-correlated maps of total dose rate (all particles) are given.

Influence of the rate of infusion on cyclosporine nephrotoxicity in the rat.

PubMed

Finn, W F; McCormack, A J; Sullivan, B A; Hak, L J; Clark, R L

1989-01-01

The effect of the rate of infusion of single and multiple doses of cyclosporine (CsA) on renal function was evaluated in Sprague-Dawley rats. CsA was dissolved in cremophore (Crem) or Tween 80 (Tween) and infused over consecutive 10-min periods at doses of 10, 20, 30 and 40 mg/kg. CsA-Crem and CsA-Tween produced similar and progressive changes in MAP, RBF, and RVR. By the end of the infusion, the mean values (% of control) of MAP (122 +/- 16% and 131 +/- 22%), RBF (56 +/- 11% and 66 +/- 20%), and RVR (222 +/- 38% and 232 +/- 134%) were significantly different from their respective preinfusion values. Infusion of Crem alone resulted in renal vasodilation at low doses and renal vasoconstriction at high doses. Vasoconstriction was not produced by infusion of Tween alone. In addition, animals were treated with vehicle alone (Gp 1), CsA 10 mg/kg/day by injection (Gp 2), or CsA 20 mg/kg/day by i.v. infusion over 4 hr (Gp 3), and were studied at 1 week. Systemic toxicity was greater with the 4-hr infusion as judged by an increase in MAP. The mean values of MAP were 107 +/- 8 (Gp 1), 101 +/- 13 (Gp 2), and 135 +/- 5 mm Hg (Gp 3; p less than 0.05). However, renal function was less severely affected with the 4-hr infusion. The mean values of CIn were 434 +/- 99 (Gp 1), 298 +/- 101 (Gp 2; p less than 0.05), and 425 +/- 114 microL/min/100 g BW (Gp 3); and the mean values for RBF were 2.72 +/- 0.74 (Gp 1), 2.08 +/- 0.17 (Gp 2; p less than 0.05), and 3.35 +/- 0.61 mL/min/100 g BW (Gp 3), respectively. Microangiograms showed marked abnormalities in the intrarenal perfusion pattern in the rats injected with CsA, 10 mg/kg BW. In rats infused over 4 hr with CsA, 20 mg/kg BW, the microangiographic pattern was normal. These studies demonstrate that the acute hemodynamic effects of CsA are directly related to the rate of infusion. Furthermore, the renal toxicity which follows repetitive injection of CsA can be minimized or avoided by administering CsA as a slow infusion. In addition to the total dose administered, the rate of infusion is an important determinant of nephrotoxicity.

Safety and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in methamphetamine-dependent volunteers

PubMed Central

Verrico, Christopher D.; Mahoney, James J.; Thompson-Lake, Daisy G. Y.; Bennett, Ryan S.; Newton, Thomas F.; De La Garza, Richard

2015-01-01

Methamphetamine use is increasing in the US. Although there are no Food and Drug Administration (FDA)-approved medications for methamphetamine dependence, preclinical and clinical studies suggest that methamphetamine users may benefit from treatments that enhance cholinergic neurotransmission. Consequently, we determined the safety and the efficacy of varenicline treatment, a partial agonist at α4β2 and a full agonist at α7 nicotinic acetylcholine receptors, to reduce positive subjective effects produced by smoked methamphetamine. Additionally, the effects of treatment with varenicline on the cardiovascular and reinforcing effects of methamphetamine were determined. We conducted a double-blind, placebo-controlled, within-subjects trial of varenicline vs. placebo in methamphetamine-dependent volunteers who were not seeking treatment. Participants were randomly assigned to receive one dose of varenicline (0, 1, or 2 mg) po BID, titrated up to the target dose over days 1–7, during each of three separate inpatient phases. Safety measures included the frequency, duration, severity, and relatedness of adverse events reported. Positive subjective effects included ‘Any drug effect’, ‘High’, ‘Good effects’, ‘Stimulated’, and ‘Drug liking’, which were rated by participants before and for 1 h after smoking methamphetamine (0, 10, and 30 mg). There were no serious adverse events and no differences in adverse events reported during the three phases. Varenicline (2 mg) significantly reduced ratings of ‘Any drug effect’ and ‘Stimulated’, as well as attenuated ratings of ‘High’, ‘Drug liking’, and ‘Good effects’, produced by methamphetamine (30 mg). The ability of varenicline to attenuate the positive subjective effects of methamphetamine in the laboratory suggests that varenicline should continue to be explored as a treatment for methamphetamine dependence. PMID:24393456

Dose-dependent effects of β-phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) on animal behavior.

PubMed

Tyurenkov, I N; Bagmetova, V V; Chernyshova, Yu V; Merkushenkova, O V

2014-12-01

β-Phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) in doses of 13-650 mg/kg suppressed depressive behavior of animals in the Porsolt test (i.e. produced antidepressant properties), reduced anxiety in the open-field, elevated plus maze, and Vogel conflict tests (i.e. produced anxiolytic effects). RGPU-135 in doses of 26-130 mg/kg exhibited more pronounced antidepressant action and in doses of 26 and 52 mg/kg had more pronounced anxiolytic effects. RGPU-135 in doses of 13-78 mg/kg increased locomotor and exploratory activity of animals in the open-field test. Activating effects of this agent decreased with increasing the dose. RGPU-135 in the subtoxic dose (650 mg/kg) suppressed locomotor activity of animals (produced sedative effect).

The effect of exposure duration on the subjective discomfort of aircraft cabin noise.

PubMed

Huang, Yu; Jiang, Weikang

2017-01-01

The time dependency for subjective responses to noise has been a controversial question over many years. For durations of up to 10 min, the discomfort produced by three levels of noise (ie 60, 70 and 80 dBA) was investigated in this experimental study to determine the relation of discomfort to the time duration of noise. The rate of increase in discomfort with increasing duration was 1.5 dB per doubling of exposure duration, whereas it is currently assumed to be 3 dB per doubling of exposure duration. The sound dose level (SDL) was proposed to predict the discomfort caused by noise of long duration. The combination of SDL and vibration dose value (VDV) provided more consistent estimates of the equivalent comfort contours between noise and vibration over durations from 2 to 32 s than the combination of sound exposure level and VDV or that of sound pressure level and r.m.s. acceleration. Practitioner Summary: The discomfort produced by noise of long duration can be well predicted from a new definition of sound dose level, where the discomfort increases at 1.5 dB per doubling of exposure duration.

Cysteine reversal of the novel neuromuscular blocking drug CW002 in dogs: pharmacodynamics, acute cardiovascular effects, and preliminary toxicology.

PubMed

Sunaga, Hiroshi; Malhotra, Jaideep K; Yoon, Edward; Savarese, John J; Heerdt, Paul M

2010-04-01

CW002 is a neuromuscular blocking drug that is inactivated by endogenous L-cysteine. This study determined the exogenous L-cysteine dose-response relationship for CW002 reversal along with acute cardiovascular effects and organ toxicity in dogs. Six dogs were each studied four times during isoflurane-nitrous oxide anesthesia and recording of muscle twitch, arterial pressure, and heart rate. CW002 (0.08 mg/kg or 9 x ED95) was injected, and the time to spontaneous muscle recovery was determined. CW002 was then administered again followed 1 min later by 10, 20, 50, or 100 mg/kg L-cysteine (1 dose/experiment). After twitch recovery, CW002 was given a third time to determine whether residual L-cysteine influenced duration. Preliminary toxicology was performed in an additional group of dogs that received CW002 followed by vehicle (n = 8) or 200 mg/kg L-cysteine (n = 8). Animals were awakened and observed for 2 or 14 days before sacrificing and anatomic, biochemical, and histopathologic analyses. L-cysteine at all doses accelerated recovery from CW002, with both 50 and 100 mg/kg decreasing median duration from more than 70 min to less than 5 min. After reversal, duration of a subsequent CW002 dose was also decreased in a dose-dependent manner. Over the studied dose range, L-cysteine had less than 10% effect on blood pressure and heart rate. Animals receiving a single 200-mg/kg dose of L-cysteine showed no clinical, anatomic, biochemical, or histologic evidence of organ toxicity. The optimal L-cysteine dose for rapidly reversing the neuromuscular blockade produced by a large dose of CW002 in dogs is approximately 50 mg/kg, which has no concomitant hemodynamic effect. A dose of 200 mg/kg had no evident organ toxicity.

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

PubMed

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

2018-04-18

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

Effect of gamma radiation on native endolithic microorganisms from a radioactive waste deposit site.

PubMed

Pitonzo, B J; Amy, P S; Rudin, M

1999-07-01

A time-course experiment was conducted to evaluate the effects of gamma radiation on the indigenous microbiota present in rock obtained from Yucca Mountain, Nevada Test Site. Microcosms were constructed by placing pulverized Yucca Mountain rock in polystyrene cylinders. Continuous exposure (96 h) at a dose rate of 1.63 Gy/min was used to mimic the near-field environment surrounding waste canisters. The expected maximum surface dose rate from one unbreached canister designed to contain spent nuclear fuels is 0.06 Gy/min. Considering the current repository packing design, multiple canisters within one vault, the cumulative dose rate may well approach that used in this experiment. The microbial communities were characterized after receiving cumulative doses of 0, 0.098, 0. 58, 2.33, 4.67, 7.01 and 9.34 kGy. Radiation-resistant microorganisms in the pulverized rock became viable but nonculturable (VBNC) after a cumulative dose of 2.33 kGy. VBNC microorganisms lose the ability to grow on media on which they have routinely been cultured in response to the environmental stress imposed (i.e. radiation) but can be detected throughout the time course using direct fluorescence microscopy techniques. Two representative exopolysaccharide-producing isolates from Yucca Mountain were exposed to the same radiation regimen in sand microcosms. One isolate was much more radiation-resistant than the other, but both had greater resistance than the general microbial community based on culturable counts. However, when respiring cell counts (VBNC) were compared after irradiation, the results would indicate much more radiation resistance of the individual isolates and the microbial community in general. These results have significant implications for underground storage of nuclear waste as they indicate that indigenous microorganisms are capable of surviving gamma irradiation in a VBNC state.

Use of the hyperinsulinemic euglycemic clamp to assess insulin sensitivity in guinea pigs: dose response, partitioned glucose metabolism, and species comparisons.

PubMed

Horton, Dane M; Saint, David A; Owens, Julie A; Gatford, Kathryn L; Kind, Karen L

2017-07-01

The guinea pig is an alternate small animal model for the study of metabolism, including insulin sensitivity. However, only one study to date has reported the use of the hyperinsulinemic euglycemic clamp in anesthetized animals in this species, and the dose response has not been reported. We therefore characterized the dose-response curve for whole body glucose uptake using recombinant human insulin in the adult guinea pig. Interspecies comparisons with published data showed species differences in maximal whole body responses (guinea pig ≈ human < rat < mouse) and the insulin concentrations at which half-maximal insulin responses occurred (guinea pig > human ≈ rat > mouse). In subsequent studies, we used concomitant d-[3- 3 H]glucose infusion to characterize insulin sensitivities of whole body glucose uptake, utilization, production, storage, and glycolysis in young adult guinea pigs at human insulin doses that produced approximately half-maximal (7.5 mU·min -1 ·kg -1 ) and near-maximal whole body responses (30 mU·min -1 ·kg -1 ). Although human insulin infusion increased rates of glucose utilization (up to 68%) and storage and, at high concentrations, increased rates of glycolysis in females, glucose production was only partially suppressed (~23%), even at high insulin doses. Fasting glucose, metabolic clearance of insulin, and rates of glucose utilization, storage, and production during insulin stimulation were higher in female than in male guinea pigs ( P < 0.05), but insulin sensitivity of these and whole body glucose uptake did not differ between sexes. This study establishes a method for measuring partitioned glucose metabolism in chronically catheterized conscious guinea pigs, allowing studies of regulation of insulin sensitivity in this species. Copyright © 2017 the American Physiological Society.

Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A1 and A2A subtype receptor agonists.

PubMed

Schindler, Charles W; Karcz-Kubicha, Marzena; Thorndike, Eric B; Müller, Christa E; Tella, Srihari R; Ferré, Sergi; Goldberg, Steven R

2005-03-01

1. The cardiovascular effects of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the adenosine A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) were investigated in rats implanted with telemetry transmitters for the measurement of blood pressure and heart rate. 2. Intraperitoneal (i.p.) injections of the adenosine A1 receptor agonist CPA led to dose-dependent decreases in both blood pressure and heart rate. These effects of 0.3 mg kg(-1) CPA were antagonized by i.p. injections of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethyl-xanthine (CPT), but not by i.p. injections of the adenosine A2A receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3). Injections (i.p.) of the peripherally acting nonselective adenosine antagonist 8-sulfophenyltheophylline (8-SPT) and the purported nonselective adenosine antagonist caffeine also antagonized the cardiovascular effects of CPA. 3. The adenosine A2A agonist CGS 21680 given i.p. produced a dose-dependent decrease in blood pressure and an increase in heart rate. These effects of 0.5 mg kg(-1) CGS 21680 were antagonized by i.p. injections of the adenosine A2A receptor antagonist MSX-3, but not by i.p. injections of the antagonists CPT, 8-SPT or caffeine. 4. Central administration (intracerebral ventricular) of CGS 21680 produced an increase in heart rate, but no change in blood pressure. MSX-3 given i.p. antagonized the effects of the central injection of CGS 21680. 5. These results suggest that adenosine A1 receptor agonists produce decreases in blood pressure and heart rate that are mediated by A1 receptors in the periphery, with little or no contribution of central adenosine A1 receptors to those effects. 6. The heart rate increasing effect of adenosine A2A agonists appears to be mediated by adenosine A2A receptors in the central nervous system. The blood pressure decreasing effect of adenosine A2A agonists is most probably mediated in the periphery.

[Antibiotic management of acute otitis media. New recommendations].

PubMed

Longuet, P

2000-12-02

FAILURES OF ANTIBIOTIC TREATMENT: The number of failures after treatment of acute middle ear infections with the 2 main antibiotics prescribed (amoxicillin and the combination amoxicillin-clavulanic acid) is on the rise. These failures appear to be related to increased resistance of the 2 principal pathogens, pneumococci and Hemophilus influenzae. A NEW FORMULATION: In order to reduce the rate of failure, it has been necessary to both increase the dose of penicillin to overcome the reduced susceptibility of pneumococci to penicillin and to prescribe a beta-lactam because of the frequent isolation of beta-lactamase producing Hemophilus influenzae. A new formulation has been developed where the amoxicillin-clavulanic acid dose is 14 to 1. This allows a daily dose of 80 mg/kg for amoxicillin and 6.4 mg/kg for clavulanic acid. In one open multicentric study including 51 pediatric patients aged 3 to 48 months with acute middle ear infections, it was demonstrated that this new formulation can be very effective in eradicating the causal agents of acute middle ear infections, including pneumococci and penicillin-resistant Hemophilus. RECOMMENDATIONS FOR GOOD EFFICACY: Amoxicillin must always be prescribed, either alone or in combination with clavulanic acid, at the dose of 45 to 50 mg/kg b.i.d. the amoxicillin-clavulanic acid combination should be preferred for children under 2 years due to the risk of beta-lactamase producing Hemophilus.

ELDRS Characterization for a Very High Dose Mission

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

Time-Course of the Ethanol-like Discriminative Stimulus Effects of Abused Inhalants in Mice

PubMed Central

Bowen, Scott E.

2009-01-01

Abused solvents have effects similar to those of abused depressant drugs. This experiment evaluated the time course of the discriminative stimulus effects of toluene and 1,1,1-trichloroethane (TRI). Mice were trained to discriminate between i.p. injections of ethanol (EtOH;1.25 g/kg) and saline in a two-lever operant task in which responding was under the control of a fixed-ratio 20 schedule. After 20-min inhalation exposures to toluene (500–6000 ppm) or TRI (1,000–12,000 ppm), stimulus generalization was examined at 0, 5, 10, 20, and 40 min post-exposure. Ethanol doses ≥ 0.25 g/kg produced increases in EtOH-lever responding with full substitution occurring immediately after testing for doses between 1.25 and 2.5 g/kg. Toluene and TRI produced increased EtOH-lever responding at 0–10 min post exposure with some EtOH-lever responding occurring up to 20-min post exposure. Response rates were not decreased for any concentration of toluene or TRI immediately following inhalant exposure but several concentrations elevated rates from 5–40 min post exposure. These results confirm and extend previous studies and show these solvents produce similar effects in EtOH-lever responding but with potency differences. The time-dependent differences in EtOH-lever responding suggest that as solvents are cleared from the body, the EtOH-like subjective effects also fade. PMID:18722399

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

DOE PAGES

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

2016-10-07

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

Ultraviolet-B radiation increases serum 25-hydroxyvitamin D levels: the effect of UVB dose and skin color.

PubMed

Armas, Laura A G; Dowell, Susan; Akhter, Mohammed; Duthuluru, Sowjanya; Huerter, Christopher; Hollis, Bruce W; Lund, Richard; Heaney, Robert P

2007-10-01

Ultraviolet (UV)-B light increases vitamin D levels, but the dose response and the effect of skin pigmentation have not been well characterized. We sought to define the relationship between UVB exposure and 25-hydroxyvitamin D (25-OH-D) concentrations as a function of skin pigmentation. Seventy two participants with various skin tones had 90% of their skin exposed to UVB light (20-80 mJ/cm2) 3 times a week for 4 weeks. Serum 25-OH-D was measured weekly. Eighty percent of the variation in treatment response was explained by UVB dose and skin tone. Therapeutically important changes in 25-OH-D were achieved with minimal tanning. Four weeks was not long enough to reach a steady state at the higher dose rates. The response of 25-OH-D levels to UVB light is dependent on skin pigmentation and the amount of UVB given, and useful increases in vitamin D status can be achieved by defined UVB doses small enough to produce only minimal tanning.

Imidacloprid-treated seed ingestion has lethal effect on adult partridges and reduces both breeding investment and offspring immunity.

PubMed

Lopez-Antia, Ana; Ortiz-Santaliestra, Manuel E; Mougeot, François; Mateo, Rafael

2015-01-01

The ingestion of imidacloprid treated seeds by farmland birds may result in exposure to toxic amounts of this insecticide. Here we report on the effects that the exposure to the recommended application rate and to 20% of that rate may produce on birds feeding on treated seeds. Experimental exposure to imidacloprid treated seeds was performed on red-legged partridges (Alectoris rufa) (n=15 pairs per treatment group: control, 20% or 100% of the recommended application rate) during two periods that corresponded to the autumn (duration of exposure: 25 days) and late winter (10 days) cereal sowing times in Spanish farmlands. We studied effects on the survival, body condition, oxidative stress biomarkers, plasma biochemistry, carotenoid-based coloration, T-cell mediated immune response and reproduction of exposed adult partridges, and on the survival and T-cell immune response of their chicks. The high dose (recommended application rate) killed all partridges, with mortality occurring faster in females than in males. The low dose (20% the recommended application rate) had no effect on mortality, but reduced levels of plasma biochemistry parameters (glucose, magnesium and lactate dehydrogenase), increased blood superoxide dismutase activity, produced changes in carotenoid-based integument coloration, reduced the clutch size, delayed the first egg lay date, increased egg yolk vitamins and carotenoids and depressed T-cell immune response of chicks. Moreover, the analysis of the livers of dead partridges revealed an accumulation of imidacloprid during exposure time. Despite the moratorium on the use of neonicotinoids in the European Union, birds may still be at high risk of poisoning by these pesticides through direct sources of exposure to coated seeds in autumn and winter. Copyright © 2014 Elsevier Inc. All rights reserved.

