Wide-range radiation dose monitor

DOEpatents

Kopp, M.K.

1984-09-20

A radiation dose-rate monitor is provided which operates in a conventional linear mode for radiation in the 0 to 0.5 R/h range and utilizes a nonlinear mode of operation for sensing radiation from 0.5 R/h to over 500 R/h. The nonlinear mode is achieved by a feedback circuit which adjusts the high voltage bias of the proportional counter, and hence its gas gain, in accordance with the amount of radiation being monitored. This allows compression of readout onto a single scale over the range of 0 to greater than 500 R/h without scale switching operations.

Achieving a Linear Dose Rate Response in Pulse-Mode Silicon Photodiode Scintillation Detectors Over a Wide Range of Excitations

NASA Astrophysics Data System (ADS)

Carroll, Lewis

2014-02-01

We are developing a new dose calibrator for nuclear pharmacies that can measure radioactivity in a vial or syringe without handling it directly or removing it from its transport shield “pig”. The calibrator's detector comprises twin opposing scintillating crystals coupled to Si photodiodes and current-amplifying trans-resistance amplifiers. Such a scheme is inherently linear with respect to dose rate over a wide range of radiation intensities, but accuracy at low activity levels may be impaired, beyond the effects of meager photon statistics, by baseline fluctuation and drift inevitably present in high-gain, current-mode photodiode amplifiers. The work described here is motivated by our desire to enhance accuracy at low excitations while maintaining linearity at high excitations. Thus, we are also evaluating a novel “pulse-mode” analog signal processing scheme that employs a linear threshold discriminator to virtually eliminate baseline fluctuation and drift. We will show the results of a side-by-side comparison of current-mode versus pulse-mode signal processing schemes, including perturbing factors affecting linearity and accuracy at very low and very high excitations. Bench testing over a wide range of excitations is done using a Poisson random pulse generator plus an LED light source to simulate excitations up to ˜106 detected counts per second without the need to handle and store large amounts of radioactive material.

Proton recoil scintillator neutron rem meter

DOEpatents

Olsher, Richard H.; Seagraves, David T.

2003-01-01

A neutron rem meter utilizing proton recoil and thermal neutron scintillators to provide neutron detection and dose measurement. In using both fast scintillators and a thermal neutron scintillator the meter provides a wide range of sensitivity, uniform directional response, and uniform dose response. The scintillators output light to a photomultiplier tube that produces an electrical signal to an external neutron counter.

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013.

PubMed

Taylor, Carolyn W; Wang, Zhe; Macaulay, Elizabeth; Jagsi, Reshma; Duane, Frances; Darby, Sarah C

2015-11-15

Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this "mean heart dose." In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28 countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose. Copyright © 2015 Elsevier Inc. All rights reserved.

The feasibility of universal DLP-to-risk conversion coefficients for body CT protocols

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Paulson, Erik K.; Frush, Donald P.

2011-03-01

The effective dose associated with computed tomography (CT) examinations is often estimated from dose-length product (DLP) using scanner-independent conversion coefficients. Such conversion coefficients are available for a small number of examinations, each covering an entire region of the body (e.g., head, neck, chest, abdomen and/or pelvis). Similar conversion coefficients, however, do not exist for examinations that cover a single organ or a sub-region of the body, as in the case of a multi-phase liver examination. In this study, we extended the DLP-to-effective dose conversion coefficient (k factor) to a wide range of body CT protocols and derived the corresponding DLP-to-cancer risk conversion coefficient (q factor). An extended cardiactorso (XCAT) computational model was used, which represented a reference adult male patient. A range of body CT protocols used in clinical practice were categorized based on anatomical regions examined into 10 protocol classes. A validated Monte Carlo program was used to estimate the organ dose associated with each protocol class. Assuming the reference model to be 20 years old, effective dose and risk index (an index of the total risk for cancer incidence) were then calculated and normalized by DLP to obtain the k and q factors. The k and q factors varied across protocol classes; the coefficients of variation were 28% and 9%, respectively. The small variation exhibited by the q factor suggested the feasibility of universal q factors for a wide range of body CT protocols.

Variation in Prescribing Patterns and Therapeutic Drug Monitoring of Intravenous Busulfan in Pediatric Hematopoietic Cell Transplant Recipients

PubMed Central

McCune, Jeannine S.; Baker, K. Scott; Blough, David K.; Gamis, Alan; Bemer, Meagan J.; Kelton-Rehkopf, Megan C.; Winter, Laura; Barrett, Jeffrey S.

2016-01-01

Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package insert dose. The initial busulfan dose achieved the target exposure in only 24.3% of children. A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained. Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors’ group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children. PMID:23444282

Implications of current recommendations for third-generation cephalosporin use in the WHO Western Pacific Region following the emergence of multiresistant gonococci.

PubMed

Tapsall, J W

2009-08-01

To ascertain recommendations for the treatment of gonorrhoea in the WHO Western Pacific Region (WPR) following the emergence of "cephalosporin-resistant" Neisseria gonorrhoeae and to relate these to clinical and laboratory measures directed towards disease and antibiotic resistance control. WHO WPR Gonococcal Antimicrobial Resistance Programme members provided data on the type, dose and source of third-generation cephalosporins recommended for the treatment of gonorrhoea. Ceftriaxone was recommended more widely (11/15 respondents) than cefixime (five centres). No cephalosporins were recommended in three jurisdictions. One other oral (ceftibuten) and injectable (cefodizime) agent was recommended. Uniform (400 mg) doses of cefixime were recommended but ceftriaxone regimens ranged between 125 mg and 1 g, with nine of 11 respondents using a 250 mg dose. Both generic and proprietary preparations were widely used. Third-generation cephalosporins are widely recommended for the treatment of gonorrhoea in the WPR, with injectable ceftriaxone more extensively so than oral cefixime and in an expanded dose range. Few other cephalosporins were recommended. Current knowledge suggests that the trend towards ceftriaxone treatment in higher doses may decrease the impact of the circulation of "cephalosporin-resistant" gonococci in the WPR. These recommendations represent public sector practice only and of themselves are unlikely to contain the further spread of "cephalosporin-resistant" gonococci because of the general clinical use of cephalosporins. Optimisation of strategies for laboratory detection of third-generation cephalosporin resistance can be simplified in the WPR because of the restricted spectrum of cephalosporins recommended. Additional efforts are urgently required for both disease and antibiotic resistance control in gonorrhoea.

Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit.

PubMed

Stamenić, Tamara Timić; Poe, Michael M; Rehman, Sabah; Santrač, Anja; Divović, Branka; Scholze, Petra; Ernst, Margot; Cook, James M; Savić, Miroslav M

2016-11-15

We have synthesized and characterized MP-III-022 ((R)-8-ethynyl-6-(2-fluorophenyl)-N,4-dimethyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy-selective positive allosteric modulator of GABA A receptors containing the α5 subunit (α5GABA A Rs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 1-10mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of α5βγ2 GABA A receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2'F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200mg/kg), but at the price of activating non-α5 GABA A Rs as well as the desired α5GABA A Rs at the highest dose. At the dose of 10mg/kg, which elicits a strong positive modulation of α5GABA A Rs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of α5GABA A Rs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism. Copyright © 2016 Elsevier B.V. All rights reserved.

Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit

PubMed Central

Stamenić, Tamara Timić; Poe, Michael M.; Rehman, Sabah; Santrač, Anja; Divović, Branka; Scholze, Petra; Ernst, Margot; Cook, James M.; Savić, Miroslav M.

2016-01-01

We have synthesized and characterized MP-III-022 ((R)-8-ethynyl-6-(2-fluorophenyl)-N,4-dimethyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy-selective positive allosteric modulator of GABAA receptors containing the α5 subunit (α5GABAARs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 1-10 mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of α5βγ2 GABAA receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2′F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200 mg/kg), but at the price of activating non-α5 GABAARs as well as the desired α5GABAARs at the highest dose. At the dose of 10 mg/kg, which elicits a strong positive modulation of α5GABAARs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10 mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of α5GABAARs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism. PMID:27639297

SU-E-T-308: Systematic Characterization of the Energy Response of Different LiF TLD Crystals for Dosimetry Applications

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

Pena, E; Caprile, P; Sanchez-Nieto, B

Purpose: The thermoluminiscense dosimeters (TLDs) are widely used in personal and clinical dosimetry due to its small size, good sensitivity and tissue equivalence, among other advantages. This study presents the characterization of Lithium Fluoride based TLDs, in terms of their absorbed dose response to successive irradiation cycles in a broad range of beam energies, measured under reference conditions. Methods: Four types of Harshaw TLD chips were used: TLD-100, TLD-600 TLD-700 and 100-H. They were irradiated with 10 photon beams of different energy spectrums, from 28 kVp to 18MV (in 30 consecutive cycles for 6 and 18 MV). Results: It wasmore » found that the response of the dosimetric system was stabilized (less than ±3%) after 10 cycles for TLD-600 and TLD-700. In the case of TLD-100 and TLD-100H this dependence was not observed. A decreased response to increasing beam energy in terms of absorbed dose to water was observed, as expected, except for TLD-100H which showed the opposite behavior. The less energy dependent detector was the TLD-100H exhibiting a maximum deviation of 12%. The highest variation observed was 33% for TLD-100. The study allowed the determination of calibration factors in absorbed dose for a wide range of energies and materials for different dosimetric applications, such as in-vivo dosimetry during imaging and radiotherapy. Conclusion: The study allowed the determination of calibration factors in absorbed dose for a wide range of energies and materials for different dosimetric applications, such as in-vivo dosimetry during imaging and radiotherapy.« less

Assessment of the efficacy of a novel tailored vitamin K dosing regimen in lowering the International Normalised Ratio in over-anticoagulated patients: a randomised clinical trial.

PubMed

Kampouraki, Emmanouela; Avery, Peter J; Wynne, Hilary; Biss, Tina; Hanley, John; Talks, Kate; Kamali, Farhad

2017-09-01

Current guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism. We compared the performance of a novel tailored vitamin K dosing regimen to that of a fixed-dose regimen with the primary measure being the proportion of over-anticoagulated patients returning to their target INR within 24 h. One hundred and eighty-one patients with an index INR > 6·0 (asymptomatic or with minor bleeding) were randomly allocated to receive oral administration of either a tailored dose (based upon index INR and body surface area) or a fixed-dose (1 or 2 mg) of vitamin K. A greater proportion of patients treated with the tailored dose returned to within target INR range compared to the fixed-dose regimen (68·9% vs. 52·8%; P = 0·026), whilst a smaller proportion of patients remained above target INR range (12·2% vs. 34·0%; P < 0·001). Individualised vitamin K dosing is more accurate than fixed-dose regimen in lowering INR to within target range in excessively anticoagulated patients. © 2017 John Wiley & Sons Ltd.

Psychopharmacology of theobromine in healthy volunteers.

PubMed

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

2013-07-01

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

Psychopharmacology of theobromine in healthy volunteers

PubMed Central

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

2013-01-01

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

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013

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

Taylor, Carolyn W., E-mail: carolyn.taylor@ctsu.ox.ac.uk; Wang, Zhe; Macaulay, Elizabeth

Purpose: Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Methods and Materials: Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this “mean heart dose.” Results: In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28more » countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Conclusions: Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose.« less

Radiation dose enhancement of gold nanoparticle on different polymer gel dosimeters

NASA Astrophysics Data System (ADS)

Jabaseelan Samuel, E. James; Srinivasan, K.; Poopathi, V.

2017-05-01

In this work, we evaluated the dose enhancement produced by gold nanoparticle on ten different polymer gel dosimeters with a concentration of 7mgAu /g over a wide photon energy range of 15KeV to 20MeV and the results were compared with Soft tissue ICRU-44 produced. Our result showed that maximum DEF was observed at 40KeV, while it was almost negligible at higher energy range. Dose enhancement produced by AuNP on the gel dosimeter medium was varied compared to the reference ICRU-44 tissue, it was ± <1% for PAGAT, NIPAM, nPAG and ± <5% for PABIG, VIPAR, HEAG, BANG1, nMAG & ± <10% for MAGIC, ABAGIC gel dosimeters. Hence, we conclude that choosing the proper gel dosimeter is essential in dose enhancement study.

[Fixed-dose combination fluticasone propionate/formoterol for the treatment of asthma: a review of its pharmacology, efficacy and tolerability].

PubMed

Quintano Jiménez, J A; Ginel Mendoza, L; Entrenas Costa, L M; Polo García, J

2016-02-01

The fixed-dose combination fluticasone propionate/formoterol (FPF) is a novel combination of a widely known and used inhaled glucocorticoid (IGC) and a long-acting β2-adrenergic agonist (LABA), available for the first time in a single device. This fixed-dose combination of FPF has a demonstrated efficacy and safety profile in clinical trials compared with its individual components and other fixed-dose combinations of IGC/LABA and is indicated for the treatment of persistent asthma in adults and adolescents. FPF is available in a wide range of doses that can adequately cover the therapeutic steps recommended by treatment guidelines, constituting a fixed-dose combination of GCI/LABA that is effective, rapid, well tolerated and with a reasonable acquisition cost. Various assessment agencies of the Spanish Autonomous Communities consider this combination to be an appropriate alternative therapy for asthma in the primary care setting. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.

Performance of Al2O3:C optically stimulated luminescence dosimeters for clinical radiation therapy applications.

PubMed

Hu, B; Wang, Y; Zealey, W

2009-12-01

A commercial Optical Stimulated Luminescence (OSL) dosimetry system developed by Landauer was tested to analyse the possibility of using OSL dosimetry for external beam radiotherapy planning checks. Experiments were performed to determine signal sensitivity, dose response range, beam type/energy dependency, reproducibility and linearity. Optical annealing processes to test OSL material reusability were also studied. In each case the measurements were converted into absorbed dose. The experimental results show that OSL dosimetry provides a wide dose response range, good linearity and reproducibility for the doses up to 800cGy. The OSL output is linear with dose up to 600cGy range showing a maximum deviation from linearity of 2.0% for the doses above 600cGy. The standard deviation in response of 20 dosimeters was 3.0%. After optical annealing using incandescent light, the readout intensity decreased by approximately 98% in the first 30 minutes. The readout intensity, I, decreased after repeated optical annealing as a power law, given by I infinity t (-1.3). This study concludes that OSL dosimetry can provide an alternative dosimetry technique for use in in-vivo dosimetry if rigorous measurement protocols are established.

Upgrades of DARWIN, a dose and spectrum monitoring system applicable to various types of radiation over wide energy ranges

NASA Astrophysics Data System (ADS)

Sato, Tatsuhiko; Satoh, Daiki; Endo, Akira; Shigyo, Nobuhiro; Watanabe, Fusao; Sakurai, Hiroki; Arai, Yoichi

2011-05-01

A dose and spectrum monitoring system applicable to neutrons, photons and muons over wide ranges of energy, designated as DARWIN, has been developed for radiological protection in high-energy accelerator facilities. DARWIN consists of a phoswitch-type scintillation detector, a data-acquisition (DAQ) module for digital waveform analysis, and a personal computer equipped with a graphical-user-interface (GUI) program for controlling the system. The system was recently upgraded by introducing an original DAQ module based on a field programmable gate array, FPGA, and also by adding a function for estimating neutron and photon spectra based on an unfolding technique without requiring any specific scientific background of the user. The performance of the upgraded DARWIN was examined in various radiation fields, including an operational field in J-PARC. The experiments revealed that the dose rates and spectra measured by the upgraded DARWIN are quite reasonable, even in radiation fields with peak structures in terms of both spectrum and time variation. These results clearly demonstrate the usefulness of DARWIN for improving radiation safety in high-energy accelerator facilities.

Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV)

USGS Publications Warehouse

McKenney, Douglas; Kurath, Gael; Wargo, Andrew

2016-01-01

The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout.

SU-F-T-406: Verification of Total Body Irradiation Commissioned MU Lookup Table Accuracy Using Treatment Planning System for Wide Range of Patient Sizes

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

Lewis, D; Chi, P; Tailor, R

Purpose: To verify the accuracy of total body irradiation (TBI) measurement commissioning data using the treatment planning system (TPS) for a wide range of patient separations. Methods: Our institution conducts TBI treatments with an 18MV photon beam at 380cm extended SSD using an AP/PA technique. Currently, the monitor units (MU) per field for patient treatments are determined using a lookup table generated from TMR measurements in a water phantom (75 × 41 × 30.5 cm3). The dose prescribed to an umbilicus midline point at spine level is determined based on patient separation, dose/ field and dose rate/MU. One-dimensional heterogeneous dosemore » calculations from Pinnacle TPS were validated with thermoluminescent dosimeters (TLD) placed in an average adult anthropomorphic phantom and also in-vivo on four patients with large separations. Subsequently, twelve patients with various separations (17–47cm) were retrospectively analyzed. Computed tomography (CT) scans were acquired in the left and right decubitus positions from vertex to knee. A treatment plan for each patient was generated. The ratio of the lookup table MU to the heterogeneous TPS MU was compared. Results: TLD Measurements in the anthropomorphic phantom and large TBI patients agreed with Pinnacle calculated dose within 2.8% and 2%, respectively. The heterogeneous calculation compared to the lookup table agreed within 8.1% (ratio range: 1.014–1.081). A trend of reduced accuracy was observed when patient separation increases. Conclusion: The TPS dose calculation accuracy was confirmed by TLD measurements, showing that Pinnacle can model the extended SSD dose without commissioning a special beam model for the extended SSD geometry. The difference between the lookup table and TPS calculation potentially comes from lack of scatter during commissioning when compared to extreme patient sizes. The observed trend suggests the need for development of a correction factor between the lookup table and TPS dose calculations.« less

A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study.

PubMed

Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M; Kirk, Jeremy; Donaldson, Malcolm; Ivarsson, Sten-A; Söder, Olle; Roche, Edna; Hoey, Hilary; Dunger, David B; Juul, Anders

2014-10-01

Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies. In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration. The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, s.d. 0.019) and the low-dose group (35 μg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups. IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children. © 2014 European Society of Endocrinology.

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

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

NASA Astrophysics Data System (ADS)

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

2008-04-01

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

Development of Monte Carlo simulations to provide scanner-specific organ dose coefficients for contemporary CT

NASA Astrophysics Data System (ADS)

Jansen, Jan T. M.; Shrimpton, Paul C.

2016-07-01

The ImPACT (imaging performance assessment of CT scanners) CT patient dosimetry calculator is still used world-wide to estimate organ and effective doses (E) for computed tomography (CT) examinations, although the tool is based on Monte Carlo calculations reflecting practice in the early 1990’s. Subsequent developments in CT scanners, definitions of E, anthropomorphic phantoms, computers and radiation transport codes, have all fuelled an urgent need for updated organ dose conversion factors for contemporary CT. A new system for such simulations has been developed and satisfactorily tested. Benchmark comparisons of normalised organ doses presently derived for three old scanners (General Electric 9800, Philips Tomoscan LX and Siemens Somatom DRH) are within 5% of published values. Moreover, calculated normalised values of CT Dose Index for these scanners are in reasonable agreement (within measurement and computational uncertainties of  ±6% and  ±1%, respectively) with reported standard measurements. Organ dose coefficients calculated for a contemporary CT scanner (Siemens Somatom Sensation 16) demonstrate potential deviations by up to around 30% from the surrogate values presently assumed (through a scanner matching process) when using the ImPACT CT Dosimetry tool for newer scanners. Also, illustrative estimates of E for some typical examinations and a range of anthropomorphic phantoms demonstrate the significant differences (by some 10’s of percent) that can arise when changing from the previously adopted stylised mathematical phantom to the voxel phantoms presently recommended by the International Commission on Radiological Protection (ICRP), and when following the 2007 ICRP recommendations (updated from 1990) concerning tissue weighting factors. Further simulations with the validated dosimetry system will provide updated series of dose coefficients for a wide range of contemporary scanners.

The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range

PubMed Central

Kalliokoski, Annikka; Neuvonen, Mikko; Neuvonen, Pertti J; Niemi, Mikko

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTOrganic anion transporting polypeptide 1B1 is an influx transporter expressed on the basolateral membrane of hepatocytes.A common single nucleotide polymorphism, c.521T→C (p.Val174Ala), of the SLCO1B1 gene has been associated with increased plasma repaglinide concentrations in healthy volunteers.Previous studies at low repaglinide doses have suggested that the effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide could be dose-dependent. WHAT THIS STUDY ADDSRepaglinide peak plasma concentration and area under the plasma concentration–time curve increased linearly along with repaglinide dose ranging from 0.25 to 2 mg in both the predominant c.521TT and rare c.521CC genotype group.The effect of SLCO1B1 c.521T→C polymorphism on repaglinide pharmacokinetics persists over a wide dose range. AIMS To establish whether the effect of SLCO1B1[encoding organic anion transporting polypeptide 1B1 (OATP1B1)] c.521T→C (p.Val174Ala) polymorphism on the pharmacokinetics of repaglinide is dose-dependent. METHODS Twelve healthy volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the c.521CC genotype ingested a single 0.25-, 0.5-, 1- or 2-mg dose of repaglinide in a dose-escalation study with a wash-out period of ≥1 week. RESULTS The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval 47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P ≤ 0.001) larger in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT genotype, respectively. Repaglinide peak plasma concentration and AUC0–∞ increased linearly along with repaglinide dose in both genotype groups (r > 0.88, P < 0.001). There was a tendency towards lower blood glucose concentrations after repaglinide administration in the participants with the c.521CC genotype than in those with the c.521TT genotype. CONCLUSIONS The effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide persists throughout the clinically relevant dose range. PMID:18823304

A study on the suitability of the PTW microDiamond detector for kilovoltage x-ray beam dosimetry.

PubMed

Damodar, Joshita; Odgers, David; Pope, Dane; Hill, Robin

2018-05-01

Kilovoltage x-ray beams are widely used in treating skin cancers and in biological irradiators. In this work, we have evaluated four dosimeters (ionization chambers and solid state detectors) in their suitability for relative dosimetry of kilovoltage x-ray beams in the energy range of 50 - 280kVp. The solid state detectors, which have not been investigated with low energy x-rays, were the PTW 60019 microDiamond synthetic diamond detector and the PTW 60012 diode. The two ionization chambers used were the PTW Advanced Markus parallel plate chamber and the PTW PinPoint small volume chamber. For each of the dosimeters, percentage depth doses were measured in water over the full range of x-ray beams and for field sizes ranging from 2cm diameter to 12 × 12cm. In addition, depth doses were measured for a narrow aperture (7mm diameter) using the PTW microDiamond detector. For comparison, the measured data was compared with Monte Carlo calculated doses using the EGSnrc Monte Carlo package. The depth dose results indicate that the Advanced Markus parallel plate and PinPoint ionization chambers were suitable for depth dose measurements in the beam quality range with an uncertainty of less than 3%, including in the regions closer to the surface of the water as compared with Monte Carlo depth dose data for all six energy beams. The response of the PTW Diode E detector was accurate to within 4% for all field sizes in the energy range of 50-125kVp but showed larger variations for higher energies of up to 12% with the 12 × 12cm field size. In comparison, the microDiamond detector had good agreement over all energies for both smaller and larger field sizes generally within 1% as compared to the Advanced Markus chamber field and Monte Carlo calculations. The only exceptions were in measuring the dose at the surface of the water phantom where larger differences were found. For the 7mm diameter field, the agreement between the microDiamond detector and Monte Carlo calculations was good being better than 1% except at the surface. Based on these results, the PTW microDiamond detector has shown to be a suitable detector for relative dosimetry of low energy x-ray beams over a wide range of x-ray beam energies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Paediatric x-ray examinations in Rio de Janeiro

NASA Astrophysics Data System (ADS)

Azevedo, A. C. P.; Osibote, O. A.; Boechat, M. C. B.

2006-08-01

This work presents the results of a dose survey performed for paediatric patients and carried out in two large paediatric public hospitals in Rio de Janeiro city. The entrance surface dose (ESD) and the effective dose (ED) were evaluated for chest, skull, abdomen, lumbar spine, cervical spine and pelvis in antero-posterior (AP), postero-anterior (PA) and lateral (LAT) projections. For each examination, four age groups 0-1, 1-5, 5-10 and 10-15 years were studied. The DoseCal software was used to calculate these doses. Wide variations for the same type of examination and projection have been detected. These variations were evident, in Brazil, from previous work. In spite of the present results being still preliminary, they can give an idea of what paediatric ESDs are like in Brazil. Also, with respect to the entrance surface dose, some of the results are above the reference levels, which cause high ED, as well. On the other hand, the wide range of ESD reflects the disparity of radiographic techniques and demonstrates that the ALARA principle is not being applied in Brazilian hospitals and becomes a concern in terms of public health.

Ultra-wide Range Gamma Detector System for Search and Locate Operations

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

Odell, D. Mackenzie Odell; Harpring, Larry J.; Moore, Frank S. Jr.

2005-10-26

Collecting debris samples following a nuclear event requires that operations be conducted from a considerable stand-off distance. An ultra-wide range gamma detector system has been constructed to accomplish both long range radiation search and close range hot sample collection functions. Constructed and tested on a REMOTEC Andros platform, the system has demonstrated reliable operation over six orders of magnitude of gamma dose from 100's of uR/hr to over 100 R/hr. Functional elements include a remotely controlled variable collimator assembly, a NaI(Tl)/photomultiplier tube detector, a proprietary digital radiation instrument, a coaxially mounted video camera, a digital compass, and both local andmore » remote control computers with a user interface designed for long range operations. Long range sensitivity and target location, as well as close range sample selection performance are presented.« less

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

PubMed

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

2011-05-01

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

The ambient dose equivalent at flight altitudes: a fit to a large set of data using a Bayesian approach.

PubMed

Wissmann, F; Reginatto, M; Möller, T

2010-09-01

The problem of finding a simple, generally applicable description of worldwide measured ambient dose equivalent rates at aviation altitudes between 8 and 12 km is difficult to solve due to the large variety of functional forms and parametrisations that are possible. We present an approach that uses Bayesian statistics and Monte Carlo methods to fit mathematical models to a large set of data and to compare the different models. About 2500 data points measured in the periods 1997-1999 and 2003-2006 were used. Since the data cover wide ranges of barometric altitude, vertical cut-off rigidity and phases in the solar cycle 23, we developed functions which depend on these three variables. Whereas the dependence on the vertical cut-off rigidity is described by an exponential, the dependences on barometric altitude and solar activity may be approximated by linear functions in the ranges under consideration. Therefore, a simple Taylor expansion was used to define different models and to investigate the relevance of the different expansion coefficients. With the method presented here, it is possible to obtain probability distributions for each expansion coefficient and thus to extract reliable uncertainties even for the dose rate evaluated. The resulting function agrees well with new measurements made at fixed geographic positions and during long haul flights covering a wide range of latitudes.

Spectral distribution of UV range diffuse reflectivity for Si+ ion implanted polymers

NASA Astrophysics Data System (ADS)

Balabanov, S.; Tsvetkova, T.; Borisova, E.; Avramov, L.; Bischoff, L.

2008-05-01

The analysis of the UV range spectral characteristics can supply additional information on the formed sub-surface buried layer with implanted dopants. The near-surface layer (50÷150 nm) of bulk polymer samples have been implanted with silicon (Si+) ions at low energies (E = 30 keV) and a wide range of ion doses (D = 1.1013 ÷ 1, 2.1017 cm-2). The studied polymer materials were: ultra-high-molecular-weight polyethylene (UHMWPE), poly-methyl-metacrylate (PMMA) and poly-tetra-fluor-ethylene (PTFE). The diffuse optical reflectivity spectra Rd = f(λ) of the ion implanted samples have been measured in the UV range (λ = 220÷350 nm). In this paper the dose dependences of the size and sign of the diffuse optical reflectivity changes λRd = f(D) have been analysed.

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

Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?

PubMed

Craven, Meghan; Frank, Graeme R

2018-06-27

Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability. The recommended starting dose of levothyroxine (LT4) is between 10 and 15 μg/kg, an extremely wide range. We hypothesized that a sizable proportion of newborns treated for CH at the higher end of the dosage range become biochemically hyperthyroid at a follow-up visit. This study is a retrospective chart review of infants with CH between 2002 and 2012. Of the 104 patients included in this analysis, the average age at diagnosis was 11 days and the average starting dose of LT4 was 12±2.5 μg/kg. At follow-up, 36.5% required a dose reduction because of iatrogenic hyperthyroxinemia, 51% required no dose adjustment and 12.5% required a dose increase due to an elevated thyroid stimulating hormone (TSH). The starting doses of LT4 for those requiring a dose reduction, those not requiring an adjustment and those requiring an increase in the dose were 13.2±2.4, 11.5±2.1 and 10.3±2.6 μg/kg/day, respectively (p≤0.0001). Of the 34% of infants treated with an initial dose of >12.5 μg/day, 57.1% required a dose reduction at follow-up, compared to 26.1% of those whose initial starting dose was ≤12.5 μg/kg/day (p=0.007). Following the guidelines for initiating therapy for CH, 36.5% of the infants required a dose reduction for iatrogenic hyperthyroxinemia. These infants received a higher dose of LT4 than the infants who either required no adjustment or required an increase in the dose. A narrower range for initial dosing in CH may be appropriate.

Let your name be known. OB-GYN practice's marketing strategies keep it prominent in community.

PubMed

Schneck, Lisa H

2003-08-01

Take a large dose of innovation, add a dollop of shrewd business sense and a heaping measure of community awareness, mix well, and you get the marketing success enjoyed by San Dimas Medical Group Inc. of Bakersfield, Calif. The practice has established wide name recognition, become a community benefactor and positioned itself as the practice that local women want to visit for a wide range of health concerns.

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

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

PubMed

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

2015-06-01

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

An alternative arrangement of metered dosing fluid using centrifugal pump

NASA Astrophysics Data System (ADS)

Islam, Md. Arafat; Ehsan, Md.

2017-06-01

Positive displacement dosing pumps are extensively used in various types of process industries. They are widely used for metering small flow rates of a dosing fluid into a main flow. High head and low controllable flow rates make these pumps suitable for industrial flow metering applications. However their pulsating flow is not very suitable for proper mixing of fluids and they are relatively more expensive to buy and maintain. Considering such problems, alternative techniques to control the fluid flow from a low cost centrifugal pump is practiced. These include - throttling, variable speed drive, impeller geometry control and bypass control. Variable speed drive and impeller geometry control are comparatively costly and the flow control by throttling is not an energy efficient process. In this study an arrangement of metered dosing flow was developed using a typical low cost centrifugal pump using bypass flow technique. Using bypass flow control technique a wide range of metered dosing flows under a range of heads were attained using fixed pump geometry and drive speed. The bulk flow returning from the system into the main tank ensures better mixing which may eliminate the need of separate agitators. Comparative performance study was made between the bypass flow control arrangement of centrifugal pump and a diaphragm type dosing pump. Similar heads and flow rates were attainable using the bypass control system compared to the diaphragm dosing pump, but using relatively more energy. Geometrical optimization of the centrifugal pump impeller was further carried out to make the bypass flow arrangement more energy efficient. Although both the systems run at low overall efficiencies but the capital cost could be reduced by about 87% compared to the dosing pump. The savings in capital investment and lower maintenance cost very significantly exceeds the relatively higher energy cost of the bypass system. This technique can be used as a cost effective solution for industries in Bangladesh and have been implemented in two salt iodization plants at Narayangang.

Optically Stimulated Luminescence Analysis Method for High Dose Rate Using an Optical Fiber Type Dosimeter

NASA Astrophysics Data System (ADS)

Ueno, Katsunori; Tominaga, Kazuo; Tadokoro, Takahiro; Ishizawa, Koji; Takahashi, Yoshinori; Kuwabara, Hitoshi

2016-08-01

The investigation of air dose rates at locations in the Fukushima Dai-ichi Nuclear Power Station is necessary for safe removal of the molten nuclear fuel. The target performance for the investigation is to analyze a dose rate in the range of 10-3 Gy/h to 102 Gy/h with a measurement precision of ±4.0% full scale (F.S.) at a measurement interval of 60 s. In order to achieve this target, the authors proposed an optically stimulated luminescence (OSL) analysis method using prompt OSL for a wide dynamic range of dose rates; the OSL is generated using BaFBr:Eu with a fast decay time constant. The luminescence intensity by prompt OSL was formulated by the electron concentration of the trapping state during gamma ray and stimulation light irradiations. The prototype OSL monitor using BaFBr:Eu was manufactured for investigation of prompt OSL and evaluation of the measurement precision. The time dependence of the luminescence intensity by prompt OSL was analyzed by irradiating the OSL sensor in a 60Co irradiation facility. The measured dose rates were obtained in a prompt mode and an accumulating mode with a precision of ±3.3% F.S. for the dose rate range of 9.5 ×10-4 Gy/h to 1.2 ×102 Gy/h.

Hormesis as a biological hypothesis.

PubMed Central

Calabrese, E J; Baldwin, L A

1998-01-01

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

Radiobiological description of the LET dependence of the cell survival of oxic and anoxic cells irradiated by carbon ions.

PubMed

Antonovic, L; Brahme, A; Furusawa, Y; Toma-Dasu, I

2013-01-01

Light-ion radiation therapy against hypoxic tumors is highly curative due to reduced dependence on the presence of oxygen in the tumor at elevated linear energy transfer (LET) towards the Bragg peak. Clinical ion beams using spread-out Bragg peak (SOBP) are characterized by a wide spectrum of LET values. Accurate treatment optimization requires a method that can account for influence of the variation in response for a broad range of tumor hypoxia, absorbed doses and LETs. This paper presents a parameterization of the Repairable Conditionally-Repairable (RCR) cell survival model that can describe the survival of oxic and hypoxic cells over a wide range of LET values, and investigates the relationship between hypoxic radiation resistance and LET. The biological response model was tested by fitting cell survival data under oxic and anoxic conditions for V79 cells irradiated with LETs within the range of 30-500 keV/µm. The model provides good agreement with experimental cell survival data for the range of LET investigated, confirming the robustness of the parameterization method. This new version of the RCR model is suitable for describing the biological response of mixed populations of oxic and hypoxic cells and at the same time taking into account the distribution of doses and LETs in the incident beam and its variation with depth in tissue. The model offers a versatile tool for the selection of LET and dose required in the optimization of the therapeutic effect, without severely affecting normal tissue in realistic tumors presenting highly heterogeneous oxic and hypoxic regions.

Exfoliated graphite with graphene flakes as potential candidates for TL dosimeters at high gamma doses.

PubMed

Ortiz-Morales, A; López-González, E; Rueda-Morales, G; Ortega-Cervantez, G; Ortiz-Lopez, J

2018-06-06

Graphite powder (GP) subjected to microwave radiation (MWG) results in exfoliation of graphite particles into few-layered graphene flakes (GF) intermixed with partially exfoliated graphite particles (PEG). Characterization of MWG by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and Raman spectroscopy reveal few-layer GF with sizes ranging from 0.2 to 5 µm. Raman D, G, and 2D (G') bands characteristic of graphitic structures include evidence of the presence of bilayered graphene. The thermoluminescent (TL) dosimetric properties of MWG are evaluated and can be characterized as a gamma-ray sensitive and dose-resistant material with kinetic parameters (activation energy for the main peak located at 400 and 408 K is 0.69 and 0.72 eV) and threshold dose (~1 kGy and 5 kGy respectively). MWG is a low-Z material (Z eff = 6) with a wide linear range of TL dose-response (0.170-2.5 kGy) tested at doses in the 1-20 kGy range with promising results for applications in gamma-ray dosimetry. Results obtained in gamma irradiated MWG are compared with those obtained in graphite powder samples (GP) without microwave treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Medical Applications of the PHITS Code I: Recent Improvements and Biological Dose Estimation Model].

PubMed

Sato, Tatsuhiko; Furuta, Takuya; Hashimoto, Shintaro; Kuga, Naoya

2015-01-01

PHITS is a general purpose Monte Carlo particle transport simulation code developed through the collaboration of several institutes mainly in Japan. It can analyze the motion of nearly all radiations over wide energy ranges in 3-dimensional matters. It has been used for various applications including medical physics. This paper reviews the recent improvements of the code, together with the biological dose estimation method developed on the basis of the microdosimetric function implemented in PHITS.

Genetic effects of radiotherapy for childhood cancer: gonadal dose reconstruction.

PubMed

Stovall, Marilyn; Donaldson, Sarah S; Weathers, Rita E; Robison, Leslie L; Mertens, Ann C; Winther, Jeanette Falck; Olsen, Jorgen H; Boice, John D

2004-10-01

To estimate the doses of radiation to organs of interest during treatment of childhood cancer for use in an epidemiologic study of possible heritable diseases, including birth defects, chromosomal abnormalities, cancer, stillbirth, and neonatal and premature death. The study population was composed of more than 25,000 patients with cancer in Denmark and the United States who were survivors of childhood cancer and subsequently had nearly 6,500 children of their own. Radiation therapy records were sought for the survivors who parented offspring who had adverse pregnancy outcomes (>300 offspring), and for a sample of all survivors in a case-cohort design. The records were imaged and centrally abstracted. Water phantom measurements were made to estimate doses for a wide range of treatments. Mathematical phantoms were used to apply measured results to estimate doses to ovaries, uterus, testes, and pituitary for patients ranging in age from newborn to 25 years. Gonadal shielding, ovarian pinning (oophoropexy), and field blocking were taken into account. Testicular radiation doses ranged from <1 to 700 cGy (median, 7 cGy) and ovarian doses from <1 to >2,500 cGy (median, 13 cGy). Ten percent of the records were incomplete, but sufficient data were available for broad characterizations of gonadal dose. More than 49% of the gonadal doses were >10 cGy and 16% were >100 cGy. Sufficient radiation therapy data exist as far back as 1943 to enable computation of gonadal doses administered for curative therapy for childhood cancer. The range of gonadal doses is broad, and for many cancer survivors, is high and just below the threshold for infertility. Accordingly, the epidemiologic study has >90% power to detect a 1.3-fold risk of an adverse pregnancy outcome associated with radiation exposure to the gonads. This study should provide important information on the genetic consequences of radiation exposure to humans.

Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

PubMed

Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

2015-04-01

Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

Modern dosimetric tools for 60Co irradiation at high containment laboratories

PubMed Central

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

2011-01-01

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

Gamma ray induced decomposition of double nitrates of lanthanum and cerium with some mono and bivalent cations in solid state

NASA Astrophysics Data System (ADS)

Kulkarni, S. P.; Garg, A. N.

Gamma ray induced decomposition of two series of double nitrates; 2M INO 3⋯Ln(NO 3) 3⋯ x H 2O (where MI = NH+4, Na+, K+, Rb+, Cs+; LnIII = La3+, Ce3+ and x = 2 or 4) and 3M II(NO 3) 2·2Ln III(NO 3) 3⋯24H 2O (where MII = Mg2+, Co2+, Zn2+; LnIII = La3+, Ce3+) has been studied in solid state over a wide absorbed dose range at room temperature. G(NO -2) values have been found to depend on the absorbed dose and the nature of cation in both the series of double salts. Radiation sensitivity of lanthanum double nitrates with monovalent cations at an absorbed dose of 158 kGy follows the order NH +4 < Rb + ≅ Cs + < Na + < K + and those of cerium NH +4 < Rb +

High-temperature thermoluminescence of anion-deficient alumina and possibilities of its application in high-dose dosimetry

NASA Astrophysics Data System (ADS)

Surdo, A. I.; Milman, I. I.; Abashev, R. M.; Vlasov, M. I.

2014-12-01

Results of studies of the thermoluminescence (TL) of anion-deficient alumina (α-Al2O3 - δ) single crystals and based on them TLD-500 detectors exposed to pulsed X-ray and electron radiation in a wide range of doses D, pulsed dose rates P p , and temperatures are described. The TL responses of α-Al2O3 - δ for continuous and pulsed X-ray irradiation at D = 0.05-150 Gy are compared. Unlike continuous irradiation, in the case of pulsed irradiation at P p ≥ 6 × 106 Gy/s, a linear increase in the TL response as a function of D is registered in the main and "chromium" peaks at 450 and 580 K, respectively, with a decrease in the slope of the dose dependence at D > 2 Gy for the peak at 450 K. It is found that high-dose irradiation (>60 Gy) leads to the formation of a new TL peak at 830 K and the preferential redistribution of the stored light sums into this peak. The dose dependence for the TL peak at 830 K is studied. It is established that it is linear in a super-high dose range of 104 to 6 × 106 Gy at P p = 2.6 × 1011 Gy/s.

Treatment of growth hormone deficiency in children, adolescents and at the transitional age.

PubMed

Richmond, Erick; Rogol, Alan D

2016-12-01

Recombinant human growth hormone (rhGH) has been available since 1985. Before 1985 growth hormone (GH) was extracted from cadaveric pituitary glands, but this was stopped in most countries that year, following the recognition that it could transmit Creutzfeldt-Jacob disease. The primary goal of rhGH treatment in GHD patients is to normalize height during childhood and adolescence and attain an adult height within the normal range and within the target height range (genetic potential). Genome-wide association studies have been used increasingly to study the genetic influence on height. There is a wide response to rhGH therapy, likely due to compliance issues, severity of GH deficiency and patient's sensitivity to rhGH. While some pediatric endocrinologists will use a fixed dose of rhGH, most will use an auxology-based dosing approach. This will involve starting at the lower end of the dose range and then titrating upwards based on the patient's response to therapy with measurement of IGF-1 concentrations to ensure that the patient is not over treated or undertreated. Although treatment of children with GHD with rhGH has generally been safe, careful follow-up by a pediatric endocrinologist in partnership with the pediatrician or primary care physician is recommended. The aim of this paper is to review the strategies and recommendations for treatment of GHD in children and patients in the transition to adult care. Copyright © 2016 Elsevier Ltd. All rights reserved.

Affirmative Communication as Health: The New Paradigm.

ERIC Educational Resources Information Center

Cooper, Thomas W.

A wide range of interesting observations of the past decade, which may now cast their shadow as the health communication paradigm of the forthcoming decade, can be clarified and correlated. One example of effective communication therapy was Norman Cousins's hospitalization with the crippling disease, "ankylosing spondylitis." Using large doses of…

A novel approach for estimating ingested dose associated with paracetamol overdose

PubMed Central

Zurlinden, Todd J.; Heard, Kennon

2015-01-01

Aim In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue‐specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow‐up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. Methods The core component of the computational framework was a physiologically‐based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter‐study variability, and facilitating the calculation of uncertainty in model outputs. Results Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Conclusions Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow‐up plan. PMID:26441245

A novel approach for estimating ingested dose associated with paracetamol overdose.

PubMed

Zurlinden, Todd J; Heard, Kennon; Reisfeld, Brad

2016-04-01

In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. The core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs. Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan. © 2015 The British Pharmacological Society.

Submillisievert median radiation dose for coronary angiography with a second-generation 320-detector row CT scanner in 107 consecutive patients.

PubMed

Chen, Marcus Y; Shanbhag, Sujata M; Arai, Andrew E

2013-04-01

To (a) use a new second-generation wide-volume 320-detector row computed tomographic (CT) scanner to explore optimization of radiation exposure in coronary CT angiography in an unselected and consecutive cohort of patients referred for clinical purposes and (b) compare estimated radiation exposure and image quality with that from a cohort of similar patients who underwent imaging with a previous first-generation CT system. The study was approved by the institutional review board, and all subjects provided written consent. Coronary CT angiography was performed in 107 consecutive patients with a new second-generation 320-detector row unit. Estimated radiation exposure and image quality were compared with those from 100 consecutive patients who underwent imaging with a previous first-generation scanner. Effective radiation dose was estimated by multiplying the dose-length product by an effective dose conversion factor of 0.014 mSv/mGy ⋅ cm and reported with size-specific dose estimates (SSDEs). Image quality was evaluated by two independent readers. The mean age of the 107 patients was 55.4 years ± 12.0 (standard deviation); 57 patients (53.3%) were men. The median body mass index was 27.3 kg/m(2) (range, 18.1-47.2 kg/m(2)); however, 71 patients (66.4%) were overweight, obese, or morbidly obese. A tube potential of 100 kV was used in 97 patients (90.6%), single-volume acquisition was used in 104 (97.2%), and prospective electrocardiographic gating was used in 106 (99.1%). The mean heart rate was 57.1 beats per minute ± 11.2 (range, 34-96 beats per minute), which enabled single-heartbeat scans in 100 patients (93.4%). The median radiation dose was 0.93 mSv (interquartile range [IQR], 0.58-1.74 mSv) with the second-generation unit and 2.67 mSv (IQR, 1.68-4.00 mSv) with the first-generation unit (P < .0001). The median SSDE was 6.0 mGy (IQR, 4.1-10.0 mGy) with the second-generation unit and 13.2 mGy (IQR, 10.2-18.6 mGy) with the first-generation unit (P < .0001). Overall, the radiation dose was less than 0.5 mSv for 23 of the 107 CT angiography examinations (21.5%), less than 1 mSv for 58 (54.2%), and less than 4 mSv for 103 (96.3%). All studies were of diagnostic quality, with most having excellent image quality. Three of four image quality indexes were significantly better with the second-generation unit compared with the first-generation unit. The combination of a gantry rotation time of 275 msec, wide volume coverage, iterative reconstruction, automated exposure control, and larger x-ray power generator of the second-generation CT scanner provides excellent image quality over a wide range of body sizes and heart rates at low radiation doses. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122621/-/DC1. RSNA, 2013

Assessment of the occupational eye lens dose for clinical staff in interventional radiology, cardiology and neuroradiology.

PubMed

Omar, Artur; Kadesjö, Nils; Palmgren, Charlotta; Marteinsdottir, Maria; Segerdahl, Tony; Fransson, Annette

2017-03-20

In accordance with recommendations by the International Commission on Radiological Protection, the current European Basic Safety Standards has adopted a reduced occupational eye lens dose limit of 20 mSv yr -1 . The radiation safety implications of this dose limit is of concern for clinical staff that work with relatively high dose x-ray angiography and interventional radiology. Presented in this work is a thorough assessment of the occupational eye lens dose based on clinical measurements with active personal dosimeters worn by staff during various types of procedures in interventional radiology, cardiology and neuroradiology. Results are presented in terms of the estimated equivalent eye lens dose for various medical professions. In order to compare the risk of exceeding the regulatory annual eye lens dose limit for the widely different clinical situations investigated in this work, the different medical professions were separated into categories based on their distinct work pattern: staff that work (a) regularly beside the patient, (b) in proximity to the patient and (c) typically at a distance from the patient. The results demonstrate that the risk of exceeding the annual eye lens dose limit is of concern for staff category (a), i.e. mainly the primary radiologist/cardiologist. However, the results also demonstrate that the risk can be greatly mitigated if radiation protection shields are used in the clinical routine. The results presented in this work cover a wide range of clinical situations, and can be used as a first indication of the risk of exceeding the annual eye lens dose limit for staff at other medical centres.

Efficacy of immobilizing free-ranging elk with Telazol® and xylazine hydrochloride using transmitter-equipped darts

USGS Publications Warehouse

Walter, W. David; Leslie, David M.; Herner-Thogmartin, Jennifer H.; Smith, Kimberly G.; Cartwright, Michael E.

2005-01-01

From January 1999 to April 2002, 14 free-ranging elk were darted with a mixture of Telazol® reconstituted with xylazine hydrochloride (HCl) in a forested habitat in southwestern Oklahoma and north-central Arkansas. Elk were darted from ground blinds, tree stands, or a vehicle at distances of 14–46 m and were recovered 37–274 m from the dart site. Elk were located using radiotelemetry with 3-cc disposable Pneu-dart® transmitter darts. Mean±SD dose of Telazol®and xylazine HCl was 590±192 mg/ml and 276±153 mg/ml, respectively, and mean time to standing after injection of reversal agent was 27 min (range: 1–65 min). The combination of Telazol® and xylazine HCl successfully immobilized free-ranging elk, and transmitter-equipped darts permitted successful location of sedated elk by two people in areas of dense forest cover. The dose required to sedate elk appeared to vary depending on physiology and behavior, but no drug-induced mortality occurred despite the wide variance in the doses administered. We recommend 500 mg Telazol® reconstituted with 300 mg xylazine HCl as an initial dose for a ≥200 kg elk. If needed to achieve full sedation, up to 3 additional ml of the mixture may be administered without adverse effects.

Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.

PubMed

Bai, Stephen A; Xiang, Qinfang; Finn, Andrew

2016-02-01

Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 μg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-μg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 μg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. In the single-dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-µg dose to 1.43 ng/mL for the 1200-µg dose. AUC0-∞, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 μg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to healthy volunteers. The absolute bioavailability of BBUP was 46% to 51% across a 16-fold dose range, with dose-proportional increases in systemic exposure. Apparent steady-state conditions occurred within 3 days of dosing. These pharmacokinetic results suggest that therapeutic buprenorphine plasma concentrations can be obtained with BBUP across a wide dose range in a shorter time than other (eg, transdermal) dosage forms. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

UNIVERSAL RELATIONSHIP OF TOTAL LUNG DEPOSITION OF PARTICLES IN NORMAL ADULTS WITH PARTICLE SIZE AND BREATHING PATTERN

EPA Science Inventory

Particulate matter in the air is known for causing adverse health effects and yet estimating lung deposition dose is difficult because exposure conditions vary widely. We measured total deposition fraction (TDF) of monodisperse aerosols in the size range of 0.04 - 5 micron in dia...

Population Pharmacokinetics of Rifapentine and Desacetyl Rifapentine in Healthy Volunteers: Nonlinearities in Clearance and Bioavailability

PubMed Central

Lu, Yanhui; Bliven-Sizemore, Erin; Weiner, Marc; Nuermberger, Eric; Burman, William; Dorman, Susan E.; Dooley, Kelly E.

2014-01-01

Rifapentine is under active investigation as a potent drug that may help shorten the tuberculosis (TB) treatment duration. A previous rifapentine dose escalation study with daily dosing indicated a possible decrease in bioavailability as the dose increased and an increase in clearance over time for rifapentine and its active metabolite, desacetyl rifapentine. This study aimed to assess the effects of increasing doses on rifapentine absorption and bioavailability and to evaluate the clearance changes over 14 days. A population analysis was performed with nonlinear mixed-effects modeling. Absorption, time-varying clearance, bioavailability, and empirical and semimechanistic autoinduction models were investigated. A one-compartment model linked to a transit compartment absorption model best described the data. The bioavailability of rifapentine decreased linearly by 2.5% for each 100-mg increase in dose. The autoinduction model suggested a dose-independent linear increase in clearance of the parent drug and metabolite over time from 1.2 and 3.1 liters · h−1, respectively, after a single dose to 2.2 and 5.0 liters · h−1, respectively, after 14 once-daily doses, with no plateau being reached by day 14. In clinical trial simulations using the final model, rifapentine demonstrated less-than-dose-proportional pharmacokinetics, but there was no plateau in exposures over the dose range tested (450 to 1,800 mg), and divided dosing increased exposures significantly. Thus, the proposed compartmental model incorporating daily dosing of rifapentine over a wide range of doses and time-related changes in bioavailability and clearance provides a useful tool for estimation of drug exposure that can be used to optimize rifapentine dosing for TB treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01162486.) PMID:24614383

Relationships between patient size, dose and image noise under automatic tube current modulation systems.

PubMed

Sookpeng, S; Martin, C J; Gentle, D J; Lopez-Gonzalez, M R

2014-03-01

Automatic tube current modulation (ATCM) systems are now used for the majority of CT scans. The principles of ATCM operation are different in CT scanners from different manufacturers. Toshiba and GE scanners base the current modulation on a target noise setting, while Philips and Siemens scanners use reference image and reference mAs concepts respectively. Knowledge of the relationships between patient size, dose and image noise are important for CT patient dose optimisation. In this study, the CT patient doses were surveyed for 14 CT scanners from four different CT scanner manufacturers. The patient cross sectional area, the tube current modulation and the image noise from the CT images were analysed using in-house software. The Toshiba and GE scanner results showed that noise levels are relatively constant but tube currents are dependent on patient size. As a result of this there is a wide range in tube current values across different patient sizes, and doses for large patients are significantly higher in these scanners. In contrast, in the Philips and Siemens scanners, tube currents are less dependent on patient size, the range in tube current is narrower, and the doses for larger patients are not as high. Image noise is more dependent on the patient size.

Occupational dose constraints in interventional cardiology procedures: the DIMOND approach

NASA Astrophysics Data System (ADS)

Tsapaki, Virginia; Kottou, Sophia; Vano, Eliseo; Komppa, Tuomo; Padovani, Renato; Dowling, Annita; Molfetas, Michael; Neofotistou, Vassiliki

2004-03-01

Radiation fields involved in angiographic suites are most uneven with intensity and gradient varying widely with projection geometry. The European Commission DIMOND III project addressed among others, the issues regarding optimization of staff doses with an attempt to propose preliminary occupational dose constraints. Two thermoluminescent dosemeters (TLD) were used to assess operators' extremity doses (left shoulder and left foot) during 20 coronary angiographies (CAs) and 20 percutaneous transluminal coronary angioplasties (PTCAs) in five European centres. X-ray equipment, radiation protection measures used and the dose delivered to the patient in terms of dose-area product (DAP) were recorded so as to subsequently associate them with operator's dose. The range of staff doses noted for the same TLD position, centre and procedure type emphasizes the importance of protective measures and technical characteristics of x-ray equipment. Correlation of patient's DAP with staff shoulder dose is moderate whereas correlation of patient's DAP with staff foot dose is poor in both CA and PTCA. Therefore, it is difficult to predict operator's dose from patient's DAP mainly due to the different use of protective measures. A preliminary occupational dose constraint value was defined by calculating cardiologists' annual effective dose and found to be 0.6 mSv.

Potential radiation control of biofouling bacteria on intake filters

NASA Astrophysics Data System (ADS)

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

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

SU-E-I-42: Normalized Embryo/fetus Doses for Fluoroscopically Guided Pacemaker Implantation Procedures Calculated Using a Monte Carlo Technique

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

Damilakis, J; Stratakis, J; Solomou, G

Purpose: It is well known that pacemaker implantation is sometimes needed in pregnant patients with symptomatic bradycardia. To our knowledge, there is no reported experience regarding radiation doses to the unborn child resulting from fluoroscopy during pacemaker implantation. The purpose of the current study was to develop a method for estimating embryo/fetus dose from fluoroscopically guided pacemaker implantation procedures performed on pregnant patients during all trimesters of gestation. Methods: The Monte Carlo N-Particle (MCNP) radiation transport code was employed in this study. Three mathematical anthropomorphic phantoms representing the average pregnant patient at the first, second and third trimesters of gestationmore » were generated using Bodybuilder software (White Rock science, White Rock, NM). The normalized embryo/fetus dose from the posteroanterior (PA), the 30° left-anterior oblique (LAO) and the 30° right-anterior oblique (RAO) projections were calculated for a wide range of kVp (50–120 kVp) and total filtration values (2.5–9.0 mm Al). Results: The results consist of radiation doses normalized to a) entrance skin dose (ESD) and b) dose area product (DAP) so that the dose to the unborn child from any fluoroscopic technique and x-ray device used can be calculated. ESD normalized doses ranged from 0.008 (PA, first trimester) to 2.519 μGy/mGy (RAO, third trimester). DAP normalized doses ranged from 0.051 (PA, first trimester) to 12.852 μGy/Gycm2 (RAO, third trimester). Conclusion: Embryo/fetus doses from fluoroscopically guided pacemaker implantation procedures performed on pregnant patients during all stages of gestation can be estimated using the method developed in this study. 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

High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo.

PubMed

Zara, Janette N; Siu, Ronald K; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M; Ting, Kang; Soo, Chia

2011-05-01

The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL.

High Doses of Bone Morphogenetic Protein 2 Induce Structurally Abnormal Bone and Inflammation In Vivo

PubMed Central

Zara, Janette N.; Siu, Ronald K.; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M.; Ting, Kang

2011-01-01

The major Food and Drug Association–approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL. PMID:21247344

Effect of supplementation with flaxseed oil and different doses of fish oil for 2 weeks on plasma phosphatidylcholine fatty acids in young women.

PubMed

Hodson, Leanne; Crowe, Francesca L; McLachlan, Kirsten J; Skeaff, C Murray

2018-06-01

Although assumed, it remains unclear that fatty acid (FA) biomarkers of n-3 long-chain PUFA reflect wide ranges of intake. However, to be utilised as biomarkers, to predict dietary intake, dose-response curves that cover a spectrum of intakes are required. The aim of the study was to investigate whether the FA composition of plasma phosphatidylcholine (PC) is a sensitive biomarker of n-3 FAs from fish oil, across a range of supplementation doses, and alpha-linolenic acid (ALA) supplementation, in young, healthy women. A total of 303 young women were randomised to intakes ranging between 0.33 and 4.50 g EPA+DHA/day from fish oil (not all doses used in each year) or flaxseed oil (5.90-6.60 g/d) daily for 14 days in a series of trials, over 5 years. Fasting blood was collected at baseline (day 0) and day 14 and plasma PC FA composition, total and HDL-cholesterol and triglyceride concentrations measured. Fourteen days supplementation with fish oil significantly (P < 0.01) increased, in a dose-dependent fashion, plasma PC EPA, DPA and DHA at all doses except 1 and 3 mL/day. For the combined group of women who consumed any fish oil there was a 16% (P < 0.01) decrease in plasma triacylglycerol concentrations after 14 days supplementation. Flaxseed oil supplementation for 14 day resulted in significant (P < 0.01) increases in ALA, EPA and DPA, whilst DHA remained unchanged. Our data demonstrate plasma PC is a sensitive biomarker of n-3 FA intake and reflects changes within 14 days across a range of intakes.

Measurement of air dose rates over a wide area around the Fukushima Dai-ichi Nuclear Power Plant through a series of car-borne surveys.

PubMed

Andoh, Masaki; Nakahara, Yukio; Tsuda, Shuichi; Yoshida, Tadayoshi; Matsuda, Norihiro; Takahashi, Fumiaki; Mikami, Satoshi; Kinouchi, Nobuyuki; Sato, Tetsuro; Tanigaki, Minoru; Takamiya, Koichi; Sato, Nobuhiro; Okumura, Ryo; Uchihori, Yukio; Saito, Kimiaki

2015-01-01

A series of car-borne surveys using the Kyoto University RAdiation MApping (KURAMA) and KURAMA-II survey systems has been conducted over a wide area in eastern Japan since June 2011 to evaluate the distribution of air dose rates around the Fukushima Dai-ichi Nuclear Power Plant and to evaluate the time-dependent trend of decrease in air dose rates. An automated data processing system for the KURAMA-II system was established, which enabled rapid analysis of large amounts of data obtained using about 100 KURAMA-II units. The initial data used for evaluating the migration status of radioactive cesium were obtained in the first survey, followed by other car-borne surveys conducted over more extensive and wider measurement ranges. By comparing the measured air dose rates obtained in each survey (until December 2012), the decreasing trend of air dose rates measured through car-borne surveys was found to be more pronounced than those expected on the basis of the physical decay of radioactive cesium and of the air dose rates measured using NaI (Tl) survey meters in the areas surrounding the roadways. In addition, it was found that the extent of decrease in air dose rates depended on land use, wherein it decreased faster for land used as building sites than for forested areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

Performance of a GM tube based environmental dose rate monitor operating in the Time-To-Count mode

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

Zickefoose, J.; Kulkarni, T.; Martinson, T.

The events at the Fukushima Daiichi power plant in the aftermath of a natural disaster underline the importance of a large array of networked environmental monitors to cover areas around nuclear power plants. These monitors should meet a few basic criteria: have a uniform response over a wide range of gamma energies, have a uniform response over a wide range of incident angles, and have a large dynamic range. Many of these criteria are met if the probe is qualified to the international standard IEC 60532 (Radiation protection instrumentation - Installed dose rate meters, warning assemblies and monitors - Xmore » and gamma radiation of energy between 50 keV and 7 MeV), which specifically deals with energy response, angle of incidence, dynamic range, response time, and a number of environmental characteristics. EcoGamma is a dual GM tube environmental gamma radiation monitor designed specifically to meet the requirements of IEC 60532 and operate in the most extreme conditions. EcoGamma utilizes two energy compensated GM tubes operating with a Time-To-Count (TTC) collection algorithm. The TTC algorithm extends the lifetime and range of a GM tube significantly and allows the dual GM tube probe to achieve linearity over approximately 10 decades of gamma dose rate (from the Sv/hr range to 100 Sv/hr). In the TTC mode of operation, the GM tube is not maintained in a biased condition continuously. This is different from a traditional counting system where the GM tube is held at a constant bias continuously and the total number of strikes that the tube registers are counted. The traditional approach allows for good sensitivity, but does not lend itself to a long lifetime of the tube and is susceptible to linearity issues at high count rates. TTC on the other hand only biases the tube for short periods of time and in effect measures the time between events, which is statistically representative of the total strike rate. Since the tube is not continually biased, the life of the tube is extended and the linearity is greatly improved. Testing has been performed at Pacific Northwest National Laboratory (PNNL) in the USA and confirms compliance to IEC 60532 as well as linearity (± 10%) up to 100 Sv/hr. Furthermore, a network of EcoGamma probes may be linked through available supervisory software to provide a dose rate map of an area. This allows for real time monitoring of dose rates from one (or multiple) remote locations. (authors)« less

OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN TUNGSTEN

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

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.

2015-04-16

We used our recently developed lattice-based object kinetic Monte Carlo code; KSOME [1] to carryout simulations of radiation damage in bulk tungsten at temperatures of 300, and 2050 K for various dose rates. Displacement cascades generated from molecular dynamics (MD) simulations for PKA energies at 60, 75 and 100 keV provided residual point defect distributions. It was found that the number density of vacancies in the simulation box does not change with dose rate while the number density of vacancy clusters slightly decreases with dose rate indicating that bigger clusters are formed at larger dose rates. At 300 K, althoughmore » the average vacancy cluster size increases slightly, the vast majority of vacancies exist as mono-vacancies. At 2050 K no accumulation of defects was observed during irradiation over a wide range of dose rates for all PKA energies studied in this work.« less

Complex, non-monotonic dose-response curves with multiple maxima: Do we (ever) sample densely enough?

PubMed

Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor

2015-01-01

We usually expect the dose-response curves of biological responses to quantifiable stimuli to be simple, either monotonic or exhibiting a single maximum or minimum. Deviations are often viewed as experimental noise. However, detailed measurements in plant primary tissue cultures (stem pith explants of kale and tobacco) exposed to varying doses of sucrose, cytokinins (BA or kinetin) or auxins (IAA or NAA) revealed that growth and several biochemical parameters exhibit multiple reproducible, statistically significant maxima over a wide range of exogenous substance concentrations. This results in complex, non-monotonic dose-response curves, reminiscent of previous reports of analogous observations in both metazoan and plant systems responding to diverse pharmacological treatments. These findings suggest the existence of a hitherto neglected class of biological phenomena resulting in dose-response curves exhibiting periodic patterns of maxima and minima, whose causes remain so far uncharacterized, partly due to insufficient sampling frequency used in many studies.

Analysis of patient CT dose data using virtualdose

NASA Astrophysics Data System (ADS)

Bennett, Richard

X-ray computer tomography has many benefits to medical and research applications. Recently, over the last decade CT has had a large increase in usage in hospitals and medical diagnosis. In pediatric care, from 2000 to 2006, abdominal CT scans increased by 49 % and chest CT by 425 % in the emergency room (Broder 2007). Enormous amounts of effort have been performed across multiple academic and government groups to determine an accurate measure of organ dose to patients who undergo a CT scan due to the inherent risks with ionizing radiation. Considering these intrinsic risks, CT dose estimating software becomes a necessary tool that health care providers and radiologist must use to determine many metrics to base the risks versus rewards of having an x-ray CT scan. This thesis models the resultant organ dose as body mass increases for patients with all other related scan parameters fixed. In addition to this,this thesis compares a modern dose estimating software, VirtualDose CT to two other programs, CT-Expo and ImPACT CT. The comparison shows how the software's theoretical basis and the phantom they use to represent the human body affect the range of results in organ dose. CT-Expo and ImPACT CT dose estimating software uses a different model for anatomical representation of the organs in the human body and the results show how that approach dramatically changes the outcome. The results categorizes four datasets as compared to the three software types where the appropriate phantom was available. Modeling was done to simulate chest abdominal pelvis scans and whole body scans. Organ dose difference versus body mass index shows as body mass index (BMI) ranges from 23.5 kg/m 2 to 45 kg/m2 the amount of organ dose also trends a percent change from -4.58 to -176.19 %. Comparing organ dose difference with increasing x-ray tube potential from 120 kVp to 140 kVp the percent change in organ dose increases from 55 % to 65 % across all phantoms. In comparing VirtualDose to CT-Expo for organ dose difference versus age, male phantoms show percent difference of -19 % to 25 % for various organs minus bone surface and breast tissues results. Finally, for organ dose difference across all software for average adult phantom the results range from -45 % to 6 % in the comparison of ImPACT CT to VirtualDose and -27 % to 66 % for the comparison of CT-Expo to VirtualDose. In the comparison for increased BMI (done only in VirtualDose), results show that with all other parameters fixed, the organ dose goes down as BMI increases, which is due to the increase in adipose tissue and bulk of the patient model. The range of results when comparing all the three softwares have a wide range, in some cases greater than 150 %, it is evident that using a different anatomical basis for the human phantom and the theoretical basis for the dose estimation will cause fluctuation in the results. Therefore, choosing the software with the most accurate human phantom will provide a closer range to the true dose to the organ.

Low dose evaluation of the antiandrogen flutamide following a Mode of Action approach

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

Sarrabay, A.; UniverSud, INSERM, UMR-996 “Inflammation, Chemokines and Immunopathology”, Châtenay-Malabry; Bayer SAS, 16, rue Jean Marie Leclair, 69009 Lyon

ABSTRACT: The dose–response characterization of endocrine mediated toxicity is an on-going debate which is controversial when exploring the nature of the dose–response curve and the effect at the low-end of the curve. To contribute to this debate we have assessed the effects of a wide range of dose levels of the antiandrogen flutamide (FLU) on 7-week male Wistar rats. FLU was administered by oral gavage at doses of 0, 0.001, 0.01, 0.1, 1 and 10 mg/kg/day for 28 days. To evaluate the reproducibility, the study was performed 3 times. The molecular initiating event (MIE; AR antagonism), the key events (LHmore » increase, Leydig cell proliferation and hyperplasia increases) and associated events involved in the mode of action (MOA) of FLU induced testicular toxicity were characterized to address the dose response concordance. Results showed no effects at low doses (< 0.1 mg/kg/day) for the different key events studied. The histopathological changes (Leydig cell hyperplasia) observed at 1 and 10 mg/kg/day were associated with an increase in steroidogenesis gene expression in the testis from 1 mg/kg/day, as well as an increase in testosterone blood level at 10 mg/kg/day. Each key event dose–response was in good concordance with the MOA of FLU on the testis. From the available results, only monotonic dose–response curves were observed for the MIE, the key events, associated events and in effects observed in other sex related tissues. All the results, so far, show that the reference endocrine disruptor FLU induces threshold effects in a standard 28-day toxicity study on adult male rats. - Highlights: • Dose–response characterization of endocrine mediated toxicity is an on-going debate. • A wide range of dose levels of flutamide was evaluated on young adult male rats. • Flutamide induces threshold effects using on standard and molecular tools.« less

TH-E-209-00: Radiation Dose Monitoring and Protocol Management

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

NONE

Radiation dose monitoring solutions have opened up new opportunities for medical physicists to be more involved in modern clinical radiology practices. In particular, with the help of comprehensive radiation dose data, data-driven protocol management and informed case follow up are now feasible. Significant challenges remain however and the problems faced by medical physicists are highly heterogeneous. Imaging systems from multiple vendors and a wide range of vintages co-exist in the same department and employ data communication protocols that are not fully standardized or implemented making harmonization complex. Many different solutions for radiation dose monitoring have been implemented by imaging facilitiesmore » over the past few years. Such systems are based on commercial software, home-grown IT solutions, manual PACS data dumping, etc., and diverse pathways can be used to bring the data to impact clinical practice. The speakers will share their experiences with creating or tailoring radiation dose monitoring/management systems and procedures over the past few years, which vary significantly in design and scope. Topics to cover: (1) fluoroscopic dose monitoring and high radiation event handling from a large academic hospital; (2) dose monitoring and protocol optimization in pediatric radiology; and (3) development of a home-grown IT solution and dose data analysis framework. Learning Objectives: Describe the scope and range of radiation dose monitoring and protocol management in a modern radiology practice Review examples of data available from a variety of systems and how it managed and conveyed. Reflect on the role of the physicist in radiation dose awareness.« less

TH-E-209-01: Fluoroscopic Dose Monitoring and Patient Follow-Up Program at Massachusetts General Hospital

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

Liu, B.

2016-06-15

Radiation dose monitoring solutions have opened up new opportunities for medical physicists to be more involved in modern clinical radiology practices. In particular, with the help of comprehensive radiation dose data, data-driven protocol management and informed case follow up are now feasible. Significant challenges remain however and the problems faced by medical physicists are highly heterogeneous. Imaging systems from multiple vendors and a wide range of vintages co-exist in the same department and employ data communication protocols that are not fully standardized or implemented making harmonization complex. Many different solutions for radiation dose monitoring have been implemented by imaging facilitiesmore » over the past few years. Such systems are based on commercial software, home-grown IT solutions, manual PACS data dumping, etc., and diverse pathways can be used to bring the data to impact clinical practice. The speakers will share their experiences with creating or tailoring radiation dose monitoring/management systems and procedures over the past few years, which vary significantly in design and scope. Topics to cover: (1) fluoroscopic dose monitoring and high radiation event handling from a large academic hospital; (2) dose monitoring and protocol optimization in pediatric radiology; and (3) development of a home-grown IT solution and dose data analysis framework. Learning Objectives: Describe the scope and range of radiation dose monitoring and protocol management in a modern radiology practice Review examples of data available from a variety of systems and how it managed and conveyed. Reflect on the role of the physicist in radiation dose awareness.« less

TH-E-209-02: Dose Monitoring and Protocol Optimization: The Pediatric Perspective

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

MacDougall, R.

Radiation dose monitoring solutions have opened up new opportunities for medical physicists to be more involved in modern clinical radiology practices. In particular, with the help of comprehensive radiation dose data, data-driven protocol management and informed case follow up are now feasible. Significant challenges remain however and the problems faced by medical physicists are highly heterogeneous. Imaging systems from multiple vendors and a wide range of vintages co-exist in the same department and employ data communication protocols that are not fully standardized or implemented making harmonization complex. Many different solutions for radiation dose monitoring have been implemented by imaging facilitiesmore » over the past few years. Such systems are based on commercial software, home-grown IT solutions, manual PACS data dumping, etc., and diverse pathways can be used to bring the data to impact clinical practice. The speakers will share their experiences with creating or tailoring radiation dose monitoring/management systems and procedures over the past few years, which vary significantly in design and scope. Topics to cover: (1) fluoroscopic dose monitoring and high radiation event handling from a large academic hospital; (2) dose monitoring and protocol optimization in pediatric radiology; and (3) development of a home-grown IT solution and dose data analysis framework. Learning Objectives: Describe the scope and range of radiation dose monitoring and protocol management in a modern radiology practice Review examples of data available from a variety of systems and how it managed and conveyed. Reflect on the role of the physicist in radiation dose awareness.« less

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

PubMed Central

Upton, A C

1983-01-01

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

SU-F-T-22: Clinical Implications When Using TG-186 (ACE) Heterogeneity Software

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

Likhacheva, A; Grade, E; Sadeghi, A

Purpose: The purpose of this study is to compare dosimetric calculations using traditional TG-43 formalism and Oncentra Brachy Advanced Collapsed cone Engine (ACE) TG-186 calculation algorithm in clinical setting. Methods: We analyzed dosimetry of four patients treated with accelerated partial breast irradiation using a multi-channel intracavitary device (SAVI). All patients were treated to 34 Gy in 10 fractions using a high-dose-rate (192) Ir source. The plans were designed and treated using the TG-43 model. ACE was used to assess the effect heterogeneity correction on various dosimetric parameters. Mass density was estimated using Hounsfield units. Results: Compared to TG-43 formalism, ACEmore » estimated lower doses to targets and organs at risk. The mean difference was 19.8% (range 15.3–24.1%) for PTV-eval V200, 12.0% (range 9.7–17.7%) for PTV-eval V150, 4.3% (range 3.3–6.5%) for PTV-eval D95, 3.3% (range 1.4–5.4%) for PTV-eval D90, 5.4% (range 2.9–9.9%) for maximum rib dose, and 5.7% (2.4–7.4%) for maximum skin dose. There was no correlation between the magnitude of the difference and the PTV-eval volume, air volume, or tissue-applicator conformance. Conclusion: Based on our preliminary study, the TG-43 algorithm appears to overestimate the dose to targets and organs at risk when compared to the ACE TG-186 software. We hypothesize that air adjacent to the SAVI struts contributes to lack of scatter thereby contributing a significant difference in dose calculation when using ACE. We believe that ACE calculation provides a more realistic isodose distribution than TG-43. We plan to further investigate the impact of heterogeneity correction on brachytherapy planning for a wide variety of clinical scenarios, include skin, cervix/uterus, prostate, and lung.« less

New approach to CT pixel-based photon dose calculations in heterogeneous media

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

Wong, J.W.; Henkelman, R.M.

The effects of small cavities on dose in water and the dose in a homogeneous nonunit density medium illustrate that inhomogeneities do not act independently in photon dose perturbation, and serve as two constraints which should be satisfied by approximate methods of computed tomography (CT) pixel-based dose calculations. Current methods at best satisfy only one of the two constraints and show inadequacies in some intermediate geometries. We have developed an approximate method that satisfies both these constraints and treats much of the synergistic effect of multiple inhomogeneities correctly. The method calculates primary and first-scatter doses by first-order ray tracing withmore » the first-scatter contribution augmented by a component of second scatter that behaves like first scatter. Multiple-scatter dose perturbation values extracted from small cavity experiments are used in a function which approximates the small residual multiple-scatter dose. For a wide range of geometries tested, our method agrees very well with measurements. The average deviation is less than 2% with a maximum of 3%. In comparison, calculations based on existing methods can have errors larger than 10%.« less

MO-E-18A-01: Imaging: Best Practices In Pediatric Imaging

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

Willis, C; Strauss, K; MacDougall, R

This imaging educational program will focus on solutions to common pediatric imaging challenges. The speakers will present collective knowledge on best practices in pediatric imaging from their experience at dedicated children's hospitals. Areas of focus will include general radiography, the use of manual and automatic dose management in computed tomography, and enterprise-wide radiation dose management in the pediatric practice. The educational program will begin with a discussion of the complexities of exposure factor control in pediatric projection radiography. Following this introduction will be two lectures addressing the challenges of computed tomography (CT) protocol optimization in the pediatric population. The firstmore » will address manual CT protocol design in order to establish a managed radiation dose for any pediatric exam on any CT scanner. The second CT lecture will focus on the intricacies of automatic dose modulation in pediatric imaging with an emphasis on getting reliable results in algorithmbased technique selection. The fourth and final lecture will address the key elements needed to developing a comprehensive radiation dose management program for the pediatric environment with particular attention paid to new regulations and obligations of practicing medical physicists. Learning Objectives: To understand how general radiographic techniques can be optimized using exposure indices in order to improve pediatric radiography. To learn how to establish diagnostic dose reference levels for pediatric patients as a function of the type of examination, patient size, and individual design characteristics of the CT scanner. To learn how to predict the patient's radiation dose prior to the exam and manually adjust technique factors if necessary to match the patient's dose to the department's established dose reference levels. To learn how to utilize manufacturer-provided automatic dose modulation technology to consistently achieve patient doses within the department's established size-based diagnostic reference range. To understand the key components of an enterprise-wide pediatric dose management program that integrates the expanding responsibilities of medial physicists in the new era of dose monitoring.« less

Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window

PubMed Central

2016-01-01

Background: Abundant evidence at the anatomical, electrophysiological, and molecular levels implicates metabotropic glutamate receptor subtype 5 (mGluR5) in addiction. Consistently, the effects of a wide range of doses of different mGluR5 negative allosteric modulators (NAMs) have been tested in various animal models of addiction. Here, these studies were subjected to a systematic review to find out if mGluR5 NAMs have a therapeutic potential that can be translated to the clinic. Methods: Literature on consumption/self-administration and reinstatement of drug seeking as outcomes of interest published up to April 2015 was retrieved via PubMed. The review focused on the effects of systemic (i.p., i.v., s.c.) administration of the mGluR5 NAMs 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) and 2-Methyl-6-(phenylethynyl)pyridine (MPEP) on paradigms with cocaine, ethanol, nicotine, and food in rats. Results: MTEP and MPEP were found to reduce self-administration of cocaine, ethanol, and nicotine at doses ≥1mg/kg and 2.5mg/kg, respectively. Dose-response relationship resembled a sigmoidal curve, with low doses not reaching statistical significance and high doses reliably inhibiting self-administration of drugs of abuse. Importantly, self-administration of cocaine, ethanol, and nicotine, but not food, was reduced by MTEP and MPEP in the dose range of 1 to 2mg/kg and 2.5 to 3.2mg/kg, respectively. This dose range corresponds to approximately 50% to 80% mGluR5 occupancy. Interestingly, the limited data found in mice and monkeys showed a similar therapeutic window. Conclusion: Altogether, this review suggests a therapeutic window for mGluR5 NAMs that can be translated to the treatment of substance-related and addictive disorders. PMID:26802568

Comparison of skin dose measurement using nanoDot® dosimeter and machine readings of radiation dose during cardiac catheterization in children

PubMed Central

Balaguru, Duraisamy; Rodriguez, Matthew; Leon, Stephanie; Wagner, Louis K; Beasley, Charles W; Sultzer, Andrew; Numan, Mohammed T

2018-01-01

Objectives: Direct measurement of skin dose of radiation for children using optically stimulated luminescence (OSL) technology using nanoDot® (Landauer, Glenwood, IL, USA). Background: Radiation dose is estimated as cumulative air kerma (AK) and dosearea product based on standards established for adult size patients. Body size of pediatric patients who undergo cardiac catheterization for congenital heart disease vary widely from newborn to adolescence. Direct, skindose measurement applying OSL technology may eliminate errors in the estimate. Materials and Methods: The nanoDot® (1 cm × 1 cm × flat plastic cassette) is applied to patient's skin using adhesive tape during cardiac catheterization and radiation skin doses were read within 24 hrs. nanoDot® values were compared to the currently available cumulative AK values estimated and displayed on fluoroscopy monitor. Results: A total of 12 children were studied, aged 4 months to 18 years (median 1.1 years) and weight range 5.3–86 kg (median 8.4 kg). nanoDot® readings ranged from 2.58 mGy to 424.8 mGy (median 84.1 mGy). Cumulative AK ranged from 16.2 mGy to 571.2 mGy (median 171.1 mGy). Linear correlation was noted between nanoDot® values and AK values (R2 = 0.88, R = 0.94). nanoDot® readings were approximately 65% of the estimated cumulative AK estimated using the International Electrotechnical Commission standards. Conclusions: Application of OSL technology using nanoDot® provides an alternative to directly measure fluoroscopic skin dose in children during cardiac catheterization. Our data show that the actual skin dose for children is approximately one-third lower than the AK estimated using international standards for adult size patients. PMID:29440825

Comparison of skin dose measurement using nanoDot® dosimeter and machine readings of radiation dose during cardiac catheterization in children.

PubMed

Balaguru, Duraisamy; Rodriguez, Matthew; Leon, Stephanie; Wagner, Louis K; Beasley, Charles W; Sultzer, Andrew; Numan, Mohammed T

2018-01-01

Direct measurement of skin dose of radiation for children using optically stimulated luminescence (OSL) technology using nanoDot ® (Landauer, Glenwood, IL, USA). Radiation dose is estimated as cumulative air kerma (AK) and dosearea product based on standards established for adult size patients. Body size of pediatric patients who undergo cardiac catheterization for congenital heart disease vary widely from newborn to adolescence. Direct, skindose measurement applying OSL technology may eliminate errors in the estimate. The nanoDot ® (1 cm × 1 cm × flat plastic cassette) is applied to patient's skin using adhesive tape during cardiac catheterization and radiation skin doses were read within 24 hrs. nanoDot ® values were compared to the currently available cumulative AK values estimated and displayed on fluoroscopy monitor. A total of 12 children were studied, aged 4 months to 18 years (median 1.1 years) and weight range 5.3-86 kg (median 8.4 kg). nanoDot® readings ranged from 2.58 mGy to 424.8 mGy (median 84.1 mGy). Cumulative AK ranged from 16.2 mGy to 571.2 mGy (median 171.1 mGy). Linear correlation was noted between nanoDot® values and AK values ( R 2 = 0.88, R = 0.94). nanoDot® readings were approximately 65% of the estimated cumulative AK estimated using the International Electrotechnical Commission standards. Application of OSL technology using nanoDot® provides an alternative to directly measure fluoroscopic skin dose in children during cardiac catheterization. Our data show that the actual skin dose for children is approximately one-third lower than the AK estimated using international standards for adult size patients.

Mice and the A-Bomb: Irradiation Systems for Realistic Exposure Scenarios.

PubMed

Garty, Guy; Xu, Yanping; Elliston, Carl; Marino, Stephen A; Randers-Pehrson, Gerhard; Brenner, David J

2017-04-01

Validation of biodosimetry assays is normally performed with acute exposures to uniform external photon fields. Realistically, exposure to a radiological dispersal device or reactor leak will include exposure to low dose rates and likely exposure to ingested radionuclides. An improvised nuclear device will likely include a significant neutron component in addition to a mixture of high- and low-dose-rate photons and ingested radionuclides. We present here several novel irradiation systems developed at the Center for High Throughput Minimally Invasive Radiation Biodosimetry to provide more realistic exposures for testing of novel biodosimetric assays. These irradiators provide a wide range of dose rates (from Gy/s to Gy/week) as well as mixed neutron/photon fields mimicking an improvised nuclear device.

Mice and the A-Bomb: Irradiation Systems for Realistic Exposure Scenarios

PubMed Central

Garty, Guy; Xu, Yanping; Elliston, Carl; Marino, Stephen A.; Randers-Pehrson, Gerhard; Brenner, David J.

2017-01-01

Validation of biodosimetry assays is normally performed with acute exposures to uniform external photon fields. Realistically, exposure to a radiological dispersal device or reactor leak will include exposure to low dose rates and likely exposure to ingested radionuclides. An improvised nuclear device will likely include a significant neutron component in addition to a mixture of high- and low-dose-rate photons and ingested radionuclides. We present here several novel irradiation systems developed at the Center for High Throughput Minimally Invasive Radiation Biodosimetry to provide more realistic exposures for testing of novel biodosimetric assays. These irradiators provide a wide range of dose rates (from Gy/s to Gy/week) as well as mixed neutron/photon fields mimicking an improvised nuclear device. PMID:28211757

Radiation-associated circulatory disease mortality in a pooled analysis of 77,275 patients from the Massachusetts and Canadian tuberculosis fluoroscopy cohorts.

PubMed

Tran, Van; Zablotska, Lydia B; Brenner, Alina V; Little, Mark P

2017-03-13

High-dose ionising radiation is associated with circulatory disease. Risks associated with lower-dose (<0.5 Gy) exposures remain unclear, with little information on risk modification by age at exposure, years since exposure or dose-rate. Tuberculosis patients in Canada and Massachusetts received multiple diagnostic x-ray fluoroscopic exposures, over a wide range of ages, many at doses <0.5 Gy. We evaluated risks of circulatory-disease mortality associated with <0.5 Gy radiation exposure in a pooled cohort of 63,707 patients in Canada and 13,568 patients in Massachusetts. Under 0.5 Gy there are increasing trends for all circulatory disease (n = 10,209; excess relative risk/Gy = 0.246; 95% CI 0.036, 0.469; p = 0.021) and for ischaemic heart disease (n = 6410; excess relative risk/Gy = 0.267; 95% CI 0.003, 0.552; p = 0.048). All circulatory-disease and ischaemic-heart-disease risk reduces with increasing time since exposure (p < 0.005). Over the entire dose range, there are negative mortality dose trends for all circulatory disease (p = 0.014) and ischaemic heart disease (p = 0.003), possibly due to competing causes of death over this dose interval.These results confirm and extend earlier findings and strengthen the evidence for circulatory-disease mortality radiation risk at doses <0.5 Gy. The limited information on well-known lifestyle/medical risk factors for circulatory disease implies that confounding of the dose trend cannot be entirely excluded.

Setting Age Limits for TT-OSL Dating - the Local Effect

NASA Astrophysics Data System (ADS)

Faershtein, G.; Porat, N.; Guralnik, B.; Matmon, A.

2017-12-01

Luminescence dating techniques, especially Optically Stimulated Luminescence (OSL) on quartz, are widely used for dating middle Pleistocene to late Holocene sediments from different geological settings. The dating limit of a particular luminescence method depends on signal saturation and its thermal stability. The OSL signal saturates at doses of 200 Gy, equivalent to ages of 150-300 ka. Thermally Transferred OSL (TT-OSL) is a developmental technique, which potentially extends the luminescence dating range up to 1000 ka. For the Chinese Loess Plateau, experiments have shown that the natural TT-OSL signal saturates at 2200 Gy (Chapot et al., 2016). Regarding thermal stability, different studies report a wide range of estimates (0.24-861 Ma), suggesting that the thermal lifetime of TT-OSL is (i) currently poorly constrained, and (ii) may vary both by sample and region. Here, we investigated the dating limit of TT-OSL, using quartz of Nilotic origin (Israel), obtained from two sediment sections of similar depth but different dose rates. Natural dose response curves (DRC) of the TT-OSL signal were constructed for each section separately. In both sections, luminescence intensity grows sub-linearly up to 450 Gy, beyond which it remains constant with depth. The absence of equivalent doses (De) over 600 Gy, at both sections (as well as elsewhere regionally), suggest that TT-OSL signal saturation may be an intrinsic property, related to quartz provenance, and independent of the specific ionizing dose rate at each section. The thermal stability of TT-OSL was investigated on a modern sample from one section, using a combination of analytical techniques (varying heating rates, and isothermal storage). The obtained TT-OSL lifetimes range between 105-107 ka, and reinforce a significant inter sample variability. A synthesis of our results suggests that TT-OSL ages of Nilotic quartz derived from De values over 450 Gy, are likely underestimates, and should be treated as minimum ages. The limiting value of 600 Gy for local quartz TT-OSL is likely representative of a steady-state between TT-OSL trap filling due to ionizing radiation, and the concurrent thermal empting of these traps.

Kilovoltage energy imaging with a radiotherapy linac with a continuously variable energy range.

PubMed

Roberts, D A; Hansen, V N; Thompson, M G; Poludniowski, G; Niven, A; Seco, J; Evans, P M

2012-03-01

In this paper, the effect on image quality of significantly reducing the primary electron energy of a radiotherapy accelerator is investigated using a novel waveguide test piece. The waveguide contains a novel variable coupling device (rotovane), allowing for a wide continuously variable energy range of between 1.4 and 9 MeV suitable for both imaging and therapy. Imaging at linac accelerating potentials close to 1 MV was investigated experimentally and via Monte Carlo simulations. An imaging beam line was designed, and planar and cone beam computed tomography images were obtained to enable qualitative and quantitative comparisons with kilovoltage and megavoltage imaging systems. The imaging beam had an electron energy of 1.4 MeV, which was incident on a water cooled electron window consisting of stainless steel, a 5 mm carbon electron absorber and 2.5 mm aluminium filtration. Images were acquired with an amorphous silicon detector sensitive to diagnostic x-ray energies. The x-ray beam had an average energy of 220 keV and half value layer of 5.9 mm of copper. Cone beam CT images with the same contrast to noise ratio as a gantry mounted kilovoltage imaging system were obtained with doses as low as 2 cGy. This dose is equivalent to a single 6 MV portal image. While 12 times higher than a 100 kVp CBCT system (Elekta XVI), this dose is 140 times lower than a 6 MV cone beam imaging system and 6 times lower than previously published LowZ imaging beams operating at higher (4-5 MeV) energies. The novel coupling device provides for a wide range of electron energies that are suitable for kilovoltage quality imaging and therapy. The imaging system provides high contrast images from the therapy portal at low dose, approaching that of gantry mounted kilovoltage x-ray systems. Additionally, the system provides low dose imaging directly from the therapy portal, potentially allowing for target tracking during radiotherapy treatment. There is the scope with such a tuneable system for further energy reduction and subsequent improvement in image quality.

The SATRAM Timepix spacecraft payload in open space on board the Proba-V satellite for wide range radiation monitoring in LEO orbit

NASA Astrophysics Data System (ADS)

Granja, Carlos; Polansky, Stepan; Vykydal, Zdenek; Pospisil, Stanislav; Owens, Alan; Kozacek, Zdenek; Mellab, Karim; Simcak, Marek

2016-06-01

The Space Application of Timepix based Radiation Monitor (SATRAM) is a spacecraft platform radiation monitor on board the Proba-V satellite launched in an 820 km altitude low Earth orbit in 2013. The is a technology demonstration payload is based on the Timepix chip equipped with a 300 μm silicon sensor with signal threshold of 8 keV/pixel to low-energy X-rays and all charged particles including minimum ionizing particles. For X-rays the energy working range is 10-30 keV. Event count rates can be up to 106 cnt/(cm2 s) for detailed event-by-event analysis or over 1011 cnt/(cm2 s) for particle-counting only measurements. The single quantum sensitivity (zero-dark current noise level) combined with per-pixel spectrometry and micro-scale pattern recognition analysis of single particle tracks enables the composition (particle type) and spectral characterization (energy loss) of mixed radiation fields to be determined. Timepix's pixel granularity and particle tracking capability also provides directional sensitivity for energetic charged particles. The payload detector response operates in wide dynamic range in terms of absorbed dose starting from single particle doses in the pGy level, particle count rate up to 106-10 /cm2/s and particle energy loss (threshold at 150 eV/μm). The flight model in orbit was successfully commissioned in 2013 and has been sampling the space radiation field in the satellite environment along its orbit at a rate of several frames per minute of varying exposure time. This article describes the design and operation of SATRAM together with an overview of the response and resolving power to the mixed radiation field including summary of the principal data products (dose rate, equivalent dose rate, particle-type count rate). The preliminary evaluation of response of the embedded Timepix detector to space radiation in the satellite environment is presented together with first results in the form of a detailed visualization of the mixed radiation field at the position of the payload and resulting spatial- and time-correlated radiation maps of cumulative dose rate along the satellite orbit.

National reference doses for dental cephalometric radiography.

PubMed

Holroyd, J R

2011-12-01

Diagnostic reference levels (DRLs) are an important tool in the optimisation of clinical radiography. Although national DRLs are provided for many diagnostic procedures including dental intra-oral radiography, there are currently no national DRLs set for cephalometric radiography. In the absence of formal national DRLs, the Health Protection Agency (HPA) has previously published National Reference Doses (NRDs) covering a wide range of diagnostic X-ray examinations. The aim of this study was to determine provisional NRDs for cephalometric radiography. Measurements made by the Dental X-ray Protection Service (DXPS) of the HPA, as part of the cephalometric X-ray equipment testing service provided to dentists and dental trade companies throughout the UK, were used to derive provisional NRDs. Dose-area product measurements were made on 42 X-ray sets. Third quartile dose-area product values for adult and child lateral cephalometric radiography were found to be 41 mGy cm² and 25 mGy cm², respectively, with individual measurements ranging from 3 mGy cm² to 108 mGy cm². This report proposes provisional NRDs of 40 mGy cm² and 25 mGy cm² for adult and child lateral cephalometric radiographs, respectively; these doses could be considered by employers when establishing their local DRLs.