Systemic Effects of Intracoronary Nitroglycerin during Coronary Angiography in Children after Heart Transplantation

PubMed Central

Lara, Diego A.; Olive, Mary K.; George, James F.; Brown, Robert N.; Carlo, Waldemar F.; Colvin, Edward V.; Steenwyck, Brad L.

2014-01-01

Coronary spasm during coronary angiography for vasculopathy in children can be prevented by the intracoronary administration of nitroglycerin. We reviewed the anesthesia and catheterization reports and charts for pediatric transplant recipients who underwent angiography from 2005 through 2010. Correlation analysis was used to study the relation of post-injection systolic blood pressure (SBP) to nitroglycerin dose. Forty-one angiographic evaluations were performed on 25 patients (13 male and 12 female). Mean age was 9.9 ± 3.2 years (range, 3.3–16.1 yr). The mean total dose of nitroglycerin was 2.93 ± 1.60 µg/kg (range, 1–8 µg/kg). There was a significant drop between the baseline SBP (mean, 106 ± 21.6 mmHg) and the lowest mean SBP before nitroglycerin administration (78 ± 13.2, P <0.0001, paired t test). There was no significant additional change in SBP (mean after nitroglycerin administration, 80.7 ± 13.1 mmHg; P = 0.2). There was a significant drop in lowest heart rate between baseline (109 ± 16.5 beats/min) and before nitroglycerin administration (89 ± 14.3 beats/min; P <0.0001, paired t test). There was no significant additional change in heart rate (mean heart rate after nitroglycerin, 84 ± 17.7 beats/min; P = 0.09). There were 2 interventions for SBP before nitroglycerin and 2 after nitroglycerin. One child experienced a transient ST-T–segment change during angiography after nitroglycerin. In the highest dose range, the additional decrease in SBP was 7.2 mmHg (P=0.03). Routine intracoronary nitroglycerin administration in this dose range produced no significant changes in SBP or heart rate in children. PMID:24512395

Systemic effects of intracoronary nitroglycerin during coronary angiography in children after heart transplantation.

PubMed

Lara, Diego A; Olive, Mary K; George, James F; Brown, Robert N; Carlo, Waldemar F; Colvin, Edward V; Steenwyck, Brad L; Pearce, F Bennett

2014-02-01

Coronary spasm during coronary angiography for vasculopathy in children can be prevented by the intracoronary administration of nitroglycerin. We reviewed the anesthesia and catheterization reports and charts for pediatric transplant recipients who underwent angiography from 2005 through 2010. Correlation analysis was used to study the relation of post-injection systolic blood pressure (SBP) to nitroglycerin dose. Forty-one angiographic evaluations were performed on 25 patients (13 male and 12 female). Mean age was 9.9 ± 3.2 years (range, 3.3-16.1 yr). The mean total dose of nitroglycerin was 2.93 ± 1.60 µg/kg (range, 1-8 µg/kg). There was a significant drop between the baseline SBP (mean, 106 ± 21.6 mmHg) and the lowest mean SBP before nitroglycerin administration (78 ± 13.2, P <0.0001, paired t test). There was no significant additional change in SBP (mean after nitroglycerin administration, 80.7 ± 13.1 mmHg; P = 0.2). There was a significant drop in lowest heart rate between baseline (109 ± 16.5 beats/min) and before nitroglycerin administration (89 ± 14.3 beats/min; P <0.0001, paired t test). There was no significant additional change in heart rate (mean heart rate after nitroglycerin, 84 ± 17.7 beats/min; P = 0.09). There were 2 interventions for SBP before nitroglycerin and 2 after nitroglycerin. One child experienced a transient ST-T-segment change during angiography after nitroglycerin. In the highest dose range, the additional decrease in SBP was 7.2 mmHg (P=0.03). Routine intracoronary nitroglycerin administration in this dose range produced no significant changes in SBP or heart rate in children.

[Anaphylaxis related to measles, mumps, and rubella vaccine in Santa Catarina State, Brazil, 2014 and 2015].

PubMed

Fantinato, Francieli Fontana Sutile Tardetti; Vargas, Alexander; Carvalho, Sandra Maria Deotti; Domingues, Carla Magda Allan Santos; Barreto, Gisele; Fialho, Arieli Schiessl; Silva, Roselita Heinen da; Saad, Eduardo; Agredo, Ivonne Natalia Solarte

2018-03-12

The study aimed to describe cases and verify the frequency of anaphylaxis related to measles, mumps, and rubella (MMR) vaccine produced by manufacturer A and to assess associated risk factors. This was a case-control study (1:4) in Santa Catarina State, Brazil, from July 14, 2014, to January 12, 2015, in children from one year to less than five years of age, vaccinated with MMR and reported with anaphylaxis, while the controls were without anaphylaxis. The measure of association was odds ratio (OR) with 95% confidence interval (95%CI), using the chi-square and Fisher's exact tests. Anaphylaxis rates were calculated per doses distributed/administered. Fifteen cases and 60 controls were interviewed in 12 municipalities (counties). Anaphylaxis rates were 2.46 and 5.05 cases per 100,000 doses distributed and administered, respectively. Among the cases of anaphylaxis, eight (53.4%) were males, and among the controls, 36 (60%), with p = 0.64. The bivariate analysis of anaphylaxis and cow's milk protein allergy (CMPA) showed OR = 51.62, with p = 0.00002 and 95%CI: 5.59-476.11. The variables family food allergy, breastfeeding, previous post-vaccine adverse event (PVAE), and simultaneous vaccination were not statistically significant (p = 0.48; p = 1.00; p = 0.49; p = 0.61). Anaphylaxis rates per doses distributed/administered exceeded 1/100,000 doses administered (expected rate). Anaphylaxis and CMPA showed a statistically significant association. No statistically significant associations were found with simultaneous vaccination, breastfeeding, family food allergy, or history of PVAE. the manufacturer should specify the product's components in the package insert, and children with a history of CMPA should not be vaccinated with this vaccine.

Short-term mechanisms of toxic action of airborne particulates underlie dose-rate dependent health risks and support control of one-hour airborne particle levels

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

Michaels, R.A.; Kleinman, M.T.

1999-07-01

Twenty-four-hour airborne particle mass levels permissible under the NAAQS have been associated with mortality and morbidity in communities, motivating reconsideration of the standard. Reports of shorter-term mechanisms of toxic action exerted by airborne PM and PM constituents are emerging. The mechanisms are diverse, but have in common a short time frame of toxic action, from minutes to hours. In view of documented PM excursions also lasting minutes to hours, this study inquires whether such short-term mechanisms might contribute to explaining daily morbidity and mortality. Toxicology experiments have demonstrated the harmfulness of brief exposure to PM levels in the range ofmore » observed excursions. This suggests that toxicological processes initiated by short-term inhalation of PM may exert clinically important effects, and that weak associations of 24-hour-average particle mass with mortality and morbidity may represent artifacts of stronger, shorter-term associations whose full magnitude remains to be quantified. In one study, the area of lung surface developing lesions was elevated in rats breathing the same four-hour dose of aerosols, when the four-hour average rate of aerosol delivery included a short-term (five-minute) burst fifty percent above the average dose rate. Elevations were observed with each of two aerosols tested. The magnitude of the effect was higher with one of the two aerosols, whose dose rate included four excursions rather than just one excursion. Particulate matter inhaled or instilled intratracheally has produced morbidity in animals, including apnea and electrophysiological effects in dogs. Other studies reveal that PM can kill rats via electrophysiological and possibly other mechanisms. PM has also adversely affected asthmatic people in controlled clinical settings during exercise or, in one study, at rest.« less

Ultrafast 2-dimensional image monitoring and array-based passive cavitation detection for ultrasound contrast agent destruction in a variably sized region.

PubMed

Xu, Shanshan; Hu, Hong; Jiang, Hujie; Xu, Zhi'an; Wan, Mingxi

2014-11-01

A combined approach was proposed, based on programmable ultrasound equipment, to simultaneously monitor surviving microbubbles and detect cavitation activity during microbubble destruction in a variably sized region for use in ultrasound contrast agent (UCA)-enhanced therapeutic ultrasound applications. A variably sized focal region wherein the acoustic pressure was above the UCA fragmentation threshold was synthesized at frequencies of 3, 4, 5, and 6 MHz with a linear broadband imaging probe. The UCAs' temporal and spatial distribution during the microbubbles' destruction was monitored in a 2-dimensional imaging plane at 5 MHz and a frame rate of 400 Hz, and simultaneously, broadband noise emissions during the microbubbles' fragmentation were extracted by using the backscattered signals produced by the focused release bursts (ie, destruction pulses) themselves. Afterward, the temporal evolution of broadband noise emission, the surviving microbubbles in a region of interest (ROI), and the destruction area in a static UCA suspension were computed. Then the inertial cavitation dose, destruction rate of microbubbles in the ROI, and area of the destruction region were determined. It was found that an increasing pulse length and a decreasing transmit aperture and excitation frequency were correlated with an increased inertial cavitation dose, microbubble destruction rate, and destruction area. Furthermore, it was obvious that the microbubble destruction rate was significantly correlated with the inertial cavitation dose (P < .05). In addition, the intensity decrease in the ROI was significantly correlated with the destruction area (P < .05). By the proposed strategy, microbubbles could be destroyed in a variably sized region, and destruction efficiency as well as the corresponding inertial cavitation dose could be regulated by manipulating the transmission parameters. © 2014 by the American Institute of Ultrasound in Medicine.

Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization?

PubMed

Chen, Xin; Feng, Shu-xian; Guo, Ping-ping; He, Yu-xia; Liu, Yu-dong; Ye, De-sheng; Chen, Shi-ling

2016-04-01

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

Development of a PET cyclotron based irradiation setup for proton radiobiology

NASA Astrophysics Data System (ADS)

Ghithan, Sharif; Crespo, Paulo; do Carmo, S. J. C.; Ferreira Marques, Rui; Fraga, F. A. F.; Simões, Hugo; Alves, Francisco; Rachinhas, P. J. B. M.

2015-02-01

An out-of-yoke irradiation setup using the proton beam from a cyclotron that ordinary produces radioisotopes for positron emission tomography (PET) has been developed, characterized, calibrated and validated. The current from a 20 μm thick aluminum transmission foil is readout by home-made transimpedance electronics, providing online dose information. The main monitoring variables, delivered in real-time, include beam current, integrated charge and dose rate. Hence the dose and integrated current delivered at a given instant to an experimental setup can be computer-controlled with a shutter. In this work, we report on experimental results and Geant4 simulations of a setup which exploits for the first time the 18 MeV proton beam from a PET cyclotron to irradiate a selected region of a target using the developed irradiation system. By using this system, we are able to deliver a homogeneous beam on targets with 18 mm diameter, allowing to achieve the controlled irradiation of cell cultures located in biological multi-well dishes of 16 mm diameter. We found that the magnetic field applied inside the cyclotron plays a major role for achieving the referred to homogeneity. The quasi-Gaussian curve obtained by scanning the magnet current and measuring the corresponding dose rate must be measured before any irradiation procedure, with the shutter closed. At the optimum magnet current, which corresponds to the center of the Gaussian, a homogenous dose is observed over the whole target area. Making use of a rotating disk with a slit of 0.5 mm at a radius of 150 mm, we could measure dose rates on target ranging from 500 mGy/s down to 5 mGy/s. For validating the developed irradiation setup, several Gafchromic® EBT2 films were exposed to different values of dose. The absolute dose in the irradiated films were assessed in the 2D film dosimetry system of the Department of Radiotherapy of Coimbra University Hospital Center with a precision better than 2%. In the future, we plan to irradiate small animals, cell cultures, or other materials or samples.

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

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

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

Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.

Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses ofmore » 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.« less

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

PubMed

Oakes, Jennifer; Seifert, Steven

2008-12-01

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

Current clinical use of reteplase for thrombolysis. A pharmacokinetic-pharmacodynamic perspective.

PubMed

Martin, U; Kaufmann, B; Neugebauer, G

1999-04-01

Clinical evaluation of a new thrombolytic agent should start with a dose that provides adequate efficacy and has an acceptably low bleeding risk; this results in a narrow therapeutic window at the upper end of the dose-response curve. Angiographic patency of the infarct-related artery is still the clinical surrogate end-point for mortality in phase II dose-ranging studies. There is experimental and clinical evidence that the area under the concentration-time curve (AUC) for plasminogenolytic activity of a thrombolytic agent is positively correlated with patency of the infarct-related artery. Dose-ranging studies of the novel recombinant plasminogen activator reteplase in healthy volunteers enabled computation of a linear regression curve by which a clinical starting dose could be calculated for an adapted target AUC that would be clinically effective. Pharmacokinetic analysis also revealed that the half-life of reteplase is 4 times longer than that of the reference thrombolytic alteplase, thus allowing bolus injection. The suggested single bolus starting dose of 10U was supported by results from studies in a canine model of coronary thrombolysis. The feedback of insufficiently high patency rates compared with the increased efficacy of front-loaded and accelerated alteplase demanded optimisation strategies for reteplase. Animal experiments suggested that a double bolus regimen of reteplase would be preferable to doubling the single bolus dose. Pharmacokinetic modelling suggested a time interval of 30 min between the 2 bolus injections. Selection of the tested double bolus regimens was conservative and empirical. First, the previously tested single bolus of 15U was divided to 10 + 5U; secondly, the second bolus dose was increased to 10U. This strategy proved to be successful. The current dosage recommendation for reteplase is a double bolus intravenous injection of 10 + 10U, each over 2 min, 30 min apart. This produces a reduction in mortality in patients with acute myocardial infarction that is equivalent to that produced by front-loaded and accelerated infusion of alteplase.

(-)-Norpseudoephedrine, a metabolite of cathinone with amphetamine-like stimulus properties, enhances the analgesic and rate decreasing effects of morphine, but inhibits its discriminative properties.

PubMed

Nencini, P; Fraioli, S; Pascucci, T; Nucerito, C V

1998-04-01

Like psychomotor stimulants, a weak amphetamine-like agent, such as phenylpropanolamine, enhances the analgesic effects of morphine (MOR). Thus, it is possible that full psychomotor stimulant potency is not required to increase the analgesic action of opiates. The validity of this assumption is here tested by studying the ability of (-)-norpseudoephedrine (NPE), an enantiomer of phenylpropanolamine and a metabolite of cathinone, to influence both the analgesic effects of MOR and its discriminative stimulus properties. In mice NPE (5.6-10.0-17.0 mg/kg i.p.) did not prolong the latency to lick or to remove paws from a plate warmed at 54 degrees C. However, it significantly potentiated the analgesic effect of 3.2 mg/kg of MOR. These results were replicated in rats by use of the formalin test, which measures the numbers of hind paw flinches produced by injecting 50 microl of formalin into the dorsal surface of the paw. The higher dose of NPE (17 mg/kg) increased the effect of sub-analgesic doses of MOR (0.56 and 1.0 mg/kg). In rats trained to discriminate between 0.5 mg/kg of amphetamine and solvent in a two-lever operant behavior reinforced by water access. NPE induced a dose-dependent increment of drug lever responding from 0% at 1.0 mg/kg to 100% at 32.0 mg/kg. In contrast, NPE did not generalize for the MOR cue up to the dose of 56.0 mg/kg, which produced a substantial reduction of the response rate. However, when given in combination, NPE attenuated the discriminative effects of MOR and potentiated its inhibitory action on the response rate. These results exclude a direct action of NPE on the mu opiate system. In conclusion, NPE preserves amphetamine-like properties and these properties are probably responsible for the interaction of the drug with the analgesic and discriminative effects of MOR. Therefore, this study contradicts the assumption that the analgesic effects of MOR can be enhanced by a sympathomimetic drug that lacks significant psychostimulant actions.

Effects of acute and repeated oral exposure to the organophosphate insecticide chlorpyrifos on open-field activity in chicks.

PubMed

Al-Badrany, Y M A; Mohammad, F K

2007-11-01

The effects of the organophosphate insecticide chlorpyrifos on 5min open-field activity were examined in a 7-15 days old chick model. Chlorpyrifos was acutely administered taking into account cholinesterase inhibition and determination of the acute (24h) median lethal dose (LD50). The oral LD50 value of chlorpyrifos in chicks was 18.14mg/kg, with cholinergic toxicosis observed on intoxicated chicks. Chlorpyrifos at the dose rates of 5,10 and 20mg/kg orally produced within 2h signs of cholinergic toxicosis in the chicks and significantly inhibited plasma (40-70%), whole brain (43-69%) and liver (31-46%) cholinesterase activities in a dose-dependent manner. Chlorpyrifos at 2 and 4mg/kg, orally did not produce overt signs of cholinergic toxicosis, but decreased (30, 60 and 90min after dosing) the general locomotor activity of the chicks as seen by a significant increase in the latency to move from the central square of the open-field arena, decreases in the numbers of lines crossed and vocalization score. Repeated daily chlorpyrifos treatments (2 and 4mg/kg, orally) for seven consecutive days also caused hypoactivity in chicks in the open-field behavioral paradigm. Only the high dose of chlorpyrifos (4mg/kg, orally) given repeatedly for 7 days caused significant cholinesterase inhibition in the whole brain (37%) and the liver (22%). In conclusion, chlorpyrifos at single or short-term repeated doses-induced behavioral changes in 7-15 days old chicks, in a model that could be used for further neurobehavioral studies involving subtle effects of organophosphates on chicks.

Protective role of ascorbic acid in the decontamination of cow milk casein by gamma-irradiation.

PubMed

Kouass Sahbani, Saloua; Klarskov, Klaus; Aloui, Amine; Kouass, Salah; Landoulsi, Ahmed

2013-06-01

The aim of this work was to investigate the protective role of ascorbic acid on irradiation-induced modification of casein. Casein stock solutions were irradiated with increasing doses 2-10 kGy using (60)Co Gamma rays at a dose rate D• = 136.73 Gy/min at room temperature. The total viable microorganism content of cow milk casein was evaluated by Plate Count Agar (PCA) incubation for 48 h at 37°C. Sodium dodecylsulfate gel electrophoresis (SDS-PAGE) and Matrix-Assisted Laser Desorption-Ionization Time-of-Flight mass spectrometry (MALDI-TOF-MS) analysis were used to evaluate the effect of gamma irradiation on casein integrity. Gamma irradiation reduced the bacterial contamination of casein solutions at a lower irradiation dose when performed in the presence of ascorbic acid. The irradiation treatment of casein in the absence of ascorbic acid with a dose of 4 kGy could reduce 99% of the original amount of bacterial colonies. However, in the presence of ascorbic acid the irradiation treatment of casein with a dose lower than 2 kGy could reduce 99% of the original amount of bacterial colonies which suggested that the irradiation dose lower than 2 kGy achieved almost the entire decontamination result. SDS-PAGE and MALDI-TOF-MS analysis showed that ascorbic acid protected cow milk casein from degradation and subsequent aggregation probably by scavenging oxygen and protein radicals produced by the irradiation. It is demonstrated that the combination of gamma irradiation and ascorbic acid produce additive effects, providing acceptable hygienic quality of cow milk casein and protects caseins against Reactive Oxygen Species (ROS) generated, during the irradiation process.

Cardiovascular and behavioral responses of gray wolves to ketamine-xylazine immobilization and antagonism by yohimbine

USGS Publications Warehouse

Kreeger, T.J.; Faggella, A.M.; Seal, U.S.; Mech, L.D.; Callahan, Margaret; Hall, B.

1987-01-01

Adult wolves (Canis lupus) were immobilized with 6.6 mg/kg ketamine hydrochloride (KET) and 2.2 mg/kg xylazine hydrochloride (XYL) administered intramuscularly. Induction time was 4.6 ± 0.3 min (x̄ ± SE). Immobilization resulted in significant bradycardia and hypertension (P < 0.05). Twenty min after induction, the wolves were given 0.05–0.60 mg/kg yohimbine hydrochloride (YOH). Yohimbine given intravenously produced dose-related increases in heart rate (HR) with doses >0.15 mg/kg resulting in extreme tachycardia (>300 bpm). All doses of YOH caused a temporary decrease in mean arterial blood pressure (MABP) with some individual animals manifesting profound hypotension (<30 torr) at doses >0.15 mg/kg. Increasing the dose of YOH above 0.15 mg/kg did not significantly decrease either arousal or ambulation times. Administering YOH at 40 or 60 min after induction resulted in decreased arousal and ambulation times. Stimulation by weighing and taking repeated blood samples during anesthesia did not shorten arousal times. We recommend that wolves immobilized with XYL-KET be antagonized with doses of YOH <0.15 mg/kg.

Novel delivery device for monolithical solid oral dosage forms for personalized medicine.

PubMed

Wening, Klaus; Breitkreutz, Jörg

2010-08-16

There is an evident need for solid oral dosage forms allowing patients' tailor-made dosing due to variations in metabolization or small therapeutic indexes of drug substances. The objective of this work is the development of a device equipped with a novel solid dosage form, containing carvedilol as model drug, for the delivery of monolithical drug carriers in individual doses. The device was developed and constructed enabling an exact feed rate and dose adjustment by a cutting mechanism. A twin-screw extruder was used for producing cylindrical solid dosage forms. Divided doses were characterized by mass variation, cutting behavior and drug dissolution in order to investigate their applicability for practical use. Different formulations could be extruded obtaining straight cylindrical rods, which are divisible in exact slices by using the novel device. Forces below 20 N were needed to divide doses which comply with pharmacopoeial specification "conformity of mass". The developed formulations exhibit a sustained release of carvedilol within a range from 7 up to 16 h. A novel system consisting of a device and a cylindrical dosage form was developed. Patients' individual doses can be applied as monolithical solid dosage forms for oral use.

Low dose X -ray effects on catalase activity in animal tissue

NASA Astrophysics Data System (ADS)

Focea, R.; Nadejde, C.; Creanga, D.; Luchian, T.

2012-12-01

This study was intended to investigate the effect of low-dose X ray-irradiation upon the activity of catalase (CAT) in freshly excised chicken tissues (liver, kidney, brain, muscle). The tissue samples were irradiated with 0.5Gy and 2Gy respectively, in a 6 MV photon beam produced by a clinical linear accelerator (VARIAN CLINAC 2100SC). The dose rate was of 260.88cGy/min. at 100 cm source to sample distance. The catalase level was assayed spectrophotometrically, based on reaction kinetics, using a catalase UV assay kit (SIGMA). Catalase increased activity in various tissue samples exposed to the studied X ray doses (for example with 24 % in the liver cells, p<0.05) suggested the stimulation of the antioxidant enzyme biosynthesis within several hours after exposure at doses of 0.5 Gy and 2 Gy; the putative enzyme inactivation could also occur (due to the injuries on the hydrogen bonds that ensure the specificity of CAT active site) but the resulted balance of the two concurrent processes indicates the cell ability of decomposing the hydrogen peroxide-with benefits for the cell physiology restoration for the chosen low dose radiation.

Discriminative stimulus effects of caffeine and benzphetamine in amphetamine-trained volunteers.

PubMed

Chait, L D; Johanson, C E

1988-01-01

The discriminative stimulus (DS) and subjective effects of caffeine (100 and 300 mg, PO) and benzphetamine (12.5 and 50 mg, PO) were studied in 18 normal human volunteers trained to discriminate between d-amphetamine (10 mg) and placebo. d-Amphetamine increased ratings of drug liking and activity level and produced a profile of subjective effects characteristic of amphetamine and related psychomotor stimulants. The DS effects of d-amphetamine generalized only partially to caffeine and benzphetamine; mean percent d-amphetamine-appropriate responding was 42 and 58 after 100 and 300 mg caffeine, respectively, and 17 and 56 after 12.5 and 50 mg benzphetamine, respectively. Neither dose of caffeine affected ratings of drug liking or activity level, but 300 mg caffeine did produce a profile of subjective effects that partially overlapped with that produced by d-amphetamine. Benzphetamine 50 mg, but not 12.5 mg, increased ratings of drug liking and activity level and produced a profile of subjective effects qualitatively similar to, but weaker than, that produced by d-amphetamine. For both caffeine and benzphetamine, a close relationship was observed between their subjective effects and their ability to substitute for the DS effects of d-amphetamine. These results correspond well with findings obtained from similar studies conducted with laboratory animals, providing further support for the reliability and validity of human drug discrimination paradigms.

Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise.

PubMed

Hubbell, J A E; Sams, R A; Schmall, L M; Robertson, J T; Hinchcliff, K W; Muir, W W

2009-05-01

Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatography-mass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.

Effects of intravenous nonsteroidal antiinflammatory drugs on a C-fiber reflex elicited by a wide range of stimulus intensities in the rat.

PubMed

Bustamante, D; Paeile, C; Willer, J C; Le Bars, D

1996-03-01

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve, was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. The i.v. administration of aspirin, indomethacin, ketoprofen, paracetamol (= acetaminophen) and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex by up to 30 to 40%. By contrast, saline was ineffective. High doses of the effective drugs that produced large disturbances in heart rate and/or acid-base equilibrium were not considered in the pharmacological analysis. When a constant level of stimulation was used, different dose-dependent profiles of drug action were observed. Aspirin induced a slow and gradual depression, although indomethacin, ketoprofen and paracetamol produced a peak effect within the first 10-min period and then reached a steady state phase for up to 30 min. The depressive effects of lysine clonixinate appeared more stable. When recruitment curves were built with a range of nociceptive stimulus intensities, all the drugs produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without any major modification in the thresholds. The order of potency was the same for both stimulation paradigms, e.g., aspirin < paracetamol < lysine clonixinate = ketoprofen < indomethacin. It is concluded that NSAID elicit significant antinociceptive effects at a central level, which do not depend on the existence of a hyperalgesic or inflammatory state.

Design of a boron neutron capture enhanced fast neutron therapy assembly

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

Wang, Zhonglu

The use of boron neutron capture to boost tumor dose in fast neutron therapy has been investigated at several fast neutron therapy centers worldwide. This treatment is termed boron neutron capture enhanced fast neutron therapy (BNCEFNT). It is a combination of boron neutron capture therapy (BNCT) and fast neutron therapy (FNT). It is believed that BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiform (GBM). A boron neutron capture enhanced fast neutron therapy assembly has been designed for the Fermilab Neutron Therapy Facility (NTF). This assembly uses a tungsten filter and collimator nearmore » the patient's head, with a graphite reflector surrounding the head to significantly increase the dose due to boron neutron capture reactions. The assembly was designed using Monte Carlo radiation transport code MCNP version 5 for a standard 20x20 cm 2 treatment beam. The calculated boron dose enhancement at 5.7-cm depth in a water-filled head phantom in the assembly with a 5x5 cm 2 collimation was 21.9% per 100-ppm 10B for a 5.0-cm tungsten filter and 29.8% for a 8.5-cm tungsten filter. The corresponding dose rate for the 5.0-cm and 8.5-cm thick filters were 0.221 and 0.127 Gy/min, respectively; about 48.5% and 27.9% of the dose rate of the standard 10x10 cm 2 fast neutron treatment beam. To validate the design calculations, a simplified BNCEFNT assembly was built using four lead bricks to form a 5x5 cm 2 collimator. Five 1.0-cm thick 20x20 cm 2 tungsten plates were used to obtain different filter thicknesses and graphite bricks/blocks were used to form a reflector. Measurements of the dose enhancement of the simplified assembly in a water-filled head phantom were performed using a pair of tissue-equivalent ion chambers. One of the ion chambers is loaded with 1000-ppm natural boron (184-ppm 10B) to measure dose due to boron neutron capture. The measured dose enhancement at 5.0-cm depth in the head phantom for the 5.0-cm thick tungsten filter is (16.6 ± 1.8)%, which agrees well with the MCNP simulation of the simplified BNCEFNT assembly, (16.4 ± 0.5)%. The error in the calculated dose enhancement only considers the statistical uncertainties. The total dose rate measured at 5.0-cm depth using the non-borated ion chamber is (0.765 ± 0.076) Gy/MU, about 61% of the fast neutron standard dose rate (1.255Gy/MU) at 5.0-cm depth for the standard 10x10 cm 2 treatment beam. The increased doses to other organs due to the use of the BNCEFNT assembly were calculated using MCNP5 and a MIRD phantom. The activities of the activation products produced in the BNCEFNT assembly after neutron beam delivery were computed. The photon ambient dose rate due to the radioactive activation products was also estimated.« less

The action of bombesin on the kidney of the anaesthetized dog.

PubMed

Erspamer, V; Melchiorri, P; Sopranzi, N

1973-07-01

1. In the anaesthetized dog bombesin had a potent antidiuretic effect, and sometimes arrested urine flow completely. Threshold doses, by i.v. infusion, were of the order of 0.5-1 (ng/kg)/minute. Antidiuresis was the result of a reduction in glomerular filtration rate provoked by a fall in intraglomerular hydrostatic pressure. This, in its turn, was due to afferent vasoconstriction.2. The spasmogenic effect of bombesin on the smooth muscle of the afferent arterioles was directly demonstrated by the radioactive microspheres technique and indirectly by the (85)Kr washout method and by [(3)H]-p-aminohippurate clearance. The vascular compartment most sensitive to bombesin was that of the outer cortical zone, especially in its external half.3. Filtration fraction decreased under the influence of bombesin, indicating that the effect of the polypeptide on postglomerular arterioles was, if present, only of minor importance.4. At high infusion rates (above 6 (ng/kg)/min), bombesin produced a decrease in [(3)H]-p-aminohippurate extraction. The effect of the polypeptide on fractional distal delivery of sodium varied with the dose: at moderate infusion rates it decreased, at high infusion rates it increased. The total glucose appearing in urine following a glucose load was sharply reduced by bombesin. However, the glomerular filtration rate/maximum tubular glucose transport ratio did not show any appreciable change.5. Afferent vasoconstriction produced by bombesin was accompanied by an intense activation of the renin-angiotensin system, as shown by a conspicuous increase in renin secretion, followed by increases in renin activity and angiotensin II concentration in arterial blood. When bombesin was infused into one renal artery only the infused kidney showed afferent vasoconstriction and increased renin secretion. The time-course of renin secretion produced by bombesin depended upon the rate of infusion of the polypeptide. At low rates an increased renin secretion was observed throughout the infusion period, at high rates two peaks of renin secretion could be seen, one at the beginning of the infusion, the other soon after the infusion had finished.6. The mechanism of action of bombesin is discussed and the interest of the polypeptide as a possible hormonal regulator of the circulation and function of the kidney is pointed out.

Radiation dose-rate meter using an energy-sensitive counter

DOEpatents

Kopp, Manfred K.

1988-01-01

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

Proton Radiotherapy for Solid Tumors of Childhood

PubMed Central

Cotter, Shane E.; McBride, Sean M.; Yock, Torunn I.

2012-01-01

The increasing efficacy of pediatric cancer therapy over the past four decades has produced many long-term survivors that now struggle with serious treatment related morbidities affecting their quality of life. Radiation therapy is responsible for a significant proportion of these late effects, but a relatively new and emerging modality, proton radiotherapy hold great promise to drastically reduce these treatment related late effects in long term survivors by sparing dose to normal tissues. Dosimetric studies of proton radiotherapy compared with best available photon based treatment show significant dose sparing to developing normal tissues. Furthermore, clinical data are now emerging that begin to quantify the benefit in decreased late treatment effects while maintaining excellent cancer control rates. PMID:22417062

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

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

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.

The susceptibility of TaO x-based memristors to high dose rate ionizing radiation and total ionizing dose

DOE PAGES

McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; ...

2014-11-11

This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaO x) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×10 7 rad(Si)/s to 4.7 ×10 8 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×10 8 rad(Si)/s. This is the first dose rate study on any type ofmore » memristive memory technology. In addition to assessing the tolerance of TaO x memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor-prognosis pediatric brain tumors1

PubMed Central

Ziegler, David S.; Cohn, Richard J.; McCowage, Geoffrey; Alvaro, Frank; Oswald, Cecilia; Mrongovius, Robert; White, Les

2006-01-01

The objective of this study was to assess the efficacy of the VETOPEC regimen, a regimen of vincristine and etoposide with escalating doses of cyclophosphamide (CPA), in pediatric patients with high-risk brain tumors. Three consecutive studies by the Australia and New Zealand Children’s Cancer Study Group—VETOPEC I, Baby Brain 91, and VETOPEC II—have used a specific chemotherapy regimen of vincristine (VCR), etoposide (VP-16) and escalating CPA in patients with relapsed, refractory, or high-risk solid tumors. Patients in the VETOPEC II cohort were treated with very high dose CPA with peripheral blood stem cell (PBSC) rescue. We analyzed the subset of patients with high-risk brain tumors treated with these intensive VETOPEC-based protocols to assess the response, toxicity, and survival. We also assessed whether the use of very high dose chemotherapy with stem cell rescue improved the response rate or affected toxicity. Seventy-one brain tumor patients were treated with VETOPEC-based protocols. Of the 54 patients evaluable for tumor response, 17 had a complete response (CR) and 20 a partial response (PR) to treatment, which yielded an overall response rate of 69%. The CR + PR was 83% (19/23) for medulloblastomas, 56% (5/9) for primitive neuroectodermal tumors, 55% (6/11) for grade 3 and 4 astrocytomas, and 80% (6/8) for ependymomas. At a median follow-up of 36 months, overall survival for the entire cohort of 71 patients was 32%, with event-free survival of 13%. There were no toxic deaths within the PBSC-supported VETOPEC II cohort, despite higher CPA doses, compared with 7% among the non-PBSC patients. This regimen produces high response rates in a variety of very poor prognosis pediatric brain tumors. The maximum tolerated dose of CPA was not reached. Higher escalation in doses of CPA did not deliver a further improvement in response. With PBSC rescue in the VETOPEC II study, hematologic toxicity was no longer a limiting factor. The response rates observed support further development of this chemotherapy regimen. PMID:16443948

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.

Beta-adrenoceptive responses in the unanaesthetized ovine foetus.

PubMed

Van Petten, G R; Willes, R F

1970-05-01

1. Isoprenaline injection into either the unanaesthetized ovine foetus or the pregnant ewe produced a transient tachycardia and hypotension in either the ewe or the foetus. No evidence was obtained for placental transfer, in either direction, of pharmacologically active isoprenaline.2. Propranolol, when given to the ewe intravenously, produced bradycardia and increased pulse pressure and inhibited the response of both the ewe and her foetus to isoprenaline. Propranolol, when given to the foetus intravenously, produced bradycardia and increased pulse pressure in both the foetus and the ewe, but only the foetal response to isoprenaline was inhibited. These data demonstrated that propranolol crossed the ovine placenta in both directions in a pharmacologically active form.3. Dose-heart rate curves of the foetus and pregnant ewe to isoprenaline and the shift to the right of the isoprenaline dose-response curves by propranolol were similar in both the ewe and the foetus.4. Notwithstanding the similarities between the ewe and foetus in their responses to isoprenaline or propranolol and in the antagonism of isoprenaline by propranolol, the duration of blockade following propranolol administration to the ewe was 2 to 3 times longer in the foetus compared with the ewe.5. Measurement of blood levels of propranolol showed that the maximum concentration of propranolol in foetal plasma was only 5% of that in the pregnant ewe when propranolol was infused into the ewe; the rate of clearance of propranolol was similar from the foetal and maternal plasma.6. From these data the long duration of beta-adrenoceptor blockade in the ovine foetus by propranolol cannot be fully explained. However, these data serve as examples of the dangers involved when extrapolating pharmacological actions of drugs on the foetus purely from data on foetal plasma levels of the drug.7. The data suggest that multiple doses of propranolol, given to maintain a beta-adrenoceptor blockade in the mother, could result in serious cumulative effects in the foetus.

Self-limiting atomic layer deposition of conformal nanostructured silver films

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

TH-C-12A-04: Dosimetric Evaluation of a Modulated Arc Technique for Total Body Irradiation

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

Tsiamas, P; Czerminska, M; Makrigiorgos, G

2014-06-15

Purpose: A simplified Total Body Irradiation (TBI) was developed to work with minimal requirements in a compact linac room without custom motorized TBI couch. Results were compared to our existing fixed-gantry double 4 MV linac TBI system with prone patient and simultaneous AP/PA irradiation. Methods: Modulated arc irradiates patient positioned in prone/supine positions along the craniocaudal axis. A simplified inverse planning method developed to optimize dose rate as a function of gantry angle for various patient sizes without the need of graphical 3D treatment planning system. This method can be easily adapted and used with minimal resources. Fixed maximum fieldmore » size (40×40 cm2) is used to decrease radiation delivery time. Dose rate as a function of gantry angle is optimized to result in uniform dose inside rectangular phantoms of various sizes and a custom VMAT DICOM plans were generated using a DICOM editor tool. Monte Carlo simulations, film and ionization chamber dosimetry for various setups were used to derive and test an extended SSD beam model based on PDD/OAR profiles for Varian 6EX/ TX. Measurements were obtained using solid water phantoms. Dose rate modulation function was determined for various size patients (100cm − 200cm). Depending on the size of the patient arc range varied from 100° to 120°. Results: A PDD/OAR based beam model for modulated arc TBI therapy was developed. Lateral dose profiles produced were similar to profiles of our existing TBI facility. Calculated delivery time and full arc depended on the size of the patient (∼8min/ 100° − 10min/ 120°, 100 cGy). Dose heterogeneity varied by about ±5% − ±10% depending on the patient size and distance to the surface (buildup region). Conclusion: TBI using simplified modulated arc along craniocaudal axis of different size patients positioned on the floor can be achieved without graphical / inverse 3D planning.« less

pH and Organic Carbon Dose Rates Control Microbially Driven Bioremediation Efficacy in Alkaline Bauxite Residue.

PubMed

Santini, Talitha C; Malcolm, Laura I; Tyson, Gene W; Warren, Lesley A

2016-10-18

Bioremediation of alkaline tailings, based on fermentative microbial metabolisms, is a novel strategy for achieving rapid pH neutralization and thus improving environmental outcomes associated with mining and refining activities. Laboratory-scale bioreactors containing bauxite residue (an alkaline, saline tailings material generated as a byproduct of alumina refining), to which a diverse microbial inoculum was added, were used in this study to identify key factors (pH, salinity, organic carbon supply) controlling the rates and extent of microbially driven pH neutralization (bioremediation) in alkaline tailings. Initial tailings pH and organic carbon dose rates both significantly affected bioremediation extent and efficiency with lower minimum pHs and higher extents of pH neutralization occurring under low initial pH or high organic carbon conditions. Rates of pH neutralization (up to 0.13 mM H + produced per day with pH decreasing from 9.5 to ≤6.5 in three days) were significantly higher in low initial pH treatments. Representatives of the Bacillaceae and Enterobacteriaceae, which contain many known facultative anaerobes and fermenters, were identified as key contributors to 2,3-butanediol and/or mixed acid fermentation as the major mechanism(s) of pH neutralization. Initial pH and salinity significantly influenced microbial community successional trajectories, and microbial community structure was significantly related to markers of fermentation activity. This study provides the first experimental demonstration of bioremediation in bauxite residue, identifying pH and organic carbon dose rates as key controls on bioremediation efficacy, and will enable future development of bioreactor technologies at full field scale.