A retrospective study on annual evaluation of radiation processing for frozen bone allografts complying to quality system requirements.

PubMed

Ramalingam, Saravana; Mohd, Suhaili; Samsuddin, Sharifah Mazni; Min, N G Wuey; Yusof, Norimah; Mansor, Azura

2015-12-01

Bone allografts have been used widely to fill up essential void in orthopaedic surgeries. The benefit of using allografts to replace and reconstruct musculoskeletal injuries, fractures or disease has obtained overwhelming acceptance from orthopaedic surgeons worldwide. However, bacterial infection and disease transmission through bone allograft transplantation have always been a significant issue. Sterilization by radiation is an effective method to eliminate unwanted microorganisms thus assist in preventing life threatening allograft associated infections. Femoral heads procured from living donors and long bones (femur and tibia) procured from cadaveric donors were sterilized at 25 kGy in compliance with international standard ISO 11137. According to quality requirements, all records of bone banking were evaluated annually. This retrospective study was carried out on annual evaluation of radiation records from 1998 until 2012. The minimum doses absorbed by the bones were ranging from 25.3 to 38.2 kGy while the absorbed maximum doses were from 25.4 to 42.3 kGy. All the bones supplied by our UMMC Bone Bank were sterile at the required minimum dose of 25 kGy. Our analysis on dose variation showed that the dose uniformity ratios in 37 irradiated boxes of 31 radiation batches were in the range of 1.003-1.251, which indicated the doses were well distributed.

Estimation of annual effective dose due to ingestion of natural radionuclides in foodstuffs and water at a proposed uranium mining site in India.

PubMed

Giri, Soma; Jha, V N; Singh, Gurdeep; Tripathi, R M

2013-12-01

To study the distribution of (210)Po, (226)Ra, (230)Th and U(nat) (naturally occurring radioisotopes of uranium [(234)U, (235)U and (238)U]) in food and water around the Bagjata uranium mining area in India. Radionuclides were analyzed in food samples of plant and animal origin after acid digestion. Intake and ingestion dose of the radionuclides were estimated. (210)Po, (226)Ra, (230)Th and U(nat) in all the dietary components ranged widely from < 0.2-36, < 0.02-1.58, < 0.01-2.8 and < 0.017-0.39 Bqkg(-1), respectively. The range of (226)Ra and U(nat) in water was < 3.5-206 and < 12.6-693 mBql(-1), respectively. The intake of radionuclides considering food and water was calculated to be 760 BqY(-1) while the ingestion dose was 601 μSvY(-1). The estimated doses reflect the natural background dose via route of ingestion, which is below the 1 mSvY(-1) limit set by the International Commission on Radiological Protection (ICRP). However, the doses are more than the dose constraint of 300 μSvY(-1) as suggested by the ICRP for members of the public for planned disposal of long-lived radioactive waste. The study confirms that current levels of radionuclides do not pose significant radiological risk to the local inhabitants, but they need close investigation in the near future.

Extrapolation of plasma clearance to understand species differences in toxicokinetics of bisphenol A.

PubMed

Poet, Torka; Hays, Sean

2017-10-13

1. Understanding species differences in the toxicokinetics of bisphenol A (BPA) is central to setting acceptable exposure limits for human exposures to BPA. BPA toxicokinetics have been well studied, with controlled oral dosing studies in several species and across a wide dose range. 2. We analyzed the available toxicokinetic data for BPA following oral dosing to assess potential species differences and dose dependencies. BPA is rapidly conjugated and detoxified in all species. The toxicokinetics of BPA can be well described using non-compartmental analyses. 3. Several studies measured free (unconjugated) BPA in blood and reported area under the curve (AUC) of free BPA in blood of mice, rats, monkeys, chimpanzees and humans following controlled oral doses. Extrinsic clearance was calculated and analyzed across species and dose using allometric scaling. 4. The results indicate free BPA clearance is well described using allometric scaling with high correlation coefficients across all species and doses up to 10 mg/kg. The results indicate a human equivalent dose factor (HEDf) of 0.9 is appropriate for extrapolating a point of departure from mice and rats to a human equivalent dose (HED), thereby replacing default uncertainty factors for animal to human toxicokinetics.

TH-E-209-03: Development of An In-House CT Dose Monitoring and Management System Based On Open-Source Software Resources -- Pearls and Pitfalls

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

Zhang, D.

Radiation dose monitoring solutions have opened up new opportunities for medical physicists to be more involved in modern clinical radiology practices. In particular, with the help of comprehensive radiation dose data, data-driven protocol management and informed case follow up are now feasible. Significant challenges remain however and the problems faced by medical physicists are highly heterogeneous. Imaging systems from multiple vendors and a wide range of vintages co-exist in the same department and employ data communication protocols that are not fully standardized or implemented making harmonization complex. Many different solutions for radiation dose monitoring have been implemented by imaging facilitiesmore » over the past few years. Such systems are based on commercial software, home-grown IT solutions, manual PACS data dumping, etc., and diverse pathways can be used to bring the data to impact clinical practice. The speakers will share their experiences with creating or tailoring radiation dose monitoring/management systems and procedures over the past few years, which vary significantly in design and scope. Topics to cover: (1) fluoroscopic dose monitoring and high radiation event handling from a large academic hospital; (2) dose monitoring and protocol optimization in pediatric radiology; and (3) development of a home-grown IT solution and dose data analysis framework. Learning Objectives: Describe the scope and range of radiation dose monitoring and protocol management in a modern radiology practice Review examples of data available from a variety of systems and how it managed and conveyed. Reflect on the role of the physicist in radiation dose awareness.« less

Maintained cocaine self-administration is determined by quantal responses: implications for the measurement of antagonist potency.

PubMed

Norman, Andrew B; Tabet, Michael R; Norman, Mantana K; Tsibulsky, Vladimir L

2014-02-01

The change in frequency of cocaine self-administration as a function of the unit dose is widely assumed to represent a graded pharmacodynamic response. Alternatively, a pharmacological theory states that during maintained self-administration, a quantal response occurs at a minimum maintained cocaine concentration (satiety threshold). Rats self-administered cocaine at unit doses spanning an 8-fold range from 0.75 to 6 µmol/kg. Despite an approximately 7-fold difference in the interinjection intervals, there were no differences in the plasma cocaine concentration at the time of lever press across this range of unit doses, consistent with the satiety threshold representing an equiactive cocaine concentration. Because self-administration always occurs when cocaine concentrations decline back to the satiety threshold, this behavior represents a process of automatic back titration of equiactive agonist concentrations. Therefore, the lower frequency of self-administration at higher unit doses is caused by an increase in the duration of the cocaine-induced satiety response, and the graded dose-frequency relationship is due to cocaine pharmacokinetics. After the interinjection intervals at a particular unit dose were stable, rats were injected with the competitive D₁-like dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390; 15 nmol/kg intravenously) and the session continued. At all cocaine unit doses, SCH23390 accelerated self-administration with a concomitant increase in the calculated satiety threshold, and these equiactive cocaine concentration ratios were independent of the cocaine unit dose. Therefore, the measurement of antagonist potency requires only a single unit dose of cocaine, selected on the basis of convenience, and using multiple cocaine unit doses is redundant.

Photoresist and stochastic modeling

NASA Astrophysics Data System (ADS)

Hansen, Steven G.

2018-01-01

Analysis of physical modeling results can provide unique insights into extreme ultraviolet stochastic variation, which augment, and sometimes refute, conclusions based on physical intuition and even wafer experiments. Simulations verify the primacy of "imaging critical" counting statistics (photons, electrons, and net acids) and the image/blur-dependent dose sensitivity in describing the local edge or critical dimension variation. But the failure of simple counting when resist thickness is varied highlights a limitation of this exact analytical approach, so a calibratable empirical model offers useful simplicity and convenience. Results presented here show that a wide range of physical simulation results can be well matched by an empirical two-parameter model based on blurred image log-slope (ILS) for lines/spaces and normalized ILS for holes. These results are largely consistent with a wide range of published experimental results; however, there is some disagreement with the recently published dataset of De Bisschop. The present analysis suggests that the origin of this model failure is an unexpected blurred ILS:dose-sensitivity relationship failure in that resist process. It is shown that a photoresist mechanism based on high photodecomposable quencher loading and high quencher diffusivity can give rise to pitch-dependent blur, which may explain the discrepancy.

A versatile indirect detector design for hard X-ray microimaging

NASA Astrophysics Data System (ADS)

Douissard, P.-A.; Cecilia, A.; Rochet, X.; Chapel, X.; Martin, T.; van de Kamp, T.; Helfen, L.; Baumbach, T.; Luquot, L.; Xiao, X.; Meinhardt, J.; Rack, A.

2012-09-01

Indirect X-ray detectors are of outstanding importance for high resolution imaging, especially at synchrotron light sources: while consisting mostly of components which are widely commercially available, they allow for a broad range of applications in terms of the X-ray energy employed, radiation dose to the detector, data acquisition rate and spatial resolving power. Frequently, an indirect detector consists of a thin-film single crystal scintillator and a high-resolution visible light microscope as well as a camera. In this article, a novel modular-based indirect design is introduced, which offers several advantages: it can be adapted for different cameras, i.e. different sensor sizes, and can be trimmed to work either with (quasi-)monochromatic illumination and the correspondingly lower absorbed dose or with intense white beam irradiation. In addition, it allows for a motorized quick exchange between different magnifications / spatial resolutions. Developed within the European project SCINTAX, it is now commercially available. The characteristics of the detector in its different configurations (i.e. for low dose or for high dose irradiation) as measured within the SCINTAX project will be outlined. Together with selected applications from materials research, non-destructive evaluation and life sciences they underline the potential of this design to make high resolution X-ray imaging widely available.

Lower limits of detection in using carbon nanotubes as thermoluminescent dosimeters of beta radiation

NASA Astrophysics Data System (ADS)

Alanazi, Abdulaziz; Jurewicz, Izabela; Alalawi, Amani I.; Alyahyawi, Amjad; Alsubaie, Abdullah; Hinder, Steven; Bañuls-Ciscar, Jorge; Alkhorayef, Mohammed; Bradley, D. A.

2017-11-01

World-wide, on-going intensive research is being seen in adaptation of carbon nanotubes (CNTs) for a wide variety of applications, particular interest herein being in the thermoluminescent (TL) properties of CNTs and their sensitivity towards energetic radiations. Using beta radiation delivering dose levels of a few Gy it has been observed in previous study that strain and impurity defects in CNTs give rise to significant TL yields, providing an initial measure of the extent to which electron trapping centres exist in various qualities of CNT, from super-pure to raw. This in turn points to the possibility that there may be considerable advantage in using such media for radiation dosimetry applications, including for in vivo dosimetry. CNTs also have an effective atomic number similar to that of adipose tissue, making them suitable for soft tissue dosimetry. In present investigations various single-wall carbon nanotubes (SWCNT) samples in the form of buckypaper have been irradiated to doses in the range 35-1.3 Gy, use being made of a 90Sr beta source, the response of the CNTs buckypaper with dose showing a trend towards linearity. It is shown for present production methodology for buckypaper samples that the raw SWCNT buckypaper offer the greatest sensitivity, detecting doses down to some few tens of mGy.

Bisphenol A Exposure, Ovarian Follicle Numbers, and Female Sex Steroid Hormone Levels: Results From a CLARITY-BPA Study

PubMed Central

Patel, Shreya; Brehm, Emily; Gao, Liying; Rattan, Saniya; Ziv-Gal, Ayelet

2017-01-01

Bisphenol A (BPA) is an industrial chemical found in thermal receipts and food and beverage containers. Previous studies have shown that BPA can affect the numbers and health of ovarian follicles and the production of sex steroid hormones, but they often did not include a wide range of doses of BPA, used a small sample size, focused on relatively short-term exposures to BPA, and/or did not examine the consequences of chronic BPA exposure on the ovaries or steroid levels. Thus, this study was designed to examine the effects of a wide range of doses of BPA on ovarian morphology and sex steroid hormone production. Specifically, this study tested the hypothesis that prenatal and continuous BPA exposure reduces ovarian follicle numbers and sex steroid hormone levels. To test this hypothesis, rats were dosed with vehicle, ethinyl estradiol (0.05 and 0.5 μg/kg body weight/d), or BPA (2.5, 25, 250, 2500, and 25,000 μg/kg body weight/d) from gestation day 6 until 1 year as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). Ovaries and sera were collected on postnatal days 1, 21, and 90, and at 6 months and 1 year. The ovaries were subjected to histological evaluation of follicle numbers and the sera were subjected to measurements of estradiol and progesterone. Collectively, these data indicate that BPA exposure at some doses and time points affects ovarian follicle numbers and sex steroid levels, but these effects are different than those observed with ethinyl estradiol exposure and some previous studies on BPA. PMID:28324068

Bisphenol A Exposure, Ovarian Follicle Numbers, and Female Sex Steroid Hormone Levels: Results From a CLARITY-BPA Study.

PubMed

Patel, Shreya; Brehm, Emily; Gao, Liying; Rattan, Saniya; Ziv-Gal, Ayelet; Flaws, Jodi A

2017-06-01

Bisphenol A (BPA) is an industrial chemical found in thermal receipts and food and beverage containers. Previous studies have shown that BPA can affect the numbers and health of ovarian follicles and the production of sex steroid hormones, but they often did not include a wide range of doses of BPA, used a small sample size, focused on relatively short-term exposures to BPA, and/or did not examine the consequences of chronic BPA exposure on the ovaries or steroid levels. Thus, this study was designed to examine the effects of a wide range of doses of BPA on ovarian morphology and sex steroid hormone production. Specifically, this study tested the hypothesis that prenatal and continuous BPA exposure reduces ovarian follicle numbers and sex steroid hormone levels. To test this hypothesis, rats were dosed with vehicle, ethinyl estradiol (0.05 and 0.5 μg/kg body weight/d), or BPA (2.5, 25, 250, 2500, and 25,000 μg/kg body weight/d) from gestation day 6 until 1 year as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). Ovaries and sera were collected on postnatal days 1, 21, and 90, and at 6 months and 1 year. The ovaries were subjected to histological evaluation of follicle numbers and the sera were subjected to measurements of estradiol and progesterone. Collectively, these data indicate that BPA exposure at some doses and time points affects ovarian follicle numbers and sex steroid levels, but these effects are different than those observed with ethinyl estradiol exposure and some previous studies on BPA. Copyright © 2017 Endocrine Society.

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

PubMed

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

2016-01-01

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

Investigation of EBT2 and EBT3 films for proton dosimetry in the 4-20 MeV energy range.

PubMed

Reinhardt, S; Würl, M; Greubel, C; Humble, N; Wilkens, J J; Hillbrand, M; Mairani, A; Assmann, W; Parodi, K

2015-03-01

Radiochromic films such as Gafchromic EBT2 or EBT3 films are widely used for dose determination in radiation therapy because they offer a superior spatial resolution compared to any other digital dosimetric 2D detector array. The possibility to detect steep dose gradients is not only attractive for intensity-modulated radiation therapy with photons but also for intensity-modulated proton therapy. Their characteristic dose rate-independent response makes radiochromic films also attractive for dose determination in cell irradiation experiments using laser-driven ion accelerators, which are currently being investigated as future medical ion accelerators. However, when using these films in ion beams, the energy-dependent dose response in the vicinity of the Bragg peak has to be considered. In this work, the response of these films for low-energy protons is investigated. To allow for reproducible and background-free irradiation conditions, the films were exposed to mono-energetic protons from an electrostatic accelerator, in the 4-20 MeV energy range. For comparison, irradiation with clinical photons was also performed. It turned out that in general, EBT2 and EBT3 films show a comparable performance. For example, dose-response curves for photons and protons with energies as low as 11 MeV show almost no differences. However, corrections are required for proton energies below 11 MeV. Care has to be taken when correction factors are related to an average LET from depth-dose measurements, because only the dose-averaged LET yields similar results as obtained in mono-energetic measurements.

An example of problems in dose reconstruction from doses formed by electromagnetic irradiation by different energy sources.

PubMed

Kirillov, Vladimir; Kuchuro, Joseph; Tolstik, Sergey; Leonova, Tatyana

2010-02-01

Dose reconstruction for citizens of Belarus affected by the Chernobyl accident showed an unexpectedly wide range of doses. Using the EPR tooth enamel dosimetry method, it has been demonstrated that when the tooth enamel dose was formed due to x-rays with effective energy of 34 keV and the additional irradiation of enamel samples was performed by gamma radiation with mean energy of 1,250 keV, it led to a considerable increase in the reconstructed absorbed dose as compared with the applied. In the case when the dose was formed due to gamma radiation and the additional irradiation was performed by x-rays, it led to a considerable decrease in the reconstructed dose as compared with the applied. When the dose formation and the additional irradiation were carried out from external sources of electromagnetic radiation of equal energy, the reconstructed dose value was close to that of the applied. The obtained data show that for adequate reconstruction of individual absorbed doses by the EPR tooth enamel spectra, it is necessary to take into account the contribution from diagnostic x-ray examination of the teeth, jaw, and skull of some individuals who were exposed to a combined effect of the external gamma radiation and x-rays.

Intracoronary Adenosine: Dose-Response Relationship With Hyperemia.

PubMed

Adjedj, Julien; Toth, Gabor G; Johnson, Nils P; Pellicano, Mariano; Ferrara, Angela; Floré, Vincent; Di Gioia, Giuseppe; Barbato, Emanuele; Muller, Olivier; De Bruyne, Bernard

2015-09-01

The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected. Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose. In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 μg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Qmax, %). Q/Qmax did not increase significantly beyond dosages of 60 μg for the RCA and 160 μg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 μg in the RCA and was 15% after injection of 200 μg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 μg in the RCA and 21 ± 6 s after the injection of 200 μg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 μg of adenosine. This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 μg in the RCA and 200 μg in the LCA induces maximum hyperemia while being associated with minimal side effects. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Applying an analytical method to study neutron behavior for dosimetry

NASA Astrophysics Data System (ADS)

Shirazi, S. A. Mousavi

2016-12-01

In this investigation, a new dosimetry process is studied by applying an analytical method. This novel process is associated with a human liver tissue. The human liver tissue has compositions including water, glycogen and etc. In this study, organic compound materials of liver are decomposed into their constituent elements based upon mass percentage and density of every element. The absorbed doses are computed by analytical method in all constituent elements of liver tissue. This analytical method is introduced applying mathematical equations based on neutron behavior and neutron collision rules. The results show that the absorbed doses are converged for neutron energy below 15MeV. This method can be applied to study the interaction of neutrons in other tissues and estimating the absorbed dose for a wide range of neutron energy.

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

Volotskova, O; Xu, A; Jozsef, G

Purpose: To investigate the response and dose rate dependence of a scintillation detector over a wide energy range. Methods: The energy dependence of W1 scintillation detector was tested with: 1) 50–225 keV beams generated by an animal irradiator, 2) a Leksell Gamma Knife Perfexion Co-60 source, 3) 6MV, 6FFF, 10FFF and 15MV photon beams, and 4) 6–20MeV electron beams from a linac. Calibrated linac beams were used to deliver 100 cGy to the detector at dmax in water under reference conditions. The gamma-knife measurement was performed in solid water (100 cGy with 16mm collimator). The low energy beams were calibratedmore » with an ion chamber in air (TG-61), and the scintillation detector was placed at the same location as the ionization chamber during calibration. For the linac photon and electron beams, dose rate dependence was tested for 100–2400 and 100–800 MU/min. Results: The scintillation detector demonstrated strong energy dependence in the range of 50–225keV. The measured values were lower than the delivered dose and increased as the energy increased. Therapeutic photon beams showed energy independence with variations less than 1%. Therapeutic electron beams displayed the same sensitivity of ∼2–3% at their corresponding dmax depths. The change in dose-rate of photon and electron beams within the therapeutic energy range did not affect detector output (<0.5%). Measurements acquired with the gamma knife showed that the output data agreed with the delivered dose up to 3%. Conclusion: W1 scintillation detector output has a strong energy dependence in the diagnostic and orthovoltage energy range. Therapeutic photon beams exhibited energy independence with no observable dose-rate dependence. This study may aid in the implementation of a scintillation detector in QA programs by providing energy calibration factors.« less

Validation of a Monte Carlo model used for simulating tube current modulation in computed tomography over a wide range of phantom conditions/challenges

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

Bostani, Maryam, E-mail: mbostani@mednet.ucla.edu; McMillan, Kyle; Cagnon, Chris H.

2014-11-01

Purpose: Monte Carlo (MC) simulation methods have been widely used in patient dosimetry in computed tomography (CT), including estimating patient organ doses. However, most simulation methods have undergone a limited set of validations, often using homogeneous phantoms with simple geometries. As clinical scanning has become more complex and the use of tube current modulation (TCM) has become pervasive in the clinic, MC simulations should include these techniques in their methodologies and therefore should also be validated using a variety of phantoms with different shapes and material compositions to result in a variety of differently modulated tube current profiles. The purposemore » of this work is to perform the measurements and simulations to validate a Monte Carlo model under a variety of test conditions where fixed tube current (FTC) and TCM were used. Methods: A previously developed MC model for estimating dose from CT scans that models TCM, built using the platform of MCNPX, was used for CT dose quantification. In order to validate the suitability of this model to accurately simulate patient dose from FTC and TCM CT scan, measurements and simulations were compared over a wide range of conditions. Phantoms used for testing range from simple geometries with homogeneous composition (16 and 32 cm computed tomography dose index phantoms) to more complex phantoms including a rectangular homogeneous water equivalent phantom, an elliptical shaped phantom with three sections (where each section was a homogeneous, but different material), and a heterogeneous, complex geometry anthropomorphic phantom. Each phantom requires varying levels of x-, y- and z-modulation. Each phantom was scanned on a multidetector row CT (Sensation 64) scanner under the conditions of both FTC and TCM. Dose measurements were made at various surface and depth positions within each phantom. Simulations using each phantom were performed for FTC, detailed x–y–z TCM, and z-axis-only TCM to obtain dose estimates. This allowed direct comparisons between measured and simulated dose values under each condition of phantom, location, and scan to be made. Results: For FTC scans, the percent root mean square (RMS) difference between measurements and simulations was within 5% across all phantoms. For TCM scans, the percent RMS of the difference between measured and simulated values when using detailed TCM and z-axis-only TCM simulations was 4.5% and 13.2%, respectively. For the anthropomorphic phantom, the difference between TCM measurements and detailed TCM and z-axis-only TCM simulations was 1.2% and 8.9%, respectively. For FTC measurements and simulations, the percent RMS of the difference was 5.0%. Conclusions: This work demonstrated that the Monte Carlo model developed provided good agreement between measured and simulated values under both simple and complex geometries including an anthropomorphic phantom. This work also showed the increased dose differences for z-axis-only TCM simulations, where considerable modulation in the x–y plane was present due to the shape of the rectangular water phantom. Results from this investigation highlight details that need to be included in Monte Carlo simulations of TCM CT scans in order to yield accurate, clinically viable assessments of patient dosimetry.« less

Upgrading NASA/DOSE laser ranging system control computers

NASA Technical Reports Server (NTRS)

Ricklefs, Randall L.; Cheek, Jack; Seery, Paul J.; Emenheiser, Kenneth S.; Hanrahan, William P., III; Mcgarry, Jan F.

1993-01-01

Laser ranging systems now managed by the NASA Dynamics of the Solid Earth (DOSE) and operated by the Bendix Field Engineering Corporation, the University of Hawaii, and the University of Texas have produced a wealth on interdisciplinary scientific data over the last three decades. Despite upgrades to the most of the ranging station subsystems, the control computers remain a mix of 1970's vintage minicomputers. These encompass a wide range of vendors, operating systems, and languages, making hardware and software support increasingly difficult. Current technology allows replacement of controller computers at a relatively low cost while maintaining excellent processing power and a friendly operating environment. The new controller systems are now being designed using IBM-PC-compatible 80486-based microcomputers, a real-time Unix operating system (LynxOS), and X-windows/Motif IB, and serial interfaces have been chosen. This design supports minimizing short and long term costs by relying on proven standards for both hardware and software components. Currently, the project is in the design and prototyping stage with the first systems targeted for production in mid-1993.

Safety of multiple stereotactic radiosurgery treatments for multiple brain lesions.

PubMed

Hillard, Virany H; Shih, Lynn L; Chin, Shing; Moorthy, Chitti R; Benzil, Deborah L

2003-07-01

Stereotactic radiosurgery (SRS) is a widely used therapy for multiple brain lesions, and studies have clearly established the safety and efficacy of single-dose SRS. However, as patient survival has increased, the recurrence of tumors and the development of metastases to new sites within the brain have made it desirable to repeat treatments over time. The cumulative toxicity of multi-isocenter, multiple treatments has not been well defined. We have retrospectively studied 10 patients who received multiple SRS treatments for multiple brain lesions to assess the cumulative toxicity of these treatments. In a retrospective review of all patients treated with SRS using the X-knife (Radionics, Burlington, MA) at Westchester Medical Center/New York Medical College between December 1995 and December 2000, 10 patients were identified who received at least two treatments to at least 3 isocenters and had a minimum follow-up period of 6 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain and critical brain structures. Toxicities and complications were identified by chart and radiological review. The average of the maximum doses (cGy) to a point within the whole brain was 2402 (range 1617-3953); to the brainstem, 1059 (range 48-4126); to the right optic nerve, 223 (range 14-1012); to the left optic nerve, 159 (range 17-475); and to the optic chiasm, 219 (range 15-909). There were no focal neurological toxicities, including visual disturbances, cranial nerve palsies, or ataxia in any of the 10 patients. There were also no global toxicities, including cognitive decline or secondary tumors. Only one patient developed seizures that were difficult to control in association with radiation necrosis. Multiple SRS treatments at the cumulative doses used in our study are a safe therapy for patients with multiple brain lesions.

Interoceptive conditioning with the nicotine stimulus: extinction learning as a method for assessing stimulus similarity across doses.

PubMed

Polewan, Robert J; Savala, Stephanie A; Bevins, Rick A

2013-02-01

Interoceptive conditioning involving the nicotine stimulus likely contributes to chronic tobacco use. To better understand the nature of this interoceptive conditioning, we compared generalization during repeated extinction with generalization in a 'transfer of extinction' test using a wide range of test doses. Rats were first trained in the discriminated goal-tracking task in which nicotine (0.2 or 0.4 mg/kg), but not saline, was paired with repeated intermittent access to sucrose. Across sessions, nicotine acquired control of approach behavior directed at the location of previous sucrose deliveries. Extinction followed with eight 20-min sessions without sucrose access; extinction doses of nicotine ranged from 0.05 to 0.6 mg/kg. In rats trained with 0.4 mg/kg, the 0.1, 0.2, and 0.6 mg/kg doses evoked comparable responding across extinction sessions; substitution was only partial at 0.05 and 0.075 mg/kg (i.e. above saline controls, but less than the training dose). With the 0.2 mg/kg training dose, complete generalization was seen only at the 0.1 and 0.4 mg/kg doses. After extinction, rats were given a transfer test with their training dose. Rats trained with 0.4 mg/kg showed full transfer of extinction learning with 0.1, 0.2, and 0.6 mg/kg (i.e. responding comparable with extinction with the training dose). Partial transfer was observed at 0.075 mg/kg. With the 0.2 mg/kg nicotine dose, only 0.4 mg/kg fully generalized; 0.075, 0.1, and 0.6 mg/kg showed partial transfer. Extinction with 0.05 mg/kg dose did not show transfer to either training dose. These findings indicated that conclusions regarding stimulus similarity across nicotine doses can vary with testing protocol.

Biological and dosimetric characterisation of spatially fractionated proton minibeams

NASA Astrophysics Data System (ADS)

Meyer, Juergen; Stewart, Robert D.; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-12-01

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Biological and dosimetric characterisation of spatially fractionated proton minibeams.

PubMed

Meyer, Juergen; Stewart, Robert D; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-11-21

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

New insights in the treatment by levofloxacin.

PubMed

File, Thomas M

2004-01-01

Levofloxacin is widely regarded as one of the most important fluoroquinolones available today. It possesses excellent activity against a wide range of important pathogens, including those resistant to many other antimicrobials. While rates of resistance to other previously useful antimicrobial classes has grown, levofloxacin has maintained its efficacy, with generally very low rates of resistance around the world. It is indicated for a wide range of infections including community-acquired respiratory infections in adults, particularly community-acquired pneumonia (CAP), acute bacterial exacerbations of chronic bronchitis (AECB), and acute sinusitis. In addition, it is recommended for infections of skin and soft tissue, and the urinary tract. With postmarketing surveillance data available for the last decade, levofloxacin possesses an unparalleled database to demonstrate its clinical efficacy and safety. Remarkably, levofloxacin continues to expand its list of indications. The development of a new high-dose 750-mg schedule has the potential to decrease the duration of treatment as well as reduce the emergence of resistance.

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

Wei Xiong; Liu, H. Helen; Tucker, Susan L.

Purpose: To identify clinical and dosimetric factors influencing the risk of pericardial effusion (PCE) in patients with inoperable esophageal cancer treated with definitive concurrent chemotherapy and radiation therapy (RT). Methods and Materials: Data for 101 patients with inoperable esophageal cancer treated with concurrent chemotherapy and RT from 2000 to 2003 at our institution were analyzed. The PCE was confirmed from follow-up chest computed tomography scans and radiologic reports, with freedom from PCE computed from the end of RT. Log-rank tests were used to identify clinical and dosimetric factors influencing freedom from PCE. Dosimetric factors were calculated from the dose-volume histogrammore » for the whole heart and pericardium. Results: The crude rate of PCE was 27.7% (28 of 101). Median time to onset of PCE was 5.3 months (range, 1.0-16.7 months) after RT. None of the clinical factors investigated was found to significantly influence the risk of PCE. In univariate analysis, a wide range of dose-volume histogram parameters of the pericardium and heart were associated with risk of PCE, including mean dose to the pericardium, volume of pericardium receiving a dose greater than 3 Gy (V3) to greater than 50 Gy (V50), and heart volume treated to greater than 32-38 Gy. Multivariate analysis selected V30 as the only parameter significantly associated with risk of PCE. Conclusions: High-dose radiation to the pericardium may strongly increase the risk of PCE. Such a risk may be reduced by minimizing the dose-volume of the irradiated pericardium and heart.« less

Angular distributions of absorbed dose of Bremsstrahlung and secondary electrons induced by 18-, 28- and 38-MeV electron beams in thick targets.

PubMed

Takada, Masashi; Kosako, Kazuaki; Oishi, Koji; Nakamura, Takashi; Sato, Kouichi; Kamiyama, Takashi; Kiyanagi, Yoshiaki

2013-03-01

Angular distributions of absorbed dose of Bremsstrahlung photons and secondary electrons at a wide range of emission angles from 0 to 135°, were experimentally obtained using an ion chamber with a 0.6 cm(3) air volume covered with or without a build-up cap. The Bremsstrahlung photons and electrons were produced by 18-, 28- and 38-MeV electron beams bombarding tungsten, copper, aluminium and carbon targets. The absorbed doses were also calculated from simulated photon and electron energy spectra by multiplying simulated response functions of the ion chambers, simulated with the MCNPX code. Calculated-to-experimental (C/E) dose ratios obtained are from 0.70 to 1.57 for high-Z targets of W and Cu, from 15 to 135° and the C/E range from 0.6 to 1.4 at 0°; however, the values of C/E for low-Z targets of Al and C are from 0.5 to 1.8 from 0 to 135°. Angular distributions at the forward angles decrease with increasing angles; on the other hand, the angular distributions at the backward angles depend on the target species. The dependences of absorbed doses on electron energy and target thickness were compared between the measured and simulated results. The attenuation profiles of absorbed doses of Bremsstrahlung beams at 0, 30 and 135° were also measured.

The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range.

PubMed

Kalliokoski, Annikka; Neuvonen, Mikko; Neuvonen, Pertti J; Niemi, Mikko

2008-12-01

To establish whether the effect of SLCO1B1[encoding organic anion transporting polypeptide 1B1 (OATP1B1)] c.521T-->C (p.Val174Ala) polymorphism on the pharmacokinetics of repaglinide is dose-dependent. Twelve healthy volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the c.521CC genotype ingested a single 0.25-, 0.5-, 1- or 2-mg dose of repaglinide in a dose-escalation study with a wash-out period of > or =1 week. The mean area under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval 47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P < or = 0.001) larger in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT genotype, respectively. Repaglinide peak plasma concentration and AUC(0-infinity) increased linearly along with repaglinide dose in both genotype groups (r > 0.88, P < 0.001). There was a tendency towards lower blood glucose concentrations after repaglinide administration in the participants with the c.521CC genotype than in those with the c.521TT genotype. The effect of SLCO1B1 c.521T-->C polymorphism on the pharmacokinetics of repaglinide persists throughout the clinically relevant dose range.

Radiation sterilization of skin allograft

NASA Astrophysics Data System (ADS)

Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

2009-07-01

In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6. The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2. The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

Dose estimates for the local inhabitants from 210Po ingestion via dietary sources at a proposed uranium mining site in India.

PubMed

Giri, Soma; Jha, V N; Singh, Gurdeep; Tripathi, R M

2012-07-01

To study the distribution of (210)Po activity in food in Bagjata in East Singhbhum, India. (210)Po were analyzed in the food samples of plant origin such as cereals, pulses, fruits, vegetables and food of animal origin such fish, chicken, egg, etc., in and around Bagjata uranium mining area as a part of baseline study after acid digestion. The intake and ingestion dose of the radionuclide was estimated. The general range of (210)Po activity in all the dietary components ranged widely from <0.2-36 Bqkg(-1)(fresh). In the food of plant origin, the minimum activity of (210)Po was estimated in vegetables while maximum in pulses. In food of animal origin, the observed minimum activity of (210)Po was in eggs and the maximum observed was in chicken samples. The intake of (210)Po considering all dietary components was found to be 464 Bq.Y(-1) while the ingestion dose was calculated to be 557 μSv.Y(-1), respectively. The estimated doses are reflecting the natural background dose via the route of ingestion, which is much below the 1 mSv limit set in the International Commission on Radiological Protection (ICRP) recommendations. The study confirms that current levels of (210)Po do not pose a significant radiological risk to the local inhabitants.

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits

PubMed Central

Cox, Daniel T. C.; Shanahan, Danielle F.; Hudson, Hannah L.; Fuller, Richard A.; Anderson, Karen; Hancock, Steven; Gaston, Kevin J.

2017-01-01

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare. PMID:28208789

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits.

PubMed

Cox, Daniel T C; Shanahan, Danielle F; Hudson, Hannah L; Fuller, Richard A; Anderson, Karen; Hancock, Steven; Gaston, Kevin J

2017-02-09

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare.

Growth hormone (GH) dosing during catch-up growth guided by individual responsiveness decreases growth response variability in prepubertal children with GH deficiency or idiopathic short stature.

PubMed

Kriström, Berit; Aronson, A Stefan; Dahlgren, Jovanna; Gustafsson, Jan; Halldin, Maria; Ivarsson, Sten A; Nilsson, Nils-Osten; Svensson, Johan; Tuvemo, Torsten; Albertsson-Wikland, Kerstin

2009-02-01

Weight-based GH dosing results in a wide variation in growth response in children with GH deficiency (GHD) or idiopathic short stature (ISS). The hypothesis tested was whether individualized GH doses, based on variation in GH responsiveness estimated by a prediction model, reduced variability in growth response around a set height target compared with a standardized weight-based dose. A total of 153 short prepubertal children diagnosed with isolated GHD or ISS (n = 43) and at least 1 SD score (SDS) below midparental height SDS (MPH(SDS)) were included in this 2-yr multicenter study. The children were randomized to either a standard (43 microg/kg.d) or individualized (17-100 microg/kg.d) GH dose. We measured the deviation of height(SDS) from individual MPH(SDS) (diffMPH(SDS)). The primary endpoint was the difference in the range of diffMPH(SDS) between the two groups. The diffMPH(SDS) range was reduced by 32% in the individualized-dose group relative to the standard-dose group (P < 0.003), whereas the mean diffMPH(SDS) was equal: -0.42 +/- 0.46 and -0.48 +/- 0.67, respectively. Gain in height(SDS) 0-2 yr was equal for the GH-deficient and ISS groups: 1.31 +/- 0.47 and 1.36 +/- 0.47, respectively, when ISS was classified on the basis of maximum GH peak on the arginine-insulin tolerance test or 24-h profile. Individualized GH doses during catch-up growth significantly reduce the proportion of unexpectedly good and poor responders around a predefined individual growth target and result in equal growth responses in children with GHD and ISS.

Pergolide: multiple-dose pharmacokinetics in patients with mild to moderate Parkinson disease.

PubMed

Thalamas, Claire; Rajman, Iris; Kulisevsky, Jaime; Lledó, Alberto; Mackie, Alison E; Blin, Olivier; Gillespie, Todd A; Seger, Mary; Rascol, Olivier

2005-01-01

The primary objective of this study was to describe the pharmacokinetics of oral pergolide in patients with mild to moderate Parkinson disease using a new high-performance liquid chromatography-tandem mass spectrometry assay. A secondary objective was to investigate the relationship between plasma concentrations and efficacy. Fourteen patients with a diagnosis of Parkinson disease completed this multicenter, open-label, dose-escalating study. Pergolide was administered for 58 days, using increasing daily doses from 0.05 mg daily up to 1 mg three times daily and then tapering the dose. The steady-state pharmacokinetic profile and motor score were determined at dose levels of 0.25, 0.5, and 1 mg three times a day and during elimination after the last dose. Pergolide was absorbed with a median time to maximum concentration of 2 to 3 hours across the dose range. Systemic exposure appeared to increase proportionally with dose over the range of 0.25 to 1 mg three times daily within a patient, but there was a large variability in exposures between patients (interpatient coefficients of variation were 56.4% for the area under the curve). Pergolide was widely distributed (volume of distribution, approximately 14,000 L) and was eliminated with a mean half-life of 21 hours. Motor scores improved as both peak plasma pergolide concentrations and exposure increased. No unexpected safety concerns were identified. Pergolide is absorbed relatively quickly into the systemic circulation, has a large apparent volume of distribution, and has a relatively long half-life (mean, 21 hours). This prolonged half-life is of particular interest, given the current hypothesis that more continuous dopaminergic receptor stimulation may reduce motor complications in patients with Parkinson disease.

Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.

PubMed

Yorbik, Ozgur; Mutlu, Caner; Ozilhan, Selma; Eryilmaz, Gul; Isiten, Nuket; Alparslan, Serdar; Saglam, Esra

2015-06-01

There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma. The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay. Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects. Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate dose formulations such as 45-mg tablets for OROS-MPH may contribute to the optimization.

An Algorithm and R Program for Fitting and Simulation of Pharmacokinetic and Pharmacodynamic Data.

PubMed

Li, Jijie; Yan, Kewei; Hou, Lisha; Du, Xudong; Zhu, Ping; Zheng, Li; Zhu, Cairong

2017-06-01

Pharmacokinetic/pharmacodynamic link models are widely used in dose-finding studies. By applying such models, the results of initial pharmacokinetic/pharmacodynamic studies can be used to predict the potential therapeutic dose range. This knowledge can improve the design of later comparative large-scale clinical trials by reducing the number of participants and saving time and resources. However, the modeling process can be challenging, time consuming, and costly, even when using cutting-edge, powerful pharmacological software. Here, we provide a freely available R program for expediently analyzing pharmacokinetic/pharmacodynamic data, including data importation, parameter estimation, simulation, and model diagnostics. First, we explain the theory related to the establishment of the pharmacokinetic/pharmacodynamic link model. Subsequently, we present the algorithms used for parameter estimation and potential therapeutic dose computation. The implementation of the R program is illustrated by a clinical example. The software package is then validated by comparing the model parameters and the goodness-of-fit statistics generated by our R package with those generated by the widely used pharmacological software WinNonlin. The pharmacokinetic and pharmacodynamic parameters as well as the potential recommended therapeutic dose can be acquired with the R package. The validation process shows that the parameters estimated using our package are satisfactory. The R program developed and presented here provides pharmacokinetic researchers with a simple and easy-to-access tool for pharmacokinetic/pharmacodynamic analysis on personal computers.

Heavy ion track-structure calculations for radial dose in arbitrary materials

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Dubey, Rajendra R.

1995-01-01

The delta-ray theory of track structure is compared with experimental data for the radial dose from heavy ion irradiation. The effects of electron transmission and the angular dependence of secondary electron ejection are included in the calculations. Several empirical formulas for electron range and energy are compared in a wide variety of materials in order to extend the application of the track-structure theory. The model of Rudd for the secondary electron-spectrum in proton collisions, which is based on a modified classical kinematics binary encounter model at high energies and a molecular promotion model at low energies, is employed. For heavier projectiles, the secondary electron spectrum is found by scaling the effective charge. Radial dose calculations for carbon, water, silicon, and gold are discussed. The theoretical data agreed well with the experimental data.

Single-Fraction Intraoperative Radiotherapy for Breast Cancer: Early Cosmetic Results

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

Beal, Kathryn; McCormick, Beryl; Zelefsky, Michael J.

2007-09-01

Purpose: To evaluate the cosmetic outcome of patients treated with wide local excision and intraoperative radiotherapy for early-stage breast cancer. Methods and Materials: A total of 50 women were treated on a pilot study to evaluate the feasibility of intraoperative radiotherapy at wide local excision. The eligibility criteria included age >60, tumor size {<=}2.0 cm, clinically negative lymph nodes, and biopsy-established diagnosis. After wide local excision, a custom breast applicator was placed in the excision cavity, and a dose of 20 Gy was prescribed to a depth of 1 cm. After 18 patients were treated, the dose was constrained laterallymore » to 18 Gy. The cosmetic outcome was evaluated by photographs at baseline and at 6 and 12 months postoperatively. Four examiners graded the photographs for symmetry, edema, discoloration, contour, and scarring. The grades were evaluated in relationship to the volume of irradiated tissue, tumor location, and dose at the lateral aspects of the cavity. Results: The median volume of tissue receiving 100% of the prescription dose was 47 cm{sup 3} (range, 20-97 cm{sup 3}). Patients with {<=}47 cm{sup 3} of treated tissue had better cosmetic outcomes than did the women who had >47 cm{sup 3} of treated tissue. Women who had received 18 Gy at the lateral aspects of their cavities had better cosmetic outcomes than did women who had received 20 Gy at the lateral aspects. When comparing the 6- and 12-month results, the scores remained stable for 63%, improved for 17%, and worsened for 20%. Conclusion: Intraoperative radiotherapy appears feasible for selected patients. A favorable cosmetic outcome appears to be related to a smaller treatment volume. The cosmetic outcome is acceptable, although additional follow-up is necessary.« less

Neuropharmacological effects of oleamide in male and female mice.

PubMed

Akanmu, Moses A; Adeosun, Samuel O; Ilesanmi, Olapade R

2007-08-22

Oleamide, a fatty acid amide accumulates selectively in the cerebrospinal fluid of sleep deprived cats and rats. Oleamide has been reported to have effects on a wide range of receptors and neurotransmitter systems especially the centrally acting ones for example, dopamine acetylcholine, serotonin, gamma aminobutyric acid (GABA), cannabinoid and vanilloid among others. This suggests a wide range of central nervous system effects of the compound. The effects of intraperitoneal administered oleamide on Novelty-induced behaviours, learning and memory and forced swimming-induced depression were studied. The relative effects of the compound on the male and female mice were also noted. Oleamide dose-dependently reduced (p<0.05) novelty induced rearing, grooming and locomotion. The effects on the all NIBs started within the first 10 min of the test and the peak of the effects was observed during the third 10 min period of the test. Effect of oleamide on short-term working memory was significantly (p<0.05) affected only with the dose of 5mg/kg while the other dose of 10mg/kg had no effect. In the forced swimming test, acute triple intraperitoneal administration of oleamide at 10mg/kg induced a significant reduction in the immobility duration in mice signifying an antidepressant effect. Sex differences in the effects of oleamide (10mg/kg, i.p.) were clearly evident in active behaviours in FST. These results confirm the multiplicity of central nervous system receptors and neurotransmitters that oleamide interacts with hence its numerous and diverse neuropharmacological effects. Most importantly, the present study suggests that oleamide has antidepressant-like property.

Fluorescence tissue distribution of methylene blue used for photodynamic therapy of Helicobacter Pylori

NASA Astrophysics Data System (ADS)

Millson, Charles E.; Buonaccorsi, Giovanni A.; MacRobert, Alexander J.; Mlkvy, Peter; Bown, Stephen G.

1995-03-01

Helicobacter pylori is associated with a wide range of pathologies in the upper gastrointestinal tract. Current treatments employing antibiotics are disappointing, and an endoscopic PDT might offer a better alternative. Methylene blue is a widely known histological dye and has been in use for photodynamic therapy experimentally for some years. A prospective application of MB is photosensitization of Helicobacter pylori, but little is known about its effect with light on normal mucosa of the stomach. We studied the fluorescence microscopy of the stomachs of 3 ferrets which had been sensitized by oral route with three different concentrations of MB 1 hour prior to sacrifice. MB at all doses was seen to concentrate on the surface of the mucosa and shows little deeper penetration. As Helicobacter lie on the superficial mucosa, this study suggests that oral dosing with MB should sensitize these bacteria. These findings are an important preliminary to an in vivo trial of PDT for the treatment of H pylori.

Comprehensive assessment of the quality of commercial cranberry products. Phenolic characterization and in vitro bioactivity.

PubMed

Sánchez-Patán, Fernando; Bartolomé, Begoña; Martín-Alvarez, Pedro J; Anderson, Mark; Howell, Amy; Monagas, María

2012-04-04

Cranberry (Vaccinium macrocarpon) products have been widely recommended in traditional American medicine for the treatment of urinary tract infection (UTI). A total of 19 different commercial cranberry products from American and European markets have been analyzed by different global phenolic methods and by UPLC-DAD-ESI-TQ MS. In addition, in vitro antioxidant capacity and uropathogenic bacterial antiadhesion activity tests have been performed. Results revealed that products found in the market widely differed in their phenolic content and distribution, including products completely devoid of flavan-3-ols to highly purified ones, either in A-type proanthocyanidins (PACs) or in anthocyanins. The product presentation form and polyphenolic profile widely affected the antiadhesion activity, ranging from a negative (nulel) effect to a MIC = 0.5 mg/mL for cranberry powders and a MIC=112 mg/mL for gel capsule samples. Only 4 of 19 products would provide the recommended dose of intake of 36 mg total PACs/day. Of most importance was the fact that this dose would actually provide as low as 0.00 and up to 205 μg/g of procyanidin A2, indicating the lack of product standardization and incongruence between global and individual compound analysis.

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

PubMed

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

2014-07-08

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

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

NASA Technical Reports Server (NTRS)

Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

2006-01-01

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose-rate dose to the bone marrow (mean = 2.5 Gy) was consistent with the measured ERR (0.62, 95% Cl =-0.2 to 1.9). Conclusions: An extended, biologically based model for leukemia that includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia, long-range HSC migration predicts, %Kith reasonable accuracy, risks for radiationinduced leukemia associated with exposure to therapeutic doses of radiation.

[Hematopoiesis during remote period after acute radiation syndrome].

PubMed

Kotenko, K V; Bushmanov, A Iu; Suvorova, L A; Galstian, I A; Nadezhina, N M; Nugis, V Iu

2011-01-01

Based on the long (19.7 +/- 1.8 year) hemopoiesis follow-up study in 152 patients after acute radiation syndrome (ARS) as a result of exposure to gamma-, gamma-beta and gamma-eta radiation in a wide dose range (1.2-9.8 Gy) it was detected that cytopenia appears in the late consequences period: thrombocytopenia was found in 26.9% cases, leukocytopenia, neutropenia and lymphocytopenia--in 13.1% patients. A higher ARS degree causes the increase of various disorders (cytopenia and cytosis) in the late period. It reflects a tight interrelation between blood cell contents and radiation dose. Frequency of cytopenias increases if such somatic disorders: persistent hepatitis, hepatic cirrhosis and late radiation ulcers as appear.

Prescribing patterns and the use of therapeutic drug monitoring of psychotropic medication in a psychiatric high-security unit.

PubMed

Castberg, Ingrid; Spigset, Olav

2008-10-01

The aim of this study was to investigate the use of psychotropic medication and therapeutic drug monitoring in a high-security psychiatric unit and to compare the doses and serum concentrations both with the recommended intervals and with the doses and serum concentrations in a control group. One hundred thirty-two patients were admitted in the period from January 2000 to December 2005. All available samples were used when comparing serum concentrations and doses with the recommended ranges. For the comparison of doses and serum concentration-to-dose (C:D) ratios with the control group only 1 sample from each patient was used. A total of 459 analyses of 27 different drugs in samples from 8 women and 73 men were included. The median number of therapeutic drug monitoring analyses per patient was 4 (range 1-29). Thirty-seven of the 81 patients (46%) used 2 or more antipsychotics at the same time. Clozapine, lamotrigine, olanzapine, quetiapine, ziprasidone, and zuclopenthixol were often given in doses above the recommended. The serum levels were frequently above those recommended for clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zuclopenthixol. The serum levels were significantly higher in the study group than in the control group for clozapine, lamotrigine, quetiapine, and zuclopenthixol. The given dose was significantly higher in the study group than in the control group for clozapine, lamotrigine and zuclopenthixol. The C:D ratio was significantly lower in the study group than in the control group for olanzapine but higher for quetiapine. The non-evidence based practice of high-dose polypharmacy with several antipsychotics is widely used in this unit. The use of higher doses in the study group than in the control group was not due to differences in metabolism or adherence to treatment between the 2 groups. The frequent use of therapeutic drug monitoring did not seem to have a great impact on the prescribed doses.

Microfluidic Thrombosis under Multiple Shear Rates and Antiplatelet Therapy Doses

PubMed Central

Ku, David N.; Forest, Craig R.

2014-01-01

The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but instrumentation to measure its influence has been limited by flow conditions, agonist use, and non-systematic and/or non-quantitative studies. In this work we measured occlusion times and thrombus detachment for a range of initial shear rates (500, 1500, 4000, and 10000 s−1) and therapy concentrations (0–2.4 µM for eptifibatide, 0–2 mM for acetyl-salicylic acid (ASA), 3.5–40 Units/L for heparin) using a microfluidic device. We also measured complete blood counts (CBC) and platelet activity using whole blood impedance aggregometry. Effects of shear rate and dose were analyzed using general linear models, logistic regressions, and Cox proportional hazards models. Shear rates have significant effects on thrombosis/dose-response curves for all tested therapies. ASA has little effect on high shear occlusion times, even at very high doses (up to 20 times the recommended dose). Under ASA therapy, thrombi formed at high shear rates were 4 times more prone to detachment compared to those formed under control conditions. Eptifibatide reduced occlusion when controlling for shear rate and its efficacy increased with dose concentration. In contrast, the hazard of occlusion from ASA was several orders of magnitude higher than that of eptifibatide. Our results show similar dose efficacy to our low shear measurements using whole blood aggregometry. This quantitative and statistically validated study of the effects of a wide range of shear rate and antiplatelet therapy doses on occlusive thrombosis contributes to more accurate understanding of thrombosis and to models for optimizing patient treatment. PMID:24404131

SU-F-J-56: The Connection Between Cherenkov Light Emission and Radiation Absorbed Dose in Proton Irradiated Phantoms

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

Darafsheh, A; Kassaee, A; Finlay, J

Purpose: Range verification in proton therapy is of great importance. Cherenkov light follows the photon and electron energy deposition in water phantom. The purpose of this study is to investigate the connection between Cherenkov light generation and radiation absorbed dose in a water phantom irradiated with proton beams. Methods: Monte Carlo simulation was performed by employing FLUKA Monte Carlo code to stochastically simulate radiation transport, ionizing radiation dose deposition, and Cherenkov radiation in water phantoms. The simulations were performed for proton beams with energies in the range 50–600 MeV to cover a wide range of proton energies. Results: The mechanismmore » of Cherenkov light production depends on the initial energy of protons. For proton energy with 50–400 MeV energy that is below the threshold (∼483 MeV in water) for Cherenkov light production directly from incident protons, Cherenkov light is produced mainly from the secondary electrons liberated as a result of columbic interactions with the incident protons. For proton beams with energy above 500 MeV, in the initial depth that incident protons have higher energy than the Cherenkov light production threshold, the light has higher intensity. As the slowing down process results in lower energy protons in larger depths in the water phantom, there is a knee point in the Cherenkov light curve vs. depth due to switching the Cherenkov light production mechanism from primary protons to secondary electrons. At the end of the depth dose curve the Cherenkov light intensity does not follow the dose peak because of the lack of high energy protons to produce Cherenkov light either directly or through secondary electrons. Conclusion: In contrast to photon and electron beams, Cherenkov light generation induced by proton beams does not follow the proton energy deposition specially close to the end of the proton range near the Bragg peak.« less

Dose to the Developing Dentition During Therapeutic Irradiation: Organ at Risk Determination and Clinical Implications

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

Thompson, Reid F., E-mail: Reid.Thompson@uphs.upenn.edu; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania; Schneider, Ralf A., E-mail: ralf.schneider@psi.ch

Purpose: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. Methods and Materials: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions formore » a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. Results: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. Conclusions: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the largest doses of radiation at the youngest ages; however, multiple factors including concurrent chemotherapy confounded the dose-effect relationship. Further studies with larger cohorts and appropriate controls will be required.« less

An online proton beam monitor for cancer therapy based on ionization chambers with micro pattern readout

NASA Astrophysics Data System (ADS)

Basile, E.; Carloni, A.; Castelluccio, D. M.; Cisbani, E.; Colilli, S.; De Angelis, G.; Fratoni, R.; Frullani, S.; Giuliani, F.; Gricia, M.; Lucentini, M.; Santavenere, F.; Vacca, G.

2012-03-01

A unique compact LINAC accelerator for proton therapy is under development in Italy within the TOP-IMPLART project. The proton beam will reach the kinetic energy of 230 MeV, it will have a widely variable current intensity (0.1-10 μA, with average up to 3.5 nA) associated with a high pulse repetition frequency (1-3.5 μs long pulses at 10-100 Hz). The TOP-IMPLART system will provide a fully active 3+1D dose delivery, that is longitudinal (energy modulation), transverse active spot scanning, and current intensity modulation. These accelerator features will permit a highly conformational dose distribution, which therefore requires an effective, online, beam monitor system with wide dynamic range, good sensitivity, adequate spatial resolution and rapid response. In order to fulfill these requisites a new device is under development for the monitoring of the beam intensity profile, its centroid and direction; it is based on transmission, segmented, ionization chambers with typical active area of 100 × 100 mm2. Micro pattern x/y pad like design has been used for the readout plane in order to maximize the field uniformity, reduce the chamber thickness and obtain both beam coordinates on a single chamber. The chamber prototype operates in ionization region to minimize saturation and discharge effects. Simulations (based on FLUKA) have been carried on to study the perturbation of the chamber on the beam parameters and the effects on the delivered dose (on a water phantom). The charge collected in each channel is integrated by dedicated auto-ranging readout electronics: an original scheme has been developed in order to have an input dynamic range greater than 104 with sensitivity better than 3%. This is achieved by a dynamical adjustment of the integrating capacitance to the signal intensity.

TH-AB-207A-05: A Fully-Automated Pipeline for Generating CT Images Across a Range of Doses and Reconstruction Methods

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

Young, S; Lo, P; Hoffman, J

Purpose: To evaluate the robustness of CAD or Quantitative Imaging methods, they should be tested on a variety of cases and under a variety of image acquisition and reconstruction conditions that represent the heterogeneity encountered in clinical practice. The purpose of this work was to develop a fully-automated pipeline for generating CT images that represent a wide range of dose and reconstruction conditions. Methods: The pipeline consists of three main modules: reduced-dose simulation, image reconstruction, and quantitative analysis. The first two modules of the pipeline can be operated in a completely automated fashion, using configuration files and running the modulesmore » in a batch queue. The input to the pipeline is raw projection CT data; this data is used to simulate different levels of dose reduction using a previously-published algorithm. Filtered-backprojection reconstructions are then performed using FreeCT-wFBP, a freely-available reconstruction software for helical CT. We also added support for an in-house, model-based iterative reconstruction algorithm using iterative coordinate-descent optimization, which may be run in tandem with the more conventional recon methods. The reduced-dose simulations and image reconstructions are controlled automatically by a single script, and they can be run in parallel on our research cluster. The pipeline was tested on phantom and lung screening datasets from a clinical scanner (Definition AS, Siemens Healthcare). Results: The images generated from our test datasets appeared to represent a realistic range of acquisition and reconstruction conditions that we would expect to find clinically. The time to generate images was approximately 30 minutes per dose/reconstruction combination on a hybrid CPU/GPU architecture. Conclusion: The automated research pipeline promises to be a useful tool for either training or evaluating performance of quantitative imaging software such as classifiers and CAD algorithms across the range of acquisition and reconstruction parameters present in the clinical environment. Funding support: NIH U01 CA181156; Disclosures (McNitt-Gray): Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

Defining Action Levels for In Vivo Dosimetry in Intraoperative Electron Radiotherapy.

PubMed

López-Tarjuelo, Juan; Morillo-Macías, Virginia; Bouché-Babiloni, Ana; Ferrer-Albiach, Carlos; Santos-Serra, Agustín

2016-06-01

In vivo dosimetry is recommended in intraoperative electron radiotherapy (IOERT). To perform real-time treatment monitoring, action levels (ALs) have to be calculated. Empirical approaches based on observation of samples have been reported previously, however, our aim is to present a predictive model for calculating ALs and to verify their validity with our experimental data. We considered the range of absorbed doses delivered to our detector by means of the percentage depth dose for the electron beams used. Then, we calculated the absorbed dose histograms and convoluted them with detector responses to obtain probability density functions in order to find ALs as certain probability levels. Our in vivo dosimeters were reinforced TN-502RDM-H mobile metal-oxide-semiconductor field-effect transistors (MOSFETs). Our experimental data came from 30 measurements carried out in patients undergoing IOERT for rectal, breast, sarcoma, and pancreas cancers, among others. The prescribed dose to the tumor bed was 90%, and the maximum absorbed dose was 100%. The theoretical mean absorbed dose was 90.3% and the measured mean was 93.9%. Associated confidence intervals at P = .05 were 89.2% and 91.4% and 91.6% and 96.4%, respectively. With regard to individual comparisons between the model and the experiment, 37% of MOSFET measurements lay outside particular ranges defined by the derived ALs. Calculated confidence intervals at P = .05 ranged from 8.6% to 14.7%. The model can describe global results successfully but cannot match all the experimental data reported. In terms of accuracy, this suggests an eventual underestimation of tumor bed bleeding or detector alignment. In terms of precision, it will be necessary to reduce positioning uncertainties for a wide set of location and treatment postures, and more precise detectors will be required. Planning and imaging tools currently under development will play a fundamental role. © The Author(s) 2015.

Further Characterization of the Mitigation of Radiation Lethality by Protective Wounding

PubMed Central

Dynlacht, Joseph R.; Garrett, Joy; Joel, Rebecca; Lane, Katharina; Mendonca, Marc S.; Orschell, Christie M.

2017-01-01

There continues to be a major effort in the United States to develop mitigators for the treatment of mass casualties that received high-intensity acute ionizing radiation exposures from the detonation of an improvised nuclear device during a radiological terrorist attack. The ideal countermeasure should be effective when administered after exposure, and over a wide range of absorbed doses. We have previously shown that the administration of a subcutaneous incision of a defined length, if administered within minutes after irradiation, protected young adult female C57BL/6 mice against radiation-induced lethality, and increased survival after total-body exposure to an LD50/30 X-ray dose from 50% to over 90%. We refer to this approach as “protective wounding”. In this article, we report on our efforts to further optimize, characterize and demonstrate the validity of the protective wounding response by comparing the response of female and male mice, varying the radiation dose, the size of the wound, and the timing of wounding with respect to administration of the radiation dose. Both male and female mice that received a subcutaneous incision after irradiation were significantly protected from radiation lethality. We observed that the extent of protection against lethality after an LD50/30 X-ray dose was independent of the size of the subcutaneous cut, and that a 3 mm subcutaneous incision is effective at enhancing the survival of mice exposed to a broad range of radiation doses (LD15–LD100). Over the range of 6.2–6.7 Gy, the increase in survival observed in mice that received an incision was associated with an enhanced recovery of hematopoiesis. The enhanced rate of recovery of hematopoiesis was preceded by an increase in the production of a select group of cytokines. Thus, a thorough knowledge of the timing of the cytokine cascade after wounding could aid in the development of novel pharmacological radiation countermeasures that can be administered several days after the actual radiation exposure. PMID:28437188

Electron-proton spectrometer: Summary for critical design review

NASA Technical Reports Server (NTRS)

1972-01-01

The electron-proton spectrometer (EPS) is mounted external to the Skylab module complex on the command service module. It is designed to make a 2 pi omni-directional measurement of electrons and protons which result from solar flares or enhancement of the radiation belts. The EPS data will provide accurate radiation dose information so that uncertain Relative biological effectiveness factors are eliminated by measuring the external particle spectra. Astronaut radiation safety, therefore, can be ensured, as the EPS data can be used to correct or qualify radiation dose measurements recorded by other radiation measuring instrumentation within the Skylab module complex. The EPS has the capability of measuring and extremely wide dynamic radiation dose rate range, approaching 10 to the 7th power. Simultaneously the EPS has the capability to process data from extremely high radiation fields such as might be encountered in the wake of an intense solar flare.

Organ doses, effective doses, and risk indices in adult CT: Comparison of four types of reference phantoms across different examination protocols

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

Zhang Yakun; Li Xiang; Paul Segars, W.

Purpose: Radiation exposure from computed tomography (CT) to the public has increased the concern among radiation protection professionals. Being able to accurately assess the radiation dose patients receive during CT procedures is a crucial step in the management of CT dose. Currently, various computational anthropomorphic phantoms are used to assess radiation dose by different research groups. It is desirable to better understand how the dose results are affected by different choices of phantoms. In this study, the authors assessed the uncertainties in CT dose and risk estimation associated with different types of computational phantoms for a selected group of representativemore » CT protocols. Methods: Routinely used CT examinations were categorized into ten body and three neurological examination categories. Organ doses, effective doses, risk indices, and conversion coefficients to effective dose and risk index (k and q factors, respectively) were estimated for these examinations for a clinical CT system (LightSpeed VCT, GE Healthcare). Four methods were used, each employing a different type of reference phantoms. The first and second methods employed a Monte Carlo program previously developed and validated in our laboratory. In the first method, the reference male and female extended cardiac-torso (XCAT) phantoms were used, which were initially created from the Visible Human data and later adjusted to match organ masses defined in ICRP publication 89. In the second method, the reference male and female phantoms described in ICRP publication 110 were used, which were initially developed from tomographic data of two patients and later modified to match ICRP 89 organ masses. The third method employed a commercial dosimetry spreadsheet (ImPACT group, London, England) with its own hermaphrodite stylized phantom. In the fourth method, another widely used dosimetry spreadsheet (CT-Expo, Medizinische Hochschule, Hannover, Germany) was employed together with its associated male and female stylized phantoms. Results: For fully irradiated organs, average coefficients of variation (COV) ranged from 0.07 to 0.22 across the four male phantoms and from 0.06 to 0.18 across the four female phantoms; for partially irradiated organs, average COV ranged from 0.13 to 0.30 across the four male phantoms and from 0.15 to 0.30 across the four female phantoms. Doses to the testes, breasts, and esophagus showed large variations between phantoms. COV for gender-averaged effective dose and k factor ranged from 0.03 to 0.23 and from 0.06 to 0.30, respectively. COV for male risk index and q factor ranged from 0.06 to 0.30 and from 0.05 to 0.36, respectively; COV for female risk index and q factor ranged from 0.06 to 0.49 and from 0.07 to 0.54, respectively. Conclusions: Despite closely matched organ mass, total body weight, and height, large differences in organ dose exist due to variation in organ location, spatial distribution, and dose approximation method. Dose differences for fully irradiated radiosensitive organs were much smaller than those for partially irradiated organs. Weighted dosimetry quantities including effective dose, male risk indices, k factors, and male q factors agreed well across phantoms. The female risk indices and q factors varied considerably across phantoms.« less

Organ doses, effective doses, and risk indices in adult CT: Comparison of four types of reference phantoms across different examination protocols

PubMed Central

Zhang, Yakun; Li, Xiang; Paul Segars, W.; Samei, Ehsan

2012-01-01

Purpose: Radiation exposure from computed tomography (CT) to the public has increased the concern among radiation protection professionals. Being able to accurately assess the radiation dose patients receive during CT procedures is a crucial step in the management of CT dose. Currently, various computational anthropomorphic phantoms are used to assess radiation dose by different research groups. It is desirable to better understand how the dose results are affected by different choices of phantoms. In this study, the authors assessed the uncertainties in CT dose and risk estimation associated with different types of computational phantoms for a selected group of representative CT protocols. Methods: Routinely used CT examinations were categorized into ten body and three neurological examination categories. Organ doses, effective doses, risk indices, and conversion coefficients to effective dose and risk index (k and q factors, respectively) were estimated for these examinations for a clinical CT system (LightSpeed VCT, GE Healthcare). Four methods were used, each employing a different type of reference phantoms. The first and second methods employed a Monte Carlo program previously developed and validated in our laboratory. In the first method, the reference male and female extended cardiac-torso (XCAT) phantoms were used, which were initially created from the Visible Human data and later adjusted to match organ masses defined in ICRP publication 89. In the second method, the reference male and female phantoms described in ICRP publication 110 were used, which were initially developed from tomographic data of two patients and later modified to match ICRP 89 organ masses. The third method employed a commercial dosimetry spreadsheet (ImPACT group, London, England) with its own hermaphrodite stylized phantom. In the fourth method, another widely used dosimetry spreadsheet (CT-Expo, Medizinische Hochschule, Hannover, Germany) was employed together with its associated male and female stylized phantoms. Results: For fully irradiated organs, average coefficients of variation (COV) ranged from 0.07 to 0.22 across the four male phantoms and from 0.06 to 0.18 across the four female phantoms; for partially irradiated organs, average COV ranged from 0.13 to 0.30 across the four male phantoms and from 0.15 to 0.30 across the four female phantoms. Doses to the testes, breasts, and esophagus showed large variations between phantoms. COV for gender-averaged effective dose and k factor ranged from 0.03 to 0.23 and from 0.06 to 0.30, respectively. COV for male risk index and q factor ranged from 0.06 to 0.30 and from 0.05 to 0.36, respectively; COV for female risk index and q factor ranged from 0.06 to 0.49 and from 0.07 to 0.54, respectively. Conclusions: Despite closely matched organ mass, total body weight, and height, large differences in organ dose exist due to variation in organ location, spatial distribution, and dose approximation method. Dose differences for fully irradiated radiosensitive organs were much smaller than those for partially irradiated organs. Weighted dosimetry quantities including effective dose, male risk indices, k factors, and male q factors agreed well across phantoms. The female risk indices and q factors varied considerably across phantoms. PMID:22755721

Locally acting ACE-083 increases muscle volume in healthy volunteers.

PubMed

Glasser, Chad E; Gartner, Michael R; Wilson, Dawn; Miller, Barry; Sherman, Matthew L; Attie, Kenneth M

2018-02-27

ACE-083 is a locally acting follistatin-based therapeutic that binds myostatin and other muscle regulators and has been shown to increase muscle mass and force in neuromuscular disease mouse models. This first-in-human study examined these effects. In this phase 1, randomized, double-blind, placebo-controlled, dose-ranging study in healthy postmenopausal women, ACE-083 (50-200 mg) or placebo was administered unilaterally into rectus femoris (RF) or tibialis anterior (TA) muscles as 1 or 2 doses 3 weeks apart. Fifty-eight postmenopausal women were enrolled, 42 ACE-083 and 16 placebo. No serious adverse events (AE), dose-limiting toxicities, or discontinuations resulting from AEs occurred. Maximum (mean ± SD) increases in RF and TA muscle volume were 14.5% ± 4.5% and 8.9% ± 4.7%, respectively. No significant changes in mean muscle strength were observed. ACE-083 was well tolerated and resulted in significant targeted muscle growth. ACE-083 may have the potential to increase muscle mass in a wide range of neuromuscular disorders. Muscle Nerve, 2018. © 2018 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.

Stereotactic ablative radiotherapy for oligometastatic disease in liver.

PubMed

Kim, Myungsoo; Son, Seok Hyun; Won, Yong Kyun; Kay, Chul Seung

2014-01-01

Liver metastasis in solid tumors, including colorectal cancer, is the most frequent and lethal complication. The development of systemic therapy has led to prolonged survival. However, in selected patients with a finite number of discrete lesions in liver, defined as oligometastatic state, additional local therapies such as surgical resection, radiofrequency ablation, cryotherapy, and radiotherapy can lead to permanent local disease control and improve survival. Among these, an advance in radiation therapy made it possible to deliver high dose radiation to the tumor more accurately, without impairing the liver function. In recent years, the introduction of stereotactic ablative radiotherapy (SABR) has offered even more intensive tumor dose escalation in a few fractions with reduced dose to the adjacent normal liver. Many studies have shown that SABR for oligometastases is effective and safe, with local control rates widely ranging from 50% to 100% at one or two years. And actuarial survival at one and two years has been reported ranging from 72% to 94% and from 30% to 62%, respectively, without severe toxicities. In this paper, we described the definition and technical aspects of SABR, clinical outcomes including efficacy and toxicity, and related parameters after SABR in liver oligometastases from colorectal cancer.

Multi residue screening of intact testosterone esters and boldenone undecylenate in bovine hair using liquid chromatography electrospray tandem mass spectrometry.

PubMed

Nielen, Michel W F; Lasaroms, Johan J P; Mulder, Patrick P J; Van Hende, Johan; van Rhijn, J Hans A; Groot, Maria J

2006-01-02

The abuse of esters of natural androgenic steroids in cattle fattening and sports is hard to control via routine urine testing. The esters are rapidly hydrolysed in vivo into substances which are also endogenously present in urine. In veterinary control strange findings of 17beta-testosterone and 17alpha-testosterone in urine are often ignored because of the lack of statistically sound reference data of naturally occurring levels. An interesting alternative for inconclusive urine analyses in veterinary control can be provided by the analysis of the administered steroids themselves, i.e. the analysis of intact steroid esters in hair. Unfortunately, the analysis of intact steroid esters is complicated not only by the vulnerability of the esters which precludes alkaline hydrolysis of the hair, but also by the wide polarity range of short and long-chain esters yielding very poor recoveries for either the one or the other. In this study, a multi-steroid esters LC/MS/MS screening method is presented for trace analysis of the synthetic intact esters of 17beta-testosterone and the undecylenate ester of 17beta-boldenone in bovine hair. The method, requiring only 200 mg of pulverised hair, features a mild digestion procedure using tris(2-carboxyethyl)phosphine hydrochloride (TCEP) and the use of four deuterium-labelled steroid esters as internal standards covering the wide polarity range of the analytes. In spiked hair samples for most of the analytes the limit of detection and the accuracy using isotope dilution were 2-5 ng/g and 97-105%, respectively. The applicability was demonstrated using hair samples from a controlled experiment in which six bovines were injected intramuscularly with two different doses of two commercial mixtures of testosterone esters, and with two different doses of boldenone undecylenate. Depending on the dose all administered testosterone- and boldenone esters were found to be incorporated in bovine hair following a single intramuscular injection, except testosterone propionate which dose might have been too low.

An atlas-based organ dose estimator for tomosynthesis and radiography

NASA Astrophysics Data System (ADS)

Hoye, Jocelyn; Zhang, Yakun; Agasthya, Greeshma; Sturgeon, Greg; Kapadia, Anuj; Segars, W. Paul; Samei, Ehsan

2017-03-01

The purpose of this study was to provide patient-specific organ dose estimation based on an atlas of human models for twenty tomosynthesis and radiography protocols. The study utilized a library of 54 adult computational phantoms (age: 18-78 years, weight 52-117 kg) and a validated Monte-Carlo simulation (PENELOPE) of a tomosynthesis and radiography system to estimate organ dose. Positioning of patient anatomy was based on radiographic positioning handbooks. The field of view for each exam was calculated to include relevant organs per protocol. Through simulations, the energy deposited in each organ was binned to estimate normalized organ doses into a reference database. The database can be used as the basis to devise a dose calculator to predict patient-specific organ dose values based on kVp, mAs, exposure in air, and patient habitus for a given protocol. As an example of the utility of this tool, dose to an organ was studied as a function of average patient thickness in the field of view for a given exam and as a function of Body Mass Index (BMI). For tomosynthesis, organ doses can also be studied as a function of x-ray tube position. This work developed comprehensive information for organ dose dependencies across tomosynthesis and radiography. There was a general exponential decrease dependency with increasing patient size that is highly protocol dependent. There was a wide range of variability in organ dose across the patient population, which needs to be incorporated in the metrology of organ dose.

Extrapolation of the dna fragment-size distribution after high-dose irradiation to predict effects at low doses

NASA Technical Reports Server (NTRS)

Ponomarev, A. L.; Cucinotta, F. A.; Sachs, R. K.; Brenner, D. J.; Peterson, L. E.

2001-01-01

The patterns of DSBs induced in the genome are different for sparsely and densely ionizing radiations: In the former case, the patterns are well described by a random-breakage model; in the latter, a more sophisticated tool is needed. We used a Monte Carlo algorithm with a random-walk geometry of chromatin, and a track structure defined by the radial distribution of energy deposition from an incident ion, to fit the PFGE data for fragment-size distribution after high-dose irradiation. These fits determined the unknown parameters of the model, enabling the extrapolation of data for high-dose irradiation to the low doses that are relevant for NASA space radiation research. The randomly-located-clusters formalism was used to speed the simulations. It was shown that only one adjustable parameter, Q, the track efficiency parameter, was necessary to predict DNA fragment sizes for wide ranges of doses. This parameter was determined for a variety of radiations and LETs and was used to predict the DSB patterns at the HPRT locus of the human X chromosome after low-dose irradiation. It was found that high-LET radiation would be more likely than low-LET radiation to induce additional DSBs within the HPRT gene if this gene already contained one DSB.

Quality of anticoagulation management with warfarin among outpatients in a tertiary hospital in Addis Ababa, Ethiopia: a retrospective cross-sectional study.

PubMed

Fenta, Teferi Gedif; Assefa, Tamrat; Alemayehu, Bekele

2017-06-06

Warfarin is the most widely used anticoagulant in the world. The difficulty of managing warfarin contributes to great potential for patient harm, both from excessive anticoagulation and insufficient anticoagulation. This study assessed the International Normalized Ratio (INR) control outcome measures and warfarin dose adjustment practices at cardiology and hematology outpatient clinics at a teaching hospital in Addis Ababa, Ethiopia. The study was based on a cross - sectional study design involving 360 retrospective patients' chart review among outpatients who received warfarin for its various indications. The mean frequency of INR monitoring per patient was 62.9 days (17.2-143.7 days). Patients spent 52.2%, 29.0% and 18.8% of the time in sub-therapeutic, therapeutic and supra-therapeutic ranges, respectively. The daily warfarin dose was increased 50.9% and 36.9% and decreased in 52.8% and 60.9% of the time for occurrences of sub-therapeutic and supra-therapeutic INRs to achieve target ranges of 2.0-3.0 and 2.5-3.5, respectively. The quality of anticoagulation management with warfarin among outpatients in Tikur Anbessa Specialized Hospital was sub-optimal. This was reflected by low Time in Therapeutic Range (TTR), longer than recommended INR monitoring frequency, and minimal actions taken to adjust warfarin dose after occurrences of non-therapeutic INRs.

Putrescine as indicator of manganese neurotoxicity: Dose-response study in human SH-SY5Y cells.

PubMed

Fernandes, Jolyn; Chandler, Joshua D; Liu, Ken H; Uppal, Karan; Go, Young-Mi; Jones, Dean P

2018-06-01

Disrupted polyamine metabolism with elevated putrescine is associated with neuronal dysfunction. Manganese (Mn) is an essential nutrient that causes neurotoxicity in excess, but methods to evaluate biochemical responses to high Mn are limited. No information is available on dose-response effects of Mn on putrescine abundance and related polyamine metabolism. The present research was to test the hypothesis that Mn causes putrescine accumulation over a physiologically adequate to toxic concentration range in a neuronal cell line. We used human SH-SY5Y neuroblastoma cells treated with MnCl 2 under conditions that resulted in cell death or no cell death after 48 h. Putrescine and other metabolites were analyzed by liquid chromatography-ultra high-resolution mass spectrometry. Putrescine-related pathway changes were identified with metabolome-wide association study (MWAS). Results show that Mn caused a dose-dependent increase in putrescine over a non-toxic to toxic concentration range. MWAS of putrescine showed positive correlations with the polyamine metabolite N8-acetylspermidine, methionine-related precursors, and arginine-associated urea cycle metabolites, while putrescine was negatively correlated with γ-aminobutyric acid (GABA)-related and succinate-related metabolites (P < 0.001, FDR < 0.01). These data suggest that measurement of putrescine and correlated metabolites may be useful to study effects of Mn intake in the high adequate to UL range. Copyright © 2018. Published by Elsevier Ltd.

Evaluation of a lithium formate EPR dosimetry system for dose measurements around {sup 192}Ir brachytherapy sources

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

Antonovic, Laura; Gustafsson, Haakan; Alm Carlsson, Gudrun

2009-06-15

A dosimetry system using lithium formate monohydrate (HCO{sub 2}Li{center_dot}H{sub 2}O) as detector material and electron paramagnetic resonance (EPR) spectroscopy for readout has been used to measure absorbed dose distributions around clinical {sup 192}Ir sources. Cylindrical tablets with diameter of 4.5 mm, height of 4.8 mm, and density of 1.26 g/cm{sup 3} were manufactured. Homogeneity test and calibration of the dosimeters were performed in a 6 MV photon beam. {sup 192}Ir irradiations were performed in a PMMA phantom using two different source models, the GammaMed Plus HDR and the microSelectron PDR-v1 model. Measured absorbed doses to water in the PMMA phantommore » were converted to the corresponding absorbed doses to water in water phantoms of dimensions used by the treatment planning systems (TPSs) using correction factors explicitly derived for this experiment. Experimentally determined absorbed doses agreed with the absorbed doses to water calculated by the TPS to within {+-}2.9%. Relative standard uncertainties in the experimentally determined absorbed doses were estimated to be within the range of 1.7%-1.3% depending on the radial distance from the source, the type of source (HDR or PDR), and the particular absorbed doses used. This work shows that a lithium formate dosimetry system is well suited for measurements of absorbed dose to water around clinical HDR and PDR {sup 192}Ir sources. Being less energy dependent than the commonly used thermoluminescent lithium fluoride (LiF) dosimeters, lithium formate monohydrate dosimeters are well suited to measure absorbed doses in situations where the energy dependence cannot easily be accounted for such as in multiple-source irradiations to verify treatment plans. Their wide dynamic range and linear dose response over the dose interval of 0.2-1000 Gy make them suitable for measurements on sources of the strengths used in clinical applications. The dosimeter size needs, however, to be reduced for application to single-source dosimetry.« less

Dose-Related Effects of Alcohol on Cognitive Functioning

PubMed Central

Dry, Matthew J.; Burns, Nicholas R.; Nettelbeck, Ted; Farquharson, Aaron L.; White, Jason M.

2012-01-01

We assessed the suitability of six applied tests of cognitive functioning to provide a single marker for dose-related alcohol intoxication. Numerous studies have demonstrated that alcohol has a deleterious effect on specific areas of cognitive processing but few have compared the effects of alcohol across a wide range of different cognitive processes. Adult participants (N = 56, 32 males, 24 females aged 18–45 years) were randomized to control or alcohol treatments within a mixed design experiment involving multiple-dosages at approximately one hour intervals (attained mean blood alcohol concentrations (BACs) of 0.00, 0.048, 0.082 and 0.10%), employing a battery of six psychometric tests; the Useful Field of View test (UFOV; processing speed together with directed attention); the Self-Ordered Pointing Task (SOPT; working memory); Inspection Time (IT; speed of processing independent from motor responding); the Traveling Salesperson Problem (TSP; strategic optimization); the Sustained Attention to Response Task (SART; vigilance, response inhibition and psychomotor function); and the Trail-Making Test (TMT; cognitive flexibility and psychomotor function). Results demonstrated that impairment is not uniform across different domains of cognitive processing and that both the size of the alcohol effect and the magnitude of effect change across different dose levels are quantitatively different for different cognitive processes. Only IT met the criteria for a marker for wide-spread application: reliable dose-related decline in a basic process as a function of rising BAC level and easy to use non-invasive task properties. PMID:23209840

A Biomathematical Model of Lymphopoiesis and Its Application to Acute and Chronic Irradiation Assessment

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Cucinotta, Francis A.

2010-01-01

After the events of September 11, 2001, there is an increasing concern of the occurrence of radiological terrorism that may result in significant casualties in densely populated areas. Much effort has been made to establish various biomarkers to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios, which are demanded for effective medical management and treatment of the exposed victims. Among these the count of lymphocytes in peripheral blood and their depletion kinetics are the most important early indicators of the severity of the radiation injury. In this study, we examine a biomathematical model of lymphopoiesis which has been successfully utilized to simulate and interpret experimental data of acute and chronic irradiations on rodents [1]. With revised parameters for humans, we find this model can reproduce several sets of clinical lymphocyte data of accident victims over a wide range of absorbed doses. In addition, the absolute lymphocyte counts and the depletion rate constants calculated by this model also show good correlation with the Guskova formula and the Goans model, the two empirical tools which have been widely recognized for early estimation of the exposed dose after radiation accidents [2]. We also use the model to analyze the hematological data of the Techa River residents which were exposed to chronic low-dose irradiation during 1950-1956 [3]. This model can serve as a computational tool in radiation accident management, military operations involving nuclear warfare, radiation therapy, and space radiation risk assessment.

Methylphenidate produces selective enhancement of declarative memory consolidation in healthy volunteers.

PubMed

Linssen, A M W; Vuurman, E F P M; Sambeth, A; Riedel, W J

2012-06-01

Methylphenidate inhibits the reuptake of dopamine and noradrenaline and is used to treat children with attention deficit hyperactivity disorder (ADHD). Besides reducing behavioral symptoms, it improves their cognitive function. There are also observations of methylphenidate-induced cognition enhancement in healthy adults, although studies in this area are relatively sparse. We assessed the possible memory-enhancing properties of methylphenidate. In the current study, the possible enhancing effects of three doses of methylphenidate on declarative and working memory, attention, response inhibition and planning were investigated in healthy volunteers. In a double blind placebo-controlled crossover study, 19 healthy young male volunteers were tested after a single dose of placebo or 10, 20 or 40 mg of methylphenidate. Cognitive performance testing included a word learning test as a measure of declarative memory, a spatial working memory test, a set-shifting test, a stop signal test and a computerized version of the Tower of London planning test. Declarative memory consolidation was significantly improved relative to placebo after 20 and 40 mg of methylphenidate. Methylphenidate also improved set shifting and stopped signal task performance but did not affect spatial working memory or planning. To the best of our knowledge, this is the first study reporting enhanced declarative memory consolidation after methylphenidate in a dose-related fashion over a dose range that is presumed to reflect a wide range of dopamine reuptake inhibition.

Unenhanced 320-row multidetector computed tomography of the brain in children: comparison of image quality and radiation dose among wide-volume, one-shot volume, and helical scan modes.

PubMed

Jeon, Sun Kyung; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun; Cho, Yeon Jin; Ha, Ji Young; Lee, Seung Hyun; Hyun, Hyejin; Kim, In-One

2018-04-01

The 320-row multidetector computed tomography (CT) scanner has multiple scan modes, including volumetric modes. To compare the image quality and radiation dose of 320-row CT in three acquisition modes - helical, one-shot volume, and wide-volume scan - at pediatric brain imaging. Fifty-seven children underwent unenhanced brain CT using one of three scan modes (helical scan, n=21; one-shot volume scan, n=17; wide-volume scan, n=19). For qualitative analysis, two reviewers evaluated overall image quality and image noise using a 5-point grading system. For quantitative analysis, signal-to-noise ratio, image noise and posterior fossa artifact index were calculated. To measure the radiation dose, adjusted CT dose index per unit volume (CTDI adj ) and dose length product (DLP) were compared. Qualitatively, the wide-volume scan showed significantly less image noise than the helical scan (P=0.009), and less streak artifact than the one-shot volume scan (P=0.001). The helical mode showed significantly lower signal-to-noise ratio, with a higher image noise level compared with the one-shot volume and wide-volume modes (all P<0.05). The CTDI adj and DLP were significantly lower in the one-shot volume and wide-volume modes compared with those in the helical scan mode (all P<0.05). For pediatric unenhanced brain CT, both the wide-volume and one-shot volume scans reduced radiation dose compared to the helical scan mode, while the wide-volume scan mode showed fewer streak artifacts in the skull vertex and posterior fossa than the one-shot volume scan.

SU-F-T-85: Energy Modulated Electron Postmastectomy Unreconstructed (PU) Chest Wall (CW) Irradiation Technique to Achieve Heart Sparing

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

Hong, L; Ballangrud, A; Mechalakos, J

Purpose: For left-sided PU patients requiring CW and nodal irradiation, sometimes partial wide tangents (PWT) are not feasible due to abnormal chest wall contour or heart position close to the anterior chest wall or unusual wide excision scar. We developed an energy modulated electron chest wall irradiation technique that will achieve heart sparing. Methods: Ten left-sided PU patients were selected for this dosimetry study. If PWT were used, the amount of the ipsilateral lung would be ranged 3.4 to 4.4 cm, and the amount of heart would be ranged 1.3 to 3.8 cm. We used electron paired fields that matchedmore » on the skin to achieve dose conformity to the chest wall. The enface electron fields were designed at extended SSD from a single isocenter and gantry angle with different energy beams using different cutout. Lower energy was used in the central chest wall part and higher energy was used in the periphery of the chest wall. Bolus was used for the electron fields to ensure adequate skin dose coverage. The electron fields were matched to the photon supra-clavicle field in the superior region. Daily field junctions were used to feather the match lines between all the fields. Target volumes and normal tissues were drawn according to institutional protocols. Prescription dose was 2Gy per fraction for a total 50Gy. Dose calculations were done with Eclipse EMC-11031 for Electron and AAA-11031 for photons. Results: Six patients were planned using 6/9MeV, three using 9/12MeV and one 6/12MeV. Target volumes achieved adequate coverage. For heart, V30Gy, V20Gy and Mean Dose were 0.6%±0.6%, 2.7%±1.7%, and 3.0Gy±0.8Gy respectively. For ipsilateral lung, V50Gy, V20Gy, V10Gy and V5Gy were 0.9%±1.1%, 34.3%±5.1%, 51.6%±6.3% and 64.1%±7.5% respectively. Conclusion: For left-sided PU patients with unusual anatomy, energy modulated electron CW irradiation technique can achieve heart sparing with acceptable lung dose.« less

Dose accuracy and injection force dynamics of a novel disposable insulin pen.

PubMed

Clarke, Alastair; Spollett, Geralyn

2007-03-01

SoloStar (sanofi-aventis) is a new, disposable insulin pen for the administration of insulin glargine (Lantus, sanofi-aventis) or insulin glulisine (Apidra, sanofi-aventis). SoloStar was developed to address a wide range of patient needs and demonstrates advancement over previous devices, owing to its appropriate combination of ergonomically-tested and mechanically improved features. The authors report the results of key investigations carried out by sanofi-aventis as part of the SoloStar development plan, including dose accuracy and injection force testing. Comparisons between SoloStar and two commonly used pens, FlexPen (Novo Nordisk) and the Humulin/Humalog pen (Eli Lilly) establish SoloStar as a state of the art pen that is suitable for most patients with diabetes.

Morinda citrifolia Linn leaf extract possesses antioxidant activities and reduces nociceptive behavior and leukocyte migration.

PubMed

Serafini, Mairim Russo; Santos, Rodrigo Correia; Guimarães, Adriana Gibara; Dos Santos, João Paulo Almeida; da Conceicão Santos, Alan Diego; Alves, Izabel Almeida; Gelain, Daniel Pens; de Lima Nogueira, Paulo Cesar; Quintans-Júnior, Lucindo José; Bonjardim, Leonardo Rigoldi; de Souza Araújo, Adriano Antunes

2011-10-01

Herbal drugs have been used since ancient times to treat a wide range of diseases. Morinda citrifolia Linn (popularly known as "Noni") has been used in folk medicine by Polynesians for over 2,000 years. It is reported to have a broad range of therapeutic effects, including effects against headache, fever, arthritis, gingivitis, respiratory disorders, infections, tuberculosis, and diabetes. The aim of this study was to investigate the antioxidant, anti-inflammatory, antinociceptive, and antibacterial properties of the aqueous extract from M. citrifolia leaves (AEMC). Antioxidant activity was observed against lipid peroxidation, nitric oxide, and hydroxyl radicals. The antinociceptive effect of AEMC was observed in the acetic acid-induced writhing test at the higher dose. Moreover, AEMC significantly reduced the leukocyte migration in doses of 200 and 400 mg/kg and showed mild antibacterial activity. Together, the results suggest that properties of M. citrifolia leaf extract should be explored further in order to achieve newer tools for managing painful and inflammation conditions, including those related to oxidant states.

Temperature effect on radiation induced reactions in ethylene and tetrafluoroethylene copolymer (ETFE)

NASA Astrophysics Data System (ADS)

Oshima, Akihiro; Ikeda, Shigetoshi; Seguchi, Tadao; Tabata, Yoneho

1997-11-01

Ethylene and tetrafluoroethylene copolymer (ETFE) was irradiated by γ-rays or electron beam (EB) under oxygen-free atmosphere at various temperatures ranging from 77 to 573 K. Mechanical and thermal properties, and absorption spectra of the irradiated ETFEs were measured. The mechanical properties of the film have been observed to change by irradiation. The modulus and yield strength increase with increasing dose, and these phenomena are clearly distinguished above the melting temperature of ETFE (533 K). Heat of crystallization changes drastically as a function of irradiation dose around the melting temperature, compared with other temperatures. The absorption band around 250 nm of irradiated ETFE shifts to a longer wavelength region with increase of irradiation temperature. Therefore, it was concluded from those experimental results mentioned above that crosslinking takes place and conjugated double bonds formation proceeds in a wide range of irradiation temperatures. Those reactions are enhanced by increasing temperature. The homogeneous crosslinking takes place in the molten state, while the heterogeneous crosslinking does in the crystalline solid state.

Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate.