A generic high-dose rate {sup 192}Ir brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism

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

Ballester, Facundo, E-mail: Facundo.Ballester@uv.es; Carlsson Tedgren, Åsa; Granero, Domingo

Purpose: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) {sup 192}Ir source and a virtual watermore » phantom were designed, which can be imported into a TPS. Methods: A hypothetical, generic HDR {sup 192}Ir source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic {sup 192}Ir source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra{sup ®} Brachy with advanced collapsed-cone engine (ACE) and BrachyVision ACUROS{sup TM}]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and PENELOPE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201){sup 3} voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR {sup 192}Ir source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by different investigators. MC results were then compared against dose calculated using TG-43 and MBDCA methods. Results: TG-43 and PSS datasets were generated for the generic source, the PSS data for use with the ACE algorithm. The dose-rate constant values obtained from seven MC simulations, performed independently using different codes, were in excellent agreement, yielding an average of 1.1109 ± 0.0004 cGy/(h U) (k = 1, Type A uncertainty). MC calculated dose-rate distributions for the two plans were also found to be in excellent agreement, with differences within type A uncertainties. Differences between commercial MBDCA and MC results were test, position, and calculation parameter dependent. On average, however, these differences were within 1% for ACUROS and 2% for ACE at clinically relevant distances. Conclusions: A hypothetical, generic HDR {sup 192}Ir source was designed and implemented in two commercially available TPSs employing different MBDCAs. Reference dose distributions for this source were benchmarked and used for the evaluation of MBDCA calculations employing a virtual, cubic water phantom in the form of a CT DICOM image series. The implementation of a generic source of identical design in all TPSs using MBDCAs is an important step toward supporting univocal commissioning procedures and direct comparisons between TPSs.« less

Comparison of fundamental and wideband harmonic contrast imaging of liver tumors.

PubMed

Forsberg, F; Liu, J B; Chiou, H J; Rawool, N M; Parker, L; Goldberg, B B

2000-03-01

Wideband harmonic imaging (with phase inversion for improved tissue suppression) was compared to fundamental imaging in vivo. Four woodchucks with naturally occurring liver tumors were injected with Imagent (Alliance Pharmaceutical Corp., San Diego, CA). Randomized combinations of dose (0.05, 0.2 and 0.4 ml/kg) and acoustic output power (AO; 5, 25 and 63% or MI < or = 0.9) were imaged in gray scale using a Sonoline Elegra scanner (Siemens Medical Systems, Issaquah, WA). Tumor vascularity, conspicuity and contrast enhancement were rated by three independent observers. Imagent produced marked tumor enhancement and improved depiction of neovascularity at all dosages and AO settings in both modes. Tumor vascularity and enhancement correlated with mode, dose and AO (P < 0.002). Fundamental imaging produced more enhancement (P < 0.05), but tumor vascularity and conspicuity were best appreciated in harmonic mode (P < 0.05). Under the conditions studied here, the best approach was wideband harmonic imaging with 0.2 ml/kg of Imagent at an AO of 25%.

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

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

Starkenburg, Daken J.; Johns, Paul M.; Baciak, James E.

Here, developments in the field of organic semiconductors have generated organic photodetectors with high quantum efficiency, wide spectral sensitivity, low power consumption, and unique form factors that are flexible and conformable to their substrate shape. In this work, organic photodetectors coupled with inorganic CsI(Tl) scintillators are used to showcase the low dose rate sensitivity that is enabled when high performance organic photodetectors and scintillator crystals are integrated. The detection capability of these organic-inorganic coupled systems to high energy radiation highlights their potential as an alternative to traditional photomultiplier tubes for nuclear spectroscopy applications. When exposed to Bremsstrahlung radiation produced frommore » an X-ray generator, SubPc:C 60, AlPcCl:C 70, and P3HT:PC 61BM thin film photodetectors with active layer thicknesses less than 100 nm show detection of incident radiation at low and no applied bias. Remarkably low dose rates, down to at least 0.28 µGy/s, were detectable with a characteristic linear relationship between exposure rate and photodetector current output. These devices also demonstrate sensitivities as high as 5.37 mC Gy -1 cm -2 when coupled to CsI(Tl). Additionally, as the tube voltage across the X-ray generator was varied, these organic-inorganic systems showed their ability to detect a range of continuous radiation spectra spanning several hundred keV.« less

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

DOE PAGES

Starkenburg, Daken J.; Johns, Paul M.; Baciak, James E.; ...

2017-12-14

Developments in the field of organic semiconductors have generated organic photodetectors with high quantum efficiency, wide spectral sensitivity, low power consumption, and unique form factors that are flexible and conformable to their substrate shape. In this work, organic photodetectors coupled with inorganic CsI(Tl) scintillators are used to showcase the low dose rate sensitivity that is enabled when high performance organic photodetectors and scintillator crystals are integrated. The detection capability of these organic-inorganic coupled systems to high energy radiation highlights their potential as an alternative to traditional photomultiplier tubes for nuclear spectroscopy applications. When exposed to Bremsstrahlung radiation produced from anmore » X-ray generator, SubPc:C60, AlPcCl:C70, and P3HT:PC61BM thin film photodetectors with active layer thicknesses less than 100 nm show detection of incident radiation at low and no applied bias. Remarkably low dose rates, down to at least 0.28 µGy/s, were detectable with a characteristic linear relationship between exposure rate and photodetector current output. These devices also demonstrate sensitivities as high as 5.37 mC Gy-1 cm-2 when coupled to CsI(Tl). Additionally, as the tube voltage across the X-ray generator was varied, these organic-inorganic systems showed their ability to detect a range of continuous radiation spectra spanning several hundred keV.« less

Probiotic Lactobacillus rhamnosus GG Enhanced Th1 Cellular Immunity but Did Not Affect Antibody Responses in a Human Gut Microbiota Transplanted Neonatal Gnotobiotic Pig Model

PubMed Central

Wen, Ke; Tin, Christine; Wang, Haifeng; Yang, Xingdong; Li, Guohua; Giri-Rachman, Ernawati; Kocher, Jacob; Bui, Tammy; Clark-Deener, Sherrie; Yuan, Lijuan

2014-01-01

This study aims to establish a human gut microbiota (HGM) transplanted gnotobiotic (Gn) pig model of human rotavirus (HRV) infection and diarrhea, and to verify the dose-effects of probiotics on HRV vaccine-induced immune responses. Our previous studies using the Gn pig model found that probiotics dose-dependently regulated both T cell and B cell immune responses induced by rotavirus vaccines. We generated the HGM transplanted neonatal Gn pigs through daily feeding of neonatal human fecal suspension to germ-free pigs for 3 days starting at 12 hours after birth. We found that attenuated HRV (AttHRV) vaccination conferred similar overall protection against rotavirus diarrhea and virus shedding in Gn pigs and HGM transplanted Gn pigs. HGM promoted the development of the neonatal immune system, as evidenced by the significantly enhanced IFN-γ producing T cell responses and reduction of regulatory T cells and their cytokine production in the AttHRV-vaccinated pigs. The higher dose Lactobacillus rhamnosus GG (LGG) feeding (14 doses, up to 109 colony-forming-unit [CFU]/dose) effectively increased the LGG counts in the HGM Gn pig intestinal contents and significantly enhanced HRV-specific IFN-γ producing T cell responses to the AttHRV vaccine. Lower dose LGG (9 doses, up to 106 CFU/dose) was ineffective. Neither doses of LGG significantly improved the protection rate, HRV-specific IgA and IgG antibody titers in serum, or IgA antibody titers in intestinal contents compared to the AttHRV vaccine alone, suggesting that an even higher dose of LGG is needed to overcome the influence of the microbiota to achieve the immunostimulatory effect in the HGM pigs. This study demonstrated that HGM Gn pig is an applicable animal model for studying immune responses to rotavirus vaccines and can be used for studying interventions (i.e., probiotics and prebiotics) that may enhance the immunogenicity and protective efficacy of vaccines through improving the gut microbiota. PMID:24722168

[Brachytherapy for head and neck cancers].

PubMed

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

2018-05-29

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

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.

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

NASA Astrophysics Data System (ADS)

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

2015-04-01

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

Statistical analysis of nonmonotonic dose-response relationships: research design and analysis of nasal cell proliferation in rats exposed to formaldehyde.

PubMed

Gaylor, David W; Lutz, Werner K; Conolly, Rory B

2004-01-01

Statistical analyses of nonmonotonic dose-response curves are proposed, experimental designs to detect low-dose effects of J-shaped curves are suggested, and sample sizes are provided. For quantal data such as cancer incidence rates, much larger numbers of animals are required than for continuous data such as biomarker measurements. For example, 155 animals per dose group are required to have at least an 80% chance of detecting a decrease from a 20% incidence in controls to an incidence of 10% at a low dose. For a continuous measurement, only 14 animals per group are required to have at least an 80% chance of detecting a change of the mean by one standard deviation of the control group. Experimental designs based on three dose groups plus controls are discussed to detect nonmonotonicity or to estimate the zero equivalent dose (ZED), i.e., the dose that produces a response equal to the average response in the controls. Cell proliferation data in the nasal respiratory epithelium of rats exposed to formaldehyde by inhalation are used to illustrate the statistical procedures. Statistically significant departures from a monotonic dose response were obtained for time-weighted average labeling indices with an estimated ZED at a formaldehyde dose of 5.4 ppm, with a lower 95% confidence limit of 2.7 ppm. It is concluded that demonstration of a statistically significant bi-phasic dose-response curve, together with estimation of the resulting ZED, could serve as a point-of departure in establishing a reference dose for low-dose risk assessment.

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

NASA Technical Reports Server (NTRS)

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

2001-01-01

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

Estimation of the Dose and Dose Rate Effectiveness Factor

NASA Technical Reports Server (NTRS)

Chappell, L.; Cucinotta, F. A.

2013-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2015-02-01

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

Dose Rate Effects in Linear Bipolar Transistors

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Method and apparatus for measuring low currents in capacitance devices

DOEpatents

Kopp, M.K.; Manning, F.W.; Guerrant, G.C.

1986-06-04

A method and apparatus for measuring subnanoampere currents in capacitance devices is reported. The method is based on a comparison of the voltages developed across the capacitance device with that of a reference capacitor in which the current is adjusted by means of a variable current source to produce a stable voltage difference. The current varying means of the variable current source is calibrated to provide a read out of the measured current. Current gain may be provided by using a reference capacitor which is larger than the device capacitance with a corresponding increase in current supplied through the reference capacitor. The gain is then the ratio of the reference capacitance to the device capacitance. In one illustrated embodiment, the invention makes possible a new type of ionizing radiation dose-rate monitor where dose-rate is measured by discharging a reference capacitor with a variable current source at the same rate that radiation is discharging an ionization chamber. The invention eliminates high-megohm resistors and low current ammeters used in low-current measuring instruments.

Gamma-radiolytic stability of new methylated TODGA derivatives for minor actinide recycling

DOE PAGES

Galan, Hitos; Zarzana, Christopher A.; Wilden, Andreas; ...

2015-09-15

The stability against gamma radiation of MeTODGA (methyl tetraoctyldiglycolamide) and Me2TODGA (dimethyl tetraoctyldiglycolamide), derivatives from the well-known extractant TODGA (N,N,N',N';-tetraoctyldiglycolamide), were studied and compared. Solutions of MeTODGA and Me2TODGA in alkane diluents were subjected to 60Co γ-irradiation in the presence and absence of nitric acid and analyzed using LC-MS to determine their rates of radiolytic concentration decrease, as well as to identify radiolysis products. The results of product identification from three different laboratories are compared and found to be in good agreement. The diglycolamide (DGA) concentrations decreased exponentially with increasing absorbed dose. The MeTODGA degradation rate constants (dose constants) weremore » uninfluenced by the presence of nitric acid, but the acid increased the rate of degradation for Me2TODGA. The degradation products formed by irradiation are also initially produced in greater amounts in acid-contacted solution, but products may also be degraded by continued radiolysis. As a result, the identified radiolysis products suggest that the weakest bonds are those in the diglycolamide center of these molecules.« less

Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

PubMed Central

Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

2012-01-01

Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

SUMMARY OF FRUIT IRRADIATION AT WAGENINGEN

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

de Zeeuw, D.

Use was made of l Mev electrons produced by a normal Van de Graaff accelerator in fresh soft fruit. In order to obtain an even dose distribution over the surface of fruit, it was packed one layer thick in small plastic boxes. Both upper and lower sides of these boxes were irradiated. In case of firmer fruit species, such as plums, these were also placed on mechanically driven rollers on which they were slowly rotated during irradiation. With this method the irradiation time was chosen twice as long as for the packed fruit so as to meet the total dosemore » requirement. Dosimetry measurements were made by both chemical and physical methods. The dose rate was 2 Krad per second. Results obtained with 100 to 500 Krad doses are given for strawberries, raspberries, red and black currants, blackberries, cherries, and plums. (auth)« less

A new radiochromic dosimeter film

NASA Astrophysics Data System (ADS)

Sidney, L. N.; Lynch, D. C.; Willet, P. S.

By employing acid-sensitive leuco dyes in a chlorine-containing polymer matrix, a new radiochromic dosimeter film has been developed for gamma, electron beam, and ultraviolet radiation. These dosimeter films undergo a color change from colorless to royal blue, red fuchsia, or black, depending on dye selection, and have been characterized using a visible spectrophotometer over an absorbed dose range of 1 to 100 kGy. The primary features of the film are improved color stability before and after irradiation, whether stored in the dark or under artificial lights, and improved moisture resistance. The effects of absorbed dose, dose rate, and storage conditions on dosimeter performance are discussed. The dosimeter material may be produced as a free film or coated onto a transparent substrate and optionally backed with adhesive. Potential applications for these materials include gamma sterilization indicator films for food and medical products, electron beam dosimeters, and in-line radiation monitors for electron beam and ultraviolet processing.

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

PubMed

Leonard, B E; Lucas, A C

2009-02-01

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

Undulator Radiation Damage Experience at LCLS

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

Nuhn, H. D.; Field, C.; Mao, S.

2015-01-06

The SLAC National Accelerator Laboratory has been running the Linac Coherent Light Source (LCLS), the first x-ray Free Electron Laser since 2009. Undulator magnet damage from radiation, produced by the electron beam traveling through the 133-m long straight vacuum tube, has been and is a concern. A damage measurement experiment has been performed in 2007 in order to obtain dose versus damage calibrations. Radiation reduction and detection devices have been integrated into the LCLS undulator system. The accumulated radiation dose rate was continuously monitored and recorded. In addition, undulator segments have been routinely removed from the beamline to be checkedmore » for magnetic (50 ppm, rms) and mechanic (about 0.25 µm, rms) changes. A reduction in strength of the undulator segments is being observed, at a level, which is now clearly above the noise. Recently, potential sources for the observed integrated radiation levels have been investigated. The paper discusses the results of these investigation as well as comparison between observed damage and measured dose accumulations and discusses, briefly, strategies for the new LCLS-II upgrade, which will be operating at more than 300 times larger beam rate.« less

Radiation investigations with Liulin-5 charged particle telescope on the International Space Station: review of results for years 2007-2015

NASA Astrophysics Data System (ADS)

Koleva, Rositza; Semkova, Jordanka; Krastev, Krasimir; Bankov, Nikolay; Malchev, Stefan; Benghin, Victor; Shurshakov, Vyacheslav

2017-04-01

The radiation field around the Earth is complex, composed of galactic cosmic rays, trapped particles of the Earth's radiation belts, solar energetic particles, albedo particles from the Earth's atmosphere and secondary radiation produced in the space vehicle shielding materials around the biological objects. Dose characteristics in near Earth and space radiation environment also depend on many other parameters such as the orbit parameters, solar cycle phase and current helio-and geophysical conditions. Since June 2007 till 2015 the Liulin-5 charged particle telescope has been observing the radiation characteristics in two different modules of the International Space Station (ISS). In the period from 2007 to 2009 measurements were conducted in the spherical tissue-equivalent phantom of MATROSHKA-R project located in the PIRS module of ISS. In the period from 2012 to 2015 measurements were conducted in and outside the phantom located in the Small Research Module of ISS. In this presentation attention is drawn to the obtained results for the dose rates, particle fluxes and dose equivalent rates in and outside the phantom from the galactic cosmic rays, trapped protons and solar energetic particle events which occurred in that period.

Rapid Acute Dose Assessment Using MCNP6

NASA Astrophysics Data System (ADS)

Owens, Andrew Steven

Acute radiation doses due to physical contact with a high-activity radioactive source have proven to be an occupational hazard. Multiple radiation injuries have been reported due to manipulating a radioactive source with bare hands or by placing a radioactive source inside a shirt or pants pocket. An effort to reconstruct the radiation dose must be performed to properly assess and medically manage the potential biological effects from such doses. Using the reference computational phantoms defined by the International Commission on Radiological Protection (ICRP) and the Monte Carlo N-Particle transport code (MCNP6), dose rate coefficients are calculated to assess doses for common acute doses due to beta and photon radiation sources. The research investigates doses due to having a radioactive source in either a breast pocket or pants back pocket. The dose rate coefficients are calculated for discrete energies and can be used to interpolate for any given energy of photon or beta emission. The dose rate coefficients allow for quick calculation of whole-body dose, organ dose, and/or skin dose if the source, activity, and time of exposure are known. Doses are calculated with the dose rate coefficients and compared to results from the International Atomic Energy Agency (IAEA) reports from accidents that occurred in Gilan, Iran and Yanango, Peru. Skin and organ doses calculated with the dose rate coefficients appear to agree, but there is a large discrepancy when comparing whole-body doses assessed using biodosimetry and whole-body doses assessed using the dose rate coefficients.

AREA RADIATION MONITOR

DOEpatents

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

1962-06-12

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

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

DOEpatents

Horn, Kevin M.

2013-07-09

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

Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute treatment of migraine--results from phase 1 of the REALIZE Study.

PubMed

Gawel, Marek; Aschoff, Jürgen; May, Arne; Charlesworth, Bruce R

2005-01-01

The objective of phase 1 (reported here) of this two-phase study was to assess the efficacy of zolmitriptan 5 mg nasal spray, in terms of ability to provide relief from all migraine symptoms, in a controlled setting, designed to replicate clinical practice. Zolmitriptan nasal spray has been shown to be fast acting and highly effective in the treatment of migraine, as assessed using standard endpoints, such as headache response and pain-free rates. In the double-blind first phase of the study, patients with migraine were randomized to receive zolmitriptan 5 mg nasal spray or placebo to treat a single migraine attack. Attacks were treated according to patients' normal patterns of use, in order to closely reflect clinical practice; that is, no specific regimen was dictated in terms of time to treatment or at what level of pain intensity the headache should be treated. Patients could take a second dose of study medication or an agreed escape medication if adequate pain relief had not been achieved 2 hours after the first dose. The primary efficacy endpoint was total symptom relief (freedom from pain, nausea, photophobia, and phonophobia) 1 hour after the first dose. Secondary efficacy endpoints included headache response, pain-free status and sustained pain-free status, and ability to perform normal activities. The intention-to-treat population comprised 461 zolmitriptan nasal spray recipients and 451 placebo recipients. The total symptom relief rate 1 hour post-dose was significantly higher in the zolmitriptan 5 mg nasal spray group than in the placebo group (14.5% vs. 5.1%; P < .0001); the difference between the groups was significant from 30 minutes post-dose. Treatment with zolmitriptan nasal spray, compared with placebo, also produced a higher headache response rate from 10 minutes post-dose (15.1% vs. 9.1%; P = .0079) and a higher pain-free rate from 30 minutes post-dose (7.7% vs. 3.2%; P = .0039). Zolmitriptan nasal spray was also significantly superior to placebo in terms of sustained pain-free status and patients' ability to perform normal activities. Zolmitriptan nasal spray was well tolerated. These findings confirm the efficacy demonstrated by zolmitriptan nasal spray in previous clinical trials.