PubMed

Batzloff, Michael R; Fane, Anne; Gorton, Davina; Pandey, Manisha; Rivera-Hernandez, Tania; Calcutt, Ainslie; Yeung, Grace; Hartas, Jon; Johnson, Linda; Rush, Catherine M; McCarthy, James; Ketheesan, Natkunam; Good, Michael F

2016-12-01

Streptococcus pyogenes (group A streptococcus, GAS) causes a wide range of clinical manifestations ranging from mild self-limiting pyoderma to invasive diseases such as sepsis. Also of concern are the post-infectious immune-mediated diseases including rheumatic heart disease. The development of a vaccine against GAS would have a large health impact on populations at risk of these diseases. However, there is a lack of suitable models for the safety evaluation of vaccines with respect to post-infectious complications. We have utilized the Lewis Rat model for cardiac valvulitis to evaluate the safety of the J8-DT vaccine formulation in parallel with a rabbit toxicology study. These studies demonstrated that the vaccine did not induce abnormal pathology. We also show that in mice the vaccine is highly immunogenic but that 3 doses are required to induce protection from a GAS skin challenge even though 2 doses are sufficient to induce a high antibody titer.

Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate

PubMed Central

Batzloff, Michael R.; Fane, Anne; Gorton, Davina; Pandey, Manisha; Rivera-Hernandez, Tania; Calcutt, Ainslie; Yeung, Grace; Hartas, Jon; Johnson, Linda; Rush, Catherine M.; McCarthy, James; Ketheesan, Natkunam; Good, Michael F.

2016-01-01

ABSTRACT Streptococcus pyogenes (group A streptococcus, GAS) causes a wide range of clinical manifestations ranging from mild self-limiting pyoderma to invasive diseases such as sepsis. Also of concern are the post-infectious immune-mediated diseases including rheumatic heart disease. The development of a vaccine against GAS would have a large health impact on populations at risk of these diseases. However, there is a lack of suitable models for the safety evaluation of vaccines with respect to post-infectious complications. We have utilized the Lewis Rat model for cardiac valvulitis to evaluate the safety of the J8-DT vaccine formulation in parallel with a rabbit toxicology study. These studies demonstrated that the vaccine did not induce abnormal pathology. We also show that in mice the vaccine is highly immunogenic but that 3 doses are required to induce protection from a GAS skin challenge even though 2 doses are sufficient to induce a high antibody titer. PMID:27541593

Economics of food irradiation

NASA Astrophysics Data System (ADS)

Kunstadt, Peter; Eng, P.; Steeves, Colyn; Beaulieu, Daniel; Eng, P.

1993-07-01

The number of products being radiation processed worldwide is constantly increasing and today includes such diverse items as medical disposables, fruits and vegetables, spices, meats, seafoods and waste products. This range of products to be processed has resulted in a wide range of irradiator designs and capital and operating cost requirements. This paper discusses the economics of low dose food irradiation applications and the effects of various parameters on unit processing costs. It provides a model for calculating specific unit processing costs by correlating known capital costs with annual operating costs and annual throughputs. It is intended to provide the reader with a general knowledge of how unit processing costs are derived.

Unidirectional x-ray microbeam radiosurgery of infantile neuraxial malignancies: estimations of tolerable valley doses

NASA Astrophysics Data System (ADS)

Hanson, A. L.; Slatkin, D. N.; Laissue, J. A.

2013-03-01

Hindbrains of sedated, prone, suckling rats were irradiated 11-13 days postpartum horizontally from the left with an array of upright wiggler-generated synchrotron X-ray microbeams spaced either 105 or 210 μm apart. The microbeams were in an array of 48 (for the 205 μm interval) or of 96 (for the 105 μm interval), with microbeam widths ranging from 19 to 39 μm, the array having an approximately 1-cm-square cross section. The microbeams imparted doses of either ≍50 or ≍150 Gy to the inner skin (computed here as the average dose 0.5-1.5 mm deep to the surface of our phantom) at their entrance to the head, where their median energy was ≍120 keV. The array traversed the postero-superior quadrant of the phantom, which represented the occiput of the head, so that about one in five photons in the array bypassed the head altogether. The resultant radiation doses to the head were simulated by computing the tracks of thirty billion X-ray photons incident on the multislit collimator along with all >=1 keV secondary electrons from interactions in water of the photons entering the left circular wall of the 1.00 cm-radius, 1.55 cm-wide (i.e., "15.5 mm-long") cylindrical head phantom. The computations were performed using the Los Alamos National Laboratory Monte Carlo radiation transport computer program MCNPX, yielding ionization energies imparted to approximately twenty-four thousand 1.00 mmdeep, 10 μm-wide, up to 3.33 mm-high voxels distributed throughout one quadrant of the phantom, each representing up to 33.3 μg water. Computed nadir doses between microbeams were defined as the average of the three lowest doses between horizontally adjacent peak doses. We notice that nadir interbeam doses under 5 Gy were associated with neurologically minor and/or inconsequential sequelae fifteen months after irradiation and thus postulate that unidirectional microbeam radiosurgery using hindbrain nadir doses under 5 Gy may safely ameliorate the symptoms of some presently intractable human infantile neuraxial malignancies.

Thromboelastography Utilization in Delayed Recurrent Coagulopathy after Severe Eastern Diamondback Rattlesnake Envenomation.

PubMed

McBride, Katherine M; Bromberg, William; Dunne, James

2017-04-01

Venomous snakebites are fairly common in the United States and can present with a wide range of symptoms. A 48-year-old man presented after Eastern Diamondback rattlesnake envenomation. His hospital course was complicated by right leg compartment syndrome and delayed recurrent coagulopathy, requiring multiple doses of Crotalidae Polyvalent Immune Fab (CroFab) antivenom and transfusions. Thromboelastography was used as an adjunct to standard coagulation studies in monitoring his delayed recurrent coagulopathy.

Simplified fast neutron dosimeter

DOEpatents

Sohrabi, Mehdi

1979-01-01

Direct fast-neutron-induced recoil and alpha particle tracks in polycarbonate films may be enlarged for direct visual observation and automated counting procedures employing electrochemical etching techniques. Electrochemical etching is, for example, carried out in a 28% KOH solution at room temperature by applying a 2000 V peak-to-peak voltage at 1 kHz frequency. Such recoil particle amplification can be used for the detection of wide neutron dose ranges from 1 mrad. to 1000 rads. or higher, if desired.

Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models.

PubMed

Penny, Melissa A; Verity, Robert; Bever, Caitlin A; Sauboin, Christophe; Galactionova, Katya; Flasche, Stefan; White, Michael T; Wenger, Edward A; Van de Velde, Nicolas; Pemberton-Ross, Peter; Griffin, Jamie T; Smith, Thomas A; Eckhoff, Philip A; Muhib, Farzana; Jit, Mark; Ghani, Azra C

2016-01-23

The phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings. We compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5-17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2-10 year olds (PfPR2-10; range 3-65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2-10 per dose. In regions with a PfPR2-10 of 10-65%, RTS,S/AS01 is predicted to avert a median of 93,940 (range 20,490-126,540) clinical cases and 394 (127-708) deaths for the three-dose schedule, or 116,480 (31,450-160,410) clinical cases and 484 (189-859) deaths for the four-dose schedule, per 100,000 fully vaccinated children. A positive impact is also predicted at a PfPR2-10 of 5-10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2-10 of 10-65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18-211) per clinical case averted and $80 (44-279) per DALY averted for the three-dose schedule, and of $25 (16-222) and $87 (48-244), respectively, for the four-dose schedule. Higher ICERs were estimated at low PfPR2-10 levels. We predict a significant public health impact and high cost-effectiveness of the RTS,S/AS01 vaccine across a wide range of settings. Decisions about implementation will need to consider levels of malaria burden, the cost-effectiveness and coverage of other malaria interventions, health priorities, financing, and the capacity of the health system to deliver the vaccine. PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO. Copyright © 2016 Penny et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models

PubMed Central

Penny, Melissa A; Verity, Robert; Bever, Caitlin A; Sauboin, Christophe; Galactionova, Katya; Flasche, Stefan; White, Michael T; Wenger, Edward A; Van de Velde, Nicolas; Pemberton-Ross, Peter; Griffin, Jamie T; Smith, Thomas A; Eckhoff, Philip A; Muhib, Farzana; Jit, Mark; Ghani, Azra C

2016-01-01

Summary Background The phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings. Methods We compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5–17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2–10 year olds (PfPR2–10; range 3–65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2–10 per dose. Findings In regions with a PfPR2–10 of 10–65%, RTS,S/AS01 is predicted to avert a median of 93 940 (range 20 490–126 540) clinical cases and 394 (127–708) deaths for the three-dose schedule, or 116 480 (31 450–160 410) clinical cases and 484 (189–859) deaths for the four-dose schedule, per 100 000 fully vaccinated children. A positive impact is also predicted at a PfPR2–10 of 5–10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2–10 of 10–65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18–211) per clinical case averted and $80 (44–279) per DALY averted for the three-dose schedule, and of $25 (16–222) and $87 (48–244), respectively, for the four-dose schedule. Higher ICERs were estimated at low PfPR2–10 levels. Interpretation We predict a significant public health impact and high cost-effectiveness of the RTS,S/AS01 vaccine across a wide range of settings. Decisions about implementation will need to consider levels of malaria burden, the cost-effectiveness and coverage of other malaria interventions, health priorities, financing, and the capacity of the health system to deliver the vaccine. Funding PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO. PMID:26549466

Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole

PubMed Central

Buschini, Annamaria; Ferrarini, Lisa; Franzoni, Susanna; Galati, Serena; Lazzaretti, Mirca; Mussi, Francesca; Northfleet de Albuquerque, Cristina; Maria Araújo Domingues Zucchi, Tânia; Poli, Paola

2009-01-01

Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells. PMID:20981287

Genotoxicity revaluation of three commercial nitroheterocyclic drugs: nifurtimox, benznidazole, and metronidazole.

PubMed

Buschini, Annamaria; Ferrarini, Lisa; Franzoni, Susanna; Galati, Serena; Lazzaretti, Mirca; Mussi, Francesca; Northfleet de Albuquerque, Cristina; Maria Araújo Domingues Zucchi, Tânia; Poli, Paola

2009-01-01

Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells.

Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers.

PubMed

Smit, H J; Rogers, P J

2000-10-01

Caffeine is present in many widely consumed drinks and some foods. In the fairly extensive literature on the psychostimulant effects of caffeine, there are few dose-response studies and even fewer studies of the effects of doses of caffeine lower than 50 mg (the range of the amounts of caffeine contained in, for example, a typical serving of tea or cola). This study measured the effects of 0, 12.5, 25, 50 and 100 mg caffeine on cognitive performance, mood and thirst in adults with low and moderate to high habitual caffeine intakes. This was a double-blind, within-subjects study. Following overnight caffeine abstinence, participants (n=23) completed a test battery once before and three times after placebo or caffeine administration. The test battery consisted of two performance tests, a long duration simple reaction time task and a rapid visual information processing task, and a mood questionnaire (including also an item on thirst). Effects on performance and mood confirmed a psychostimulant action of caffeine. All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat. The effects on performance were more marked in individuals with a higher level of habitual caffeine intake, whereas caffeine increased thirst only in low caffeine consumers. After overnight caffeine abstinence, caffeine can significantly affect cognitive performance, mood and thirst at doses within and even lower than the range of amounts of caffeine contained in a single serving of popular caffeine-containing drinks. Regular caffeine consumers appear to show substantial tolerance to the thirst-increasing but not to the performance and mood effects of caffeine.

The effects of two different doses of hydrocortisone on cognition in patients with secondary adrenal insufficiency--results from a randomized controlled trial.

PubMed

Werumeus Buning, Jorien; Brummelman, Pauline; Koerts, Janneke; Dullaart, Robin P F; van den Berg, Gerrit; van der Klauw, Melanie M; Tucha, Oliver; Wolffenbuttel, Bruce H R; van Beek, André P

2015-05-01

A wide variety in hydrocortisone (HC) substitution dose-regimens are considered physiological for patients with secondary adrenal insufficiency (SAI). However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. To examine the effects of a high physiological HC dose in comparison to a low physiological HC dose on cognition. This study was a randomized double blind cross-over study at the University Medical Center Groningen. This study is registered with ClinicalTrials.gov, number NCT01546922. Forty-seven patients (29 males, 18 females; mean [SD] age, 51 [14] years, range 19-73) with SAI participated. Patients randomly received first a low dose of HC (0.2-0.3 mg/kg body weight/day) during 10 weeks followed by a high dose (0.4-0.6 mg/kg body weight/day) for another 10 weeks, or vice versa. HC substitution was given in three divided doses with the highest dose in the morning. Cognitive performance (memory, attention, executive functioning and social cognition) of patients was measured at baseline and after each treatment period using a battery of 12 standardized cognitive tests. The higher dose of HC resulted in significantly higher systemic cortisol exposure for example measured at 1h after first dose ingestion (mean [SD], low dose: 653 [281] nmol/L; high dose: 930 [148] nmol/L; P<0.001). No differences in cognitive performance were found between the two dose regimens. No negative influence on memory, attention, executive functioning and social cognition was observed after 10 weeks of treatment with a higher physiological dose of HC in patients with SAI when compared to a lower dose. Copyright © 2015 Elsevier Ltd. All rights reserved.

A generic biokinetic model for carbon-14 labelled compounds

NASA Astrophysics Data System (ADS)

Manger, Ryan Paul

Carbon-14, a radioactive nuclide, is used in many industrial applications. Due to its wide range of uses in industry, many workers are at risk of accidental internal exposure to 14C. Being a low energy beta emitter, 14C is not a significant external radiation hazard, but the internal consequences posed by 14C are important, especially because of its long half life of 5730 years [46]. The current biokinetic model recommended by the International Commission on Radiological Protection (ICRP) is a conservative estimate of how radiocarbon is treated by the human body. The ICRP generic radiocarbon model consists of a single compartment representing the entire human body. This compartment has a biological half life of 40 days yielding an effective dose coefficient of 5.8x10-10 Sv B q-1 [44, 45, 49, 53, 54]. This overestimates the dose of all radiocarbon compounds that have been studied [96]. An improved model has been developed that includes and alimentary tract, a urinary bladder, CO2 model, and an "Other" compartment used to model systemic tissues. The model can be adapted to replicate any excretion curve and excretion pattern. In addition, the effective dose coefficient produced by the updated model is near the mean effective dose coefficient of carbon compounds that have been considered in this research. The major areas of improvement are: more anatomically significant, a less conservative dose coefficient, and the ability to manipulate the model for known excretion data. Due to the wide variety of carbon compounds, it is suggested that specific biokinetic models be implemented for known radiocarbon substances. If the source of radiocarbon is dietary, then the physiologically based model proposed by Whillans [102] that splits all ingested radiocarbon compounds into carbohydrates, fats, and proteins should be used.

Benefit-harm analysis and charts for individualized and preference-sensitive prevention: example of low dose aspirin for primary prevention of cardiovascular disease and cancer.

PubMed

Puhan, Milo A; Yu, Tsung; Stegeman, Inge; Varadhan, Ravi; Singh, Sonal; Boyd, Cynthia M

2015-10-01

Clinical practice guidelines provide separate recommendations for different diseases that may be prevented or treated by the same intervention. Also, they commonly provide recommendations for entire populations but not for individuals. To address these two limitations, our aim was to conduct benefit-harm analyses for a wide range of individuals using the example of low dose aspirin for primary prevention of cardiovascular disease and cancer and to develop Benefit-Harm Charts that show the overall benefit-harm balance for individuals. We used quantitative benefit-harm modeling that included 16 outcomes to estimate the probability that low dose aspirin provides more benefits than harms for a wide range of men and women between 45 and 84 years of age and without a previous myocardial infarction, severe ischemic stroke, or cancer. We repeated the quantitative benefit-harm modeling for different combinations of age, sex, and outcome risks for severe ischemic and hemorrhagic stroke, myocardial infarction, cancers, and severe gastrointestinal bleeds. The analyses considered weights for the outcomes, statistical uncertainty of the effects of aspirin, and death as a competing risk. We constructed Benefit-Harm Charts that show the benefit-harm balance for different combinations of outcome risks. The Benefit-Harm Charts ( http://www.benefit-harm-balance.com ) we have created show that the benefit-harm balance differs largely across a primary prevention population. Low dose aspirin is likely to provide more benefits than harms in men, elderly people, and in those at low risk for severe gastrointestinal bleeds. Individual preferences have a major impact on the benefit-harm balance. If, for example, it is a high priority for individuals to prevent stroke and severe cancers while severe gastrointestinal bleeds are deemed to be of little importance, the benefit-harm balance is likely to favor low dose aspirin for most individuals. Instead, if severe gastrointestinal bleeds are judged to be similarly important compared to the benefit outcomes, low dose aspirin is unlikely to provide more benefits than harms. Benefit-Harm Charts support individualized benefit-harm assessments and decision making. Similarly, individualized benefit-harm assessments may allow guideline developers to issue more finely granulated recommendations that reduce the risk of over- and underuse of interventions. The example of low dose aspirin for primary prevention of cardiovascular disease and cancer shows that it may be time for guideline developers to provide combined recommendations for different diseases that may be prevented or treated by the same intervention.

Insights into the mechanism of X-ray-induced disulfide-bond cleavage in lysozyme crystals based on EPR, optical absorption and X-ray diffraction studies.

PubMed

Sutton, Kristin A; Black, Paul J; Mercer, Kermit R; Garman, Elspeth F; Owen, Robin L; Snell, Edward H; Bernhard, William A

2013-12-01

Electron paramagnetic resonance (EPR) and online UV-visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage. Online UV-visible spectroscopy showed that upon X-irradiation, disulfide radicalization appeared to saturate at an absorbed dose of approximately 0.5-0.8 MGy, in contrast to the saturating dose of ∼0.2 MGy observed using EPR at much lower dose rates. The observations suggest that a multi-track model involving product formation owing to the interaction of two separate tracks is a valid model for radiation damage in protein crystals. The saturation levels are remarkably consistent given the widely different experimental parameters and the range of total absorbed doses studied. The results indicate that even at the lowest doses used for structural investigations disulfide bonds are already radicalized. Multi-track considerations offer the first step in a comprehensive model of radiation damage that could potentially lead to a combined computational and experimental approach to identifying when damage is likely to be present, to quantitate it and to provide the ability to recover the native unperturbed structure.

Dosimetric characteristics of fabricated silica fibre for postal radiotherapy dose audits

NASA Astrophysics Data System (ADS)

Fadzil, M. S. Ahmad; Ramli, N. N. H.; Jusoh, M. A.; Kadni, T.; Bradley, D. A.; Ung, N. M.; Suhairul, H.; Mohd Noor, N.

2014-11-01

Present investigation aims to establish the dosimetric characteristics of a novel fabricated flat fibre TLD system for postal radiotherapy dose audits. Various thermoluminescence (TL) properties have been investigated for five sizes of 6 mol% Ge-doped optical fibres. Key dosimetric characteristics including reproducibility, linearity, fading and energy dependence have been established. Irradiations were carried out using a linear accelerator (linac) and a Cobalt-60 machine. For doses from 0.5 Gy up to 10 Gy, Ge-doped flat fibres exhibit linearity between TL yield and dose, reproducible to better than 8% standard deviation (SD) following repeat measurements (n = 3). For photons generated at potentials from 1.25 MeV to 10 MV an energy-dependent response is noted, with a coefficient of variation (CV) of less than 40% over the range of energies investigated. For 6.0 mm length flat fibres 100 μm thick × 350 pm wide, the TL fading loss following 30 days of storage at room temperature was < 8%. The Ge-doped flat fibre system represents a viable basis for use in postal radiotherapy dose audits, corrections being made for the various factors influencing the TL yield.

Development of phantom and methodology for 3D and 4D dose intercomparisons for advanced lung radiotherapy

NASA Astrophysics Data System (ADS)

Caloz, Misael; Kafrouni, Marilyne; Leturgie, Quentin; Corde, Stéphanie; Downes, Simon; Lehmann, Joerg; Thwaites, David

2015-01-01

There are few reported intercomparisons or audits of combinations of advanced radiotherapy methods, particularly for 4D treatments. As part of an evaluation of the implementation of advanced radiotherapy technology, a phantom and associated methods, initially developed for in-house commissioning and QA of 4D lung treatments, has been developed further with the aim of using it for end-to-end dose intercomparison of 4D treatment planning and delivery. The respiratory thorax phantom can house moving inserts with variable speed (breathing rate) and motion amplitude. In one set-up mode it contains a small ion chamber for point dose measurements, or alternatively it can hold strips of radiochromic film to measure dose distributions. Initial pilot and feasibility measurements have been carried out in one hospital to thoroughly test the methods and procedures before using it more widely across a range of hospitals and treatment systems. Overall, the results show good agreement between measured and calculated doses and distributions, supporting the use of the phantom and methodology for multi-centre intercomparisons. However, before wider use, refinements of the method and analysis are currently underway particularly for the film measurements.

Shared Dosimetry Error in Epidemiological Dose-Response Analyses

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

Stram, Daniel O.; Preston, Dale L.; Sokolnikov, Mikhail

2015-03-23

Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takesmore » up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. Use of these methods for several studies, including the Mayak Worker Cohort and the U.S. Atomic Veterans Study, is discussed.« less

Development of a Bayesian response-adaptive trial design for the Dexamethasone for Excessive Menstruation study.

PubMed

Holm Hansen, Christian; Warner, Pamela; Parker, Richard A; Walker, Brian R; Critchley, Hilary Od; Weir, Christopher J

2017-12-01

It is often unclear what specific adaptive trial design features lead to an efficient design which is also feasible to implement. This article describes the preparatory simulation study for a Bayesian response-adaptive dose-finding trial design. Dexamethasone for Excessive Menstruation aims to assess the efficacy of Dexamethasone in reducing excessive menstrual bleeding and to determine the best dose for further study. To maximise learning about the dose response, patients receive placebo or an active dose with randomisation probabilities adapting based on evidence from patients already recruited. The dose-response relationship is estimated using a flexible Bayesian Normal Dynamic Linear Model. Several competing design options were considered including: number of doses, proportion assigned to placebo, adaptation criterion, and number and timing of adaptations. We performed a fractional factorial study using SAS software to simulate virtual trial data for candidate adaptive designs under a variety of scenarios and to invoke WinBUGS for Bayesian model estimation. We analysed the simulated trial results using Normal linear models to estimate the effects of each design feature on empirical type I error and statistical power. Our readily-implemented approach using widely available statistical software identified a final design which performed robustly across a range of potential trial scenarios.

Range Verification Methods in Particle Therapy: Underlying Physics and Monte Carlo Modeling

PubMed Central

Kraan, Aafke Christine

2015-01-01

Hadron therapy allows for highly conformal dose distributions and better sparing of organs-at-risk, thanks to the characteristic dose deposition as function of depth. However, the quality of hadron therapy treatments is closely connected with the ability to predict and achieve a given beam range in the patient. Currently, uncertainties in particle range lead to the employment of safety margins, at the expense of treatment quality. Much research in particle therapy is therefore aimed at developing methods to verify the particle range in patients. Non-invasive in vivo monitoring of the particle range can be performed by detecting secondary radiation, emitted from the patient as a result of nuclear interactions of charged hadrons with tissue, including β+ emitters, prompt photons, and charged fragments. The correctness of the dose delivery can be verified by comparing measured and pre-calculated distributions of the secondary particles. The reliability of Monte Carlo (MC) predictions is a key issue. Correctly modeling the production of secondaries is a non-trivial task, because it involves nuclear physics interactions at energies, where no rigorous theories exist to describe them. The goal of this review is to provide a comprehensive overview of various aspects in modeling the physics processes for range verification with secondary particles produced in proton, carbon, and heavier ion irradiation. We discuss electromagnetic and nuclear interactions of charged hadrons in matter, which is followed by a summary of some widely used MC codes in hadron therapy. Then, we describe selected examples of how these codes have been validated and used in three range verification techniques: PET, prompt gamma, and charged particle detection. We include research studies and clinically applied methods. For each of the techniques, we point out advantages and disadvantages, as well as clinical challenges still to be addressed, focusing on MC simulation aspects. PMID:26217586

Accounting for neutron exposure in the Japanese atomic bomb survivors.

PubMed

Cullings, Harry M; Pierce, Donald A; Kellerer, Albrecht M

2014-12-01

The Japanese atomic bomb survivors that were directly exposed to both γ rays and neutrons have been followed by the Radiation Effects Research Foundation (RERF). The estimation of the γ-ray risks requires some adjustment for the greater biological effect of the neutrons per unit dose. Because the small neutron doses and the predominant γ-ray doses are highly correlated, the neutron relative biological effectiveness (RBE) cannot be reliably estimated from the survivors' data and information from radiobiology must be invoked. As data became available on neutron doses, RERF has used a constant neutron RBE value of 10, even though radiobiological studies indicate that the RBE values appear to have considerably larger values at low doses. The approximation RBE = 10 assumes that if the RBE is variable it takes roughly this value in the range of total dose most relevant for linear risk estimation, namely about 1 Gy. We consider some possible RBE functions to explain the correct use and the impact of a dose-dependent RBE. However, we do not advocate any particular choice or even that a variable RBE be employed. Rather we show that the assumed neutron RBE, within a wide range of choices, is far less important to the outcome of risk assessment of the RERF data than generally believed. Some of these misperceptions have been related to the consideration of variable RBE functions, and without due attention to the fact that in the case of the A-bomb survivors' data, the mixed field of neutrons and γ rays must be considered. Therefore, the RBE value of neutrons is much lower than the RBE in pure neutron fields that are used in radiobiological experiments. Thus, applying the pure neutron field RBE to the mixed-field A-bomb radiation can lead to an overestimation of the actual neutron RBE for moderate total dose levels of 1 Gy by a factor of more than four. While in a pure neutron exposure the RBE depends on the neutron dose, in the mixed field it depends on both components of exposure, and in particular, we show that in the RERF setting the RBE depends mainly on the accompanying γ-ray dose.

MO-E-17A-08: Attenuation-Based Size Adjusted, Scanner-Independent Organ Dose Estimates for Head CT Exams: TG 204 for Head CT

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

McMillan, K; Bostani, M; Cagnon, C

Purpose: AAPM Task Group 204 described size specific dose estimates (SSDE) for body scans. The purpose of this work is to use a similar approach to develop patient-specific, scanner-independent organ dose estimates for head CT exams using an attenuation-based size metric. Methods: For eight patient models from the GSF family of voxelized phantoms, dose to brain and lens of the eye was estimated using Monte Carlo simulations of contiguous axial scans for 64-slice MDCT scanners from four major manufacturers. Organ doses were normalized by scannerspecific 16 cm CTDIvol values and averaged across all scanners to obtain scanner-independent CTDIvol-to-organ-dose conversion coefficientsmore » for each patient model. Head size was measured at the first slice superior to the eyes; patient perimeter and effective diameter (ED) were measured directly from the GSF data. Because the GSF models use organ identification codes instead of Hounsfield units, water equivalent diameter (WED) was estimated indirectly. Using the image data from 42 patients ranging from 2 weeks old to adult, the perimeter, ED and WED size metrics were obtained and correlations between each metric were established. Applying these correlations to the GSF perimeter and ED measurements, WED was calculated for each model. The relationship between the various patient size metrics and CTDIvol-to-organ-dose conversion coefficients was then described. Results: The analysis of patient images demonstrated the correlation between WED and ED across a wide range of patient sizes. When applied to the GSF patient models, an exponential relationship between CTDIvol-to-organ-dose conversion coefficients and the WED size metric was observed with correlation coefficients of 0.93 and 0.77 for the brain and lens of the eye, respectively. Conclusion: Strong correlation exists between CTDIvol normalized brain dose and WED. For the lens of the eye, a lower correlation is observed, primarily due to surface dose variations. Funding Support: Siemens-UCLA Radiology Master Research Agreement; Disclosures - Michael McNitt-Gray: Institutional Research Agreement, Siemens AG; Research Support, Siemens AG; Consultant, Flaherty Sensabaugh Bonasso PLLC; Consultant, Fulbright and Jaworski.« less

Introducing iron isomaltoside 1000 (Monofer®)-development rationale and clinical experience.

PubMed

Kalra, Philip A

2011-06-01

Patients with chronic kidney disease (CKD) often suffer from iron deficiency anaemia necessitating treatment with intravenous (IV) iron. Several studies demonstrate that oral iron is insufficient in these patients and that IV supplementation is a more effective treatment. Until now, use of available parenteral iron preparations has been limited by dosing schedules and the need, in some cases, for a test dose, and despite the availability of a range of different IV iron compounds, there is still a need for improved compounds. The new IV iron, iron isomaltoside 1000 Monofer®, is composed of iron and chemically modified isomalto-oligosaccharides which have a mean molecular weight of 1000 Da and consist predominantly of 3-5 glucose units. In contrast to dextrans, the carbohydrate isomaltoside 1000 is a linear and unbranched structure with theoretically a low immunological potential. Hence, a test dose is not necessary. Iron isomaltoside 1000 contains strongly bound iron within the iron-isomaltoside formulation, which enables a controlled slow release of bioavailable iron to the iron-binding proteins, with potentially a reduced risk of free iron toxicity. This allows flexible dosing including high and rapid dosing securing convenient iron therapy for a wide range of patients. The development of Monofer® has been enthusiastically acknowledged by clinicians, and in 2009, there has been fast approval by European authorities via a decentralized registration procedure. This new IV iron is currently being marketed in several European countries. This article describes the development rationale and summarizes the clinical data assessing the use of iron isomaltoside 1000 administered without a test dose by either repeated bolus injections or fast high single iron infusions [defined as total dose infusion (TDI)] to patients suffering from CKD. Since CKD is associated with a high prevalence of cardiovascular disease, data from a small trial applying high single doses of iron isomatoside 1000 in patients with chronic heart failure (CHF) are also reviewed. Collectively, the available data demonstrate adequate efficacy and a good safety profile of iron isomaltoside 1000 in CKD and CHF patients even when administered without a test dose and as single rapid high-dose infusions.

SU-F-18C-01: Minimum Detectability Analysis for Comprehensive Sized Based Optimization of Image Quality and Radiation Dose Across CT Protocols

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

Smitherman, C; Chen, B; Samei, E

2014-06-15

Purpose: This work involved a comprehensive modeling of task-based performance of CT across a wide range of protocols. The approach was used for optimization and consistency of dose and image quality within a large multi-vendor clinical facility. Methods: 150 adult protocols from the Duke University Medical Center were grouped into sub-protocols with similar acquisition characteristics. A size based image quality phantom (Duke Mercury Phantom) was imaged using these sub-protocols for a range of clinically relevant doses on two CT manufacturer platforms (Siemens, GE). The images were analyzed to extract task-based image quality metrics such as the Task Transfer Function (TTF),more » Noise Power Spectrum, and Az based on designer nodule task functions. The data were analyzed in terms of the detectability of a lesion size/contrast as a function of dose, patient size, and protocol. A graphical user interface (GUI) was developed to predict image quality and dose to achieve a minimum level of detectability. Results: Image quality trends with variations in dose, patient size, and lesion contrast/size were evaluated and calculated data behaved as predicted. The GUI proved effective to predict the Az values representing radiologist confidence for a targeted lesion, patient size, and dose. As an example, an abdomen pelvis exam for the GE scanner, with a task size/contrast of 5-mm/50-HU, and an Az of 0.9 requires a dose of 4.0, 8.9, and 16.9 mGy for patient diameters of 25, 30, and 35 cm, respectively. For a constant patient diameter of 30 cm, the minimum detected lesion size at those dose levels would be 8.4, 5, and 3.9 mm, respectively. Conclusion: The designed CT protocol optimization platform can be used to evaluate minimum detectability across dose levels and patient diameters. The method can be used to improve individual protocols as well as to improve protocol consistency across CT scanners.« less

Proton therapy treatment monitoring with the DoPET system: activity range, positron emitters evaluation and comparison with Monte Carlo predictions

NASA Astrophysics Data System (ADS)

Muraro, S.; Battistoni, G.; Belcari, N.; Bisogni, M. G.; Camarlinghi, N.; Cristoforetti, L.; Del Guerra, A.; Ferrari, A.; Fracchiolla, F.; Morrocchi, M.; Righetto, R.; Sala, P.; Schwarz, M.; Sportelli, G.; Topi, A.; Rosso, V.

2017-12-01

Ion beam irradiations can deliver conformal dose distributions minimizing damage to healthy tissues thanks to their characteristic dose profiles. Nevertheless, the location of the Bragg peak can be affected by different sources of range uncertainties: a critical issue is the treatment verification. During the treatment delivery, nuclear interactions between the ions and the irradiated tissues generate β+ emitters: the detection of this activity signal can be used to perform the treatment monitoring if an expected activity distribution is available for comparison. Monte Carlo (MC) codes are widely used in the particle therapy community to evaluate the radiation transport and interaction with matter. In this work, FLUKA MC code was used to simulate the experimental conditions of irradiations performed at the Proton Therapy Center in Trento (IT). Several mono-energetic pencil beams were delivered on phantoms mimicking human tissues. The activity signals were acquired with a PET system (DoPET) based on two planar heads, and designed to be installed along the beam line to acquire data also during the irradiation. Different acquisitions are analyzed and compared with the MC predictions, with a special focus on validating the PET detectors response for activity range verification.

Selective Control of Eurasian Watermilfoil and Curlyleaf Pondweed Using Low Doses of Endothall Combined With 2,4-D

DTIC Science & Technology

2006-10-01

a wide range of aquatic plants, including monocotyledons (monocots) and dicotyledons (dicots) ( Westerdahl and Getsinger 1988, Madsen 1997a). This...watermilfoil using 2,4-D has been reported (Elliston and Steward 1972, Lim and Lozoway 1976, Hoeppel and Westerdahl 1983); however good control of that plant...was achieved when 2,4-D exposure times exceeded 24 hr (Green and Westerdahl 1990). Because 2,4-D is specific to dicots, it can frequently be used

Dose-equivalent neutron dosimeter

DOEpatents

Griffith, R.V.; Hankins, D.E.; Tomasino, L.; Gomaa, M.A.M.

1981-01-07

A neutron dosimeter is disclosed which provides a single measurement indicating the amount of potential biological damage resulting from the neutron exposure of the wearer, for a wide range of neutron energies. The dosimeter includes a detecting sheet of track etch detecting material such as a carbonate plastic, for detecting higher energy neutrons, and a radiator layer contaning conversion material such as /sup 6/Li and /sup 10/B lying adjacent to the detecting sheet for converting moderate energy neutrons to alpha particles that produce tracks in the adjacent detecting sheet.

Thermoluminescence dosimetry and its applications in medicine--Part 2: History and applications.

PubMed

Kron, T

1995-03-01

Thermoluminescence dosimetry (TLD) has been available for dosimetry of ionising radiation for nearly 100 years. The variety of materials and their different physical forms allow the determination of different radiation qualities over a wide range of absorbed dose. This makes TL dosimeters useful in radiation protection where dose levels of microGy are monitored as well as in radiotherapy where doses up to several Gray are to be measured. The major advantages of TL detectors are their small physical size and that no cables or auxiliary equipment is required during the dose assessment. Therefore TLD is a good method for point dose measurements in phantoms as well as for in vivo dosimetry on patients during radiotherapy treatment. As an integrative dosimetric technique, it can be applied to personal dosimetry and it lends itself to the determination of dose distributions due to multiple or moving radiation sources (e.g. conformal and dynamic radiotherapy, computed tomography). In addition, TL dosimeters are easy to transport, and they can be mailed. This makes them well suited for intercomparison of doses delivered in different institutions. The present article aims at describing the various applications TLD has found in medicine by taking into consideration the physics and practice of TLD measurements which have been discussed in the first part of this review (Australas. Phys. Eng. Sci. Med. 17: 175-199, 1994).

Low-dose strontium stimulates osteogenesis but high-dose doses cause apoptosis in human adipose-derived stem cells via regulation of the ERK1/2 signaling pathway.

PubMed

Aimaiti, Abudousaimi; Maimaitiyiming, Asihaerjiang; Boyong, Xu; Aji, Kaisaier; Li, Cao; Cui, Lei

2017-12-19

Strontium is a widely used anti-osteoporotic agent due to its dual effects on inhibiting bone resorption and stimulating bone formation. Thus, we studied the dose response of strontium on osteo-inductive efficiency in human adipose-derived stem cells (hASCs). Qualitative alkaline phosphatase (ALP) staining, quantitative ALP activity, Alizarin Red staining, real-time polymerase chain reaction and Western blot were used to investigate the in vitro effects of a range of strontium concentrations on hASC osteogenesis and associated signaling pathways. In vitro work revealed that strontium (25-500 μM) promoted osteogenic differentiation of hASCs according to ALP activity, extracellular calcium deposition, and expression of osteogenic genes such as runt-related transcription factor 2, ALP, collagen-1, and osteocalcin. However, osteogenic differentiation of hASCs was significantly inhibited with higher doses of strontium (1000-3000 μM). These latter doses of strontium promoted apoptosis, and phosphorylation of ERK1/2 signaling was increased and accompanied by the downregulation of Bcl-2 and increased phosphorylation of BAX. The inhibition of ERK1/2 decreased apoptosis in hASCs. Lower concentrations of strontium facilitate osteogenic differentiation of hASCs up to a point; higher doses cause apoptosis of hASCs, with activation of the ERK1/2 signaling pathway contributing to this process.

Potential High Resolution Dosimeters For MRT

NASA Astrophysics Data System (ADS)

Bräuer-Krisch, E.; Rosenfeld, A.; Lerch, M.; Petasecca, M.; Akselrod, M.; Sykora, J.; Bartz, J.; Ptaszkiewicz, M.; Olko, P.; Berg, A.; Wieland, M.; Doran, S.; Brochard, T.; Kamlowski, A.; Cellere, G.; Paccagnella, A.; Siegbahn, E. A.; Prezado, Y.; Martinez-Rovira, I.; Bravin, A.; Dusseau, L.; Berkvens, P.

2010-07-01

Microbeam Radiation Therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50-600 keV, produced by 2nd and 3rd generation synchrotron sources, such as the National Synchrotron Light Source (NSLS) in the U.S., and the European Synchrotron Radiation Facility (ESRF) in France, respectively. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. A small beam divergence and a filtered white beam spectrum in the energy range between 30 and 250 keV results in the advantage of steep dose gradients with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has allowed a vast number of results from preclinical trials on different animal models, including mice, rats, piglets and rabbits. Microbeams in the range between 10 and 100 micron width show an unprecedented sparing of normal radiosensitive tissues as well as preferential damage to malignant tumor tissues. Typically, MRT uses arrays of narrow (˜25-100 micron-wide) microplanar beams separated by wider (100-400 microns centre-to-centre, c-t-c) microplanar spaces. We note that thicker microbeams of 0.1-0.68 mm used by investigators at the NSLS are still called microbeams, although some invesigators in the community prefer to call them minibeams. This report, however, limits it discussion to 25-100 μm microbeams. Peak entrance doses of several hundreds of Gy are surprisingly well tolerated by normal tissues. High resolution dosimetry has been developed over the last two decades, but typical dose ranges are adapted to dose delivery in conventional Radiation Therapy (RT). Spatial resolution in the sub-millimetric range has been achieved, which is currently required for quality assurance measurements in Gamma-knife RT. Most typical commercially available detectors are not suitable for MRT applications at a dose rate of 16000 Gy/s, micron resolution and a dose range over several orders of magnitude. This paper will give an overview of all dosimeters tested in the past at the ESRF with their advantages and drawbacks. These detectors comprise: Ionization chambers, Alanine Dosimeters, MOSFET detectors, Gafchromic® films, Radiochromic polymers, TLDs, Polymer gels, Fluorescent Nuclear Track Detectors (Al2O3:C, Mg single crystal detectors), OSL detectors and Floating Gate-based dosimetry system. The aim of such a comparison shall help with a decision on which of these approaches is most suitable for high resolution dose measurements in MRT. The principle of these detectors will be presented including a comparison for some dosimeters exposed with the same irradiation geometry, namely a 1×1 cm5 field size with microbeam exposures at the surface, 0.1 cm and 1 cm in depth of a PMMA phantom. For these test exposures, the most relevant irradiation parameters for future clinical trials have been chosen: 50 micron FWHM and 400 micron c-t-c distance. The experimental data are compared with Monte Carlo calculations.

Range and trend of expected toxicity level (ETL) in standard A + B designs: a report from the Children's Oncology Group.

PubMed

Chen, Zhengjia; Krailo, Mark D; Sun, Junfeng; Azen, Stanley P

2009-03-01

The traditional algorithm-based 3+3 designs are most widely used for their practical simplicity in phase I clinical trials. At early stage, a common belief was that the expected toxicity level (ETL) at the maximum tolerated dose (MTD) should be 33% [Storer, B. Design and analysis of phase I clinical trials. Biometrics 1989;45;925-937, Gorden, N., Willson, J. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Statistics in Medicine 1992; 11: 2063-2075, Mick, R. Phase I Clinical Trial Design. In Schilsky, R., Milano, G., Ratain, M., eds. Principles of Antineoplastic Drug Development and Pharmacology New York, NY: Marcel Dekker, 1996; 29-36]. Recently, Kang and Ahn [Kang, S., Ahn, C. The expected toxicity rate at the maximum tolerated dose in the standard phase I cancer clinical trial design. Drug Information Journal 2001; 35:1189-1199, Kang, S., Ahn, C. An investigation of the traditional algorithm-based designs for phase I cancer clinical trials. Drug Information Journal 2002; 36:865-873] found that the ETL is between 17% and 21% and He et al [He, W., Liu, J., Binkowitz, B., Quan, H. A model-based approach in the estimation of the maximum tolerated dose in phase I cancer clinical trials. Statistics in Medicine 2006; 25(12):2027-42] further reported that the ETL ranges from 19% to 24%. However they only investigated designs where the number of dose levels was at most 20. It has practical significance in designing and conducting phase I clinical trial to definitely assess the full range and trend of ETL by all possible number of tested dose levels in traditional algorithm-based A+B designs, especially 3+3 designs. In this simulation study, we originally find that the ETL decreases monotonically from about 30% to 0% as the number of dose levels increase from 3 to infinity, which will correct the inaccuracy in the common belief among phase I trial investigators. To help better design and conduct phase I trials, we create a table as a reference for the association between ETL and number of dose levels considered in a design when the exact shape of the dose-toxicity relationship is not well understood. We conclude that the number of specified dose levels is an important factor affecting substantially the ETL at MTD and recommend that fewer than 20 dose levels be designated.

Thermoluminescence characteristics of flat optical fiber in radiation dosimetry under different electron irradiation conditions

NASA Astrophysics Data System (ADS)

Alawiah, A.; Intan, A. M.; Bauk, S.; Abdul-Rashid, H. A.; Yusoff, Z.; Mokhtar, M. R.; Wan Abdullah, W. S.; Mat Sharif, K. A.; Mahdiraji, G. A.; Mahamd Adikan, F. R.; Tamchek, N.; Noor, N. M.; Bradley, D. A.

2013-05-01

Thermoluminescence (TL) flat optical fibers (FF) have been proposed as radiation sensor in medical dosimetry for both diagnostic and radiotherapy applications. A flat optical fiber with nominal dimensions of (3.226 × 3.417 × 0.980) mm3 contains pure silica SiO2 was selected for this research. The FF was annealed at 400°C for 1 h before irradiated. Kinetic parameters and dosimetric glow curve of TL response were studied in FF with respect to electron irradiation of 6 MeV, 15 MeV and 21 MeV using linear accelerator (LINAC) in the dose range of 2.0-10.0 Gy. The TL response was read using a TLD reader Harshaw Model 3500. The Time-Temperature-Profile (TTP) of the reader used includes; initial preheat temperature of 80°C, maximum readout temperature is 400°C and the heating rate of 30°Cs-1. The proposed FF shows excellent linear radiation response behavior within the clinical relevant dose range for all of these energies, good reproducibility, independence of radiation energy, independence of dose rate and exhibits a very low thermal fading. From these results, the proposed FF can be used as radiation dosimeter and favorably compares with the widely used of LiF:MgTi dosimeter in medical radiotherapy application.

Relation of serum molindone levels to serum prolactin levels and antipsychotic response.

PubMed

Pandurangi, A K; Narasimhachari, N; Blackard, W G; Landa, B S

1989-10-01

The antipsychotic drug molindone is considered to be atypical in its mode of action and to have mild side effects. Currently no data are available on the range of serum levels of this drug during treatment. By means of a high performance liquid chromatographic technique, serum molindone levels were measured in 14 psychotic patients receiving a wide range of doses of this drug. Molindone levels as high as 350 ng/mL were obtained and were not associated with any toxic effects. Significant relations were noted between the serum level of the drug and both serum prolactin level and treatment response. The authors suggest that molindone may have a range of serum levels consistent with therapeutic benefit. Serum molindone and prolactin levels might help assess resistance to molindone treatment.

Deep learning in pharmacogenomics: from gene regulation to patient stratification.

PubMed

Kalinin, Alexandr A; Higgins, Gerald A; Reamaroon, Narathip; Soroushmehr, Sayedmohammadreza; Allyn-Feuer, Ari; Dinov, Ivo D; Najarian, Kayvan; Athey, Brian D

2018-05-01

This Perspective provides examples of current and future applications of deep learning in pharmacogenomics, including: identification of novel regulatory variants located in noncoding domains of the genome and their function as applied to pharmacoepigenomics; patient stratification from medical records; and the mechanistic prediction of drug response, targets and their interactions. Deep learning encapsulates a family of machine learning algorithms that has transformed many important subfields of artificial intelligence over the last decade, and has demonstrated breakthrough performance improvements on a wide range of tasks in biomedicine. We anticipate that in the future, deep learning will be widely used to predict personalized drug response and optimize medication selection and dosing, using knowledge extracted from large and complex molecular, epidemiological, clinical and demographic datasets.

Dose-time relationships for post-irradiation cutaneous telangiectasia

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

Cohen, L.; Ubaldi, S.E.