Influence of grid control and object detection on radiation exposure and image quality using mobile C-arms - first results.

PubMed

Gosch, D; Ratzmer, A; Berauer, P; Kahn, T

2007-09-01

The objective of this study was to examine the extent to which the image quality on mobile C-arms can be improved by an innovative exposure rate control system (grid control). In addition, the possible dose reduction in the pulsed fluoroscopy mode using 25 pulses/sec produced by automatic adjustment of the pulse rate through motion detection was to be determined. As opposed to conventional exposure rate control systems, which use a measuring circle in the center of the field of view, grid control is based on a fine mesh of square cells which are overlaid on the entire fluoroscopic image. The system uses only those cells for exposure control that are covered by the object to be visualized. This is intended to ensure optimally exposed images, regardless of the size, shape and position of the object to be visualized. The system also automatically detects any motion of the object. If a pulse rate of 25 pulses/sec is selected and no changes in the image are observed, the pulse rate used for pulsed fluoroscopy is gradually reduced. This may decrease the radiation exposure. The influence of grid control on image quality was examined using an anthropomorphic phantom. The dose reduction achieved with the help of object detection was determined by evaluating the examination data of 146 patients from 5 different countries. The image of the static phantom made with grid control was always optimally exposed, regardless of the position of the object to be visualized. The average dose reduction when using 25 pulses/sec resulting from object detection and automatic down-pulsing was 21 %, and the maximum dose reduction was 60 %. Grid control facilitates C-arm operation, since optimum image exposure can be obtained independently of object positioning. Object detection may lead to a reduction in radiation exposure for the patient and operating staff.

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

PubMed

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

2018-01-01

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

The skin: its structure and response to ionizing radiation.

PubMed

Hopewell, J W

1990-04-01

The response of the skin to ionizing radiation has important implications both for the treatment of malignant disease by radiation and for radiological protection. The structural organization of human skin is described and compared with that of the pig, with which it shows many similarities, in order that the response of the skin to ionizing radiation may be more fully understood. Acute radiation damage to the skin is primarily a consequence of changes in the epidermis; the timing of the peak of the reaction is related to the kinetic organization of this layer. The rate of development of damage is independent of the radiation dose, since this is related to the natural rate of loss of cells from the basal layer of the epidermis. Recovery of the epidermis occurs as a result of the proliferation of surviving clonogenic basal cells from within the irradiated area. The presence of clonogenic cells in the canal of the hair follicle is important, particularly after non-uniform irradiation from intermediate energy beta-emitters. The migration of viable cells from the edges of the irradiated site is also significant when small areas of skin are irradiated. Late damage to the skin is primarily a function of radiation effects on the vasculature; this produces a wave of dermal atrophy after 16-26 weeks. Dermal necrosis develops at this time after high doses. A second phase of dermal thinning is seen to develop after greater than 52 weeks, and this later phase of damage is associated with the appearance of telangiectasia. Highly localized irradiation of the skin, either to a specific layer (as may result from exposure to very low energy beta-emitters) or after exposure to small highly radioactive particles, 'hot particles', produces gross effects that become visibly manifest within 2 weeks of exposure. These changes result from the direct killing of the cells of the skin in interphase after doses greater than 100 Gy. Dose-effect curves have been established for the majority of these deterministic endpoints in the skin from the results of both experimental and clinical studies. These are of value in the establishment of safe radiation dose limits for the skin.

RBE OF MONOENERGETIC FAST NEUTRONS: CYTOGENETIC EFFECTS IN MAIZE

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

Smith, H.H.; Bateman, J.L.; Quastler, H.

1963-01-01

>The relative biological effectiveness (RBE) of neutrons of 5 energies and x radiation at 3 exposure levels were compared in maize seeds. The maize material used in these experiments had the advantsge for RBE studies of yielding a basically first order dose-response curve (Y = alpha plus or minus BETA D) with low (x rays) as well as with high (fast neutron) LET radiations. The frequency of yellow-green (yg/sub 2/ sectors in leaves, 3, 4, and 5 of young plants grown from irradiated Yg/sub 2//Yg/syb 2/ seeds served as a quantitative measure of response. The mutant sectors are believed tomore » be due mostly to simple chromosome breakage and deletion. An exposure apparatus was used which produced essentially equal dose rates in five rings of seeds placed so as to intercept neutrons of 0.43, 0.65, 1.00, 1.50, and 1.80 Mev. Dose average LET values for these energies are 72, ments were performed at dosages that gave responses which were linear, below saturation levels, and overlapping in range for x rays andd neutrons. These ranges in dosages were 32.8 to 126.4 rads of neutrons and 1500 to 15,600 rads of 250 kvp x rays. RBE values, calculated from relative slopes of linear regression lines for N and X, randged from 42 to 135. Monoenergetic fast neutrons of 0.43 Mev were the most efficient in producing yg/sub 2/sectors as shown by the yield of sectors per krad andd highest RBE values. The RBE values obtained in these experiments are higher than commonly reported. With regard to minimum permissible levels of radiation, these results suggest the alternatives that either chromosome breaks in plants have a much higher RBE than comparable reactions in mand and need not be considered; or that the problem of chromosome damage per se in human tissues be reexamined after exposure to high LET radiations andd/or low LET radiations at low doses or dose rates. (auth)« less

Recommended de minimis radiation dose rates for Canada. Report No. INFO-0355

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

Not Available

1990-01-01

A de minimis dose or dose rate as used in this report represents a level of risk which is generally accepted as being of no significance to an individual, or in the case of a population, of no significance to society. The report describes the risk of biological effects from radiation; radiation from natural and man-made sources; normal incidences of cancer and genetic defects; initiatives by other agencies in the U.S., the U.K. and internationally; the importance of collective dose and dose rate; assigning values to the de minimis dose rates; and application of the de minimis dose rates.

Dexmedetomidine Dose Dependently Enhances the Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block: A Randomized Double-Blind Study.

PubMed

Ouchi, Kentaro; Sugiyama, Kazuna

2016-01-01

Dexmedetomidine (DEX) dose dependently enhances the local anesthetic action of lidocaine in rats. We hypothesized that the effect might also be dose dependent in humans. We evaluated the effect of various concentrations of DEX with a local anesthetic in humans. Eighteen healthy volunteers were randomly assigned by a computer to receive 1.8 mL of 1 of 4 drug combinations: (1) 1% lidocaine with 2.5 ppm (parts per million) (4.5 μg) DEX, (2) lidocaine with 5.0 ppm (9.0 μg) DEX, (3) lidocaine with 7.5 ppm (13.5μg) DEX, or (4) lidocaine with 1:80,000 (22.5 μg) adrenaline (AD), to produce inferior alveolar nerve block. Pulp latency and lower lip numbness (for assessing onset and duration of anesthesia) were tested, and sedation level, blood pressure, and heart rate were recorded every 5 minutes for 20 minutes, and every 10 minutes from 20 to 60 minutes. Pulp latency of each tooth increased compared with baseline, from 5 to 15 minutes until 60 minutes. There were no significant intergroup differences at any time point. Anesthesia onset was not different between groups. Anesthesia duration was different between groups (that with DEX 7.5 ppm was significantly longer than that with DEX 2.5 ppm and AD; there was no difference between DEX 2.5 ppm and AD). Blood pressure decreased from baseline in the 5.0 and 7.5 ppm DEX groups at 30 to 60 minutes, although there was no hypotension; moreover, heart rate did not change in any group. Sedation score did not indicate deep sedation in any of the groups. Dexmedetomidine dose dependently enhances the local anesthetic action of lidocaine in humans. Dexmedetomidine at 2.5 ppm produces similar enhancement of local anesthesia effect as addition of 1:80,000 AD.

Biochemical Kinetics Model of DSB Repair and GammaH2AX FOCI by Non-homologous End Joining

NASA Technical Reports Server (NTRS)

Cucinotta, Francis, A.; Pluth, Janice M.; Anderson, Jennifer A.; Harper, Jane V.; O'Neill, Peter

2007-01-01

We developed a biochemical kinetics approach to describe the repair of double strand breaks (DSB) produced by low LET radiation by modeling molecular events associated with the mechanisms of non-homologous end-joining (NHEJ). A system of coupled non-linear ordinary differential equations describes the induction of DSB and activation pathways for major NHEJ components including Ku(sub 70/80), DNA-PK(sub cs), and the Ligase IV-XRCC4 hetero-dimer. The autophosphorylation of DNA-PK(sub cs and subsequent induction of gamma-H2AX foci observed after ionizing radiation exposure were modeled. A two-step model of DNA-PK(sub cs) regulation of repair was developed with the initial step allowing access of other NHEJ components to breaks, and a second step limiting access to Ligase IV-XRCC4. Our model assumes that the transition from the first to second-step depends on DSB complexity, with a much slower-rate for complex DSB. The model faithfully reproduced several experimental data sets, including DSB rejoining as measured by pulsed-field electrophoresis (PFGE), quantification of the induction of gamma-H2AX foci, and live cell imaging of the induction of Ku(sub 70/80). Predictions are made for the behaviors of NHEJ components at low doses and dose-rates, where a steady-state is found at dose-rates of 0.1 Gy/hr or lower.

Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

PubMed Central

2011-01-01

Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p.) 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.). IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v.) prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical) given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA. PMID:22114930

Estimation of Biological Effects of Tritium.

PubMed

Umata, Toshiyuki

2017-01-01

Nuclear fusion technology is expected to create new energy in the future. However, nuclear fusion requires a large amount of tritium as a fuel, leading to concern about the exposure of radiation workers to tritium beta radiation. Furthermore, countermeasures for tritium-polluted water produced in decommissioning of the reactor at Fukushima Daiichi Nuclear Power Station may potentially cause health problems in radiation workers. Although, internal exposure to tritium at a low dose/low dose rate can be assumed, biological effect of tritium exposure is not negligible, because tritiated water (HTO) intake to the body via the mouth/inhalation/skin would lead to homogeneous distribution throughout the whole body. Furthermore, organically-bound tritium (OBT) stays in the body as parts of the molecules that comprise living organisms resulting in long-term exposure, and the chemical form of tritium should be considered. To evaluate the biological effect of tritium, the effect should be compared with that of other radiation types. Many studies have examined the relative biological effectiveness (RBE) of tritium. Hence, we report the RBE, which was obtained with radiation carcinogenesis classified as a stochastic effect, and serves as a reference for cancer risk. We also introduce the outline of the tritium experiment and the principle of a recently developed animal experimental system using transgenic mouse to detect the biological influence of radiation exposure at a low dose/low dose rate.

Micronuclei Induction in Human Fibroblasts Exposed In Vitro to Los Alamos High-Energy Neutrons

NASA Technical Reports Server (NTRS)

Gersey, Brad; Sodolak, John; Hada, Megumi; Saganti, Prem; Wilkins, Richard; Cucinotta, Francis; Wu, Honglu

2006-01-01

High-energy secondary neutrons, produced by the interaction of galactic cosmic rays with the atmosphere, spacecraft structure and planetary surfaces, contribute to a significant fraction to the dose equivalent in crew members and passengers during commercial aviation travel, and astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility#s ICE House 30L beamline is known to generate neutrons that simulate the secondary neutron spectra of earth#s atmosphere. The neutron spectrum is also similar to that measured onboard spacecraft like the MIR and International Space Station (ISS). To evaluate the biological damage, we exposed human fibroblasts in vitro to the LANSCE neutron beams without degrader at an entrance dose rate of 25 mGy/hr and analyzed the micronuclei (MN) induction. The cells were also placed behind a 9.9 cm water column to study effect of shielding in the protection of neutron induced damages. It was found that the dose response in the MN frequency was linear for the samples with and without shielding and the slope of the MN yield behind the shielding was reduced by a factor of 3.5. Compared to the MN induction in human fibroblasts exposed to a gamma source at a low dose rate, the RBE was found to be 16.7 and 10.0 for the neutrons without and with 9.9 cm water shielding, respectively.

Study of the dose rate effect of 180 nm nMOSFETs

NASA Astrophysics Data System (ADS)

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

2015-01-01

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

Reconstruction of doses and deposition in the western trace from the Chernobyl accident.

PubMed

Sikkeland, T; Skuterud, L; Goltsova, N I; Lindmo, T

1997-05-01

A model is presented for the explosive cloud of particulates that produced the western trace of high radioactive ground contamination in the Chernobyl accident on 26 April 1986. The model was developed to reproduce measured dose rates and nuclide contamination and to relate estimated doses to observed changes in: (1) infrared emission from the foliage and (2) morphological and histological structures of individual pines. Dominant factors involved in ground contamination were initial cloud shape, particle size distribution, and rate of particle fallout. At time of formation, the cloud was assumed to be parabolical and to contain a homogeneous distribution of spherically shaped fuel particulates having a log-normal size distribution. The particulates were dispersed by steady winds and diffusion that produced a straight line deposition path. The analysis indicates that two clouds, denoted by Cloud I and Cloud II, were involved. Fallout from the former dominated the far field region and fallout from latter the region near the reactor. At formation they had a full width at half maximum of 1800 m and 500 m, respectively. For wind velocities of 5-10 m s(-1) the particulates' radial distribution at formation had a standard deviation and mode of 1.8 microm and 0.5 microm, respectively. This distribution corresponds to a release of 390 GJ in the runaway explosion. The clouds' height and mass are not uniquely determined but are coupled together. For an initial height of 3,600 m, Cloud I contained about 400 kg fuel. For Cloud II the values were, respectively, 1,500 m and 850 kg. Loss of activities from the clouds is found to be small. Values are obtained for the rate of radionuclide migration from the deposit. Various types of biological damage to pines, as reported in the literature, are shown to be mainly due to ionizing radiation from the deposit by Cloud II. A formula is presented for the particulate size distribution in the trace area.

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 1. The Russell-Muller debate

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

Calabrese, Edward J., E-mail: edwardc@schoolph.uma

This paper assesses the discovery of the dose-rate effect in radiation genetics and how it challenged fundamental tenets of the linear non-threshold (LNT) dose response model, including the assumptions that all mutational damage is cumulative and irreversible and that the dose-response is linear at low doses. Newly uncovered historical information also describes how a key 1964 report by the International Commission for Radiological Protection (ICRP) addressed the effects of dose rate in the assessment of genetic risk. This unique story involves assessments by two leading radiation geneticists, Hermann J. Muller and William L. Russell, who independently argued that the report'smore » Genetic Summary Section on dose rate was incorrect while simultaneously offering vastly different views as to what the report's summary should have contained. This paper reveals occurrences of scientific disagreements, how conflicts were resolved, which view(s) prevailed and why. During this process the Nobel Laureate, Muller, provided incorrect information to the ICRP in what appears to have been an attempt to manipulate the decision-making process and to prevent the dose-rate concept from being adopted into risk assessment practices. - Highlights: • The discovery of radiation dose rate challenged the scientific basis of LNT. • Radiation dose rate occurred in males and females. • The dose rate concept supported a threshold dose-response for radiation.« less

Evaluation of equivalent dose from neutrons and activation products from a 15-MV X-ray LINAC.

PubMed

Israngkul-Na-Ayuthaya, Isra; Suriyapee, Sivalee; Pengvanich, Phongpheath

2015-11-01

A high-energy photon beam that is more than 10 MV can produce neutron contamination. Neutrons are generated by the [γ,n] reactions with a high-Z target material. The equivalent neutron dose and gamma dose from activation products have been estimated in a LINAC equipped with a 15-MV photon beam. A Monte Carlo simulation code was employed for neutron and photon dosimetry due to mixed beam. The neutron dose was also experimentally measured using the Optically Stimulated Luminescence (OSL) under various conditions to compare with the simulation. The activation products were measured by gamma spectrometer system. The average neutron energy was calculated to be 0.25 MeV. The equivalent neutron dose at the isocenter obtained from OSL measurement and MC calculation was 5.39 and 3.44 mSv/Gy, respectively. A gamma dose rate of 4.14 µSv/h was observed as a result of activations by neutron inside the treatment machine. The gamma spectrum analysis showed (28)Al, (24)Na, (54)Mn and (60)Co. The results confirm that neutrons and gamma rays are generated, and gamma rays remain inside the treatment room after the termination of X-ray irradiation. The source of neutrons is the product of the [γ,n] reactions in the machine head, whereas gamma rays are produced from the [n,γ] reactions (i.e. neutron activation) with materials inside the treatment room. The most activated nuclide is (28)Al, which has a half life of 2.245 min. In practice, it is recommended that staff should wait for a few minutes (several (28)Al half-lives) before entering the treatment room after the treatment finishes to minimize the dose received. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Modelling of aircrew radiation exposure during solar particle events

NASA Astrophysics Data System (ADS)

Al Anid, Hani Khaled

In 1990, the International Commission on Radiological Protection recognized the occupational exposure of aircrew to cosmic radiation. In Canada, a Commercial and Business Aviation Advisory Circular was issued by Transport Canada suggesting that action should be taken to manage such exposure. In anticipation of possible regulations on exposure of Canadian-based aircrew in the near future, an extensive study was carried out at the Royal Military College of Canada to measure the radiation exposure during commercial flights. The radiation exposure to aircrew is a result of a complex mixed-radiation field resulting from Galactic Cosmic Rays (GCRs) and Solar Energetic Particles (SEPs). Supernova explosions and active galactic nuclei are responsible for GCRs which consist of 90% protons, 9% alpha particles, and 1% heavy nuclei. While they have a fairly constant fluence rate, their interaction with the magnetic field of the Earth varies throughout the solar cycles, which has a period of approximately 11 years. SEPs are highly sporadic events that are associated with solar flares and coronal mass ejections. This type of exposure may be of concern to certain aircrew members, such as pregnant flight crew, for which the annual effective dose is limited to 1 mSv over the remainder of the pregnancy. The composition of SEPs is very similar to GCRs, in that they consist of mostly protons, some alpha particles and a few heavy nuclei, but with a softer energy spectrum. An additional factor when analysing SEPs is the effect of flare anisotropy. This refers to the way charged particles are transported through the Earth's magnetosphere in an anisotropic fashion. Solar flares that are fairly isotropic produce a uniform radiation exposure for areas that have similar geomagnetic shielding, while highly anisotropic events produce variable exposures at different locations on the Earth. Studies of neutron monitor count rates from detectors sharing similar geomagnetic shielding properties show a very different response during anisotropic events, leading to variations in aircrew radiation doses that may be significant for dose assessment. To estimate the additional exposure due to solar flares, a model was developed using a Monte-Carlo radiation transport code, MCNPX. The model transports an extrapolated particle spectrum based on satellite measurements through the atmosphere using the MCNPX analysis. This code produces the estimated flux at a specific altitude where radiation dose conversion coefficients are applied to convert the particle flux into effective and ambient dose-equivalent rates. A cut-off rigidity model accounts for the shielding effects of the Earth's magnetic field. Comparisons were made between the model predictions and actual flight measurements taken with various types of instruments used to measure the mixed radiation field during Ground Level Enhancements 60 and 65. An anisotropy analysis that uses neutron monitor responses and the pitch angle distribution of energetic solar particles was used to identify particle anisotropy for a solar event in December 2006. In anticipation of future commercial use, a computer code has been developed to implement the radiation dose assessment model for routine analysis. Keywords: Radiation Dosimetry, Radiation Protection, Space Physics.

Influence of the distribution of PWO crystal radiation hardness on electromagnetic calorimeter performance

NASA Astrophysics Data System (ADS)

Drobychev, Gleb Yu.; Borisevich, Andrei E.; Korjik, Mikhail V.; Lecoq, Paul; Moroz, Valeri I.; Peigneux, Jean-Pierre

2002-06-01

The distribution of about 5000 mass-produced PWO crystals by their light yield and radiation hardness is analysed. The correlation between results of radiation hardness measurements at low and saturating dose rates is refined. A method for the evaluation of the energy resolution of the electromagnetic calorimeter accounting for a distribution of individual PWO crystal characteristics is proposed. A preliminary analysis of the PWO crystal recovery kinetics is also performed.

TU-F-CAMPUS-T-01: Dose and Energy Spectra From Neutron Induced Radioactivity in Medical Linear Accelerators Following High Energy Total Body Irradiation

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

Keehan, S; Taylor, M; Franich, R

2015-06-15

Purpose: To assess the risk posed by neutron induced activation of components in medical linear accelerators (linacs) following the delivery of high monitor unit 18 MV photon beams such as used in TBI. Methods: Gamma spectroscopy was used to identify radioisotopes produced in components of a Varian 21EX and an Elekta Synergy following delivery of photon beams. Dose and risk estimates for TBI were assessed using dose deliveries from an actual patient treatment. A 1 litre spherical ion chamber (PTW, Germany) has been used to measure the dose at the beam exit window and at the total body irradiation (TBI)more » treatment couch following large and small field beams with long beam-on times. Measurements were also made outside of the closed jaws to quantify the benefit of the attenuation provided by the jaws. Results: The radioisotopes produced in the linac head have been identified as {sup 187}W, {sup 56}Mn, {sup 24}Na and {sup 28}Al, which have half-lives from between 2.3 min to 24 hours. The dose at the beam exit window following an 18 MV 2197 MU TBI beam delivery was 12.6 µSv in ten minutes. The dose rate at the TBI treatment couch 4.8 m away is a factor of ten lower. For a typical TBI delivered in six fractions each consisting of four beams and an annual patient load of 24, the annual dose estimate for a staff member at the treatment couch for ten minutes is 750 µSv. This can be further reduced by a factor of about twelve if the jaws are closed before entering the room, resulting in a dose estimate of 65 µSv. Conclusion: The dose resulting from the activation products for a representative TBI workload at our clinic of 24 patients per year is 750 µSv, which can be further reduced to 65 µSv by closing the jaws.« less

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

PubMed

Moliterno, David J

2011-06-01

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

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

PubMed

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

1998-06-01

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

Improving Delivery Accuracy of Stereotactic Body Radiotherapy to a Moving Tumor Using Simplified Volumetric Modulated Arc Therapy

PubMed Central

Ko, Young Eun; Cho, Byungchul; Kim, Su Ssan; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Yi, Byongyong

2016-01-01

Purpose To develop a simplified volumetric modulated arc therapy (VMAT) technique for more accurate dose delivery in thoracic stereotactic body radiation therapy (SBRT). Methods and Materials For each of the 22 lung SBRT cases treated with respiratory-gated VMAT, a dose rate modulated arc therapy (DrMAT) plan was retrospectively generated. A dynamic conformal arc therapy plan with 33 adjoining coplanar arcs was designed and their beam weights were optimized by an inverse planning process. All sub-arc beams were converted into a series of control points with varying MLC segment and dose rates and merged into an arc beam for a DrMAT plan. The plan quality of original VMAT and DrMAT was compared in terms of target coverage, compactness of dose distribution, and dose sparing of organs at risk. To assess the delivery accuracy, the VMAT and DrMAT plans were delivered to a motion phantom programmed with the corresponding patients’ respiratory signal; results were compared using film dosimetry with gamma analysis. Results The plan quality of DrMAT was equivalent to that of VMAT in terms of target coverage, dose compactness, and dose sparing for the normal lung. In dose sparing for other critical organs, DrMAT was less effective than VMAT for the spinal cord, heart, and esophagus while being well within the limits specified by the Radiation Therapy Oncology Group. Delivery accuracy of DrMAT to a moving target was similar to that of VMAT using a gamma criterion of 2%/2mm but was significantly better using a 2%/1mm criterion, implying the superiority of DrMAT over VMAT in SBRT for thoracic/abdominal tumors with respiratory movement. Conclusion We developed a DrMAT technique for SBRT that produces plans of a quality similar to that achieved with VMAT but with better delivery accuracy. This technique is well-suited for small tumors with motion uncertainty. PMID:27333199

Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.

PubMed

Letko, Erik; Yeh, Steven; Foster, C Stephen; Pleyer, Uwe; Brigell, Mitchell; Grosskreutz, Cynthia L

2015-05-01

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis. Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy. Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening. Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7% and 61.5% vs. 33.3%, respectively) and remission rates (27.3% and 38.5% vs. 16.7%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared safe and was well tolerated. Intravenous secukinumab was effective and well tolerated in noninfectious uveitis requiring systemic corticosteroid-sparing immunosuppressive therapy. Greater activity with IV dosing suggests that patients may not receive sufficient drug with SC administration. High-dose IV secukinumab may be necessary to deliver secukinumab in therapeutic concentrations. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

GnRH antagonist, cetrorelix, for pituitary suppression in modern, patient-friendly assisted reproductive technology.

PubMed

Tur-Kaspa, Ilan; Ezcurra, Diego

2009-10-01

Gonadotropin-releasing hormone (GnRH) analogues are used routinely to prevent a premature luteinizing hormone (LH) surge in women undergoing assisted reproductive technology (ART) treatments. In contrast to GnRH agonists, antagonists produce rapid and reversible suppression of LH with no initial flare effect. To review the role of cetrorelix, the first GnRH antagonist approved for the prevention of premature LH surges during controlled ovarian stimulation in modern ART. A review of published literature on cetrorelix. Both multiple- and single-dose cetrorelix protocols were shown to be at least as effective as long GnRH agonist regimens for pituitary suppression in Phase II/III clinical trials. Furthermore, cetrorelix co-treatment resulted in similar live birth rates but a shorter duration of gonadotropin stimulation, a lower total gonadotropin dose requirement and lower incidence of ovarian hyperstimulation syndrome compared with long agonist regimens. A single-dose cetrorelix protocol further decreased the number of injections required. Preliminary studies have also produced promising data on the use of cetrorelix in modified ART protocols, such as frozen embryo transfer and donor oocyte recipient cycles. Cetrorelix offers a potential therapeutic alternative to GnRH agonists during controlled ovarian stimulation and has become an integral part of modern, patient-friendly reproductive medicine.

FoCa: a modular treatment planning system for proton radiotherapy with research and educational purposes

NASA Astrophysics Data System (ADS)

Sánchez-Parcerisa, D.; Kondrla, M.; Shaindlin, A.; Carabe, A.

2014-12-01

FoCa is an in-house modular treatment planning system, developed entirely in MATLAB, which includes forward dose calculation of proton radiotherapy plans in both active and passive modalities as well as a generic optimization suite for inverse treatment planning. The software has a dual education and research purpose. From the educational point of view, it can be an invaluable teaching tool for educating medical physicists, showing the insights of a treatment planning system from a well-known and widely accessible software platform. From the research point of view, its current and potential uses range from the fast calculation of any physical, radiobiological or clinical quantity in a patient CT geometry, to the development of new treatment modalities not yet available in commercial treatment planning systems. The physical models in FoCa were compared with the commissioning data from our institution and show an excellent agreement in depth dose distributions and longitudinal and transversal fluence profiles for both passive scattering and active scanning modalities. 3D dose distributions in phantom and patient geometries were compared with a commercial treatment planning system, yielding a gamma-index pass rate of above 94% (using FoCa’s most accurate algorithm) for all cases considered. Finally, the inverse treatment planning suite was used to produce the first prototype of intensity-modulated, passive-scattered proton therapy, using 13 passive scattering proton fields and multi-leaf modulation to produce a concave dose distribution on a cylindrical solid water phantom without any field-specific compensator.

Effect of water chemistry upsets on the dynamics of corrective reagent dosing systems at thermal power stations

NASA Astrophysics Data System (ADS)

Voronov, V. N.; Yegoshina, O. V.; Bolshakova, N. A.; Yarovoi, V. O.; Latt, Aie Min

2016-12-01

Typical disturbances in the dynamics of a corrective reagent dosing system under unsteady-state conditions during the unsatisfactory operation of a chemical control system with some water chemistry upsets at thermal and nuclear power stations are considered. An experimental setup representing a physical model for the water chemistry control system is described. The two disturbances, which are most frequently encountered in water chemistry control practice, such as a breakdown or shutdown of temperature compensation during pH measurement and an increase in the heat-transfer fluid flow rate, have been modeled in the process of study. The study of the effect produced by the response characteristics of chemical control analyzers on the operation of a reagent dosing system under unsteady-state conditions is important for the operative control of a water chemistry regime state. The effect of temperature compensation during pH measurement on the dynamics of an ammonia-dosing system in the manual and automatic cycle chemistry control modes has been studied. It has been demonstrated that the reading settling time of a pH meter in the manual ammonia- dosing mode grows with a breakdown in temperature compensation and a simultaneous increase in the temperature of a heat-transfer fluid sample. To improve the efficiency of water chemistry control, some systems for the quality control of a heat-transfer fluid by a chemical parameter with the obligatory compensation of a disturbance in its flow rate have been proposed for use. Experimental results will possibly differ from industrial data due to a great length of sampling lines. For this reason, corrective reagent dosing systems must be adapted to the conditions of a certain power-generating unit in the process of their implementation.

Aspirin attenuation of alcohol-induced flushing and intoxication in Oriental and Occidental subjects.

PubMed

Truitt, E B; Gaynor, C R; Mehl, D L

1987-01-01

Aspirin (ASA) was tested in a group of 8 Oriental and 3 Occidental subjects who were shown in a previous study to respond to small doses of ethanol (0.06-0.25 g/kg) with facial flushing. They were compared to a similar group of 11 non-flushing Occidental subjects following a larger ethanol dose (0.37 g/kg) to determine if similar effects could be produced in less sensitive individuals. Control tests of blood ethanol and acetaldehyde (AcH) levels (calculated from breath), facial and neck skin temperatures, body sway (Romberg test), blood pressure, heart rate and 10 Subjective High Assessment Scales (SHAS-Judd, 1977) were conducted before and at 15, 30, 60 and 90 minutes after drinking ethanol as vodka in orange juice. The tests were repeated one week later one hour after receiving 0.64 gm of ASA orally. ASA produced slight changes in the early absorption of ethanol and small decreases in AcH levels in the flushing and non-flushing groups. Facial flushing was markedly reduced in the flushing group, but was slightly increased in the non-flushing Occidentals. Body sway was reduced by ASA in both groups. An alcohol-induced increase in heart rate in the flushing group was reduced with no change in blood pressure. SHAS subjective parameters were widely variable, but indicated that ASA produced reduced sleepiness and earlier relaxation in the flushing group. It is concluded that ASA can block alcohol-induced facial flushing in sensitive subjects and also reduces body sway in the Romberg test and alters some subjective feelings of alcohol intoxication.

Behavioral and biochemical effects of the antidepressant bupropion (Wellbutrin): evidence for selective blockade of dopamine uptake in vivo.

PubMed

Cooper, B R; Hester, T J; Maxwell, R A

1980-10-01

Bupropion (BW 323U; Wellbutrin), a novel compound with antidepressant effects in man, was found to reduce immobility in an "experimental helplessness" forced swimming antidepressant test in rats as did imipramine and amitriptyline. Higher doses produced elevated locomotor activity in an automated open field and produced stereotyped sniffing which was contrasted with apomorphine. When bupropion or desmethylimipramine was given before intracisternal injections of 6-hydroxydopamine, bupropion produced a dose-related selective antagonism of the destruction of dopamine neurons, while under the same conditions, desmethylimipramine produced a dose-related selective antagonism of the destruction of noradrenergic neurons. Studies in which the dose of bupropion and the dose of 6-hydroxydopamine were varied revealed that a dose-related selective antagonism of dopamine depletion by 6-hydroxydopamine occurred when doses up to and including 50 mg/kg i.p. to bupropion were administered. Some antagonism of norepinephrine depletion also occurred at 100 mg/kg of bupropion i.p. Bupropion also selectively reversed the dopamine depletion produced by alpha-methyl-m-tyrosine, a finding which is consistent with the view that bupropion is a dopamine uptake inhibitor in vivo. The importance of dopamine systems for the behavioral effects of bupropion were also studied. When the locomotor stimulant effects of bupropion were tested in rats with chronic destruction of dopamine neurons produced by 6-hydroxydopamine, bupropion failed to elevate locomotor activity. Rats treated with procedures using 6-hydroxydopamine to produce relatively selective norepinephrine depletions responded to bupropion with locomotor activity stimulation like controls. Rats with similar depletions of either dopamine or norepinephrine were also tested for the ability of low doses of bupropion to reduce immobility in the "experimental helplessness" forced swim antidepressant test. Prior destruction of dopamine neurons prevented activity of bupropion in this test. Results indicate that bupropion is a selective dopamine uptake inhibitor in vivo and that dopaminergic systems play an important role in its central nervous system pharmacology.

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

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

Radev, R

2009-01-13

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

Clinical application of diadenosine tetraphosphate (Ap4A:F-1500) for controlled hypotension.

PubMed

Kikuta, Y; Ohiwa, E; Okada, K; Watanabe, A; Haruki, S

1999-01-01

In our animal study, it was revealed that diadenosine tetraphosphate (Ap4A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in mean arterial pressure compared to control value. Furthermore, in healthy male volunteers, the safety of Ap4A up to 4 mg.min-1 was confirmed. In patients who require surgical procedures under general anesthesia together with controlled hypotension, hypotension was induced by Ap4A in order to examine its hypotensive effect and modulating action on the blood pressure. Ten patients who required controlled hypotension and who were scheduled for elective surgery under general anesthesia were studied. Anesthesia was maintained with isoflurane (n = 7) or sevoflurane (n = 3) in oxygen-nitrous oxide. Controlled hypotension was induced by Ap4A administered at a rate of 10-20 micrograms.kg-1.min-1. The dose was adjusted at a maximum rate of 80 micrograms.kg-1.min-1 until the target blood pressure was achieved. Arterial blood pressure and heart rate were monitored. Arterial samples were drawn at 4 separate time points to measure the concentration of Ap4A in the plasma. The time required for attaining the target blood pressure after initiation of Ap4A infusion was about 16 min, and the time lapse between withdrawal of infusion to recovery of blood pressure was about 18 min. No reflex tachycardia was observed during infusion of Ap4A and no rebound hypertension was evident after withdrawal. The plasma Ap4A concentration increased in response to the acceleration rate of Ap4A administration with a tendency of augmented hypotensive effect. As it produces an excellent hypotensive effect together with a modulating action on blood pressure, Ap4A was assessed as useful in producing controlled hypotension.

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

PubMed Central

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

2004-01-01

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

Variable dose rate single-arc IMAT delivered with a constant dose rate and variable angular spacing

NASA Astrophysics Data System (ADS)

Tang, Grace; Earl, Matthew A.; Yu, Cedric X.

2009-11-01

Single-arc intensity-modulated arc therapy (IMAT) has gained worldwide interest in both research and clinical implementation due to its superior plan quality and delivery efficiency. Single-arc IMAT techniques such as the Varian RapidArc™ deliver conformal dose distributions to the target in one single gantry rotation, resulting in a delivery time in the order of 2 min. The segments in these techniques are evenly distributed within an arc and are allowed to have different monitor unit (MU) weightings. Therefore, a variable dose-rate (VDR) is required for delivery. Because the VDR requirement complicates the control hardware and software of the linear accelerators (linacs) and prevents most existing linacs from delivering IMAT, we propose an alternative planning approach for IMAT using constant dose-rate (CDR) delivery with variable angular spacing. We prove the equivalence by converting VDR-optimized RapidArc plans to CDR plans, where the evenly spaced beams in the VDR plan are redistributed to uneven spacing such that the segments with larger MU weighting occupy a greater angular interval. To minimize perturbation in the optimized dose distribution, the angular deviation of the segments was restricted to <=± 5°. This restriction requires the treatment arc to be broken into multiple sectors such that the local MU fluctuation within each sector is reduced, thereby lowering the angular deviation of the segments during redistribution. The converted CDR plans were delivered with a single gantry sweep as in the VDR plans but each sector was delivered with a different value of CDR. For four patient cases, including two head-and-neck, one brain and one prostate, all CDR plans developed with the variable spacing scheme produced similar dose distributions to the original VDR plans. For plans with complex angular MU distributions, the number of sectors increased up to four in the CDR plans in order to maintain the original plan quality. Since each sector was delivered with a different dose rate, extra mode-up time (xMOT) was needed between the transitions of the successive sectors during delivery. On average, the delivery times of the CDR plans were approximately less than 1 min longer than the treatment times of the VDR plans, with an average of about 0.33 min of xMOT per sector transition. The results have shown that VDR may not be necessary for single-arc IMAT. Using variable angular spacing, VDR RapidArc plans can be implemented into the clinics that are not equipped with the new VDR-enabled machines without compromising the plan quality or treatment efficiency. With a prospective optimization approach using variable angular spacing, CDR delivery times can be further minimized while maintaining the high delivery efficiency of single-arc IMAT treatment.

The estimation of galactic cosmic ray penetration and dose rates

NASA Technical Reports Server (NTRS)

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

1972-01-01

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

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

PubMed

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

2017-03-01

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

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

DOE PAGES

Hiller, Mauritius; Dewji, Shaheen Azim

2017-02-16

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

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

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

Hiller, Mauritius; Dewji, Shaheen Azim

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

Comparing analgesia and μ-opioid receptor internalization produced by intrathecal enkephalin

PubMed Central

Chen, Wenling; Song, Bingbing; Lao, Lijun; Pérez, Orlando A.; Kim, Woojae; Marvizón, Juan Carlos G.

2007-01-01

Summary Opioid receptors in the spinal cord produce strong analgesia, but the mechanisms controlling their activation by endogenous opioids remain unclear. We have previously shown in spinal cord slices that peptidases preclude μ-opioid receptor (MOR) internalization by opioids. Our present goals were to investigate whether enkephalin-induced analgesia is also precluded by peptidases, and whether it is mediated by MORs or δ-opioid receptors (DORs). Tail-flick analgesia and MOR internalization were measured in rats injected intrathecally with Leu-enkephalin and peptidase inhibitors. Without peptidase inhibitors, Leu-enkephalin produced neither analgesia nor MOR internalization at doses up to 100 nmol, whereas with peptidase inhibitors it produced analgesia at 0.3 nmol and MOR internalization at 1 nmol. Leu-enkephalin was ten times more potent to produce analgesia than to produce MOR internalization, suggesting that DORs were involved. Selective MOR or DOR antagonists completely blocked the analgesia elicited by 0.3 nmol Leu-enkephalin (a dose that produced little MOR internalization), indicating that it involved these two receptors, possibly by an additive or synergistic interaction. The selective MOR agonist endomorphin-2 produced analgesia even in the presence of a DOR antagonist, but at doses substantially higher than Leu-enkephalin. Unlike Leu-enkephalin, endomorphin-2 had the same potencies to induce analgesia and MOR internalization. We concluded that low doses of enkephalins produce analgesia by activating both MORs and DORs. Analgesia can also be produced exclusively by MORs at higher agonist doses. Since peptidases prevent the activation of spinal opioid receptors by enkephalins, the coincident release of opioids and endogenous peptidase inhibitors may be required for analgesia. PMID:17845806

A gEUD-based inverse planning technique for HDR prostate brachytherapy: Feasibility study

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

Giantsoudi, D.; Department of Radiation Oncology, Francis H. Burr Proton Therapy Center, Boston, Massachusetts 02114; Baltas, D.