1977-01-01

Seventy-five patients who had received electron beam radiation a year or more previously were studied. The irradiated skin portals were photographed and late reactions graded in terms of the number and severity of telangiectatic lesions observed. The skin dose, number of fractions, overall treatment time and irradiated volume were recorded in each case. A Strandqvist-type iso-effect line was derived for this response. A multi-probit search program also was used to derive best-fitting cell population kinetic parameters for the same data. From these parameters a comprehensive iso-effect table could be computed for a wide range of treatment schedules including daily treatmentmore » as well as fractionation at shorter and longer intervals; this provided a useful set of normal tissue tolerance limits for late effects.« less

Differences between the nonselective adenosine receptor antagonists caffeine and theophylline in motor and mood effects: studies using medium to high doses in animal models.

PubMed

López-Cruz, Laura; Pardo, Marta; Salamone, John D; Correa, Mercè

2014-08-15

Caffeine and theophylline are methylxanthines that are broadly consumed, sometimes at high doses, and act as minor psychostimulants. Both are nonselective adenosine antagonists for A1 and A2A receptors, which are colocalized with dopamine D1 and D2 receptors in striatal areas. Adenosine antagonists generally have opposite actions to those of dopamine antagonists. Although the effects of caffeine are widely known, theophylline has been much less well characterized, especially at high doses. Adult male CD1 mice were used to study the effect of a broad range of doses (25.0, 50.0 or 100.0mg/kg) of caffeine and theophylline on measures of spontaneous locomotion and coordination, as well as the pattern of c-Fos immunoreactivity in brain areas rich in adenosine and dopamine receptors. In addition, we evaluated possible anxiety and stress effects of these doses. Caffeine, at these doses, impaired or suppressed locomotion in several paradigms. However, theophylline was less potent than caffeine at suppressing motor parameters, and even stimulated locomotion. Both drugs induced corticosterone release, however caffeine was more efficacious at intermediate doses. While caffeine showed an anxiogenic profile at all doses, theophylline only did so at the highest dose used (50mg/kg). Only theophylline increased c-Fos immunoreactivity in cortical areas. Theophylline has fewer disruptive effects than caffeine on motor parameters and produces less stress and anxiety effects. These results are relevant for understanding the potential side effects of methylxanthines when consumed at high doses. Copyright © 2014 Elsevier B.V. All rights reserved.

Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring.

PubMed

Vassal, G; Michel, G; Espérou, H; Gentet, J C; Valteau-Couanet, D; Doz, F; Mechinaud, F; Galambrun, C; Neven, B; Zouabi, H; Nguyen, L; Puozzo, C

2008-01-01

Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. A new intravenous (IV) dosing of busulfan (Bu) based on body weight, designed to improve AUC targeting without TDM and dose-adjustment, was prospectively evaluated. Bu was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16-23 kg; 0.95 mg/kg for >23-34 kg; 0.80 mg/kg for >34 kg. Bu treatment was followed by Cyclophosphamide or Melphalan prior to allogeneic or autologous transplantation in 55 children aged 0.3-17.2 years (median 5.6 years). No difference in AUC values was observed between weight strata (mean +/- SD 1248 +/- 205 micromol.min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900-1500 micromol.min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window.

Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized, controlled trial.

PubMed

Walsh, Stephen R; Wilck, Marissa B; Dominguez, David J; Zablowsky, Elise; Bajimaya, Shringkhala; Gagne, Lisa S; Verrill, Kelly A; Kleinjan, Jane A; Patel, Alka; Zhang, Ying; Hill, Heather; Acharyya, Aruna; Fisher, David C; Antin, Joseph H; Seaman, Michael S; Dolin, Raphael; Baden, Lindsey R

2013-06-15

Modified vaccinia Ankara (MVA-BN, IMVAMUNE) is emerging as a primary immunogen and as a delivery system to treat or prevent a wide range of diseases. Defining the safety and immunogenicity of MVA-BN in key populations is therefore important. We performed a dose-escalation study of MVA-BN administered subcutaneously in 2 doses, one on day 0 and another on day 28. Twenty-four hematopoietic stem cell transplant recipients were enrolled sequentially into the study, and vaccine or placebo was administered under a randomized, double-blind allocation. Ten subjects received vaccine containing 10(7) median tissue culture infective doses (TCID50) of MVA-BN, 10 subjects received vaccine containing 10(8) TCID50 of MVA-BN, and 4 subjects received placebo. MVA-BN was generally well tolerated at both doses. No vaccine-related serious adverse events were identified. Transient local reactogenicity was more frequently seen at the higher dose. Neutralizing antibodies (NAb) to Vaccinia virus (VACV) were elicited by both doses of MVA-BN and were greater for the higher dose. Median peak anti-VACV NAb titers were 1:49 in the lower-dose group and 1:118 in the higher-dose group. T-cell immune responses to VACV were detected by an interferon γ enzyme-linked immunosorbent spot assay and were higher in the higher-dose group. MVA-BN is safe, well tolerated, and immunogenic in HSCT recipients. These data support the use of 10(8) TCID50 of MVA-BN in this population. NCT00565929.

Dose measurements in space by the Hungarian Pille TLD system.

PubMed

Apathy, I; Deme, S; Feher, I; Akatov, Y A; Reitz, G; Arkhanguelski, V V

2002-10-01

Exposure of crew, equipment, and experiments to the ambient space radiation environment in low Earth orbit poses one of the most significant problems to long-term space habitation. Accurate dose measurement has become increasingly important during the assembly (extravehicular activity (EVA)) and operation of space stations such as on Space Station Mir. Passive integrating detector systems such as thermoluminescent dosemeters (TLDs) are commonly used for dosimetry mapping and personal dosimetry on space vehicles. The well-known advantages of passive detector systems are their independence of power supply, small dimensions, high sensitivity, good stability, wide measuring range, resistance to environmental effects, and relatively low cost. Nevertheless, they have the general disadvantage that for evaluation purposes they need a laboratory or large--in mass and power consumption--terrestrial equipment, and consequently they cannot provide time-resolved dose data during long-term space flights. KFKI Atomic Energy Research Institute (KFKI AEKI) has developed and manufactured a series of thermoluminescent dosemeter systems for measuring cosmic radiation doses in the 10 microGy to 10 Gy range, consisting of a set of bulb dosemeters and a compact, self-contained, TLD reader suitable for on-board evaluation of the dosemeters. By means of such a system, highly accurate measurements were carried out on board the Salyut-6, -7 and Mir Space Stations as well as on the Space Shuttle. A detailed description of the system is given and the comprehensive results of these measurements are summarised. c2002 Elsevier Science Ltd. All rights reserved.

A general model for stray dose calculation of static and intensity-modulated photon radiation.

PubMed

Hauri, Pascal; Hälg, Roger A; Besserer, Jürgen; Schneider, Uwe

2016-04-01

There is an increasing number of cancer survivors who are at risk of developing late effects caused by ionizing radiation such as induction of second tumors. Hence, the determination of out-of-field dose for a particular treatment plan in the patient's anatomy is of great importance. The purpose of this study was to analytically model the stray dose according to its three major components. For patient scatter, a mechanistic model was developed. For collimator scatter and head leakage, an empirical approach was used. The models utilize a nominal beam energy of 6 MeV to describe two linear accelerator types of a single vendor. The parameters of the models were adjusted using ionization chamber measurements registering total absorbed dose in simple geometries. Whole-body dose measurements using thermoluminescent dosimeters in an anthropomorphic phantom for static and intensity-modulated treatment plans were compared to the 3D out-of-field dose distributions calculated by a combined model. The absolute mean difference between the whole-body predicted and the measured out-of-field dose of four different plans was 11% with a maximum difference below 44%. Computation time of 36 000 dose points for one field was around 30 s. By combining the model-calculated stray dose with the treatment planning system dose, the whole-body dose distribution can be viewed in the treatment planning system. The results suggest that the model is accurate, fast and can be used for a wide range of treatment modalities to calculate the whole-body dose distribution for clinical analysis. For similar energy spectra, the mechanistic patient scatter model can be used independently of treatment machine or beam orientation.

Randomised controlled trials define shape of dose-response for Pollinex Quattro Birch allergoid immunotherapy.

PubMed

Worm, Margitta; Higenbottam, Tim; Pfaar, Oliver; Mösges, Ralph; Aberer, Werner; Gunawardena, Kulasiri; Wessiepe, Dorothea; Lee, Denise; Kramer, Matthias F; Skinner, Murray; Lees, Bev; Zielen, Stefan

2018-05-19

The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX ® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed two phase II studies to determine its optimal cumulative dose. The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction of Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modelling analysis was used to test for the dose-response, shape of the curve, and estimation of the median effective dose (ED 50 ), a measure of potency. Statistically significant dose-responses (p<0.01 & 0.001) were seen respectively. The highest cumulative dose in PQBirch204 (27300 standardised units [SU]) approached a plateau. Potency of the PQ Birch was demonstrated by an ED 50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups. Increasing the cumulative dose of PQ Birch 5.5-fold from 5100 to 27300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase of efficacy of 50%, without compromising safety. The cumulative dose-response was confirmed to be curvilinear in shape. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Assessment of Mean Glandular Dose in Mammography System with Different Anode-Filter Combinations Using MCNP Code.

PubMed

Gholamkar, Lida; Mowlavi, Ali Asghar; Sadeghi, Mahdi; Athari, Mitra

2016-10-01

X-ray mammography is one of the general methods for early detection of breast cancer. Since glandular tissue in the breast is sensitive to radiation and it increases the risk of cancer, the given dose to the patient is very important in mammography. The aim of this study was to determine the average absorbed dose of X-ray radiation in the glandular tissue of the breast during mammography examinations as well as investigating factors that influence the mean glandular dose (MGD). One of the precise methods for determination of MGD absorbed by the breast is Monte Carlo simulation method which is widely used to assess the dose. We studied some different X-ray sources and exposure factors that affect the MGD. "Midi-future" digital mammography system with amorphous-selenium detector was simulated using the Monte Carlo N-particle extended (MCNPX) code. Different anode/filter combinations such as tungsten/silver (W/Ag), tungsten/rhodium (W/Rh), and rhodium/aluminium (Rh/Al) were simulated in this study. The voltage of X-ray tube ranged from 24 kV to 32 kV with 2 kV intervals and the breast phantom thickness ranged from 3 to 8 cm, and glandular fraction g varied from 10% to 100%. MGD was measured for different anode/filter combinations and the effects of changing tube voltage, phantom thickness, combination and glandular breast tissue on MGD were studied. As glandular g and X-ray tube voltage increased, the breast dose increased too, and the increase of breast phantom thickness led to the decrease of MGD. The obtained results for MGD were consistent with the result of Boone et al. that was previously reported. By comparing the results, we saw that W/Rh anode/filter combination is the best choice in breast mammography imaging because of the lowest delivered dose in comparison with W/Ag and Rh/Al. Moreover, breast thickness and g value have significant effects on MGD.

Pediatric Phase I Trial and Pharmacokinetic Study of Vorinostat: A Children's Oncology Group Phase I Consortium Report

PubMed Central

Fouladi, Maryam; Park, Julie R.; Stewart, Clinton F.; Gilbertson, Richard J.; Schaiquevich, Paula; Sun, Junfeng; Reid, Joel M.; Ames, Matthew M.; Speights, Roseanne; Ingle, Ashish M.; Zwiebel, James; Blaney, Susan M.; Adamson, Peter C.

2010-01-01

Purpose The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of vorinostat administered as a single agent and in combination 13-cis retinoic acid (13cRA) in children with refractory solid tumors; to evaluate the tolerability of the solid tumor MTD in children with refractory leukemias; and to characterize the pharmacokinetics of a vorinostat suspension in children. Patients and Methods Vorinostat was administered orally daily starting at 180 mg/m2/d with escalations planned in 30% increments. Pharmacokinetic studies were performed with the initial dose. Acetyl-histone (H3) accumulation was assessed by Western blotting of peripheral blood mononuclear cells (PBMC). Results Sixty-four patients were enrolled on this multipart trial. In patients with solid tumors, the MTD was 230 mg/m2/d with dose-limiting neutropenia, thrombocytopenia, and hypokalemia at 300 mg/m2/d. DLTs observed with the combination of 13cRA and vorinostat included thrombocytopenia, neutropenia, anorexia, and hypertriglyceridemia, resulting in a MTD of vorinostat 180 mg/m2/d 4 times per week and 13cRA 80 mg/m2/dose twice per day, days 1 through 14 every 28 days. Wide interpatient variability was noted in vorinostat disposition, with area under the concentration-time curves at 230 mg/m2/d for the capsule (range, 1,415 to 9,291 ng/mL × hr) and oral suspension (range, 1,186 to 4,780 ng/mL × hr). Significant accumulation of acetylated H3 histone in PBMC was observed after administration of vorinostat, particularly at higher doses. One patient with neuroblastoma experienced a complete response to the combination. Conclusion In children with recurrent solid tumors, vorinostat is well-tolerated at 230 mg/m2/d, with a modest dose reduction being required when combining vorinostat with 13cRA. Drug disposition is similar to that observed in adults. PMID:20606092

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

PubMed

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

2011-04-01

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

Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation.

PubMed

Ramakrishnan, Sridhar; Laxminarayan, Srinivas; Wesensten, Nancy J; Kamimori, Gary H; Balkin, Thomas J; Reifman, Jaques

2014-10-07

Caffeine is the most widely consumed stimulant to counter sleep-loss effects. While the pharmacokinetics of caffeine in the body is well-understood, its alertness-restoring effects are still not well characterized. In fact, mathematical models capable of predicting the effects of varying doses of caffeine on objective measures of vigilance are not available. In this paper, we describe a phenomenological model of the dose-dependent effects of caffeine on psychomotor vigilance task (PVT) performance of sleep-deprived subjects. We used the two-process model of sleep regulation to quantify performance during sleep loss in the absence of caffeine and a dose-dependent multiplier factor derived from the Hill equation to model the effects of single and repeated caffeine doses. We developed and validated the model fits and predictions on PVT lapse (number of reaction times exceeding 500 ms) data from two separate laboratory studies. At the population-average level, the model captured the effects of a range of caffeine doses (50-300 mg), yielding up to a 90% improvement over the two-process model. Individual-specific caffeine models, on average, predicted the effects up to 23% better than population-average caffeine models. The proposed model serves as a useful tool for predicting the dose-dependent effects of caffeine on the PVT performance of sleep-deprived subjects and, therefore, can be used for determining caffeine doses that optimize the timing and duration of peak performance. Published by Elsevier Ltd.

A study on the indirect urea dosing method in the Selective Catalytic Reduction system

NASA Astrophysics Data System (ADS)

Brzeżański, M.; Sala, R.

2016-09-01

This article presents the results of studies on concept solution of dosing urea in a gas phase in a selective catalytic reduction system. The idea of the concept was to heat-up and evaporate the water urea solution before introducing it into the exhaust gas stream. The aim was to enhance the processes of urea converting into ammonia, what is the target reductant for nitrogen oxides treatment. The study was conducted on a medium-duty Euro 5 diesel engine with exhaust line consisting of DOC catalyst, DPF filter and an SCR system with a changeable setup allowing to dose the urea in liquid phase (regular solution) and to dose it in a gas phase (concept solution). The main criteria was to assess the effect of physical state of urea dosed on the NOx conversion ratio in the SCR catalyst. In order to compare both urea dosing methods a special test procedure was developed which consisted of six test steps covering a wide temperature range of exhaust gas generated at steady state engine operation condition. Tests were conducted for different urea dosing quantities defined by the a equivalence ratio. Based on the obtained results, a remarkable improvement in NOx reduction was found for gas urea application in comparison to the standard liquid urea dosing. Measured results indicate a high potential to increase an efficiency of the SCR catalyst by using a gas phase urea and provide the basis for further scientific research on this type of concept.

Neutron- and photon-activation detection limits in breast milk analysis for prospective dose evaluation of the suckling infant.

PubMed

Tsipenyuk, Yu M; Firsov, V I; Cantone, M C

2009-01-01

Complex situations related to the environment, as in the regions affected by the Chernobyl accident and regions in which nuclear weapons testing were undertaken, as in Semipalatinsk, could be reflected in the trace element content in mothers' milk. The evaluation of fractional transfer to milk of ingested or inhaled activity and of the corresponding dose coefficients for the infant, following a mothers' radioactive intake, can take advantage from wide-ranging studies of elemental and radionuclide contents in mothers' milk. In this work the possibility to determine elements, such as Ru, Zr, Nb, Te, Ce, Th, U, in milk powder has been investigated. Although results from elemental analyses of breast milk are to be found in the literature, the determination of the identified elements has attracted poor attention since they are not considered essential elements from a biological point of view. Nevertheless, in the case of radioactive releases to the environment, such data could be of interest in evaluation of dose to the breast-fed infant.

Computed radiography as a gamma ray detector—dose response and applications

NASA Astrophysics Data System (ADS)

O'Keeffe, D. S.; McLeod, R. W.

2004-08-01

Computed radiography (CR) can be used for imaging the spatial distribution of photon emissions from radionuclides. Its wide dynamic range and good response to medium energy gamma rays reduces the need for long exposure times. Measurements of small doses can be performed without having to pre-sensitize the computed radiography plates via an x-ray exposure, as required with screen-film systems. Cassette-based Agfa MD30 and Kodak GP25 CR plates were used in applications involving the detection of gamma ray emissions from technetium-99m and iodine-131. Cassette entrance doses as small as 1 µGy (140 keV gamma rays) produce noisy images, but the images are suitable for applications such as the detection of breaks in radiation protection barriers. A consequence of the gamma ray sensitivity of CR plates is the possibility that some nuclear medicine patients may fog their x-rays if the x-ray is taken soon after their radiopharmaceutical injection. The investigation showed that such fogging is likely to be diffuse.

[The study of the role of the water medium in the mechanism of action of peptides in low and ultra low doses].

PubMed

Grigor'ev, E I; Khavinson, V Kh; Malinin, V V; Grigor'ev, A E; Kochnev, I N; Kudriavtseva, T A

2003-01-01

The correlation between the structures and conformations of short peptides KE, EW, AEDG and other, their influence on the dynamic properties of water and dose/biologic effect dependencies in a wide range of concentrations were regarded. Their effects on the dynamic properties of water were studied by temperature dependencies (5-45 degrees C) of infrared spectra of the solutions in the near (5180 cm-1) and far (200 cm-1). In vitro biotesting included the determination of the proliferative activity of thymocytes, a bimodal curve with the second maximum were detected at super-low doses (10(-17)-10(-15) mol/l). Authors propose a hypothesis that for superlow concentrations the formation and distance transmission of a signal from ligand to a target cell without the formation of any ligand-receptor complex take place. An active role in this model belongs to water medium acting according to the solution mechanism.

Experimental check of bremsstrahlung dosimetry predictions for 0.75 MeV electrons

NASA Astrophysics Data System (ADS)

Sanford, T. W. L.; Halbleib, J. A.; Beezhold, W.

Bremsstrahlung dose in CaF2 TLDs from the radiation produced by 0.75 MeV electrons incident on Ta/C targets is measured and compared with that calculated via the CYLTRAN Monte Carlo code. The comparison was made to validate the code, which is used to predict and analyze radiation environments of flash X-ray simulators measured by TLDs. Over a wide range of Ta target thicknesses and radiation angles the code is found to agree with the 5% measurements. For Ta thickness near those that optimize the radiation output, however, the code overestimates the radiation dose at small angles. Maximum overprediction is about 14 + or - 5%. The general agreement, nonetheless, gives confidence in using the code at this energy and in the TLD calibration procedure. For the bulk of the measurements, a standard TLD employing a 2.2 mm thick Al equilibrator was used. In this paper we also show that this thickness can significantly attenuate the free-field dose and introduces significant photon buildup in the equalibrator.

Using a conformal water bolus to adjust heating patterns of microwave waveguide applicators

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.; Rodrigues, Dario B.; Sinahon, Randolf; Sbarro, Lyndsey; Beckhoff, Valeria; Hurwitz, Mark D.

2017-02-01

Background: Hyperthermia, i.e., raising tissue temperature to 40-45°C for 60 min, has been demonstrated to increase the effectiveness of radiation and chemotherapy for cancer. Although multi-element conformal heat applicators are under development to provide more adjustable heating of contoured anatomy, to date the most often used applicator to heat superficial disease is the simple microwave waveguide. With only a single power input, the operator must be resourceful to adjust heat treatment to accommodate variable size and shape tumors spreading across contoured anatomy. Methods: We used multiphysics simulation software that couples electromagnetic, thermal and fluid dynamics physics to simulate heating patterns in superficial tumors from commercially available microwave waveguide applicators. Temperature distributions were calculated inside homogenous muscle and layered skin-fat-muscle-tumor-bone tissue loads for a typical range of applicator coupling configurations and size of waterbolus. Variable thickness waterbolus was simulated as necessary to accommodate contoured anatomy. Physical models of several treatment configurations were constructed for comparison of simulation results with experimental specific absorption rate (SAR) measurements in homogenous muscle phantom. Results: Accuracy of the simulation model was confirmed with experimental SAR measurements of three unique applicator setups. Simulations demonstrated the ability to generate a wide range of power deposition patterns with commercially available waveguide antennas by controllably varying size and thickness of the waterbolus layer. Conclusion: Heating characteristics of 915 MHz waveguide antennas can be varied over a wide range by controlled adjustment of microwave power, coupling configuration, and waterbolus lateral size and thickness. The uniformity of thermal dose delivered to superficial tumors can be improved by cyclic switching of waterbolus thickness during treatment to proactively shift heat peaks and nulls around under the aperture, thereby reducing patient pain while increasing minimum thermal dose by end of treatment.

A physiologically based pharmacokinetic model for atrazine and its main metabolites in the adult male C57BL/6 mouse

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

Lin Zhoumeng; Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602; Fisher, Jeffrey W.

Atrazine (ATR) is a chlorotriazine herbicide that is widely used and relatively persistent in the environment. In laboratory rodents, excessive exposure to ATR is detrimental to the reproductive, immune, and nervous systems. To better understand the toxicokinetics of ATR and to fill the need for a mouse model, a physiologically based pharmacokinetic (PBPK) model for ATR and its main chlorotriazine metabolites (Cl-TRIs) desethyl atrazine (DE), desisopropyl atrazine (DIP), and didealkyl atrazine (DACT) was developed for the adult male C57BL/6 mouse. Taking advantage of all relevant and recently made available mouse-specific data, a flow-limited PBPK model was constructed. The ATR andmore » DACT sub-models included blood, brain, liver, kidney, richly and slowly perfused tissue compartments, as well as plasma protein binding and red blood cell binding, whereas the DE and DIP sub-models were constructed as simple five-compartment models. The model adequately simulated plasma levels of ATR and Cl-TRIs and urinary dosimetry of Cl-TRIs at four single oral dose levels (250, 125, 25, and 5 mg/kg). Additionally, the model adequately described the dose dependency of brain and liver ATR and DACT concentrations. Cumulative urinary DACT amounts were accurately predicted across a wide dose range, suggesting the model's potential use for extrapolation to human exposures by performing reverse dosimetry. The model was validated using previously reported data for plasma ATR and DACT in mice and rats. Overall, besides being the first mouse PBPK model for ATR and its Cl-TRIs, this model, by analogy, provides insights into tissue dosimetry for rats. The model could be used in tissue dosimetry prediction and as an aid in the exposure assessment to this widely used herbicide.« less

Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators

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

Orona, N.S.; Tasat, D.R., E-mail: deborah.tasat@unsam.edu.ar; School of Dentistry, University of Buenos Aires, M. T. de Alvear 2142

2012-06-15

Uranium compounds are widely used in the nuclear fuel cycle, military and many other diverse industrial processes. Health risks associated with uranium exposure include nephrotoxicity, cancer, respiratory, and immune disorders. Macrophages present in body tissues are the main cell type involved in the internalization of uranium particles. To better understand the pathological effects associated with depleted uranium (DU) inhalation, we examined the metabolic activity, phagocytosis, genotoxicity and inflammation on DU-exposed rat alveolar macrophages (12.5–200 μM). Stability and dissolution of DU could differ depending on the dissolvent and in turn alter its biological action. We dissolved DU in sodium bicarbonate (NaHCO{submore » 3} 100 mM) and in what we consider a more physiological vehicle resembling human internal media: sodium chloride (NaCl 0.9%). We demonstrate that uranyl nitrate in NaCl solubilizes, enters the cell, and elicits its cytotoxic effect similarly to when it is diluted in NaHCO{sub 3}. We show that irrespective of the dissolvent employed, uranyl nitrate impairs cell metabolism, and at low doses induces both phagocytosis and generation of superoxide anion (O{sub 2}{sup −}). At high doses it provokes the secretion of TNFα and through all the range of doses tested, apoptosis. We herein suggest that at DU low doses O{sub 2}{sup −} may act as the principal mediator of DNA damage while at higher doses the signaling pathway mediated by O{sub 2}{sup −} may be blocked, prevailing damage to DNA by the TNFα route. The study of macrophage functions after uranyl nitrate treatment could provide insights into the pathophysiology of uranium‐related diseases. -- Highlights: ► Uranyl nitrate effect on cultured macrophages is linked to the doses and independent of its solubility. ► At low doses uranyl nitrate induces generation of superoxide anion. ► At high doses uranyl nitrate provokes secretion of TNFα. ► Uranyl nitrate induces apoptosis through all the range of doses tested.« less

Bioavailability and Preliminary Clinical Efficacy of Intrarectal Artesunate in Ghanaian Children with Moderate Malaria

PubMed Central

Krishna, Sanjeev; Planche, Tim; Agbenyega, Tsiri; Woodrow, Charles; Agranoff, Dan; Bedu-Addo, George; Owusu-Ofori, Alex K.; Appiah, John Adabie; Ramanathan, Surash; Mansor, Sharif M.; Navaratnam, Visweswaran

2001-01-01

We report the first detailed pharmacokinetic assessment of intrarectal (i.r.) artesunate (ARS) in African children. Artesunate was given intravenously (i.v.; 2.4 mg/kg of body weight) and i.r. (10 or 20 mg/kg formulated as 50- or 200-mg suppositories [Rectocaps]) in a crossover study design to 34 Ghanaian children with moderate falciparum malaria. The median relative bioavailability of dihydroartemisinin (DHA), the active antimalarial metabolite of ARS, was higher in the low-dose i.r. group (10 mg/kg) than in the high-dose i.r. group (20 mg/kg) (58 versus 23%; P = 0.018). There was wide interpatient variation in the area under the concentration-time curve after i.r. ARS administration (up to 9-fold in the high-dose group and 20-fold in the low-dose group). i.r. administered ARS was more rapidly absorbed in the low-dose group than the high-dose group (median [range] absorption half-lives, 0.7 h [0.3 to 1.24 h] versus 1.1 h [0.6 to 2.7 h] [P = 0.023]. i.r. administered ARS was eliminated with a median (range) half-life of 0.8 h (0.4 to 2.7 h) (low-dose group and 0.9 h (0.1 to 2.5 h) (high-dose group) (P = 1). The fractional clearances of DHA were 3.9, 2.6, and 1.5 liters/kg/h for the 20-mg/kg, 10-mg/kg and i.v. groups, respectively (P = 0.001 and P = 0.06 for the high-and low-dose i.r. groups compared with the i.v. groups, respectively). The median volumes of distribution for DHA were 1.5 liters kg (20 mg/kg, i.r. group), 1.8 liters/kg (10 mg/kg, i.r. group), and 0.6 liters/kg (i.v. group) (P < 0.05 for both i.r. groups compared with the i.v. group). Parasite clearance kinetics were comparable in all treatment groups. i.r. administered ARS may be a useful alternative to parenterally administered ARS in the management of moderate childhood malaria and should be studied further. PMID:11158748

Measurements of neutron dose equivalent for a proton therapy center using uniform scanning proton beams

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

Zheng Yuanshui; Liu Yaxi; Zeidan, Omar

Purpose: Neutron exposure is of concern in proton therapy, and varies with beam delivery technique, nozzle design, and treatment conditions. Uniform scanning is an emerging treatment technique in proton therapy, but neutron exposure for this technique has not been fully studied. The purpose of this study is to investigate the neutron dose equivalent per therapeutic dose, H/D, under various treatment conditions for uniform scanning beams employed at our proton therapy center. Methods: Using a wide energy neutron dose equivalent detector (SWENDI-II, ThermoScientific, MA), the authors measured H/D at 50 cm lateral to the isocenter as a function of proton range,more » modulation width, beam scanning area, collimated field size, and snout position. They also studied the influence of other factors on neutron dose equivalent, such as aperture material, the presence of a compensator, and measurement locations. They measured H/D for various treatment sites using patient-specific treatment parameters. Finally, they compared H/D values for various beam delivery techniques at various facilities under similar conditions. Results: H/D increased rapidly with proton range and modulation width, varying from about 0.2 mSv/Gy for a 5 cm range and 2 cm modulation width beam to 2.7 mSv/Gy for a 30 cm range and 30 cm modulation width beam when 18 Multiplication-Sign 18 cm{sup 2} uniform scanning beams were used. H/D increased linearly with the beam scanning area, and decreased slowly with aperture size and snout retraction. The presence of a compensator reduced the H/D slightly compared with that without a compensator present. Aperture material and compensator material also have an influence on neutron dose equivalent, but the influence is relatively small. H/D varied from about 0.5 mSv/Gy for a brain tumor treatment to about 3.5 mSv/Gy for a pelvic case. Conclusions: This study presents H/D as a function of various treatment parameters for uniform scanning proton beams. For similar treatment conditions, the H/D value per uncollimated beam size for uniform scanning beams was slightly lower than that from a passive scattering beam and higher than that from a pencil beam scanning beam, within a factor of 2. Minimizing beam scanning area could effectively reduce neutron dose equivalent for uniform scanning beams, down to the level close to pencil beam scanning.« less

Multiple energy synchrotron biomedical imaging system

NASA Astrophysics Data System (ADS)

Bassey, B.; Martinson, M.; Samadi, N.; Belev, G.; Karanfil, C.; Qi, P.; Chapman, D.

2016-12-01

A multiple energy imaging system that can extract multiple endogenous or induced contrast materials as well as water and bone images would be ideal for imaging of biological subjects. The continuous spectrum available from synchrotron light facilities provides a nearly perfect source for multiple energy x-ray imaging. A novel multiple energy x-ray imaging system, which prepares a horizontally focused polychromatic x-ray beam, has been developed at the BioMedical Imaging and Therapy bend magnet beamline at the Canadian Light Source. The imaging system is made up of a cylindrically bent Laue single silicon (5,1,1) crystal monochromator, scanning and positioning stages for the subjects, flat panel (area) detector, and a data acquisition and control system. Depending on the crystal’s bent radius, reflection type, and the horizontal beam width of the filtered synchrotron radiation (20-50 keV) used, the size and spectral energy range of the focused beam prepared varied. For example, with a bent radius of 95 cm, a (1,1,1) type reflection and a 50 mm wide beam, a 0.5 mm wide focused beam of spectral energy range 27 keV-43 keV was obtained. This spectral energy range covers the K-edges of iodine (33.17 keV), xenon (34.56 keV), cesium (35.99 keV), and barium (37.44 keV) some of these elements are used as biomedical and clinical contrast agents. Using the developed imaging system, a test subject composed of iodine, xenon, cesium, and barium along with water and bone were imaged and their projected concentrations successfully extracted. The estimated dose rate to test subjects imaged at a ring current of 200 mA is 8.7 mGy s-1, corresponding to a cumulative dose of 1.3 Gy and a dose of 26.1 mGy per image. Potential biomedical applications of the imaging system will include projection imaging that requires any of the extracted elements as a contrast agent and multi-contrast K-edge imaging.

Quality of life after gamma knife radiosurgery treatment in patients with a vestibular schwannoma: the patient’s perspective

PubMed Central

van Haren, Anniek E. P.; Mulder, Jef J. S.; Hanssens, Patrick E. J.; van Overbeeke, Jacobus J.; Cremers, Cor W. R. J.; Graamans, Kees

2009-01-01

This study evaluates the impact of gamma knife radiosurgery (GKRS) on the quality of life (QOL) of patients with a sporadic vestibular schwannoma (VS). This study pertains to 108 VS patients who had GKRS in the years 2003 through 2007. Two different QOL questionnaires were used: medical outcome study short form 36 (SF36) and Glasgow benefit inventory (GBI). Radiosurgery was performed using a Leksell 4C gamma knife. The results of the QOL questionnaires in relation to prospectively and retrospectively gathered data of the VS patients treated by GKRS. Eventually, 97 patients could be included in the study. Their mean tumor size was 17 mm (range 6–39 mm); the mean maximum dose on the tumor was 19.9 Gy (range 16–25.5 Gy) and the mean marginal dose on the tumor was 11.1 (range 9.3–12.5 Gy). SF36 scores showed results comparable to those for a normal Dutch population. GBI showed a marginal decline in QOL. No correlation was found between QOL and gender, age, tumor size, or radiation dose. Increased audiovestibular symptoms after GKRS were correlated with a decreased GBI score, and decreased symptoms were correlated with a higher QOL post-GKRS. In this study shows that GKRS for VS has little impact on the general QOL of the VS patient. However, there is a wide range in individual QOL results. Individual QOL was influenced by the audiovestibular symptoms. No predictive patient, tumor, or treatment factors for QOL outcome after GKRS could be determined. Comparison with microsurgery is difficult because of intra group variability. PMID:19894058

Isotonic designs for phase I trials in partially ordered groups.

PubMed

Conaway, Mark

2017-10-01

Dose-finding trials can be conducted such that patients are first stratified into multiple risk groups before doses are allocated. The risk groups are often completely ordered in that, for a fixed dose, the probability of toxicity is monotonically increasing across groups. In some trials, the groups are only partially ordered. For example, one of several groups in a trial may be known to have the least risk of toxicity for a given dose, but the ordering of the risk among the remaining groups may not be known. The aim of the article is to introduce a method for designing dose-finding trials of cytotoxic agents in completely or partially ordered groups of patients. This article presents a method for dose-finding that combines previously proposed mathematical models, augmented with results using order restricted inference. The resulting method is computationally convenient and allows for dose-finding in trials with completely or partially ordered groups. Extensive simulations are done to evaluate the performance of the method, using randomly generated dose-toxicity curves where, within each group, the risk of toxicity is an increasing function of dose. Our simulations show that the hybrid method, in which order-restricted estimation is applied to parameters of a parsimonious mathematical model, gives results that are similar to previously proposed methods for completely ordered groups. Our method generalizes to a wide range of partial orders among the groups. The problem of dose-finding in partially ordered groups has not been extensively studied in the statistical literature. The proposed method is computationally feasible, and provides a potential solution to the design of dose-finding studies in completely or partially ordered groups.

Open-label dose optimization of methylphenidate modified release long acting (MPH-LA): a post hoc analysis of real-life titration from a 40-week randomized trial.

PubMed

Huss, Michael; Ginsberg, Ylva; Arngrim, Torben; Philipsen, Alexandra; Carter, Katherine; Chen, Chien-Wei; Gandhi, Preetam; Kumar, Vinod

2014-09-01

In the management of attention-deficit hyperactivity disorder (ADHD) in adults it is important to recognize that individual patients respond to a wide range of methylphenidate doses. Studies with methylphenidate modified release long acting (MPH-LA) in children have reported the need for treatment optimization for improved outcomes. We report the results from a post hoc analysis of a 5-week dose optimization phase from a large randomized, placebo-controlled, multicenter 40-week study (9-week double-blind dose confirmation phase, 5-week open-label dose optimization phase, and 26-week double-blind maintenance of effect phase). Patients entering the open-label dose optimization phase initiated treatment with MPH-LA 20 mg/day; up/down titrated to their optimal dose (at which there was balance between control of symptoms and side effects) of 40, 60, or 80 mg/day in increments of 20 mg/week by week 12 or 13. Safety was assessed by monitoring the adverse events (AEs) and serious AEs. Efficacy was assessed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Attention-Deficit Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores. At the end of the dose confirmation phase, similar numbers of patients were treated optimally with each of the 40, 60, and 80 mg/day doses (152, 177, and 160, respectively) for MPH-LA. Mean improvement from baseline in the dose confirmation phase in total scores of DSM-IV ADHD RS and SDS were 23.5 ± 9.90 and 9.7 ± 7.36, respectively. Dose optimization with MPH-LA (40, 60, or 80 mg/day) improved treatment outcomes and was well-tolerated in adult ADHD patients.

Characterization of a new commercial single crystal diamond detector for photon- and proton-beam dosimetry.

PubMed

Akino, Yuichi; Gautam, Archana; Coutinho, Len; Würfel, Jan; Das, Indra J

2015-11-01

A synthetic single crystal diamond detector (SCDD) is commercially available and is characterized for radiation dosimetry in various radiation beams in this study. The characteristics of the commercial SCDD model 60019 (PTW) with 6- and 15-MV photon beams, and 208-MeV proton beams, were investigated and compared with the pre-characterized detectors: Semiflex (model 31010) and PinPoint (model 31006) ionization chambers (PTW), the EDGE diode detector (Sun Nuclear Corp) and the SFD Stereotactic Dosimetry Diode Detector (IBA). To evaluate the effects of the pre-irradiation, the diamond detector, which had not been irradiated on the day, was set up in the water tank, and the response to 100 MU was measured every 20 s. The depth-dose and profiles data were collected for various field sizes and depths. For all radiation types and field sizes, the depth-dose data of the diamond chamber showed identical curves to those of the ionization chambers. The profile of the diamond detector was very similar to those of the EDGE and SFD detectors, although the Semiflex and PinPoint chambers showed volume-averaging effects in the penumbrae region. The temperature dependency was within 0.7% in the range of 4-41°C. A dose of 900 cGy and 1200 cGy was needed to stabilize the chamber to the level within 0.5% and 0.2%, respectively. The PTW type 60019 SCDD detector showed suitable characteristics for radiation dosimetry, for relative dose, depth-dose and profile measurements for a wide range of field sizes. However, at least 1000 cGy of pre-irradiation will be needed for accurate measurements. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Comparison of Chest Wall and Lymphatic Radiotherapy Techniques in Patients with Left Breast Carcinoma.

PubMed

Gültekin, Melis; Karabuğa, Mehmet; Yıldız, Ferah; Özyiğit, Gökhan; Cengiz, Mustafa; Zorlu, Faruk; Akyol, Fadıl; Gürkaynak, Murat

2014-04-01

The aim of this study was to find the most appropriate technique for postmastectomy chest wall (CW) and lymphatic irradiation. Partially wide tangent, 30/70 photon/electron mix, 20/80 photon/electron mix and CW and internal mammary en face electron field, were studied on computerized tomography (CT) scans of 10 left breast carcinoma patients and dosimetric calculations have been studied. Dose volume histograms (DVH) obtained from treatment planning system (TPS) were used for minimal, maximal and mean doses received by the clinical target volumes and critical structures. Partially wide tangent field resulted in the most homogeneous dose distribution for the CW and a significantly lower lung and heart doses compared with all other techniques. However, right breast dose was significantly higher for partially wide tangent technique than that each of the other techniques. Approximately 0.6-7.9% differences were found between thermoluminescent dosimeter (TLD) and treatment planning system (TPS). The daily surface doses calculating using Gafchromic® external beam therapy (EBT) dosimetry films were 161.8±2.7 cGy for the naked, 241.0±1.5 cGy when 0.5 cm bolus was used and 255.3±2.7 cGy when 1 cm bolus was used. As a result of this study, partially wide tangent field was found to be the most appropriate technique in terms of the dose distribution, treatment planning and set-up procedure. The main disadvantage of this technique was the higher dose to the contralateral breast comparing the other techniques.

Total Ionizing Dose Test Report BFR92A NPN 5 GHz Wide Band Transistor from NXP

NASA Technical Reports Server (NTRS)

Phan, Anthony M.; Oldham, Timothy R.

2011-01-01

The purpose of this test was to characterize the Philips/NXP BFR92A NPN 5 gigahertz wide band silicon transistor for total dose response. This test shall serves as the radiation lot acceptance test (RLAT) for the lot date code (LDC) 1027. The BFR92A is packaged in a 3-pin plastic SOT23 package. Low dose rate (LDR/ELDRS) irradiations was performed.

The effect of dosing regimens on the antimalarial efficacy of dihydroartemisinin-piperaquine: a pooled analysis of individual patient data.

PubMed

2013-12-01

Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy. A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n = 7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan-Meier survival estimates were 97.7% (95% CI 97.3%-98.1%) at day 42 and 97.2% (95% CI 96.7%-97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3-2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%-96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of piperaquine was found to be a significant predictor for recrudescence, the risk increasing by 13% (95% CI 5.0%-21%) for every 5 mg/kg decrease in dose; p = 0.002. In a multivariable model increasing the target minimum total dose of piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would halve the risk of treatment failure and cure at least 95% of patients; such an increment was not associated with gastrointestinal toxicity in the ten studies in which this could be assessed. DP demonstrates excellent efficacy in a wide range of transmission settings; however, treatment failure is associated with a lower dose of piperaquine, particularly in young children, suggesting potential for further dose optimisation.

Differences in multiplication of virulent and vaccine strains of poliovirus type I, II, and III in laboratory animals.

PubMed

Koroleva, G A; Lashkevich, V A; Voroshilova, M K

1977-01-01

Multiplication of virulent and vaccine strains of poliovirus type I, II and III in laboratory animals of different species was studied comparatively. The main criterion of virus reproduction was the production of the photoresistant virus progeny after inoculation of the animals with proflavin-photosensitized virus strains. On the whole, virulent poliovirus strains were characterized by replication in a wide range of hosts (monkeys, cotton rats, white mice, guinea pigs, rabbits, chickens, chick embryos), a low infective dose, production of the photoresistant progeny to a high titre, clinically overt disease in some animal species. The vaccine strains multiplied in a norrower range of hosts, had a high infective dose, a low titre of virus progeny, and caused no clinical symptoms of infection. These differences may serve as a marker for differentiation between virulent and attenuated strains in vivo. Administration of guanidine before inoculation of newborn cotton rats completely prevented or delayed by several days the production of photoresistant virus progeny. This fact confirms the stability of the proflavin-poliovirus complex under conditions ruling out virus replication.

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

Li, Xinhua; Zhang, Da; Liu, Bob, E-mail: bliu7@mgh.harvard.edu

Purpose: The knowledge of longitudinal dose distribution provides the most direct view of the accumulated dose in computed tomography (CT) scanning. The purpose of this work was to perform a comprehensive study of dose distribution width and energy absorption with a wide range of subject sizes and beam irradiated lengths. Methods: Cumulative dose distribution along the z-axis was calculated based on the previously published CT dose equilibration data by Li, Zhang, and Liu [Med. Phys. 40, 031903 (10pp.) (2013)] and a mechanism for computing dose on axial lines by Li, Zhang, and Liu [Med. Phys. 39, 5347–5352 (2012)]. Full widthmore » at half maximum (FWHM), full width at tenth maximum (FWTM), the total energy (E) absorbed in a small cylinder of unit mass per centimeter square about the central or peripheral axis, and the energy (E{sub in}) absorbed inside irradiated length (L) were subsequently extracted from the dose distribution. Results: Extensive results of FWHM, FWTM, and E{sub in}/E were presented on the central and peripheral axes of infinitely long PMMA (diameters 6–50 cm) and water (diameters 6–55 cm) cylinders with L < 100 cm. FWHM was greater than the primary beam width only on the central axes of large phantoms and also with L ranging from a few centimeter to about 33 cm. FWTM generally increased with phantom diameter, and could be up to 32 cm longer than irradiated length, depending on L, phantom diameter and axis, but was insensitive to phantom material (PMMA or water). E{sub in}/E increased with L and asymptotically approached unity for large L. As phantom diameter increased, E{sub in}/E generally decreased, but asymptotically approached constant levels on the peripheral axes of large phantoms. A heuristic explanation of dose distribution width results was presented. Conclusions: This study enables the reader to gain a comprehensive view of dose distribution width and energy absorption and provides useful data for estimating doses to organs inside or beyond the irradiated region. The dose length product (DLP) presented by CT scanners is equal to neither E nor E{sub in}. Both E and E{sub in} can be evaluated using the equations and results presented in this paper and are robust with both constant and variable tube current scanning techniques.« less

Insights into the mechanism of X-ray-induced disulfide-bond cleavage in lysozyme crystals based on EPR, optical absorption and X-ray diffraction studies

PubMed Central

Sutton, Kristin A.; Black, Paul J.; Mercer, Kermit R.; Garman, Elspeth F.; Owen, Robin L.; Snell, Edward H.; Bernhard, William A.

2013-01-01

Electron paramagnetic resonance (EPR) and online UV–visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage. Online UV–visible spectroscopy showed that upon X-irradiation, disulfide radicalization appeared to saturate at an absorbed dose of approximately 0.5–0.8 MGy, in contrast to the saturating dose of ∼0.2 MGy observed using EPR at much lower dose rates. The observations suggest that a multi-track model involving product formation owing to the interaction of two separate tracks is a valid model for radiation damage in protein crystals. The saturation levels are remarkably consistent given the widely different experimental parameters and the range of total absorbed doses studied. The results indicate that even at the lowest doses used for structural investigations disulfide bonds are already radicalized. Multi-track considerations offer the first step in a comprehensive model of radiation damage that could potentially lead to a combined computational and experimental approach to identifying when damage is likely to be present, to quantitate it and to provide the ability to recover the native unperturbed structure. PMID:24311579

Relationship between dose of emamectin benzoate and molting response of ovigerous American lobsters (Homarus americanus).