2013-04-15

Purpose: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. Methods: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the differentmore » dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. Results: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D{sub 10} or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. Conclusions: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.« less

Limitations of silicon diodes for clinical electron dosimetry.

PubMed

Song, Haijun; Ahmad, Munir; Deng, Jun; Chen, Zhe; Yue, Ning J; Nath, Ravinder

2006-01-01

This work investigates the relevance of several factors affecting the response of silicon diode dosemeters in depth-dose scans of electron beams. These factors are electron energy, instantaneous dose rate, dose per pulse, photon/electron dose ratio and electron scattering angle (directional response). Data from the literature and our own experiments indicate that the impact of these factors may be up to +/-15%. Thus, the different factors would have to cancel out perfectly at all depths in order to produce true depth-dose curves. There are reports of good agreement between depth-doses measured with diodes and ionisation chambers. However, our measurements with a Scantronix electron field detector (EFD) diode and with a plane-parallel ionisation chamber show discrepancies both in the build-up and in the low-dose regions, with a ratio up to 1.4. Moreover, the absolute sensitivity of two diodes of the same EFD model was found to differ by a factor of 3, and this ratio was not constant but changed with depth between 5 and 15% in the low-dose regions of some clinical electron beams. Owing to these inhomogeneities among diodes even of the same model, corrections for each factor would have to be diode-specific and beam-specific. All these corrections would have to be determined using parallel plane chambers, as recommended by AAPM TG-25, which would be unrealistic in clinical practice. Our conclusion is that in general diodes are not reliable in the measurement of depth-dose curves of clinical electron beams.

Dynamic laser speckle applied to the analysis of maturation process of irradiated fresh fruits

NASA Astrophysics Data System (ADS)

Vincitorio, F. M.; Budini, N.; Freyre, C.; Mulone, C.; Fiorucci, M. P.; López, A. J.; Ramil, A.

2012-10-01

The treatment of fresh fruits with different doses of ionizing radiation has been found effective for delaying ripening and, in this way, to extend shelf life. This preservation method is likely to produce some functional or constitutive changes in the cellular structure of the fruit. In this work, a test of the effectiveness of fruit irradiation with relatively low doses was performed by using dynamic speckle imaging. Bananas from a same lot were chosen, being a first series of them irradiated with different doses of 0.2, 0.4 and 0.6 kGy (Gy = J/kg) and a second series with doses of 0.2, 0.4, 0.6 and 1 kGy. Non irradiated bananas (0 kGy) were considered as the lot reference for contrast. Irradiation was carried out at the Semi-Industrial Cobalt 60 facility of the Ezeiza Atomic Center, with an activity of 6 × 105 Curie and a dose rate of 28.5 Gy/min. The objective of this work is to analyze differences in the maturation process between irradiated and nonirradiated fruits by means of dynamic speckle pattern evaluation.

An environmental-level, real-time, pulsed photon dosemeter.

PubMed

Olsher, R H; Frymire, A; Gregoire, T

2005-01-01

Radiation sources producing short pulses of photon radiation are widespread. Such sources include electron linear accelerators and field emission impulse generators. It is often desirable to measure leakage and skyshine radiation for these sources in real time and at environmental levels as low as 0.02 microSv per pulse. This note provides an overview of the design and performance of a commercial, real-time, pulsed photon dosemeter (PPD) capable of single-pulse dose measurements over the range from 0.02 to 20 microSv. The PPD may also be operated in a multiple-pulse mode that integrates the dose from a train of pulses over a 3 s period. A pulse repetition rate of up to 300 Hz is accommodated.

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

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

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

2014-08-15

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

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

NASA Technical Reports Server (NTRS)

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

1972-01-01

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

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

NASA Technical Reports Server (NTRS)

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

1989-01-01

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

Mapping the space radiation environment in LEO orbit by the SATRAM Timepix payload on board the Proba-V satellite

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

Granja, Carlos, E-mail: carlos.granja@utef.cvut.cz; Polansky, Stepan

Detailed spatial- and time-correlated maps of the space radiation environment in Low Earth Orbit (LEO) are produced by the spacecraft payload SATRAM operating in open space on board the Proba-V satellite from the European Space Agency (ESA). Equipped with the hybrid semiconductor pixel detector Timepix, the compact radiation monitor payload provides the composition and spectral characterization of the mixed radiation field with quantum-counting and imaging dosimetry sensitivity, energetic charged particle tracking, directionality and energy loss response in wide dynamic range in terms of particle types, dose rates and particle fluxes. With a polar orbit (sun synchronous, 98° inclination) at themore » altitude of 820 km the payload samples the space radiation field at LEO covering basically the whole planet. First results of long-period data evaluation in the form of time-and spatially-correlated maps of total dose rate (all particles) are given.« less

American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR) Practice Guideline for the Performance of High-Dose-Rate Brachytherapy

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

Erickson, Beth A.; Demanes, D. Jeffrey; Ibbott, Geoffrey S.

2011-03-01

High-Dose-Rate (HDR) brachytherapy is a safe and efficacious treatment option for patients with a variety of different malignancies. Careful adherence to established standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and American Society for Therapeutic Radiation Oncology (ASTRO) has produced a practice guideline for HDR brachytherapy. The guideline defines the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrists. Review of the leading indications for HDR brachytherapy in the management of gynecologic, thoracic, gastrointestinal,more » breast, urologic, head and neck, and soft tissue tumors is presented. Logistics with respect to the brachytherapy implant procedures and attention to radiation safety procedures and documentation are presented. Adherence to these practice guidelines can be part of ensuring quality and safety in a successful HDR brachytherapy program.« less

Comparison of immunogenicity between inactivated and live attenuated hepatitis A vaccines: a single-blind, randomized, parallel-group clinical trial among children in Xinjiang Uighur Autonomous Region, China.

PubMed

Liu, Xue-En; Wushouer, Fuerhati; Gou, Aili; Kuerban, Mahemuti; Li, Xinlan; Sun, Yubo; Zhang, Jiamin; Liu, Yan; Li, Jie; Zhuang, Hui

2013-07-01

To compare immunogenicity among an inactivated hepatitis A vaccine (Healive(®)) with one-dose and two-dose regimens, and three kinds of live attenuated vaccines in children. A single-blind, randomized, parallel-group clinical trial was conducted among healthy children aged 1.5-6 y in Xinjiang Uighur Autonomous Region, China. Subjects were randomly assigned to 5 groups. Two groups were administered one-dose or two-dose inactivated vaccine and the remaining groups were immunized with one of three kinds of attenuated vaccines, respectively. Serum samples were collected at 6- and 12-mo follow-ups. Anti-HAV IgG was measured with a microparticle enzyme immunoassay. No significant differences were observed in seroconversion rates (seroprotection rates) among the five groups at 6 or 12 mo (p>0.05). The geometric mean concentration (GMC) of anti-HAV IgG was significantly higher in the two-dose Healive(®) group than in the one-dose Healive(®) group and the attenuated vaccine groups at 12 mo (932.4 vs. 112.7, 135.8, 203.3, 212.8 mIU/ml, respectively, p<0.05). In the one-dose Healive(®) group, the GMC was significantly lower than that in the attenuated vaccine B and C groups at 6 mo (152.6 vs. 212, 204 mIU/ml, p<0.05) and at 12 mo (112.7 vs. 203.3, 212.8, p<0.05), but was similar to the attenuated vaccine A group at 12 mo (112.7 vs. 135.8 mIU/ml, p>0.05). The GMCs were significantly higher in the 1-2 y of age group than in the 3-6 y of age group for all types of vaccines except the attenuated vaccine C (p<0.05) at 12 mo. A higher GMC of anti-HAV IgG was induced in the two-dose Healive(®) than in the one-dose and the attenuated vaccines at 12 mo. The attenuated vaccine B or C produced higher GMCs than the one-dose Healive(®) at 6-12 mo after vaccination.

Terrestrial effects of high energy cosmic rays

NASA Astrophysics Data System (ADS)

Atri, Dimitra

On geological timescales, the Earth is likely to be exposed to higher than the usual flux of high energy cosmic rays (HECRs) from astrophysical sources such as nearby supernovae, gamma ray bursts or by galactic shocks. These high-energy particles strike the Earth's atmosphere, initiating an extensive air shower. As the air shower propagates deeper, it ionizes the atmosphere by producing charged secondary particles and photons. Increased ionization leads to changes in atmospheric chemistry, resulting in ozone depletion. This increases the flux of solar UVB radiation at the surface, which is potentially harmful to living organisms. Increased ionization affects the global electrical circuit, which could enhance the low-altitude cloud formation rate. Secondary particles such as muons and thermal neutrons produced as a result of hadronic interactions of the primary cosmic rays with the atmosphere are able to reach the ground, enhancing the biological radiation dose. The muon flux dominates the radiation dose from cosmic rays causing damage to DNA and an increase in mutation rates and cancer, which can have serious biological implications for surface and sub-surface life. Using CORSIKA, we perform massive computer simulations and construct lookup tables for 10 GeV - 1 PeV primaries, which can be used to quantify these effects from enhanced cosmic ray exposure to any astrophysical source. These tables are freely available to the community and can be used for other studies. We use these tables to study the terrestrial implications of galactic shock generated by the infall of our galaxy toward the Virgo cluster. Increased radiation dose from muons could be a possible mechanism explaining the observed periodicity in biodiversity in paleobiology databases.

Terrestrial Effects of High Energy Cosmic Rays

NASA Astrophysics Data System (ADS)

Atri, Dimitra

2011-01-01

On geological timescales, the Earth is likely to be exposed to an increased flux of high energy cosmic rays (HECRs) from astrophysical sources such as nearby supernovae, gamma ray bursts or by galactic shocks. These high-energy particles strike the Earth's atmosphere initiating an extensive air shower. As the air shower propagates deeper, it ionizes the atmosphere by producing charged secondary particles. Increased ionization could lead to changes in atmospheric chemistry, resulting in ozone depletion. This could increase the flux of solar UVB radiation at the surface, which is potentially harmful to living organisms. Increased ionization affects the global electrical circuit can could possibly enhance the low-altitude cloud formation rate. Secondary particles such as muons and thermal neutrons produced as a result of nuclear interactions are able to reach the ground, enhancing the biological radiation dose. The muon flux dominates radiation dose from cosmic rays causing DNA damage and increase in the mutation rates, which can have serious biological implications for terrestrial and sub-terrestrial life. This radiation dose is an important constraint on the habitability of a planet. Using CORSIKA, we perform massive computer simulations and construct lookup tables from 10 GeV - 1 PeV primaries (1 PeV - 0.1 ZeV in progress), which can be used to quantify these effects. These tables are freely available to the community and can be used for other studies, not necessarily relevant to Astrobiology. We use these tables to study the terrestrial implications of galactic shock generated by the infall of our galaxy toward the Virgo cluster. This could be a possible mechanism explaining the observed periodicity in biodiversity in paleobiology databases.

The electrospray and its application to targeted drug inhalation.

PubMed

Gomez, Alessandro

2002-12-01

This review explains the fundamentals of electrostatic spray (electrospray) atomization, with emphasis on operation in the so called cone-jet mode, which produces droplets with a very narrow size distribution. Since the control of droplet size is key to maximizing distal lung deposition, the electrospray should be well-suited to targeted drug inhalation. Electrospray droplets are a few micrometers in diameter, but they originate from a much larger nozzle, which allows nebulization of suspensions without clogging. Also discussed are: the physical principles of the break-up of the liquid ligament; droplet dispersion by Coulombic forces; and the most important scaling law linking the droplet size to liquid flow rate and liquid physical properties. The effects of the most critical of those properties may result in some restrictions on drug formulation. Droplets produced by electrospray are electrically charged, so to prevent electrostatic image forces from causing upper respiratory tract deposition. The charge is neutralized by generating a corona discharge of opposite polarity. Briefly discussed are the main differences between the laboratory systems (with which the electrospray has been quantitatively characterized during research in the past 10 years) and commercial electrospray inhalers under development at BattellePharma. Some remarkable miniaturization has incorporated liquid pump, power supply, breath activation, and dose counter into a palm-size portable device. The maximum flow rates dispersed from these devices are in the range of 8-16 microL/s, which makes them suitable for practical drug inhalation therapy. Fabrication is economically competitive with inexpensive nebulizers. Dramatic improvements in respirable dose efficiency (up to 78% by comparison with commercial metered-dose inhalers and dry powder inhalers) should ensure the commercialization of this promising technology for targeted drug inhalation.

Dissociation between the effects of P1, P4-diadenosine tetraphosphate (Ap4A) on renal haemodynamics and tubular function in anaesthetized rats.

PubMed

Jankowski, M; Angielski, S; Szczepańska-Konkel, M

2008-03-01

Previous studies from our laboratory have reported a marked reduction in glomerular filtration rate (GFR) and sodium reabsorption in renal proximal tubule during intravenous infusion of P(1),P(4)-diadenosine tetraphosphate (Ap(4)A) at dose of 1.0 micromol/kg + 10 nmol/kg/min (i.v., injection followed by infusion) in anaesthetized Wistar rats. In the present study, the changes of GFR and urine sodium excretion were investigated in response to systemic infusion of Ap(4)A at different doses. Ap(4)A at dose of 0.1 micromol/kg + 1.0 nmol/kg/min did not change GFR and sodium urinary excretion whereas 2-fold higher dose produced significant (3.4-fold) increase in sodium excretion without changes in GFR. Significant but transient reduction in GFR by approximately 21% was observed during infusion of Ap(4)A at dose of 0.5 micromol/kg + 5.0 nmol/kg/min. Higher doses of Ap(4)A (1.0 micromol/kg + 10 nmol/kg/min and 2.0 micromol/kg + 20 nmol/kg/min) reduction in GFR and marked natriuresis. Our results suggest that tubular sodium transport systems are more sensitive to Ap(4)A than systems involved in GFR regulation.

Acute toxicity of karlotoxins to mice

PubMed Central

Place, Allen R.; Munday, R.; Munday, J.S.

2015-01-01

Karlotoxins, polyketide derivatives produced by the dinoflagellate Karlodinium veneficum, are associated with fish kills in temperate estuaries world wide. In this study, the acute effects of 3 pure karlotoxin analogs (KmTx 1, KmTx 3 and KmTx 2) have been examined in mice. Transient lethargy and increased respiratory rates were observed soon after dosing with the karlotoxins by intraperitoneal injection, but no deaths were recorded in animals dosed with KmTx 2 at up to 500 μg/kg or with KmTx 1 or KmTx 3 at up to 4000 μg/kg. Animals dosed intraperitoneally with KmTx 1 and KmTx 3 at 4000 μg/kg showed a pronounced decrease in food and water intake, lasting 3–4 days after dosing, accompanied by a significant decrease in body weight. After this time, the lost body weight was regained and the behavior and appearance of the mice remained normal throughout the following 10 day observation period. No effects were seen in mice dosed orally with KmTx 1 or KmTx 3 at a dose of 4000 μg/kg. It is concluded that contamination of seafood if it were to occur with these karlotoxins is unlikely to pose a major risk of acute intoxication in consumers. PMID:25150200

The Effect of Low Monotonic Doses of Zearalenone on Selected Reproductive Tissues in Pre-Pubertal Female Dogs--A Review.

PubMed

Gajęcka, Magdalena; Zielonka, Łukasz; Gajęcki, Maciej

2015-11-19

The growing interest in toxic substances combined with advancements in biological sciences has shed a new light on the problem of mycotoxins contaminating feeds and foods. An interdisciplinary approach was developed by identifying dose-response relationships in key research concepts, including the low dose theory of estrogen-like compounds, hormesis, NOAEL dose, compensatory response and/or food tolerance, and effects of exposure to undesirable substances. The above considerations increased the researchers' interest in risk evaluation, namely: (i) clinical symptoms associated with long-term, daily exposure to low doses of a toxic compound; and (ii) dysfunctions at cellular or tissue level that do not produce clinical symptoms. Research advancements facilitate the extrapolation of results and promote the use of novel tools for evaluating the risk of exposure, for example exposure to zearalenone in pre-pubertal female dogs. The arguments presented in this paper suggest that low doses of zearalenone in commercial feeds stimulate metabolic processes and increase weight gains. Those processes are accompanied by lower proliferation rates in the ovaries, neoangiogenesis and vasodilation in the ovaries and the uterus, changes in the steroid hormone profile, and changes in the activity of hydroxysteroid dehydrogenases. All of the above changes result from exogenous hyperestrogenizm.

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

PubMed

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

2011-05-01

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

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

NASA Astrophysics Data System (ADS)

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

2006-03-01

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

High dose rates obtained outside ISS in June 2015 during SEP event

NASA Astrophysics Data System (ADS)

Dachev, T. P.; Tomov, B. T.; Matviichuk, Yu. N.; Dimitrov, Pl. G.; Bankov, N. G.

2016-06-01

The R3DR2 instrument performed measurements in the European Space Agency (ESA) EXPOSE-R2 platform outside the Russian "Zvezda" module of the International Space Station (ISS) in the period 24 October 2014-11 January 2016. It is the Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2015a). Took place in November 2014, this was the first attempt to monitor a small solar energetic particle (SEP) event outside ISS using the Liulin-type DES (Dachev et al., 2015d). In this study, we describe the dosimetric characteristics of the largest SEP event, observed on 22 June 2015 with the R3DR2 instrument outside ISS. The main finding of this study is that SEP protons with a minimum energy of approximately 7 MeV at the surface of the R3DR2 detector produced high dose rates, reaching >5000 μGy h-1, while the inner radiation belt maximum dose was at the level of 2200 μGy h-1. If a virtual external vehicle activity (EVA) was performed in the same period of the SEP maximum on 22 June 2015, the doses obtained in the skin of cosmonauts/astronauts can reach 2.84 mGy after 6.5 h, which is similar to the average absorbed dose inside ISS for 15 days (Reitz et al., 2005). A comparison with other extreme events measured with Liulin-type instruments shows that SEPs similar to that observed on 22 June 2015 could be one of the most dangerous events for the cosmonauts/astronauts involved in EVA.

Discriminative Stimulus Effects of Tramadol in Humans

PubMed Central

Duke, Angela N.; Bigelow, George E.; Lanier, Ryan K.

2011-01-01

Tramadol is an unscheduled atypical analgesic that acts as an agonist at μ-opioid receptors and inhibits monoamine reuptake. Tramadol can suppress opioid withdrawal, and chronic administration can produce opioid physical dependence; however, diversion and abuse of tramadol is low. The present study further characterized tramadol in a three-choice discrimination procedure. Nondependent volunteers with active stimulant and opioid use (n = 8) participated in this residential laboratory study. Subjects were trained to discriminate between placebo, hydromorphone (8 mg), and methylphenidate (60 mg), and tests of acquisition confirmed that all volunteers could discriminate between the training drugs. The following drug conditions were then tested during discrimination test sessions: placebo, hydromorphone (4 and 8 mg), methylphenidate (30 and 60 mg), and tramadol (50, 100, 200, and 400 mg). In addition to discrimination measures, which included discrete choice, point distribution, and operant responding, subjective and physiological effects were measured for each test condition. Both doses of hydromorphone and methylphenidate were identified as hydromorphone- and methylphenidate-like, respectively. Lower doses of tramadol were generally identified as placebo, with higher doses (200 and 400 mg) identified as hydromorphone, or opioid-like. The highest dose of tramadol increased ratings on the stimulant scale, but was not significantly identified as methylphenidate-like. Tramadol did not significantly increase subjective ratings associated with reinforcement. Taken together, these results extend previous work with tramadol as a potential medication for the treatment of opioid dependence and withdrawal, showing acute doses of tramadol exhibit a profile of effects similar to opioid agonists and may have abuse liability in certain populations. PMID:21467190

Improved performances of CIBER-X: a new tabletop laser-driven electron and x-ray source

NASA Astrophysics Data System (ADS)

Girardeau-Montaut, Jean-Pierre; Kiraly, Bela; Girardeau-Montaut, Claire

2000-11-01

We present the most recent data concerning the performances of the table-top laser driven electron and x-ray source developed in our laboratory. X-ray pulses are produced by a three-step process which consists of the photoelectron emission from a thin metallic photocathode illuminated by 16 ps duration laser pulse at 213 nm. The e-gun is a standard pierce diode electrode type, in which electrons are accelerated by a cw electric fields of 12 MV/m. The photoinjector produced a train of 90 - 100 keV electron pulses of approximately 1 nC and 40 A peak current at a repetition rate of 10 Hz. The electrons, transported outside the diode, are focused onto a target of thulium by magnetic fields produced by two electromagnetic coils to produce x-rays. Applications to low dose imagery of inert and living materials are also presented.

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

PubMed

Barker, D P; Simpson, J; Pawula, M; Barrett, D A; Shaw, P N; Rutter, N

1995-07-01

To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective.

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

PubMed Central

Barker, D. P.; Simpson, J.; Pawula, M.; Barrett, D. A.; Shaw, P. N.; Rutter, N.

1995-01-01

AIMS--To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. METHODS--Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. RESULTS--Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. CONCLUSIONS--Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective. PMID:7552591

Amoxicillin/clavulanic acid: a review of its use in the management of paediatric patients with acute otitis media.

PubMed

Easton, Jane; Noble, Stuart; Perry, Caroline M

2003-01-01

Amoxicillin/clavulanic acid (Augmentin), Augmentin ES-600 is a well established, orally administered combination of amoxicillin (a semisynthetic antibacterial agent) and clavulanic acid (a beta-lactamase inhibitor). Amoxicillin/clavulanic acid shows good activity against the main pathogens associated with acute otitis media (AOM), including penicillin-susceptible and -intermediate strains of Streptococcus pneumoniae, and beta-lactamase producing strains of Haemophilus influenzae and Moraxella catarrhalis. It has moderate activity against penicillin-resistant S. pneumoniae; a high-dose formulation has been developed with the aim of providing better coverage for penicillin-resistant strains. Amoxicillin/clavulanic acid (conventional formulations, mostly 40/10 mg/kg/day in three divided doses) produced clinical response rates similar to those of oral cephalosporin comparators and similar to or significantly greater than those for intramuscular ceftriaxone in randomised trials in paediatric patients with AOM (mean age approximately 2 to 5 years). Clinical response rates were generally similar for amoxicillin/clavulanic acid and macrolide comparators (mean patient age approximately 1 to 6 years), although significantly better clinical and bacteriological responses were seen versus azithromycin in one randomised trial (mean patient age approximately 1 year). The high-dose formulation of amoxicillin/clavulanic acid (90/6.4 mg/kg/day in two divided doses) eradicated a high proportion of penicillin-resistant S. pneumoniae (penicillin MICs 2 or 4 mg/L) in a large noncomparative trial in children with AOM (upper limit of the US indication for S. pneumoniae is 2 mg/L). Amoxicillin/clavulanic acid is generally well tolerated. A low total incidence of adverse events (3.6%) and no serious events were reported from a large paediatric postmarketing study. The most frequently reported adverse events in children are mild gastrointestinal disturbances. Diarrhoea is generally less frequent with twice-daily than with three-times-daily treatment. The new high-dose formulation showed similar tolerability to a conventional twice-daily formulation (45/6.4 mg/kg/day) in a well controlled trial. Amoxicillin/clavulanic acid is a well established broad-spectrum antibacterial treatment which is effective and well tolerated in the treatment of AOM in paediatric patients. The high-dose combination should prove valuable in treating AOM caused by penicillin-intermediate and -resistant S. pneumoniae (approved in the US for penicillin MIC < or =2 mg/L). Based on recent recommendations and the available data, high-dose amoxicillin/clavulanic acid can be considered a treatment of choice for recurrent or persistent paediatric AOM (after failure of amoxicillin alone) where involvement of resistant pathogens is suspected.

Aripiprazole effects on self-administration and pharmacodynamics of intravenous cocaine and cigarette smoking in humans.

PubMed

Lofwall, Michelle R; Nuzzo, Paul A; Campbell, Charles; Walsh, Sharon L

2014-06-01

Aripiprazole is a partial agonist at dopamine (D2) and serotonin (5-HT1a) receptors and 5-HT2 antagonist. Because cocaine affects dopamine and serotonin, this study assessed whether aripiprazole could diminish the reinforcing efficacy of cocaine. Secondary aims evaluated aripiprazole on ad lib cigarette smoking and with a novel 40-hr smoking abstinence procedure. Adults with regular cocaine and cigarette use completed this inpatient double blind, randomized, placebo-controlled mixed-design study. A placebo lead-in was followed by randomization to aripiprazole (0, 2 or 10 mg/day/p.o.; n = 7 completed/group). Three sets of test sessions, each consisting of 3 cocaine sample-choice (i.e., self-administration) sessions and 1 dose-response session, were conducted (once during the lead-in and twice after randomization). Sample sessions tested each cocaine dose (0, 20 and 40 mg/70 kg, i.v.) in random order; subjective, observer-rated and physiologic outcomes were collected. Later that day, participants chose between the morning's sample dose or descending amounts of money over 7 trials. In dose response sessions, all doses were given 1 hr apart in ascending order for pharmacodynamic and pharmacokinetic assessment. Two sets of smoking topography sessions were conducted during the lead-in and after randomization; 1 with and 1 without 40 hr of smoking abstinence. Number of ad lib cigarettes smoked during non-session days was collected. Cocaine produced prototypic effects, but aripiprazole did not significantly alter these effects or smoking outcomes. The smoking abstinence procedure reliably produced nicotine withdrawal and craving and increased smoking modestly. These data do not support further investigation of aripiprazole for cocaine or tobacco use disorder treatment. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Gamma radiation effects on polydimethylsiloxane rubber foams under different radiation conditions

NASA Astrophysics Data System (ADS)

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

2013-07-01

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

Total dose bias dependency and ELDRS effects in bipolar linear devices

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

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

PubMed

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

2017-01-01

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

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

NASA Technical Reports Server (NTRS)

Johnston, A.; Barnes, C.

1995-01-01

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

Hormetic Response by Silver Nanoparticles on In Vitro Multiplication of Sugarcane (Saccharum spp. Cv. Mex 69-290) Using a Temporary Immersion System.

PubMed

Bello-Bello, Jericó J; Chavez-Santoscoy, Rocío A; Lecona-Guzmán, Carlos A; Bogdanchikova, Nina; Salinas-Ruíz, Josafhat; Gómez-Merino, Fernando Carlos; Pestryakov, Alexey

2017-01-01

Hormesis is considered a dose-response phenomenon characterized by growth stimulation at low doses and inhibition at high doses. The hormetic response by silver nanoparticles (AgNPs) on in vitro multiplication of sugarcane was evaluated using a temporary immersion system. Sugarcane shoots were used as explants cultured in Murashige and Skoog medium with AgNPs at concentrations of 0, 25, 50, 100, and 200 mg/L. Shoot multiplication rate and length were used to determine hormetic response. Total content of phenolic compounds of sugarcane, mineral nutrition, and reactive oxygen species (ROS) was determined. Results were presented as a dose-response curve. Stimulation phase growth was observed at 50 mg/L AgNPs, whereas inhibition phase was detected at 200 mg/L AgNPs. Mineral nutrient analysis showed changes in macronutrient and micronutrient contents due to the effect of AgNPs. Moreover, AgNPs induced ROS production and increased total phenolic content, with a dose-dependent effect. Results suggested that the production of ROS and mineral nutrition are key mechanisms of AgNP-induced hormesis and that phenolic accumulation was obtained as a response of the plant to stress produced by high doses of AgNPs. Therefore, small doses of AgNPs in the culture medium could be an efficient strategy for commercial micropropagation.

Dose responses in a normoxic polymethacrylic acid gel dosimeter using optimal CT scanning parameters

NASA Astrophysics Data System (ADS)

Cho, K. H.; Cho, S. J.; Lee, S.; Lee, S. H.; Min, C. K.; Kim, Y. H.; Moon, S. K.; Kim, E. S.; Chang, A. R.; Kwon, S. I.

2012-05-01

The dosimetric characteristics of normoxic polymethacrylic acid gels are investigated using optimal CT scanning parameters and the possibility of their clinical application is also considered. The effects of CT scanning parameters (tube voltage, tube current, scan time, slick thickness, field of view, and reconstruction algorithm) are experimentally investigated to determine the optimal parameters for minimizing the amount of noise in images obtained using normoxic polymethacrylic acid gel. In addition, the dose sensitivity, dose response, accuracy, and reproducibility of the normoxic polymethacrylic acid gel are evaluated. CT images are obtained using a head phantom that is fabricated for clinical applications. In addition, IMRT treatment planning is performed using a Tomotherapy radiation treatment planning system. A program for analyzing the results is produced using Visual C. A comparison between the treatment planning and the CT images of irradiated gels is performed. The dose sensitivity is found to be 2.41±0.04 HGy-1. The accuracies of dose evaluation at doses of 2 Gy and 4 Gy are 3.0% and 2.6%, respectively, and their reproducibilities are 2.0% and 2.1%, respectively. In the comparison of gel and Tomotherpay planning, the pass rate of the γ-index, based on the reference values of a dose error of 3% and a DTA of 3 mm, is 93.7%.

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

PubMed

Eichmann, Marion; Flühs, Dirk; Spaan, Bernhard

2009-10-01

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

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

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

Eichmann, Marion; Fluehs, Dirk; Spaan, Bernhard

2009-10-15

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

The role of nicotinic receptor beta-2 subunits in nicotine discrimination and conditioned taste aversion.

PubMed

Shoaib, M; Gommans, J; Morley, A; Stolerman, I P; Grailhe, R; Changeux, J-P

2002-03-01

The subtypes of nicotinic receptors at which the behavioural effects of nicotine originate are not fully understood. These experiments use mice lacking the beta2 subunit of nicotinic receptors to investigate its role in nicotine discrimination and conditioned taste aversion (CTA). Wild-type and mutant mice were trained either in a two-lever nicotine discrimination procedure using a tandem schedule of food reinforcement, or in a counterbalanced two-flavour CTA procedure. Rates of lever-pressing of wild-type and mutant mice did not differ. Wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) rapidly and exhibited steep dose-response curves. Mutant mice failed to acquire these nicotine discriminations and exhibited flat dose-response curves. Both wild-type and mutant mice acquired discrimination of nicotine (1.6 mg/kg) although discrimination performance was weak in the mutants. Nicotine initially reduced response rates in wild-type and mutant mice, and tolerance developed to this effect in each genotype. Both genotypes acquired discrimination of morphine (3 mg/kg) with similar degrees of accuracy, and dose-response curves for morphine discrimination in the two genotypes were indistinguishable. Nicotine produced dose-related CTA in both genotypes, but the magnitude of the effect was less in the mutants than in the wild-type controls. It is concluded that nicotinic receptors containing the beta2 subunit play a major role in the discriminative stimulus and taste aversion effects of nicotine that may reflect psychological aspects of tobacco dependence. Such receptors appear to have a less crucial role in the response-rate, reducing effects of nicotine and in nicotine tolerance.

Multiple animal studies for medical chemical defense program in soldier/patient decontamination and drug development. Task order 85-10. Final report, 1 December 1984-1 April 1987

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

Joiner, R.L.; Harroff, H.H.; Snider, H.

1987-12-04

A rabbit model has been developed and validated for screening noninvasive candidate decontamination systems for their efficacies against topical exposure to the organophosphage chemical surety materiel (CSM), GD, polymer-thickened GD (TGD), and VX. CSM was applied to rabbits in groups of 8 on their clipped dorsa over a range of doses. Dose sites were decontaminated beginning 2 minutes after exposure with both components of the M258A1 standard field kit in the recommended sequence. Replicate LD50s were calculated for each CSM with probit analyses of the doses and lethality rates from replicate studies. A composite LD50 was calculated from the datamore » pooled across replicates for each CSM. The composite LD50 was validated for each CSM by comparing the lethality rate obtained in three replicates of 8 animals each with the population mean of 50 percent. The LD50 values obtained for the three CSM tested produced valid mortality ratios when compared to the population mean. Thus the screen is ready to test candidate decontamination systems. The screen compares the lethality rate obtained from 8 animals each dosed at the established M258A1 LD50 and decontaminated according to the manufacturer's instructions with a candidate system against the population mean of 50 percent. An M258A1-decontaminated control group of 8 animals is included to check for drift via a control chart method. Any candidate decontamination system that is as effective as or more effective than the dual-component M258A1 standard passes the screen and is a candidate for further testing.« less

Ultrafast treatment plan optimization for volumetric modulated arc therapy (VMAT)

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

Men Chunhua; Romeijn, H. Edwin; Jia Xun

2010-11-15

Purpose: To develop a novel aperture-based algorithm for volumetric modulated arc therapy (VMAT) treatment plan optimization with high quality and high efficiency. Methods: The VMAT optimization problem is formulated as a large-scale convex programming problem solved by a column generation approach. The authors consider a cost function consisting two terms, the first enforcing a desired dose distribution and the second guaranteeing a smooth dose rate variation between successive gantry angles. A gantry rotation is discretized into 180 beam angles and for each beam angle, only one MLC aperture is allowed. The apertures are generated one by one in a sequentialmore » way. At each iteration of the column generation method, a deliverable MLC aperture is generated for one of the unoccupied beam angles by solving a subproblem with the consideration of MLC mechanic constraints. A subsequent master problem is then solved to determine the dose rate at all currently generated apertures by minimizing the cost function. When all 180 beam angles are occupied, the optimization completes, yielding a set of deliverable apertures and associated dose rates that produce a high quality plan. Results: The algorithm was preliminarily tested on five prostate and five head-and-neck clinical cases, each with one full gantry rotation without any couch/collimator rotations. High quality VMAT plans have been generated for all ten cases with extremely high efficiency. It takes only 5-8 min on CPU (MATLAB code on an Intel Xeon 2.27 GHz CPU) and 18-31 s on GPU (CUDA code on an NVIDIA Tesla C1060 GPU card) to generate such plans. Conclusions: The authors have developed an aperture-based VMAT optimization algorithm which can generate clinically deliverable high quality treatment plans at very high efficiency.« less

Ultrafast treatment plan optimization for volumetric modulated arc therapy (VMAT).

PubMed

Men, Chunhua; Romeijn, H Edwin; Jia, Xun; Jiang, Steve B

2010-11-01

To develop a novel aperture-based algorithm for volumetric modulated are therapy (VMAT) treatment plan optimization with high quality and high efficiency. The VMAT optimization problem is formulated as a large-scale convex programming problem solved by a column generation approach. The authors consider a cost function consisting two terms, the first enforcing a desired dose distribution and the second guaranteeing a smooth dose rate variation between successive gantry angles. A gantry rotation is discretized into 180 beam angles and for each beam angle, only one MLC aperture is allowed. The apertures are generated one by one in a sequential way. At each iteration of the column generation method, a deliverable MLC aperture is generated for one of the unoccupied beam angles by solving a subproblem with the consideration of MLC mechanic constraints. A subsequent master problem is then solved to determine the dose rate at all currently generated apertures by minimizing the cost function. When all 180 beam angles are occupied, the optimization completes, yielding a set of deliverable apertures and associated dose rates that produce a high quality plan. The algorithm was preliminarily tested on five prostate and five head-and-neck clinical cases, each with one full gantry rotation without any couch/collimator rotations. High quality VMAT plans have been generated for all ten cases with extremely high efficiency. It takes only 5-8 min on CPU (MATLAB code on an Intel Xeon 2.27 GHz CPU) and 18-31 s on GPU (CUDA code on an NVIDIA Tesla C1060 GPU card) to generate such plans. The authors have developed an aperture-based VMAT optimization algorithm which can generate clinically deliverable high quality treatment plans at very high efficiency.

Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer.

PubMed

Gettinger, Scott N; Horn, Leora; Gandhi, Leena; Spigel, David R; Antonia, Scott J; Rizvi, Naiyer A; Powderly, John D; Heist, Rebecca S; Carvajal, Richard D; Jackman, David M; Sequist, Lecia V; Smith, David C; Leming, Philip; Carbone, David P; Pinder-Schenck, Mary C; Topalian, Suzanne L; Hodi, F Stephen; Sosman, Jeffrey A; Sznol, Mario; McDermott, David F; Pardoll, Drew M; Sankar, Vindira; Ahlers, Christoph M; Salvati, Mark; Wigginton, Jon M; Hellmann, Matthew D; Kollia, Georgia D; Gupta, Ashok K; Brahmer, Julie R

2015-06-20

Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial. Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle. Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis. Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing. © 2015 by American Society of Clinical Oncology.

An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults.

PubMed

Kollins, Scott H; Schoenfelder, Erin N; English, Joseph S; Holdaway, Alex; Van Voorhees, Elizabeth; O'Brien, Benjamin R; Dew, Rachel; Chrisman, Allan K

2015-01-01

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10mg oral doses of delta-9-tetrahydocannibinol (THC); and 0mg, 10mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10mg THC+0mg, 10mg, and 40 mg MPH=89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of "Feel Drug," "Good Effects," and "Take Drug Again." THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. Copyright © 2014 Elsevier Inc. All rights reserved.

An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults

PubMed Central

Kollins, Scott H.; Schoenfelder, Erin N.; English, Joseph S.; Holdaway, Alex; Van Voorhees, Elizabeth; O’Brien, Benjamin R.; Dew, Rachel; Chrisman, Allan K.

2014-01-01

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10 mg oral doses of delta-9-tetrahydocannibinol (THC); and 0 mg, 10 mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10 mg THC + 0 mg, 10 mg, and 40 mg MPH = 89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of “Feel Drug,” “Good Effects,” and “Take Drug Again.” THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. PMID:25175495

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

PubMed

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

2000-05-01

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

Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.

PubMed

Olipitz, Werner; Wiktor-Brown, Dominika; Shuga, Joe; Pang, Bo; McFaline, Jose; Lonkar, Pallavi; Thomas, Aline; Mutamba, James T; Greenberger, Joel S; Samson, Leona D; Dedon, Peter C; Yanch, Jacquelyn C; Engelward, Bevin P

2012-08-01

In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break-induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.

Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

PubMed

Winsauer, Peter J; Sutton, Jessie L

2014-02-01

This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we and others have shown for chronic administration during adolescence. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed

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

2013-10-01

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

[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.