PubMed

Waddy, S L; Merritt, V A; Hamilton-Gibson, M N; Aiken, D E; Burridge, L E

2007-05-01

A widely-prescribed treatment to control sea lice on cultured salmon is the administration of feed medicated with SLICE (active ingredient emamectin benzoate (EMB)). High doses of EMB can disrupt the molt cycle of ovigerous American lobsters, causing them to enter proecdysis prematurely and lose their attached eggs when the shell is cast. To determine the dose response to EMB, lobsters were forced to ingest doses that ranged from 0.05 to 0.39 microg g(-1). A significant proportion of lobsters given doses of 0.39 and 0.22 microg g(-1) (37% and 23%, respectively) molted prematurely, almost a year earlier than the control group. All the lobsters in the 0.05 and 0.12 microg g(-1) groups molted at the normal time and the mean time of molt was similar to that of the control group. Thus, the no-observed-effect level (NOEL) and lowest-observed-effect level (LOEL) of EMB on the molt cycle were 0.12 and 0.22 microg EMB g(-1) lobster, respectively. To acquire the LOEL, a 500-g lobster would have to consume 22 g of salmon feed medicated with SLICE at a level of 5 microg EMB g(-1) feed.

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

Simulation of major space particles toward selected materials in a near-equatorial low earth orbit

NASA Astrophysics Data System (ADS)

Suparta, Wayan; Zulkeple, Siti Katrina

2017-05-01

A low earth orbit near the equator (LEO-NEqO) is exposed to the highest energies from galactic cosmic rays (GCR) and from trapped protons with a wide range of energies. Moreover, GCR fluxes were seen to be the highest in 2009 to 2010 when communication belonging to the RazakSAT-1 satellite was believed to have been lost. Hence, this study aimed to determine the influence of the space environment toward the operation of LEO-NEqO satellites by investigating the behavior of major space particles toward satellite materials. The space environment was referred to GCR protons and trapped protons. Their fluxes were obtained from the Space Environment Information System (SPENVIS) and their tracks were simulated through three materials using a simulation program called Geometry and Tracking (Geant4). The materials included aluminum (Al), gallium arsenide (GaAs) and silicon (Si). Then the total ionizing dose (TID) and non-ionizing dose (NIEL) were calculated for a three-year period. Simulations showed that GCR traveled at longer tracks and produced more secondary radiation than trapped protons. Al turned out to receive the lowest total dose, while GaAs showed to be susceptible toward GCR than Si. However, trapped protons contributed the most in spacecraft doses where Si received the highest doses. Finally, the comparison between two Geant4 programs revealed the estimated doses differed at <18%.

Use of a Gafchromic film HD-V2 for the profile measurement of energetic ion beams

NASA Astrophysics Data System (ADS)

Yuri, Yosuke; Ishizaka, Tomohisa; Agematsu, Takashi; Yuyama, Takahiro; Seito, Hajime; Okumura, Susumu

2017-09-01

The coloration response of a radiochromic film, Gafchromic HD-V2, to ion beams was investigated to apply the film to measuring the transverse intensity distribution of large-area ion beams. HD-V2 films were, therefore, irradiated with proton (10 MeV) and several heavy-ion (4.1-27 MeV/u) beams in a wide fluence range at the azimuthally-varying-field cyclotron facility in National Institutes for Quantum and Radiological Science and Technology, and read with an image scanner to analyze changes in the optical density. It was shown that the available fluence range (106-1011 ions/cm2) of HD-V2 depends strongly on ion species, i.e., linear energy transfer (LET). In addition, the reduction of the sensitivity to dose was shown over a wide LET range. The transverse intensity distribution of a large-area ion beam was measured using a response function determined from the measured data. We have demonstrated that the Gafchromic film HD-V2 is useful for measuring the intensity distribution at a low fluence and thus evaluating the characteristics of various ion beams.

Urinary Phenylacetylglutamine as Dosing Biomarker for Patients with Urea Cycle Disorders

PubMed Central

Mokhtarani, M; Diaz, GA; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, SA; Gallagher, R; Bartholomew, D; Harding, CO; Korson, MS; McCandless, SE; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, JL; Sreenath-Nagamani, Sandesh; Summar, M; LeMons, C; Dickinson, K; Coakley, DF; Moors, TL; Lee, B; Scharschmidt, BF

2013-01-01

We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). Study Design These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6–17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Results Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5–31.8 g/day and of sodium phenylbutyrate ranging from 1.3–31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% –5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% -to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r=0.730, p<0.001) or as total 24-hour excretion (r=0.791 p<0.001), followed by plasma phenylacetylglutamine AUC24-hour, plasma phenylacetic acid AUC24-hour and phenylbutyric acid AUC24-hour. Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. Conclusion The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples to capture trough and peak, and the inconsistency between phenylacetic acid and urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate strongly with dose and appear to be clinically useful non-invasive biomarkers for compliance and therapeutic monitoring. PMID:22958974

Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders.

PubMed

Mokhtarani, M; Diaz, G A; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, S A; Gallagher, R; Bartholomew, D; Harding, C O; Korson, M S; McCandless, S E; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, J L; Sreenath-Nagamani, Sandesh; Summar, M; Lemons, C; Dickinson, K; Coakley, D F; Moors, T L; Lee, B; Scharschmidt, B F

2012-11-01

We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6-17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5 to 31.8 g/day and of sodium phenylbutyrate ranging from 1.3 to 31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% to 5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r = 0.730, p < 0.001) or as total 24-hour excretion (r = 0.791 p<0.001), followed by plasma phenylacetylglutamine AUC(24-hour), plasma phenylacetic acid AUC(24-hour) and phenylbutyric acid AUC(24-hour). Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples to capture trough and peak, and the inconsistency between phenylacetic acid and urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate strongly with dose and appear to be clinically useful non-invasive biomarkers for compliance and therapeutic monitoring. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-F-T-157: Physics Considerations Regarding Dosimetric Accuracy of Analytical Dose Calculations for Small Field Proton Therapy: A Monte Carlo Study

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

Geng, C; Nanjing University of Aeronautics and Astronautics, Nanjing; Daartz, J

Purpose: To evaluate the accuracy of dose calculations by analytical dose calculation methods (ADC) for small field proton therapy in a gantry based passive scattering facility. Methods: 50 patients with intra-cranial disease were evaluated in the study. Treatment plans followed standard prescription and optimization procedures of proton stereotactic radiosurgery. Dose distributions calculated with the Monte Carlo (MC) toolkit TOPAS were used to represent delivered treatments. The MC dose was first adjusted using the output factor (OF) applied clinically. This factor is determined from the field size and the prescribed range. We then introduced a normalization factor to measure the differencemore » in mean dose between the delivered dose (MC dose with OF) and the dose calculated by ADC for each beam. The normalization was determined by the mean dose of the center voxels of the target area. We compared delivered dose distributions and those calculated by ADC in terms of dose volume histogram parameters and beam range distributions. Results: The mean target dose for a whole treatment is generally within 5% comparing delivered dose (MC dose with OF) and ADC dose. However, the differences can be as great as 11% for shallow and small target treated with a thick range compensator. Applying the normalization factor to the MC dose with OF can reduce the mean dose difference to less than 3%. Considering range uncertainties, the generally applied margins (3.5% of the prescribed range + 1mm) to cover uncertainties in range might not be sufficient to guarantee tumor coverage. The range difference for R90 (90% distal dose falloff) is affected by multiple factors, such as the heterogeneity index. Conclusion: This study indicates insufficient accuracy calculating proton doses using ADC. Our results suggest that uncertainties of target doses are reduced using MC techniques, improving the dosimetric accuracy for proton stereotactic radiosurgery. The work was supported by NIH/NCI under CA U19 021239. CG was partially supported by the Chinese Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087).« less

Over-exposure correction in knee cone-beam CT imaging with automatic exposure control using a partial low dose scan

NASA Astrophysics Data System (ADS)

Choi, Jang-Hwan; Muller, Kerstin; Hsieh, Scott; Maier, Andreas; Gold, Garry; Levenston, Marc; Fahrig, Rebecca

2016-03-01

C-arm-based cone-beam CT (CBCT) systems with flat-panel detectors are suitable for diagnostic knee imaging due to their potentially flexible selection of CT trajectories and wide volumetric beam coverage. In knee CT imaging, over-exposure artifacts can occur because of limitations in the dynamic range of the flat panel detectors present on most CBCT systems. We developed a straightforward but effective method for correction and detection of over-exposure for an Automatic Exposure Control (AEC)-enabled standard knee scan incorporating a prior low dose scan. The radiation dose associated with the low dose scan was negligible (0.0042mSv, 2.8% increase) which was enabled by partially sampling the projection images considering the geometry of the knees and lowering the dose further to be able to just see the skin-air interface. We combined the line integrals from the AEC and low dose scans after detecting over-exposed regions by comparing the line profiles of the two scans detector row-wise. The combined line integrals were reconstructed into a volumetric image using filtered back projection. We evaluated our method using in vivo human subject knee data. The proposed method effectively corrected and detected over-exposure, and thus recovered the visibility of exterior tissues (e.g., the shape and density of the patella, and the patellar tendon), incorporating a prior low dose scan with a negligible increase in radiation exposure.

A survey of physics and dosimetry practice of permanent prostate brachytherapy in the United States.

PubMed

Prete, J J; Prestidge, B R; Bice, W S; Friedland, J L; Stock, R G; Grimm, P D

1998-03-01

To obtain data with regard to current physics and dosimetry practice in transperineal interstitial permanent prostate brachytherapy (TIPPB) in the U.S. by conducting a survey of institutions performing this procedure with the greatest frequency. Seventy brachytherapists with the greatest volume of TIPPB cases in 1995 in the U.S. were surveyed. The four-page comprehensive questionnaire included questions on both clinical and physics and dosimetry practice. Individuals not responding initially were sent additional mailings and telephoned. Physics and dosimetry practice summary statistics are reported. Clinical practice data is reported separately. Thirty-five (50%) surveys were returned. Participants included 29 (83%) from the private sector and 6 (17%) from academic programs. Among responding clinicians, 125I (89%) is used with greater frequency than 103Pd (83%). Many use both (71%). Most brachytherapists perform preplans (86%), predominately employing ultrasound imaging (85%). Commercial treatment planning systems are used more frequently (75%) than in-house systems (25%). Preplans take 2.5 h (avg.) to perform and are most commonly performed by a physicist (69%). A wide range of apparent activities (mCi) is used for both 125I (0.16-1.00, avg. 0.41) and 103Pd (0.50-1.90, avg. 1.32). Of those assaying sources (71%), the range in number assayed (1 to all) and maximum accepted difference from vendor stated activity (2-20%) varies greatly. Most respondents feel that the manufacturers criteria for source activity are sufficiently stringent (88%); however, some report that vendors do not always meet their criteria (44%). Most postimplant dosimetry imaging occurs on day 1 (41%) and consists of conventional x-rays (83%), CT (63%), or both (46%). Postimplant dosimetry is usually performed by a physicist (72%), taking 2 h (avg.) to complete. Calculational formalisms and parameters vary substantially. At the time of the survey, few institutions have adopted AAPM TG-43 recommendations (21%). Only half (50%) of those not using TG-43 indicated an intent to do so in the future. Calculated doses at 1 cm from a single 1 mCi apparent activity source permanently implanted varied significantly. For 125I, doses calculated ranged from 13.08-40.00 Gy and for 103Pd, from 3.10 to 8.70 Gy. While several areas of current physics and dosimetry practice are consistent among institutions, treatment planning and dose calculation techniques vary considerably. These data demonstrate a relative lack of consensus with regard to these practices. Furthermore, the wide variety of calculational techniques and benchmark data lead to calculated doses which vary by clinically significant amounts. It is apparent that the lack of standardization with regard to treatment planning and dose calculation practice in TIPPB must be addressed prior to performing any meaningful comparison of clinical results between institutions.

Patterns of patient specific dosimetry in total body irradiation

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

Akino, Yuichi; Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871; McMullen, Kevin P.

2013-04-15

Purpose: Total body irradiation (TBI) has been used for bone marrow transplant for hematologic and immune deficiency conditions. The goal of TBI is to deliver a homogeneous dose to the entire body, with a generally accepted range of dose uniformity being within {+-}10% of the prescribed dose. The moving table technique for TBI could make dose uniform in whole body by adjusting couch speed. However, it is difficult to accurately estimate the actual dose by calculation and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors present patterns of patient-specific IVD in 161 TBI patients treated at ourmore » institution. Methods: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial Products, Inc., Fishers, IN) were used for TBI treatment. During treatment, OneDose{sup TM} (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect Transistor detectors were placed at patient body surface; both entrance and exit side of the beam at patient head, neck, mediastinum, umbilicus, and knee to estimate midplane dose. When large differences (>10%) between the prescribed and measured dose were observed, dose delivery was corrected for subsequent fractions by the adjustment of couch speed and/or bolus placement. Under IRB exempt status, the authors retrospectively analyzed the treatment records of 161 patients who received TBI treatment between 2006 and 2011. Results: Across the entire cohort, the median {+-} SD (range) percent variance between calculated and measured dose for head, neck, mediastinum, umbilicus, and knee was -2.3 {+-} 10.2% (-66.2 to +35.3), 1.1 {+-} 11.5% (-62.2 to +40.3), -1.9 {+-} 9.5% (-66.4 to +46.6), -1.1 {+-} 7.2% (-35.2 to +42.9), and 3.4 {+-} 12.2% (-47.9 to +108.5), respectively. More than half of treatments were within {+-}10% of the prescribed dose for all anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was within {+-}10%. However, some large differences greater than 35% were also found at several points. For one case, the knee received double the prescribed dose. When the dose differences for multiple fractions were averaged, compliance ({+-}10%) between the prescription and measured dose was improved compared to the dose difference of the first single fraction, for example, as at umbilicus, which improved from 83.9% to 98.5%. Conclusions: Actual dose measurement analysis of TBI patients revealed a potentially wide variance from the calculated dose. Based from their IVD method for TBI using Cobalt-60 irradiator and moving table, {+-}10% over entire body is hard to achieve. However, it can be significantly improved with immediate feedback after the first fraction prior to subsequent treatments.« less

Structural analysis of ion-implanted chemical-vapor-deposited diamond by transmission electron microscope

NASA Astrophysics Data System (ADS)

Jiang, N.; Deguchi, M.; Wang, C. L.; Won, J. H.; Jeon, H. M.; Mori, Y.; Hatta, A.; Kitabatake, M.; Ito, T.; Hirao, T.; Sasaki, T.; Hiraki, A.

1997-04-01

A transmission electron microscope (TEM) study of ion-implanted chemical-vapor-deposited (CVD) diamond is presented. CVD diamond used for transmission electron microscope observation was directly deposited onto Mo TEM grids. As-deposited specimens were irradiated by C (100 keV) ions at room temperature with a wide range of implantation doses (10 12-10 17/cm 2). Transmission electron diffraction (TED) patterns indicate that there exists a critical dose ( Dc) for the onset of amorphization of CVD diamond as a result of ion induced damage and the value of critical dose is confirmed to be about 3 × 10 15/cm 2. The ion-induced transformation process is clearly revealed by high resolution electron microscope (HREM) images. For a higher dose implantation (7 × 10 15/cm 2) a large amount of diamond phase is transformed into amorphous carbon and many tiny misoriented diamond blocks are found to be left in the amorphous solid. The average size of these misoriented diamond blocks is only about 1-2 nm. Further bombardment (10 17/cm 2) almost kills all of the diamond phase within the irradiated volume and moreover leads to local formation of micropolycrystalline graphite.

Methylphenidate as a cognitive enhancer in healthy young people

PubMed Central

Batistela, Silmara; Bueno, Orlando Francisco Amodeo; Vaz, Leonardo José; Galduróz, José Carlos Fernandes

2016-01-01

ABSTRACT The so-called cognitive enhancers have been widely and increasingly used by healthy individuals who seek improvements in cognitive performance despite having no pathologies. One drug used for this purpose is methylphenidate, a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD). Objective: The aim of the present study was to test the effect of acute administration of varying doses of methylphenidate (10 mg, 20 mg, 40 mg and placebo) on a wide range of cognitive functions in healthy young people. Methods: A total of 36 young university students and graduates participated in the study. The participants underwent tests of attention and of episodic, and working memory. Results: No differences in performance were observed on any of the tests. There was a dose-dependent (40 mg > placebo) effect on self-reported wellbeing. Conclusions: According to the recent literature, psychostimulant medications, such as methylphenidate, improve performance when cognitive processes are below an optimal level, which was not the case for the subjects of the present study. We suggest the impression that methylphenidate enhances cognitive performance in healthy young people, justifying its use, may be due to improvements in subjective wellbeing promoted by the drug. PMID:29213444

Dosimetric response for crystalline and nanostructured aluminium oxide to a high-current pulse electron beam.

PubMed

Nikiforov, S V; Kortov, V S

2014-11-01

The main thermoluminescent (TL) and dosimetric properties of the detectors based on anion-defective crystalline and nanostructured aluminium oxide after exposure to a high-current pulse electron beam are studied. TL peaks associated with deep-trapping centres are registered. It is shown that the use of deep-trap TL at 200-600°С allows registering absorbed doses up to 750 kGy for single-crystalline detectors and those up to 6 kGy for nanostructured ones. A wide range of the doses registered, high reproducibility of the TL signal and low fading contribute to a possibility of using single-crystalline and nanostructured aluminium oxide for the dosimetry of high-current pulse electron beams. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dosimetric Comparison in Breast Radiotherapy of 4 MV and 6 MV on Physical Chest Simulator

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

Donato da Silva, Sabrina; Passos Ribeiro Campos, Tarcisio; Batista Nogueira, Luciana

2015-07-01

According to the World Health Organization (2014) breast cancer is the main cause of death by cancer in women worldwide. The biggest challenge of radiotherapy in the treatment of cancer is to deposit the entire prescribed dose homogeneously in the breast, sparing the surrounding tissue. In this context, this paper aimed at evaluating and comparing internal dose distribution in the mammary gland based on experimental procedures submitted to two distinct energy spectra produced in breast cancer radiotherapy. The methodology consisted of reproducing opposite parallel fields used in the treatment of breast tumors in a chest phantom. This simulator with syntheticmore » breast, composed of equivalent tissue material (TE), was previously developed by the NRI Research Group (UFMG). The computer tomography (CT) scan of the simulator was obtained antecedently. The radiotherapy planning systems (TPS) in the chest phantom were performed in the ECLIPSE system from Varian Medical Systems and CAT 3D system from MEVIS. The irradiations were reproduced in the Varian linear accelerator, model SL- 20 Precise, 6 MV energy and Varian linear accelerator, 4 MV Clinac 6x SN11 model. Calibrations of the absorbed dose versus optical density from radiochromic films were generated in order to obtain experimental dosimetric distribution at the films positioned within the glandular and skin equivalent tissues of the chest phantom. The spatial dose distribution showed equivalence with the TPS on measurement data performed in the 6 MV spectrum. The average dose found in radiochromic films placed on the skin ranged from 49 to 79%, and from 39 to 49% in the mammary areola, for the prescribed dose. Dosimetric comparisons between the spectra of 4 and 6 MV, keeping the constant geometry of the fields applied in the same phantom, will be presented showing their equivalence in breast radiotherapy, as well as the variations will be discussed. To sum up, the dose distribution has reached the value expected in the breast dose of the 180 cGy in a wide range of the film in the glandular TE in both spectra. (authors)« less

Characterization of Al2O3 optically stimulated luminescence films for 2D dosimetry using a 6 MV photon beam

NASA Astrophysics Data System (ADS)

Ahmed, M. F.; Shrestha, N.; Schnell, E.; Ahmad, S.; Akselrod, M. S.; Yukihara, E. G.

2016-11-01

This work evaluates the dosimetric properties of newly developed optically stimulated luminescence (OSL) films, fabricated with either Al2O3:C or Al2O3:C,Mg, using a prototype laser scanning reader, a developed image reconstruction algorithm, and a 6 MV therapeutic photon beam. Packages containing OSL films (Al2O3:C and Al2O3:C,Mg) and a radiochromic film (Gafchromic EBT3) were irradiated using a 6 MV photon beam using different doses, field sizes, with and without wedge filter. Dependence on film orientation of the OSL system was also tested. Diode-array (MapCHECK) and ionization chamber measurements were performed for comparison. The OSLD film doses agreed with the MapCHECK and ionization chamber data within the experimental uncertainties (<2% at 1.5 Gy). The system background and minimum detectable dose (MDD) were  <0.5 mGy, and the dose response was approximately linear from the MDD up to a few grays (the linearity correction was  <10% up to ~2-4 Gy), with no saturation up to 30 Gy. The dose profiles agreed with those obtained using EBT3 films (analyzed using the triple channel method) in the high dose regions of the images. In the low dose regions, the dose profiles from the OSLD films were more reproducible than those from the EBT3 films. We also demonstrated that the OSL film data are independent on scan orientation and field size over the investigated range. The results demonstrate the potential of OSLD films for 2D dosimetry, particularly for the characterization of small fields, due to their wide dynamic range, linear response, resolution and dosimetric properties. The negligible background and potential simple calibration make these OSLD films suitable for remote audits. The characterization presented here may motivate further commercial development of a 2D dosimetry system based on the OSL from Al2O3:C or Al2O3:C,Mg.

Model Comparisons For Space Solar Cell End-Of-Life Calculations

NASA Astrophysics Data System (ADS)

Messenger, Scott; Jackson, Eric; Warner, Jeffrey; Walters, Robert; Evans, Hugh; Heynderickx, Daniel

2011-10-01

Space solar cell end-of-life (EOL) calculations are performed over a wide range of space radiation environments for GaAs-based single and multijunction solar cell technologies. Two general semi-empirical approaches will used to generate these EOL calculation results: 1) the JPL equivalent fluence (EQFLUX) and 2) the NRL displacement damage dose (SCREAM). This paper also includes the first results using the Monte Carlo-based version of SCREAM, called MC- SCREAM, which is now freely available online as part of the SPENVIS suite of programs.

[Determination of total phthalates in perfume and their exposure assessment].

PubMed

Zhao, Sihan; Wang, Zhengmeng; Deng, Hongxia; Duan, Jiahui; Wang, Jinyi; Liu, Shuhui

2017-12-08

A novel method for rapid screening of phthalates (PAEs) in perfumes was developed. The PAEs were hydrolyzed to phthalic acid (PA), and the PA in the acidified solution was extracted with tributyl phosphate (TBP) which was detected by high performance liquid chromatography-diode array detection (HPLC-DAD). Meanwhile exposure dose to PAEs was estimated by the percentage of a topically applied dose that permeates the skin. The parameters such as the concentration and volume of KOH, the volume of ethanol, hydrolysis time and temperature were employed to evaluate the hydrolysis efficiency of PAEs. The optimized hydrolysis conditions were 10 mL of 4 mol/L KOH, and 1 mL of ethanol at 80℃ for 20 min. The linear range of phthalic acid was 3-240 μmol/L with a good correlation coefficient ( R 2 =0.9991). The limits of detection (LOD) and quantification (LOQ) were 4.6 μmol/kg and 5.9 μmol/kg, respectively. The recoveries varied from 83.4% to 92.7% with relative standard deviations equal to or lower than 6.8%( n =5). A total of 35 perfume samples were determined, and the contents of total PAEs were found in the range of < LOD-77.738 mmol/kg, and the max exposure dose to PAEs for female adults was 0.4742 μg/(kg·d) through use of perfumes. The method is simple and reliable, and has a wide range of applicability. It can be used as a new choice for the detection of PAEs in perfume.

Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90days of exposure to hexavalent chromium in drinking water.

PubMed

Kopec, Anna K; Kim, Suntae; Forgacs, Agnes L; Zacharewski, Timothy R; Proctor, Deborah M; Harris, Mark A; Haws, Laurie C; Thompson, Chad M

2012-02-15

Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90days of exposure to 0, 0.3, 4, 14, 60, 170 or 520mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose-response modeling identified >80% of the differentially expressed genes exhibited sigmoidal dose-response curves with EC(50) values ranging from 10 to 100mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC(50) values <10mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluation of 16 genotype-guided Warfarin Dosing Algorithms in 310 Korean Patients Receiving Warfarin Treatment: Poor Prediction Performance in VKORC1 1173C Carriers.

PubMed

Yang, Mina; Choi, Rihwa; Kim, June Soo; On, Young Keun; Bang, Oh Young; Cho, Hyun-Jung; Lee, Soo-Youn

2016-12-01

The purpose of this study was to evaluate the performance of 16 previously published warfarin dosing algorithms in Korean patients. The 16 algorithms were selected through a literature search and evaluated using a cohort of 310 Korean patients with atrial fibrillation or cerebral infarction who were receiving warfarin therapy. A large interindividual variation (up to 11-fold) in warfarin dose was observed (median, 25 mg/wk; range, 7-77 mg/wk). Estimated dose and actual maintenance dose correlated well overall (r range, 0.52-0.73). Mean absolute error (MAE) of the 16 algorithms ranged from -1.2 to -20.1 mg/wk. The percentage of patients whose estimated dose fell within 20% of the actual dose ranged from 1.0% to 49%. All algorithms showed poor accuracy with increased MAE in a higher dose range. Performance of the dosing algorithms was worse in patients with VKORC1 1173TC or CC than in total (r range, 0.38-0.61 vs 0.52-0.73; MAE range, -2.6 to -28.0 mg/wk vs -1.2 to -20.1 mg/wk). The algorithms had comparable prediction abilities but showed limited accuracy depending on ethnicity, warfarin dose, and VKORC1 genotype. Further studies are needed to develop genotype-guided warfarin dosing algorithms with greater accuracy in the Korean population. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Shared dosimetry error in epidemiological dose-response analyses

DOE PAGES

Stram, Daniel O.; Preston, Dale L.; Sokolnikov, Mikhail; ...

2015-03-23

Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takesmore » up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed.« less

Suppression of ciprofloxacin-induced resistant Pseudomonas aeruginosa in a dynamic kill curve system.

PubMed

Wu, Benjamin M; Sabarinath, Sreedharan N; Rand, Kenneth; Johnson, Judith; Derendorf, Hartmut

2011-06-01

Current dosing approaches for treating microbial infections ignore resistant subpopulations. A clinical isolate of Pseudomonas aeruginosa was cultured in a dynamic in vitro kill curve system designed to simulate the half-lives of drugs in order to evaluate the drug-microbial response relationship. The first dose of ciprofloxacin (CIP) uses a concentration equivalent to the unbound fraction of a 200mg clinical dose. A second dose of 200mg or 600 mg CIP, or ceftriaxone (CFX) or gentamicin (GEN) was administered at 12h. Dynamics of the minimum inhibitory concentration (MIC) were assessed using Etest strips before and throughout the CIP treatment period. In addition, the microbroth dilution method was used to evaluate drug susceptibility across a wide range of antibiotics using samples from before and after CIP exposure. A significant loss of CIP effects was observed at the second dose. Cross-resistance to many antibiotics (cefoxitin, cefuroxime, cefotetan, ampicillin and ertapenem) was observed. GEN, but not CFX or high-dose CIP, was sufficient to suppress the developed resistant subpopulation following the initial CIP exposure. The CIP MIC increased substantially from 0.13 μg/mL pre dose to 4 μg/mL at 12h after a CIP dose. In addition, aztreonam induced a similar resistance pattern as CIP, indicating that induction of resistance was not limited to fluoroquinolones. In conclusion, the in vitro dynamic kill curve system revealed that aminoglycosides, more than other classes of antibiotics, were effective against the CIP-induced resistant subpopulations. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Routine Vaccination Coverage in Northern Nigeria: Results from 40 District-Level Cluster Surveys, 2014-2015

PubMed Central

Ogbuanu, Ikechukwu U.; Adegoke, Oluwasegun J.; Scobie, Heather M.; Uba, Belinda V.; Wannemuehler, Kathleen A.; Ruiz, Alicia; Elmousaad, Hashim; Ohuabunwo, Chima J.; Mustafa, Mahmud; Nguku, Patrick; Waziri, Ndadilnasiya Endie; Vertefeuille, John F.

2016-01-01

Background Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. Methods Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014–2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12–23 months was documented based on vaccination card or caretaker’s recall. District-level coverage estimates were calculated using survey methods. Results Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1–63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guérin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%–139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). Conclusions Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and providing data to assess and remediate issues contributing to poor vaccination coverage could serve as an example in countries with sub-optimal vaccination coverage, similar to Nigeria. PMID:27936077

Routine Vaccination Coverage in Northern Nigeria: Results from 40 District-Level Cluster Surveys, 2014-2015.

PubMed

Gunnala, Rajni; Ogbuanu, Ikechukwu U; Adegoke, Oluwasegun J; Scobie, Heather M; Uba, Belinda V; Wannemuehler, Kathleen A; Ruiz, Alicia; Elmousaad, Hashim; Ohuabunwo, Chima J; Mustafa, Mahmud; Nguku, Patrick; Waziri, Ndadilnasiya Endie; Vertefeuille, John F

2016-01-01

Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014-2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12-23 months was documented based on vaccination card or caretaker's recall. District-level coverage estimates were calculated using survey methods. Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1-63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guérin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%-139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and providing data to assess and remediate issues contributing to poor vaccination coverage could serve as an example in countries with sub-optimal vaccination coverage, similar to Nigeria.

Genome-wide association study of therapeutic opioid dosing identifies a novel locus upstream of OPRM1

PubMed Central

Smith, Andrew H.; Jensen, Kevin P.; Li, Jin; Nunez, Yaira; Farrer, Lindsay A.; Hakonarson, Hakon; Cook-Sather, Scott D.; Kranzler, Henry R.; Gelernter, Joel

2017-01-01

Opioids are very effective analgesics, but they are also highly addictive. Methadone is used to treat opioid dependence (OD), acting as a selective agonist at the μ-opioid receptor encoded by the gene OPRM1. Determining the optimal methadone maintenance dose is time-consuming; currently, no biomarkers are available to guide treatment. In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study (GWAS) of usual daily methadone dose. In African-American (AA) OD subjects (n = 383), we identified a genome-wide significant association between therapeutic methadone dose (mean = 68.0 mg, standard deviation (SD) = 30.1 mg) and rs73568641 (P = 2.8 × 10−8), the nearest gene (306 kilobases) being OPRM1. Each minor (C) allele corresponded to an additional ~20 mg/day of oral methadone, an effect specific to AAs. In European-Americans (EAs) (n = 1,027), no genome-wide significant associations with methadone dose (mean = 77.8 mg, SD = 33.9 mg) were observed. In an independent set of opioid-naïve AA children being treated for surgical pain, rs73568641-C was associated with a higher required dose of morphine (n = 241, P = 3.9 × 10−2). Similarly, independent genomic loci previously shown to associate with higher opioid analgesic dose were associated with higher methadone dose in the OD sample (AA and EA: n = 1,410, genetic score P = 1.3 × 10−3). The present results in AAs indicate that genetic variants influencing opioid sensitivity across different clinical settings could contribute to precision pharmacotherapy for pain and addiction. PMID:28115739

Dosimetric predictors of radiation-induced pericardial effusion in esophageal cancer.

PubMed

Ogino, Ichiro; Watanabe, Shigenobu; Sakamaki, Kentaro; Ogino, Yuka; Kunisaki, Chikara; Kimura, Kazuo

2017-07-01

To evaluate the dose-volume parameters of the pericardium and heart in order to reduce the risk of radiation-induced pericardial effusion (PE) and symptomatic PE (SPE) in esophageal cancer patients treated with concurrent chemoradiotherapy. In 86 of 303 esophageal cancer patients, follow-up CT was obtained at least 24 months after concurrent chemoradiotherapy. Correlations between clinical factors, including risk factors for cardiac disease, dosimetric factors, and the incidence of PE and SPE after radiotherapy were analyzed using Cox proportional hazard regression analysis. Significant dosimetric factors with the highest hazard ratios were investigated using zones separated according to their distance from esophagus. PE developed in 49 patients. Univariate analysis showed the mean heart dose, heart V 5 -V 55 , mean pericardium dose, and pericardium V 5 -V 50 to all significantly affect the incidence of PE. Additionally, body surface area was correlated with the incidence of PE in multivariate analysis. Grade 3 and 4 SPE developed in 5 patients. The pericardium V 50 and pericardium D 10 significantly affected the incidence of SPE. The pericardium V 50 in patients with SPE ranged from 17.1 to 21.7%. Factors affecting the incidence of SPE were the V 50 of the pericardium zones within 3 cm and 4 cm of the esophagus. A wide range of radiation doses to the heart and pericardium were related to the incidence of PE. A pericardium V 50  ≤ 17% is important to avoid symptomatic PE in esophageal cancer patients treated with concurrent chemoradiotherapy.

Food avoidance behavior to dietary octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) exposure in the northern bobwhite (Colinusvirginianus).

PubMed

Johnson, Mark S; Gogal, Robert M; Larsen, Calvert T

2005-08-13

High-melting explosive (HMX; octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) is a widely utilized explosive component of munitions used by the military. Consequently, production and use through testing and training at military installations has resulted in deposition of HMX in soil. Since these areas are often used by birds, the oral toxicity of HMX exposure to northern bobwhite (Colinus virginianus) was evaluated. Attempts to determine the acute lethal dose were unsuccessful. Initially, 8 birds (1 male/1 female per dose group) were orally dosed at levels ranging from 125 to 2125 mg HMX/kg body weight. A single death at the midrange resulted in subsequent trials of oral doses up to 10,760 mg/kg body weight. Only a single death occurred at 7173 mg/kg. A subsequent 28-d feeding study was then conducted to evaluate the potential for toxicity resulting from repetitive oral exposures. Northern bobwhite were exposed to concentrations of HMX in feed of either 10000, 1000, 100, or 0 mg/kg. These exposures resulted in a clear concentration-related reduction in feed consumption and body mass. Reductions in egg production in females were correlated with changes in body mass and feed consumption. Other physiological indicators were consistent with a considerable reduction in feed intake. These results suggest that HMX concentration is responsible for intense feed aversion behavior and thus not likely a factor that would appreciably contribute to risk for wild birds at military ranges.

Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants

PubMed Central

Lalwani, Sanjay K.; Agarkhedkar, Sharad; Sundaram, Balasubramanian; Mahantashetti, Niranjana S.; Malshe, Nandini; Agarkhedkar, Shalaka; Van Der Meeren, Olivier; Mehta, Shailesh; Karkada, Naveen; Han, Htay Htay; Mesaros, Narcisa

2017-01-01

ABSTRACT Multivalent combination vaccines have reduced the number of injections and therefore improved vaccine acceptance, timeliness of administration and global coverage. The hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib; Infanrix hexa™) vaccine, administered according to various schedules, is widely used for the primary vaccination of infants worldwide. In the current publication, we are presenting the immunogenicity and safety of 3 doses of DTPa-HBV-IPV/Hib vaccine when administered to Indian infants. 224 healthy infants (mean age 6.8 weeks) were vaccinated at 6–10–14 weeks (W) of age (n = 112) or 2–4–6 months (M) of age (n = 112). One month after the third vaccine dose, the seroprotection/seropositivity status against diphtheria, pertussis, tetanus, polio, hepatitis B and Hib antigens ranged from 98.6% to 100% in both groups. The vaccine response rate to the pertussis antigens ranged from 97% to 100%. Pain (6–10–14W group: 25.2%; 2–4–6M group: 13.4%) and fever (15.3% and; 15.2%, respectively) were the most frequently reported solicited local and general symptoms. Unsolicited adverse events were reported for 35.7% (6–10–14W group) and 22.3% (2–4–6M group) of subjects. No vaccine related serious adverse events were reported. In conclusion, the hexavalent DTPa-HBV-IPV/Hib vaccine was immunogenic and well tolerated, irrespective of the dosing schedule. PMID:27629913

Use of social media is associated with short sleep duration in a dose-response manner in students aged 11 to 20 years.

PubMed

Sampasa-Kanyinga, Hugues; Hamilton, Hayley A; Chaput, Jean-Philippe

2018-04-01

This study examined the association between social media and sleep duration among Canadian students aged 11-20. Data from 5242 students were obtained from the 2015 Ontario Student Drug Use and Health Survey, a province-wide, school-based survey that has been conducted every two years since 1977. We measured the respondents' sleep duration against the recommended ranges of 9-11 h per night at 11-13 years of age, 8-10 h at 14-17 and 7-9 h per night for those aged 18 years or more. Overall, 36.4% of students met or exceeded the recommended sleep duration and 63.6% slept less than recommended, with 73.4% of students reporting that they used social media for at least one hour per day. After adjusting for various covariates, the use of social media was associated with greater odds of short sleep duration in a dose-response manner (p for linear trend <0.001). Odds ratios ranged from 1.82 for social media use of at least one hour per day to 2.98 for at least five hours per day. Greater use of social media was associated with shorter sleep duration in a dose-response fashion among Canadian students aged 11-20. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Management of neonatal abstinence syndrome: a national survey and review of practice.

PubMed

O'Grady, M J; Hopewell, J; White, M J

2009-07-01

To ascertain the present management of neonatal abstinence syndrome (NAS) in neonatal units in the United Kingdom (UK) and Ireland. Postal questionnaire to 235 neonatal units, with telephone follow-up of non-respondents. The response rate was 90%, and 96% of respondents had a formal NAS guideline. The median number of infants treated annually for NAS was 6 (range 1-100). The method of Finnegan was the most widely used scoring system (52%). Morphine sulphate was the most commonly used first line agent for both opiate (92%) and polysubstance (69%) withdrawal. Dosing regimens varied widely. Units using a maximum daily morphine dose of <400 microg/kg/day were more likely to require the addition of a second agent (76% vs 58%, p = 0.027). Phenobarbitone was the drug of choice to treat seizures secondary to both opiate and polydrug withdrawal in 73% and 81% of units, respectively. 29% of units allowed infants to be discharged home on medication. 58% of these allowed administration of opiates in the community and in almost half of cases this was managed by a parent. Mothers on methadone whose serology was positive for hepatitis B and/or C were four times more likely to be discouraged from breastfeeding. The majority of units currently use an opiate as the drug of first choice as recommended. Doses utilised and second agents added vary significantly between units. Many of our findings reflect the lack of high-quality randomised studies regarding management of NAS.

Dosimetric Implications of Residual Tracking Errors During Robotic SBRT of Liver Metastases

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

Chan, Mark; Tuen Mun Hospital, Hong Kong; Grehn, Melanie

Purpose: Although the metric precision of robotic stereotactic body radiation therapy in the presence of breathing motion is widely known, we investigated the dosimetric implications of breathing phase–related residual tracking errors. Methods and Materials: In 24 patients (28 liver metastases) treated with the CyberKnife, we recorded the residual correlation, prediction, and rotational tracking errors from 90 fractions and binned them into 10 breathing phases. The average breathing phase errors were used to shift and rotate the clinical tumor volume (CTV) and planning target volume (PTV) for each phase to calculate a pseudo 4-dimensional error dose distribution for comparison with themore » original planned dose distribution. Results: The median systematic directional correlation, prediction, and absolute aggregate rotation errors were 0.3 mm (range, 0.1-1.3 mm), 0.01 mm (range, 0.00-0.05 mm), and 1.5° (range, 0.4°-2.7°), respectively. Dosimetrically, 44%, 81%, and 92% of all voxels differed by less than 1%, 3%, and 5% of the planned local dose, respectively. The median coverage reduction for the PTV was 1.1% (range in coverage difference, −7.8% to +0.8%), significantly depending on correlation (P=.026) and rotational (P=.005) error. With a 3-mm PTV margin, the median coverage change for the CTV was 0.0% (range, −1.0% to +5.4%), not significantly depending on any investigated parameter. In 42% of patients, the 3-mm margin did not fully compensate for the residual tracking errors, resulting in a CTV coverage reduction of 0.1% to 1.0%. Conclusions: For liver tumors treated with robotic stereotactic body radiation therapy, a safety margin of 3 mm is not always sufficient to cover all residual tracking errors. Dosimetrically, this translates into only small CTV coverage reductions.« less

A PK-PD model of ketamine-induced high-frequency oscillations

NASA Astrophysics Data System (ADS)

Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Fath, Amanda B.; Purdon, Patrick L.; Wilson, Matthew A.; Brown, Emery N.

2015-10-01

Objective. Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PDs) of ketamine and the observed HFO power. Approach. In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by an HFO observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results. We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance. Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent range of effects that ketamine has.

Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?

PubMed

Sibley, Matthew; Roshan, Abishek; Alshami, Alanoud; Catapang, Marisa; Jöbsis, Jasper J; Kwok, Trevor; Polderman, Nonnie; Sibley, Jennifer; Matsell, Douglas G; Mammen, Cherry

2018-05-22

Historically, children with nephrotic syndrome (NS) across British Columbia (BC), Canada have been cared for without formal standardization of induction prednisone dosing. We hypothesized that local historical practice variation in induction dosing was wide and that children treated with lower doses had worse relapsing outcomes. This retrospective cohort study included 92 NS patients from BC Children's Hospital (1990-2010). We excluded secondary causes of NS, age < 1 year at diagnosis, steroid resistance, and incomplete induction due to early relapse. We explored cumulative induction dose and defined dosing quartiles. Relapsing outcomes above and below each quartile threshold were compared including total relapses in 2 years, time to first relapse, and proportions developing frequently relapsing NS (FRNS) or starting a steroid-sparing agent (SSA). Cumulative prednisone was widely distributed with approximated median, 1st, and 3rd quartile doses of 2500, 2000, and 3000 mg/m 2 respectively. Doses ≤ 2000 mg/m 2 showed significantly higher relapses (4.2 vs 2.7), shorter time to first relapse (61 vs 175 days), and higher SSA use (36 vs 14%) compared to higher doses. Doses ≤ 2500 mg/m 2 also showed significantly more relapses (3.9 vs 2.2), quicker first relapse (79 vs 208 days), and higher FRNS (37 vs 17%) and SSA use (28 vs 11%). Relapsing outcomes lacked statistical difference in ≤ 3000 vs > 3000 mg/m 2 doses. Results strongly justify our development of a standardized, province-wide NS clinical pathway to reduce practice variation and minimize under-treatment. The lowest induction prednisone dosing threshold to minimize future relapsing risks is likely between 2000 and 2500 mg/m 2 . Further prospective studies are warranted.

Hybrid dose calculation: a dose calculation algorithm for microbeam radiation therapy

NASA Astrophysics Data System (ADS)

Donzelli, Mattia; Bräuer-Krisch, Elke; Oelfke, Uwe; Wilkens, Jan J.; Bartzsch, Stefan

2018-02-01

Microbeam radiation therapy (MRT) is still a preclinical approach in radiation oncology that uses planar micrometre wide beamlets with extremely high peak doses, separated by a few hundred micrometre wide low dose regions. Abundant preclinical evidence demonstrates that MRT spares normal tissue more effectively than conventional radiation therapy, at equivalent tumour control. In order to launch first clinical trials, accurate and efficient dose calculation methods are an inevitable prerequisite. In this work a hybrid dose calculation approach is presented that is based on a combination of Monte Carlo and kernel based dose calculation. In various examples the performance of the algorithm is compared to purely Monte Carlo and purely kernel based dose calculations. The accuracy of the developed algorithm is comparable to conventional pure Monte Carlo calculations. In particular for inhomogeneous materials the hybrid dose calculation algorithm out-performs purely convolution based dose calculation approaches. It is demonstrated that the hybrid algorithm can efficiently calculate even complicated pencil beam and cross firing beam geometries. The required calculation times are substantially lower than for pure Monte Carlo calculations.

Development, validation, and implementation of a patient-specific Monte Carlo 3D internal dosimetry platform

NASA Astrophysics Data System (ADS)

Besemer, Abigail E.

Targeted radionuclide therapy is emerging as an attractive treatment option for a broad spectrum of tumor types because it has the potential to simultaneously eradicate both the primary tumor site as well as the metastatic disease throughout the body. Patient-specific absorbed dose calculations for radionuclide therapies are important for reducing the risk of normal tissue complications and optimizing tumor response. However, the only FDA approved software for internal dosimetry calculates doses based on the MIRD methodology which estimates mean organ doses using activity-to-dose scaling factors tabulated from standard phantom geometries. Despite the improved dosimetric accuracy afforded by direct Monte Carlo dosimetry methods these methods are not widely used in routine clinical practice because of the complexity of implementation, lack of relevant standard protocols, and longer dose calculation times. The main goal of this work was to develop a Monte Carlo internal dosimetry platform in order to (1) calculate patient-specific voxelized dose distributions in a clinically feasible time frame, (2) examine and quantify the dosimetric impact of various parameters and methodologies used in 3D internal dosimetry methods, and (3) develop a multi-criteria treatment planning optimization framework for multi-radiopharmaceutical combination therapies. This platform utilizes serial PET/CT or SPECT/CT images to calculate voxelized 3D internal dose distributions with the Monte Carlo code Geant4. Dosimetry can be computed for any diagnostic or therapeutic radiopharmaceutical and for both pre-clinical and clinical applications. In this work, the platform's dosimetry calculations were successfully validated against previously published reference doses values calculated in standard phantoms for a variety of radionuclides, over a wide range of photon and electron energies, and for many different organs and tumor sizes. Retrospective dosimetry was also calculated for various pre-clinical and clinical patients and large dosimetric differences resulted when using conventional organ-level methods and the patient-specific voxelized methods described in this work. The dosimetric impact of various steps in the 3D voxelized dosimetry process were evaluated including quantitative imaging acquisition, image coregistration, voxel resampling, ROI contouring, CT-based material segmentation, and pharmacokinetic fitting. Finally, a multi-objective treatment planning optimization framework was developed for multi-radiopharmaceutical combination therapies.

SU-F-T-654: Pacemaker Dose Estimate Using Optically Stimulated Luminescent Dosimeter for Left Breast Intraoperative Radiation Therapy

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

Chen, Y; Goenka, A; Sharma, A

Purpose: To assess and report the in vivo dose for a patient with a pacemaker being treated in left breast intraoperative radiation therapy (IORT). The ZEISS Intrabeam 50 kVp X-ray beam with a spherical applicator was used. Methods: The optically stimulated luminescent dosimeters (OSLDs) (Landauer nanoDots) were employed and calibrated under the conditions of the Intrabeam 50 kVp X-rays. The nanoDots were placed on the patient at approximately 15 cm away from the lumpectomy cavity both under and above a shield of lead equivalence 0.25 mm (RayShield X-Drape D-110) covering the pacemaker area during IORT with a 5 cm sphericalmore » applicator. Results: The skin surface dose near the pacemaker during the IORT with a prescription of 20 Gy was measured as 4.0±0.8 cGy. The dose behind the shield was 0.06±0.01 Gy, demonstrating more than 98% dose reduction. The in vivo skin surface doses during a typical breast IORT at a 4.5 cm spherical applicator surface were further measured at 5, 10, 15, and 20 cm away to be 159±11 cGy, 15±1 cGy, 6.6±0.5 cGy, and 1.8±0.1 cGy, respectively. A power law fit to the dose versus the distance z from the applicator surface yields the dose fall off at the skin surface following z^-2.5, which can be used to estimate skin doses in future cases. The comparison to an extrapolation of depth dose in water reveals an underestimate of far field dose using the manufactory provided data. Conclusion: The study suggests the appropriateness of OSLD as an in vivo skin dosimeter in IORT using the Intrabeam system in a wide dose range. The pacemaker dose measured during the left breast IORT was within a safe limit.« less

Individualized adjustments to reference phantom internal organ dosimetry—scaling factors given knowledge of patient internal anatomy

NASA Astrophysics Data System (ADS)

Wayson, Michael B.; Bolch, Wesley E.

2018-04-01

Various computational tools are currently available that facilitate patient organ dosimetry in diagnostic nuclear medicine, yet they are typically restricted to reporting organ doses to ICRP-defined reference phantoms. The present study, while remaining computational phantom based, provides straightforward tools to adjust reference phantom organ dose for both internal photon and electron sources. A wide variety of monoenergetic specific absorbed fractions were computed using radiation transport simulations for tissue spheres of varying size and separation distance. Scaling methods were then constructed for both photon and electron self-dose and cross-dose, with data validation provided from patient-specific voxel phantom simulations, as well as via comparison to the scaling methodology given in MIRD Pamphlet No. 11. Photon and electron self-dose was found to be dependent on both radiation energy and sphere size. Photon cross-dose was found to be mostly independent of sphere size. Electron cross-dose was found to be dependent on sphere size when the spheres were in close proximity, owing to differences in electron range. The validation studies showed that this dataset was more effective than the MIRD 11 method at predicting patient-specific photon doses for at both high and low energies, but gave similar results at photon energies between 100 keV and 1 MeV. The MIRD 11 method for electron self-dose scaling was accurate for lower energies but began to break down at higher energies. The photon cross-dose scaling methodology developed in this study showed gains in accuracy of up to 9% for actual patient studies, and the electron cross-dose scaling methodology showed gains in accuracy up to 9% as well when only the bremsstrahlung component of the cross-dose was scaled. These dose scaling methods are readily available for incorporation into internal dosimetry software for diagnostic phantom-based organ dosimetry.

Individualized adjustments to reference phantom internal organ dosimetry-scaling factors given knowledge of patient internal anatomy.

PubMed

Wayson, Michael B; Bolch, Wesley E

2018-04-13

Various computational tools are currently available that facilitate patient organ dosimetry in diagnostic nuclear medicine, yet they are typically restricted to reporting organ doses to ICRP-defined reference phantoms. The present study, while remaining computational phantom based, provides straightforward tools to adjust reference phantom organ dose for both internal photon and electron sources. A wide variety of monoenergetic specific absorbed fractions were computed using radiation transport simulations for tissue spheres of varying size and separation distance. Scaling methods were then constructed for both photon and electron self-dose and cross-dose, with data validation provided from patient-specific voxel phantom simulations, as well as via comparison to the scaling methodology given in MIRD Pamphlet No. 11. Photon and electron self-dose was found to be dependent on both radiation energy and sphere size. Photon cross-dose was found to be mostly independent of sphere size. Electron cross-dose was found to be dependent on sphere size when the spheres were in close proximity, owing to differences in electron range. The validation studies showed that this dataset was more effective than the MIRD 11 method at predicting patient-specific photon doses for at both high and low energies, but gave similar results at photon energies between 100 keV and 1 MeV. The MIRD 11 method for electron self-dose scaling was accurate for lower energies but began to break down at higher energies. The photon cross-dose scaling methodology developed in this study showed gains in accuracy of up to 9% for actual patient studies, and the electron cross-dose scaling methodology showed gains in accuracy up to 9% as well when only the bremsstrahlung component of the cross-dose was scaled. These dose scaling methods are readily available for incorporation into internal dosimetry software for diagnostic phantom-based organ dosimetry.

Field evaluations of the VD max approach for substantiation of a 25 kGy sterilization dose and its application to other preselected doses

NASA Astrophysics Data System (ADS)

Kowalski, John B.; Herring, Craig; Baryschpolec, Lisa; Reger, John; Patel, Jay; Feeney, Mary; Tallentire, Alan

2002-08-01

The International and European standards for radiation sterilization require evidence of the effectiveness of a minimum sterilization dose of 25 kGy but do not provide detailed guidance on how this evidence can be generated. An approach, designated VD max, has recently been described and computer evaluated to provide safe and unambiguous substantiation of a 25 kGy sterilization dose. The approach has been further developed into a practical method, which has been subjected to field evaluations at three manufacturing facilities which produce different types of medical devices. The three facilities each used a different overall evaluation strategy: Facility A used VD max for quarterly dose audits; Facility B compared VD max and Method 1 in side-by-side parallel experiments; and Facility C, a new facility at start-up, used VD max for initial substantiation of 25 kGy and subsequent quarterly dose audits. A common element at all three facilities was the use of 10 product units for irradiation in the verification dose experiment. The field evaluations of the VD max method were successful at all three facilities; they included many different types of medical devices/product families with a wide range of average bioburden and sample item portion values used in the verification dose experiments. Overall, around 500 verification dose experiments were performed and no failures were observed. In the side-by-side parallel experiments, the outcomes of the VD max experiments were consistent with the outcomes observed with Method 1. The VD max approach has been extended to sterilization doses >25 and <25 kGy; verification doses have been derived for sterilization doses of 15, 20, 30, and 35 kGy. Widespread application of the VD max method for doses other than 25 kGy must await controlled field evaluations and the development of appropriate specifications/standards.

Low dose evaluation of the antiandrogen flutamide following a Mode of Action approach.

PubMed

Sarrabay, A; Hilmi, C; Tinwell, H; Schorsch, F; Pallardy, M; Bars, R; Rouquié, D

2015-12-15

The dose-response characterization of endocrine mediated toxicity is an on-going debate which is controversial when exploring the nature of the dose-response curve and the effect at the low-end of the curve. To contribute to this debate we have assessed the effects of a wide range of dose levels of the antiandrogen flutamide (FLU) on 7-week male Wistar rats. FLU was administered by oral gavage at doses of 0, 0.001, 0.01, 0.1, 1 and 10mg/kg/day for 28 days. To evaluate the reproducibility, the study was performed 3 times. The molecular initiating event (MIE; AR antagonism), the key events (LH increase, Leydig cell proliferation and hyperplasia increases) and associated events involved in the mode of action (MOA) of FLU induced testicular toxicity were characterized to address the dose response concordance. Results showed no effects at low doses (<0.1mg/kg/day) for the different key events studied. The histopathological changes (Leydig cell hyperplasia) observed at 1 and 10mg/kg/day were associated with an increase in steroidogenesis gene expression in the testis from 1mg/kg/day, as well as an increase in testosterone blood level at 10mg/kg/day. Each key event dose-response was in good concordance with the MOA of FLU on the testis. From the available results, only monotonic dose-response curves were observed for the MIE, the key events, associated events and in effects observed in other sex related tissues. All the results, so far, show that the reference endocrine disruptor FLU induces threshold effects in a standard 28-day toxicity study on adult male rats. Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiac rehabilitation costs.

PubMed

Moghei, Mahshid; Turk-Adawi, Karam; Isaranuwatchai, Wanrudee; Sarrafzadegan, Nizal; Oh, Paul; Chessex, Caroline; Grace, Sherry L

2017-10-01

Despite the clinical benefits of cardiac rehabilitation (CR) and its cost-effectiveness, it is not widely received. Arguably, capacity could be greatly increased if lower-cost models were implemented. The aims of this review were to describe: the costs associated with CR delivery, approaches to reduce these costs, and associated implications. Upon finalizing the PICO statement, information scientists were enlisted to develop the search strategy of MEDLINE, Embase, CDSR, Google Scholar and Scopus. Citations identified were considered for inclusion by the first author. Extracted cost data were summarized in tabular format and qualitatively synthesized. There is wide variability in the cost of CR delivery around the world, and patients pay out-of-pocket for some or all of services in 55% of countries. Supervised CR costs in high-income countries ranged from PPP$294 (Purchasing Power Parity; 2016 United States Dollars) in the United Kingdom to PPP$12,409 in Italy, and in middle-income countries ranged from PPP$146 in Venezuela to PPP$1095 in Brazil. Costs relate to facilities, personnel, and session dose. Delivering CR using information and communication technology (mean cost PPP$753/patient/program), lowering the dose and using lower-cost personnel and equipment are important strategies to consider in containing costs, however few explicitly low-cost models are available in the literature. More research is needed regarding the costs to deliver CR in community settings, the cost-effectiveness of CR in most countries, and the economic impact of return-to-work with CR participation. A low-cost model of CR should be standardized and tested for efficacy across multiple healthcare systems. Copyright © 2017 Elsevier B.V. All rights reserved.

CHARACTERIZATION OF SPONTANEOUS AND INDUCED PUBERTY IN GIRLS WITH TURNER SYNDROME.

PubMed

Folsom, Lisal J; Slaven, James E; Nabhan, Zeina M; Eugster, Erica A

2017-07-01

To characterize puberty in girls with Turner syndrome (TS) and determine whether specific patient characteristics are associated with the timing of menarche. We also sought to compare spontaneous versus induced puberty in these patients. Medical records of girls followed in our Pediatric Endocrine clinic for TS from 2007 to 2015 were reviewed. Fifty-three girls were included, of whom 10 (19%) achieved menarche spontaneously and 43 (81%) received hormone replacement therapy (HRT). Of girls receiving HRT, a younger age at estrogen initiation correlated with a longer time to menarche (P = .02), and a mosaic karyotype was associated with a shorter time to menarche (P = .02), whereas no relationship was seen for body mass index, estrogen regimen, or maternal age at menarche. Nineteen girls (44%) receiving HRT had bleeding on estrogen alone at a wide dose range and were more likely to be on transdermal than oral preparations (P = .01). Girls with spontaneous puberty achieved menarche at a younger age (P<.01) and were more likely to have mosaic TS (P = .02). Significant variability in the timing of menarche exists among girls with TS. However, age at pubertal induction and karyotype were significantly correlated with age at menarche in our patients. A wide range of estrogen doses is seen in girls who bleed prior to progesterone, suggesting extreme variability in estrogen sensitivity among patients with TS. Girls achieving spontaneous menarche are younger and more likely to have a mosaic karyotype than those with induced menarche. Large-scale prospective studies are needed to confirm these results. BMI = body mass index; HRT = hormone replacement therapy; TS = Turner syndrome.

Bolus Guide: A Novel Insulin Bolus Dosing Decision Support Tool Based on Selection of Carbohydrate Ranges

PubMed Central

Shapira, Gali; Yodfat, Ofer; HaCohen, Arava; Feigin, Paul; Rubin, Richard

2010-01-01

Background Optimal continuous subcutaneous insulin infusion (CSII) therapy emphasizes the relationship between insulin dose and carbohydrate consumption. One widely used tool (bolus calculator) requires the user to enter discrete carbohydrate values; however, many patients might not estimate carbohydrates accurately. This study assessed carbohydrate estimation accuracy in type 1 diabetes CSII users and compared simulated blood glucose (BG) outcomes using the bolus calculator and the “bolus guide,” an alternative system based on ranges of carbohydrate load. Methods Patients (n = 60) estimated the carbohydrate load of a representative sample of meals of known carbohydrate value. The estimated error distribution [coefficient of variation (CV)] was the basis for a computer simulation (n = 1.6 million observations) of insulin recommendations for the bolus guide and bolus calculator, translated into outcome blood glucose (OBG) ranges (≤60, 61–200, >201 mg/dl). Patients (n = 30) completed questionnaires assessing satisfaction with the bolus guide. Results The CV of typical meals ranged from 27.9% to 44.5%. The percentage of simulated OBG for the calculator and the bolus guide in the <60 mg/dl range were 20.8% and 17.2%, respectively, and 13.8% and 15.8%, respectively, in the >200 mg/dl range. The mean and median scores of all bolus guide satisfaction items and ease of learning and use were 4.17 and 4.2, respectively (of 5.0). Conclusion The bolus guide recommendation based on carbohydrate range selection is substantially similar to the calculator based on carbohydrate point estimation and appears to be highly accepted by type 1 diabetes insulin pump users. PMID:20663453

Disposition of acetaminophen in milk, saliva, and plasma of lactating women.

PubMed

Berlin, C M; Yaffe, S J; Ragni, M

1980-01-01

Acetaminophen (APAP) is a widely used analgesic and antipyretic, but its disposition in human milk has not yet been reported. Twelve nursing mothers (nursing two to 22 months) were given a single 650-mg peroral dose of APAP. Simultaneous saliva and milk samples were collected at zero, 1/4, 1/2, 3/4, 1, 2, 3, 5, 8, 12, and 24 hours after maternal dosing. In two mothers, plasma samples were also obtained at several points during the first six hours. Single voided urine samples were collected from the infants three to five hours after maternal dosing (two hours after nursing at peak maternal milk levels). All samples were assayed for APAP by high pressure liquid chromatography (HPCL) using a mobile phase of 0.05 M Na acetate pH 4.0-acetonitrile (93:10) with n-butyryl-p-aminophenol as the internal standard. APAP appeared in saliva and milk in the 1/4-hour samples; peak level (10-15 micrograms/ml) were achieved by one to two hours. Saliva/milk ratios during the elimination phase ranged from 0.7 to 1.1, with most values between 0.8 and 0.9. In two patients studied, saliva/plasma ratios were 0.9 to 1.0. Elimination phase t 1/2 (calculated from beta) ranged from 1.35 to 3.50 (x = 2.28 +/- SD 0.69) hours for milk, and from 1.72 to 3.30 (x = 2.48 +/- 0.56) hours for saliva. There was close agreement between saliva t 1/2 and milk t 1/2 for each patient. Assuming each infant ingested 90 ml milk at 3, 6, and 9 hours after maternal ingestion of APAP, the amount of APAP available for ingestion ranged from 0.28 to 1.51 mg (x = 0.88 +/- 0.31) or from 0.04% to 0.23% (x = 0.14 +/- 0.04) of maternal dose. Neither APAP nor metabolite was detected in nursing infants' urine. Maternal APAP ingestion in usual analgesic doses does not appear to present a risk to the nursing infant.

BaSO4:Eu as an energy independent thermoluminescent radiation dosimeter for gamma rays and C6+ ion beam

NASA Astrophysics Data System (ADS)

Sharma, Kanika; Bahl, Shaila; Singh, Birendra; Kumar, Pratik; Lochab, S. P.; Pandey, Anant

2018-04-01

BaSO4:Eu nanophosphor is delicately optimized by varying the concentration of the impurity element and compared to the commercially available thermoluminescent dosimeter (TLD) LiF:Mg,Ti (TLD-100) and by extension also to CaSO4:Dy (TLD-900) so as to achieve its maximum thermoluminescence (TL) sensitivity. Further, the energy dependence property of this barite nanophosphor is also explored at length by exposing the phosphor with 1.25 MeV of Co-60, 0.662 MeV of Cs-137, 85 MeV and 65 MeV of Carbon ion beams. Various batches of the phosphor at hand (with impurity concentrations being 0.05, 0.10, 0.20, 0.50 and 1.00 mol%) are prepared by the chemical co-precipitation method out of which BaSO4:Eu with 0.20 mol% Eu exhibits the maximum TL sensitivity. Further, the optimized nanophosphor exhibits a whopping 28.52 times higher TL sensitivity than the commercially available TLD-100 and 1.426 times higher sensitivity than TLD-900, a noteworthy linear response curve for an exceptionally wide range of doses i.e. 10 Gy to 2 kGy and a simple glow curve structure. Furthermore, when the newly optimized nanophosphor is exposed with two different energies of gamma radiations, namely 1.25 MeV of Co-60 (dose range- 10-300 Gy) and 0.662 MeV of Cs-137 (dose range- 1-300 Gy), it is observed that the shape and structure of the glow curves remain remarkably similar for different energies of radiation while the TL response curve shows little to no variation. When exposed to different energies of carbon ion beam BaSO4:Eu displays energy independence at lower doses i.e. from 6.059 to 14.497 kGy. Finally, even though energy independence is lost at higher doses, the material shows high sensitivity to higher energy (85 MeV) of carbon beam compared to the lower energy (65 MeV of C6+) and saturation is apparent only after 121.199 kGy. Therefore the present nanophosphor displays potential as an energy independent TLD.

Matching of electron beams for conformal therapy of target volumes at moderate depths.

PubMed

Zackrisson, B; Karlsson, M

1996-06-01

The basic requirements for conformal electron therapy are an accelerator with a wide range of energies and field shapes. The beams should be well characterised in a full 3-D dose planning system which has been verified for the geometries of the current application. Differences in the basic design of treatment units have been shown to have a large influence on beam quality and dosimetry. Modern equipment can deliver electron beams of good quality with a high degree of accuracy. A race-track microtron with minimised electron scattering and a multi-leaf collimator (MLC) for electron collimating will facilitate the isocentric technique as a general treatment technique for electrons. This will improve the possibility of performing combined electron field techniques in order to conform the dose distribution with no or minimal use of a bolus. Furthermore, the isocentric technique will facilitate multiple field arrangements that decrease the problems with distortion of the dose distribution due to inhomogeneities, etc. These situations are demonstrated by clinical examples where isocentric, matched electron fields for treatment of the nose, thyroid and thoracic wall have been used.

A comparative study of optical and radiative characteristics of X-ray-induced luminescent defects in Ag-doped glass and LiF thin films and their applications in 2-D imaging

NASA Astrophysics Data System (ADS)

Kurobori, T.; Miyamoto, Y.; Maruyama, Y.; Yamamoto, T.; Sasaki, T.

2014-05-01

We report novel disk-type X-ray two-dimensional (2-D) imaging detectors utilising Ag-doped phosphate glass and lithium fluoride (LiF) thin films based on the radiophotoluminescence (RPL) and photoluminescence (PL) phenomena, respectively. The accumulated X-ray doses written in the form of atomic-scale Ag-related luminescent centres in Ag-doped glass and F-aggregated centres in LiF thin films were rapidly reconstructed as a dose distribution using a homemade readout system. The 2-D images reconstructed from the RPL and PL detectors are compared with that from the optically stimulated luminescence (OSL) detector. In addition, the optical and dosimetric characteristics of LiF thin films are investigated and evaluated. The possibilities of dose distributions with a high spatial resolution on the order of microns over large areas, a wide dynamic range covering 11 orders of magnitude and a non-destructive readout are successfully demonstrated by combining the Ag-doped glass with LiF thin films.

Sedative and Hypnotic Activities of the Methanolic and Aqueous Extracts of Lavandula officinalis from Morocco

PubMed Central

Alnamer, Rachad; Alaoui, Katim; Bouidida, El Houcine; Benjouad, Abdelaziz; Cherrah, Yahia

2012-01-01

We evaluate the sedative and hypnotic activities of the methanolic and aqueous extract of Lavandula officinalis L. on central nervous system (CNS). In this study, the effect of the methanolic and aqueous extracts of this plant was investigated in a battery of behavioural models in mice. Stems and flowers of Lavandula officinalis L. have several therapeutic applications in folk medicine in curing or managing a wide range of diseases, including insomnia. The methanolic extract produced significant sedative effect at the doses of 200, 400, and 600 mg/kg (by oral route), compared to reference substance diazepam (DZP), and an hypnotic effect at the doses of 800 and 1000 mg/kg while the treatment of mice with the aqueous extract at the doses of 200 and 400 mg/kg via oral pathway significantly reduced in both the reestablishment time and number of head dips during the traction and hole-board tests. In conclusion, these results suggest that the methanolic and aqueous extracts of Lavandula officinalis possess potent sedative and hypnotic activities, which supported its therapeutic use for insomnia. PMID:22162677

SU-F-T-194: Analyzing the Effect of Range Shifter Air Gap On TPS Dose Modeling Accuracy in Superficial PBS Proton Therapy

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

Shirey, R; Wu, H

2016-06-15

Purpose: Treatment planning systems (TPS) may not accurately model superficial dose distributions of range shifted proton pencil beam scanning (PBS) treatments. Numerous patient-specific QA tests performed on superficially treated PBS plans have shown a consistent overestimate of dose by the TPS. This study quantifies variations between TPS planned dose and measured dose as a function of range shifter air gap and treatment depths up to 5 cm. Methods: PBS treatment plans were created in the TPS to uniformly irradiate a volume of solid water. One plan was created for each range shifter position analyzed, and all plans utilized identical dosemore » optimization parameters. Each optimized plan was analyzed in the TPS to determine the planned dose at varying depths. A PBS proton therapy system with a 3.5 cm lucite range shifter delivered the treatment plans, and a parallel plate chamber embedded in RW3 solid water measured dose at shallow depths for each air gap. Differences between measured and planned doses were plotted and analyzed. Results: The data show that the TPS more accurately models superficial dose as the air gap between the range shifter and patient surface decreases. Air gaps less than 10 cm have an average dose difference of only 1.6%, whereas air gaps between 10 and 20 cm differ by 3.0% and gaps greater than 20 cm differ by 4.4%. Conclusion: This study has shown that the TPS is unable to accurately model superficial dose with a large range shifter air gap. Dose differences greater than 3% will likely cause QA failure, as many institutions analyze patient QA with a 3%/3mm gamma analysis. For superficial PBS therapy, range shifter positions should be chosen to keep the air gap less then 10 cm when patient setup and gantry geometry allow.« less

Mobilization of hematopoietic progenitor stem cells in allogeneic setting with lenograstim by subcutaneous injection, in daily or twice-daily dosing: a single-center prospective study with historical control.

PubMed

Martino, Massimo; Moscato, Tiziana; Barillà, Santina; Dattola, Antonia; Pontari, Antonella; Fedele, Roberta; Furlò, Giuseppe; Marzia Stilo, Carmen; Alberto Gallo, Giuseppe; Tripepi, Giovanni

2015-08-01

Although the mobilization of hematopoietic progenitor stem cells from healthy donors (HDs) using granulocyte-colony-stimulating factor is widely used, the ideal method for the administration of the cytokine has not yet been determined. Seventy-five consecutive HDs received lenograstim (LENO) as mobilization agent. LENO was given subcutaneously at a dose of 10 µg/kg in a once-daily dose (ODD) every 24 hours. Results were compared with a historical control group of 181 HDs treated with 5 µg/kg LENO twice-daily dose (TDD) with a time interval of 12 hours. CD34+ cell concentrations evaluated on Day 4 and on Day 5 were 45 × 10(6) (range, 6 × 10(6) -217 × 10(6) )/L and 75 × 10(6) (range, 7 × 10(6) -279 × 10(6) )/L with ODD versus 36 × 10(6) (range, 3 × 10(6) -200 × 10(6) )/L and 55 × 10(6) (range, 3 × 10(6) -738 × 10(6) )/L with TDD (p = 0.067 and p = 0.001). The collected CD34+ cell counts in first apheresis procedure were 5.6 × 10(6)  ± 2.9 × 10(6) and 5.7 × 10(6)  ± 3 × 10(6) /kg donor and recipient body weight in the ODD versus 5.4 × 10(6)  ± 3.8 × 10(6) and 5.3 × 10(6)  ± 3.5 × 10(6) /kg in the TDD cohort, respectively (p = 0.08 and p = 0.02). Five HDs (6.7%) mobilized CD34+ cells of fewer than 2 × 10(6) /kg recipient body weight in the ODD group compared with seven HDs (3.9%) in the TDD group (p = 0.3). Once-daily administration of LENO is at least as effective as twice-daily administration for the mobilization of CD34+ cells in HDs. © 2015 AABB.

Toxicology of brotizolam

PubMed Central

Hewett, C.; Kreuzer, H.; Köllmer, H.; Niggeschulze, A.; Stötzer, H.

1983-01-01

1 Acute studies. Following oral or intraperitoneal administration, toxicity was very low (LD50 in rodents > 10,000 and > 900 mg/kg, respectively). 2 Subacute and chronic studies in rodents. Signs of toxicity were seen only at doses of 400 mg/kg or more. Histopathological changes were found only in the 78-week study. 3 Subacute studies in dogs (intravenous) and primates (oral). In dogs, doses of 0.1 and 0.3 mg/kg produced ataxia, salivation, and diarrhoea. In monkeys doses of 7 mg/kg or higher produced ataxia, increased appetite, hyperreflexive muscular spasms, increase in liver weight, and lipid depletion of the adrenal cortex. 4 Reproductive studies in the rat and rabbit. Repeated doses of up to 30 mg/kg were not associated with any disturbance in fertility; nor were any embryotoxic or teratogenic effects observed. When dams were treated with 400 mg/kg, litter mortality was markedly increased. 5 Mutagenicity studies. The four different tests performed gave no indication of any mutagenic effect. 6 Local tolerance tests in the rabbit. Brotizolam was well tolerated when administered intramuscularly, intra-arterially, or intravenously. 7 Carcinogenicity studies in rodents. The mouse study showed no evidence of a tumourigenic effect. The rat study is still being evaluated. 8 The toxicological studies demonstrate that brotizolam has an unusually wide therapeutic range. Findings of toxicological significance, most of which were reversible, were first recorded at doses of 7-10 mg/kg, i.e. at more than 100-times the intended human therapeutic dose. PMID:6686462

Species- and dose-specific pancreatic responses and progression in single- and repeat-dose studies with GI181771X: a novel cholecystokinin 1 receptor agonist in mice, rats, and monkeys.

PubMed

Myer, James R; Romach, Elizabeth H; Elangbam, Chandikumar S

2014-01-01

Compound-induced pancreatic injury is a serious liability in preclinical toxicity studies. However, its relevance to humans should be cautiously evaluated because of interspecies variations. To highlight such variations, we evaluated the species- and dose-specific pancreatic responses and progression caused by GI181771X, a novel cholecystokinin 1 receptor agonist investigated by GlaxoSmithKline for the treatment of obesity. Acute (up to 2,000 mg/kg GI181771X, as single dose) and repeat-dose studies in mice and/or rats (0.25-250 mg/kg/day for 7 days to 26 weeks) showed wide-ranging morphological changes in the pancreas that were dose and duration dependent, including necrotizing pancreatitis, acinar cell hypertrophy/atrophy, zymogen degranulation, focal acinar cell hyperplasia, and interstitial inflammation. In contrast to rodents, pancreatic changes were not observed in cynomolgus monkeys given GI181771X (1-500 mg/kg/day with higher systemic exposure than rats) for up to 52 weeks. Similarly, no GI181771X treatment-associated abnormalities in pancreatic structure were noted in a 24-week clinical trial with obese patients (body mass index >30 or >27 kg/m(2)) as assessed by abdominal ultrasound or by magnetic resonance imaging. Mechanisms for interspecies variations in the pancreatic response to CCK among rodents, monkeys, and humans and their relevance to human risk are discussed.

Environmental radioactivity in the UK: the airborne geophysical view of dose rate estimates.

PubMed

Beamish, David

2014-12-01

This study considers UK airborne gamma-ray data obtained through a series of high spatial resolution, low altitude surveys over the past decade. The ground concentrations of the naturally occurring radionuclides Potassium, Thorium and Uranium are converted to air absorbed dose rates and these are used to assess terrestrial exposure levels from both natural and technologically enhanced sources. The high resolution airborne information is also assessed alongside existing knowledge from soil sampling and ground-based measurements of exposure levels. The surveys have sampled an extensive number of the UK lithological bedrock formations and the statistical information provides examples of low dose rate lithologies (the formations that characterise much of southern England) to the highest sustained values associated with granitic terrains. The maximum dose rates (e.g. >300 nGy h(-1)) encountered across the sampled granitic terrains are found to vary by a factor of 2. Excluding granitic terrains, the most spatially extensive dose rates (>50 nGy h(-1)) are found in association with the Mercia Mudstone Group (Triassic argillaceous mudstones) of eastern England. Geological associations between high dose rate and high radon values are also noted. Recent studies of the datasets have revealed the extent of source rock (i.e. bedrock) flux attenuation by soil moisture in conjunction with the density and porosity of the temperate latitude soils found in the UK. The presence or absence of soil cover (and associated presence or absence of attenuation) appears to account for a range of localised variations in the exposure levels encountered. The hypothesis is supported by a study of an extensive combined data set of dose rates obtained from soil sampling and by airborne geophysical survey. With no attenuation factors applied, except those intrinsic to the airborne estimates, a bias to high values of between 10 and 15 nGy h(-1) is observed in the soil data. A wide range of technologically enhanced, localised contributions to dose rate values are also apparent in the data sets. Two detailed examples are provided that reveal the detectability of site-scale environmental impacts due to former industrial activities and the high dose values (>500 nGy h(-1)) that are associated with former, small-scale Uranium mining operations. Copyright © 2014. Published by Elsevier Ltd.

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

Assessment of Mean Glandular Dose in Mammography System with Different Anode-Filter Combinations Using MCNP Code

PubMed Central

Gholamkar, Lida; Mowlavi, Ali Asghar; Sadeghi, Mahdi; Athari, Mitra

2016-01-01

Background X-ray mammography is one of the general methods for early detection of breast cancer. Since glandular tissue in the breast is sensitive to radiation and it increases the risk of cancer, the given dose to the patient is very important in mammography. Objectives The aim of this study was to determine the average absorbed dose of X-ray radiation in the glandular tissue of the breast during mammography examinations as well as investigating factors that influence the mean glandular dose (MGD). One of the precise methods for determination of MGD absorbed by the breast is Monte Carlo simulation method which is widely used to assess the dose. Materials and Methods We studied some different X-ray sources and exposure factors that affect the MGD. “Midi-future” digital mammography system with amorphous-selenium detector was simulated using the Monte Carlo N-particle extended (MCNPX) code. Different anode/filter combinations such as tungsten/silver (W/Ag), tungsten/rhodium (W/Rh), and rhodium/aluminium (Rh/Al) were simulated in this study. The voltage of X-ray tube ranged from 24 kV to 32 kV with 2 kV intervals and the breast phantom thickness ranged from 3 to 8 cm, and glandular fraction g varied from 10% to 100%. Results MGD was measured for different anode/filter combinations and the effects of changing tube voltage, phantom thickness, combination and glandular breast tissue on MGD were studied. As glandular g and X-ray tube voltage increased, the breast dose increased too, and the increase of breast phantom thickness led to the decrease of MGD. The obtained results for MGD were consistent with the result of Boone et al. that was previously reported. Conclusion By comparing the results, we saw that W/Rh anode/filter combination is the best choice in breast mammography imaging because of the lowest delivered dose in comparison with W/Ag and Rh/Al. Moreover, breast thickness and g value have significant effects on MGD. PMID:27895876

SU-E-J-21: Setup Variability of Colorectal Cancer Patients Treated in the Prone Position and Dosimetric Comparison with the Supine Position

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

Kim, A; Foster, J; Chu, W

2015-06-15

Purpose: Many cancer centers treat colorectal patients in the prone position on a belly board to minimize dose to the small bowel. That may potentially Result in patient setup instability with corresponding impact on dose delivery accuracy for highly conformal techniques such as IMRT/VMAT. Two aims of this work are 1) to investigate setup accuracy of rectum patients treated in the prone position on a belly board using CBCT and 2) to evaluate dosimetric impact on bladder and small bowel of treating rectum patients in supine vs. prone position. Methods: For the setup accuracy study, 10 patients were selected. Weeklymore » CBCTs were acquired and matched to bone. The CBCT-determined shifts were recorded. For the dosimetric study, 7 prone-setup patients and 7 supine-setup patients were randomly selected from our clinical database. Various clinically relevant dose volume histogram values were recorded for the small bowel and bladder. Results: The CBCT-determined rotational shifts had a wide variation. For the dataset acquired at the time of this writing, the ranges of rotational setup errors for pitch, roll, and yaw were [−3.6° 4.7°], [−4.3° 3.2°], and [−1.4° 1.4°]. For the dosimetric study: the small bowel V(45Gy) and mean dose for the prone position was 5.6±12.1% and 18.4±6.2Gy (ranges indicate standard deviations); for the supine position the corresponding dose values were 12.9±15.8% and 24.7±8.8Gy. For the bladder, the V(30Gy) and mean dose for prone position were 68.7±12.7% and 38.4±3.3Gy; for supine position these dose values were 77.1±13.7% and 40.7±3.1Gy. Conclusion: There is evidence of significant rotational instability in the prone position. The OAR dosimetry study indicates that there are some patients that may still benefit from the prone position, though many patients can be safely treated supine.« less

Conversion of mammographic images to appear with the noise and sharpness characteristics of a different detector and x-ray system.

PubMed

Mackenzie, Alistair; Dance, David R; Workman, Adam; Yip, Mary; Wells, Kevin; Young, Kenneth C

2012-05-01

Undertaking observer studies to compare imaging technology using clinical radiological images is challenging due to patient variability. To achieve a significant result, a large number of patients would be required to compare cancer detection rates for different image detectors and systems. The aim of this work was to create a methodology where only one set of images is collected on one particular imaging system. These images are then converted to appear as if they had been acquired on a different detector and x-ray system. Therefore, the effect of a wide range of digital detectors on cancer detection or diagnosis can be examined without the need for multiple patient exposures. Three detectors and x-ray systems [Hologic Selenia (ASE), GE Essential (CSI), Carestream CR (CR)] were characterized in terms of signal transfer properties, noise power spectra (NPS), modulation transfer function, and grid properties. The contributions of the three noise sources (electronic, quantum, and structure noise) to the NPS were calculated by fitting a quadratic polynomial at each spatial frequency of the NPS against air kerma. A methodology was developed to degrade the images to have the characteristics of a different (target) imaging system. The simulated images were created by first linearizing the original images such that the pixel values were equivalent to the air kerma incident at the detector. The linearized image was then blurred to match the sharpness characteristics of the target detector. Noise was then added to the blurred image to correct for differences between the detectors and any required change in dose. The electronic, quantum, and structure noise were added appropriate to the air kerma selected for the simulated image and thus ensuring that the noise in the simulated image had the same magnitude and correlation as the target image. A correction was also made for differences in primary grid transmission, scatter, and veiling glare. The method was validated by acquiring images of a CDMAM contrast detail test object (Artinis, The Netherlands) at five different doses for the three systems. The ASE CDMAM images were then converted to appear with the imaging characteristics of target CR and CSI detectors. The measured threshold gold thicknesses of the simulated and target CDMAM images were closely matched at normal dose level and the average differences across the range of detail diameters were -4% and 0% for the CR and CSI systems, respectively. The conversion was successful for images acquired over a wide dose range. The average difference between simulated and target images for a given dose was a maximum of 11%. The validation shows that the image quality of a digital mammography image obtained with a particular system can be degraded, in terms of noise magnitude and color, sharpness, and contrast to account for differences in the detector and antiscatter grid. Potentially, this is a powerful tool for observer studies, as a range of image qualities can be examined by modifying an image set obtained at a single (better) image quality thus removing the patient variability when comparing systems.

Combined ionizing radiation and thermal injury in the rat. Evaluation of early excision and closure of the burn wound

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

Hirsch, E.F.; Vezina, R.; Corbett, S.

1990-01-01

The present study was undertaken to establish an animal model of combined whole-body irradiation and thermal injury and to determine the effectiveness of early excision and closure of the burn wound in such a model. Whole-body irradiation over a range of doses resulted in a predictable mortality rate, with an LD50/30 of 783 rad with 95% confidence limits of 737 and 823 rad. A controlled 10% body surface area full-thickness thermal injury resulted in no deaths in 30 animals. When combined with a standard nonlethal 10% thermal injury, varying doses of whole-body irradiation resulted in widely differing LD50/30 values inmore » three separate cohorts of rats. Excision and closure of a 10% burn 24 hours after exposure to 200 rads did not improve survival.« less

Kinetics model for initiation and promotion for describing tumor prevalence from HZE radiation

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Wilson, John W.

1994-01-01

A kinetics model for cellular repair and misrepair for multiple radiation-induced lesions (mutation-inactivation) is coupled to a two-mutation model of initiation and promotion in tissue to provide a parametric description of tumor prevalence in the Harderian gland in a mouse. Dose-response curves are described for gamma-rays and relativistic ions. The effects of nuclear fragmentation are also considered for high-energy proton and alpha particle exposures The model described provides a parametric description of age-dependent cancer induction for a wide range of radiation fields. We also consider the two hypotheses that radiation acts either solely as an initiator or as both initiator and promoter and make model calculations for fractionation exposures from gamma-rays and relativistic Fe ions. For fractionated Fe exposures, an inverse dose-rate effect is provided by a promotion hypothesis using a mutation rate for promotion typical of single-gene mutations.

A clinical trial of single dose rectal and oral administration of diazepam for the prevention of serial seizures in adult epileptic patients.

PubMed Central

Milligan, N M; Dhillon, S; Griffiths, A; Oxley, J; Richens, A

1984-01-01

The clinical anticonvulsant efficacy of single dose rectal and oral administration of diazepam 20 mg was examined in two double-blind placebo-controlled trials in adult epileptic patients. All subjects suffered from drug resistant epilepsy and frequently experienced serial seizures. Diazepam was administered rectally as a new experimental suppository formulation immediately after a seizure and was highly effective in preventing recurrent fits within a 24 h observation period (p less than 0.001). Pharmacokinetic studies revealed a wide range of serum diazepam concentrations 60 min after administration of the suppository (mean serum diazepam level 190 +/- 73 (SD ng/ml). In a similar study oral administration of diazepam 20 mg significantly reduced the incidence of serial seizures compared with a placebo (p less than 0.01) and the mean 60 min serum diazepam level was 273 +/- 190 (SD) ng/ml. PMID:6368753

Gestational Alcohol Exposure Altered DNA Methylation Status in the Developing Fetus

PubMed Central

Mandal, Chanchal; Halder, Debasish; Jung, Kyoung Hwa; Chai, Young Gyu

2017-01-01

Ethanol is well known as a teratogenic factor that is capable of inducing a wide range of developmental abnormalities if the developing fetus is exposed to it. Duration and dose are the critical parameters of exposure that affect teratogenic variation to the developing fetus. It is suggested that ethanol interferes with epigenetic processes especially DNA methylation. We aimed to organize all of the available information on the alteration of DNA methylation by ethanol in utero. Thus, we have summarized all published information regarding alcohol-mediated alterations in DNA methylation during gestation. We tried to arrange information in a way that anyone can easily find the alcohol exposure time, doses, sampling time, and major changes in genomic level. Manuscript texts will also represent the correlation between ethanol metabolites and subsequent changes in methylome patterns. We hope that this review will help future researchers to further examine the issues associated with ethanol exposure. PMID:28657590

Modulatory effects of garlic extract against the cyclophosphamide induced genotoxicity in human lymphocytes in vitro.

PubMed

Sowjanya, B Lakshmi; Devi, K Rudrama; Madhavi, D

2009-09-01

Cyclophosphamide (CP) is a commonly used chemotherapeutic and immunosuppressive agent which is used in the treatment of wide range of cancers and autoimmune diseases. Besides that it is a well known carcinogen. In this study by using chromosomal aberrations (CA) and sister chromatid exchanges (SCE) assays method, the modulatory effects exerted by the extract of garlic against the CP induced genotoxicity in the human lymphocyte cultures in vitro were tested. Three different doses of garlic extract were tested for their modulatory capacity on the mutagenecity exerted by 100 microg ml(-1) of CR The results indicate a significant decrease in the frequency of CA and SCE suggesting that the garlic extract modulates the CP induced genotoxicity in a dose dependent manner. These findings provide the future directions for the research on design and development of possible modulatory drugs containing garlic extract.

An in vivo evaluation of the antiseizure activity and acute neurotoxicity of agmatine.

PubMed

Bence, Aimee K; Worthen, David R; Stables, James P; Crooks, Peter A

2003-02-01

Agmatine, an endogenous cationic amine, exerts a wide range of biological effects, including modulation of glutamate-activated N-methyl-D-aspartate (NMDA) receptor function in the central nervous system (CNS). Since glutamate and the NMDA receptor have been implicated in the initiation and spread of seizure activity, the capacity of agmatine to inhibit seizure spread was evaluated in vivo. Orally administered agmatine (30 mg/kg) protected against maximal electroshock seizure (MES)-induced seizure spread in rats as rapidly as 15 min and for as long as 6 h after administration. Inhibition of MES-induced seizure spread was also observed when agmatine was administered intraperitoneally. Agmatine's antiseizure activity did not appear to be dose-dependent. An in vivo neurotoxicity screen indicated that agmatine was devoid of any acute neurological toxicity at the doses tested. These preliminary data suggest that agmatine has promising anticonvulsant activity.

Ultrastable gold substrates: Properties of a support for high-resolution electron cryomicroscopy of biological specimens

PubMed Central

Russo, Christopher J.; Passmore, Lori A.

2016-01-01

Electron cryomicroscopy (cryo-EM) allows structure determination of a wide range of biological molecules and specimens. All-gold supports improve cryo-EM images by reducing radiation-induced motion and image blurring. Here we compare the mechanical and electrical properties of all-gold supports to amorphous carbon foils. Gold supports are more conductive, and have suspended foils that are not compressed by differential contraction when cooled to liquid nitrogen temperatures. These measurements show how the choice of support material and geometry can reduce specimen movement by more than an order of magnitude during low-dose imaging. We provide methods for fabrication of all-gold supports and preparation of vitrified specimens. We also analyse illumination geometry for optimal collection of high resolution, low-dose data. Together, the support structures and methods herein can improve the resolution and quality of images from any electron cryomicroscope. PMID:26592474

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.

Amitriptyline for the treatment of fibromyalgia: a comprehensive review.

PubMed

Rico-Villademoros, Fernando; Slim, Mahmoud; Calandre, Elena P

2015-10-01

Fibromyalgia is characterized by chronic generalized pain accompanied by a wide range of clinical manifestations. Most clinical practice guidelines recommend multidisciplinary treatment using a combination of pharmacological and non-pharmacological therapies. The tricyclic antidepressant amitriptyline has been most thoroughly studied in fibromyalgia. Amitriptyline has been evaluated in placebo-controlled studies, and it has served as an active comparator to other therapeutic interventions in the treatment of fibromyalgia. In addition, several systematic reviews and meta-analyses have evaluated its efficacy and safety for the treatment of fibromyalgia. Data from individual studies as well as from systematic reviews indicate that low doses (10-75 mg/day) of amitriptyline are effective for the treatment of fibromyalgia and, despite the limited quality of the data, they do not seem to be associated with relevant tolerability or safety issues. Consistent with some clinical guidelines, we believe amitriptyline in low doses should be considered a first-line drug for the treatment of fibromyalgia.

The effect of IVPCA morphine on post-hysterectomy bowel function.

PubMed

Chan, Kuang-Cheng; Cheng, Ya-Jung; Huang, Guang-Ta; Wen, Yuan-Jui; Lin, Chen-Jung; Chen, Li-Kuei; Sun, Wei-Zen

2002-06-01

Although morphine has been shown to induce bowel dysfunction in a dose-dependent fashion, in most relevant studies it was investigated in single bolus injection. Recently, intravenous morphine via patient-controlled analgesia (IVPCA) has been widely used to provide analgesia by divided bolus doses on patients' demand with satisfactory effects. This approach, by reducing the peak serum surge, largely resembles the pharmacokinetic and pharmacodynamic advantage of continuous infusion. There is yet no report on the investigation of its effect on post-operative bowel dysfunction. Fifty-one women who underwent abdominal total hysterectomy (ATH) due to uterine myoma were enrolled to investigate the association between the doses of morphine consumption by PCA and the time of first passage of flatus. In all patients morphine was administered intravenously via a PCA pump immediately after recovery from general anesthesia. We found that 49 out of 51 patients (96%) exhibited mild pain with IVPCA morphine. They had consumed an average dose of 16.9 mg morphine (range, 0-46 mg) upon the first passage of flatus which occurred 2036.4 min (average) post-operatively. There was no correlation between the dose of morphine and the time of first passage of flatus (r = 0.053, P > 0.05). The absence of suppression of bowel movement by IVPCA morphine for post-operative pain control suggests that favorable pharmacokinetic profile of IVPCA can help reduce the morphine-induced bowel dysfunction at its therapeutic level.

Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner.

PubMed

Tsutsui-Kimura, Iku; Ohmura, Yu; Yoshida, Takayuki; Yoshioka, Mitsuhiro

2017-07-01

Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, resident-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC) but not in the nucleus accumbens (NAc). Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

A graphical user interface (GUI) toolkit for the calculation of three-dimensional (3D) multi-phase biological effective dose (BED) distributions including statistical analyses.

PubMed

Kauweloa, Kevin I; Gutierrez, Alonso N; Stathakis, Sotirios; Papanikolaou, Niko; Mavroidis, Panayiotis

2016-07-01

A toolkit has been developed for calculating the 3-dimensional biological effective dose (BED) distributions in multi-phase, external beam radiotherapy treatments such as those applied in liver stereotactic body radiation therapy (SBRT) and in multi-prescription treatments. This toolkit also provides a wide range of statistical results related to dose and BED distributions. MATLAB 2010a, version 7.10 was used to create this GUI toolkit. The input data consist of the dose distribution matrices, organ contour coordinates, and treatment planning parameters from the treatment planning system (TPS). The toolkit has the capability of calculating the multi-phase BED distributions using different formulas (denoted as true and approximate). Following the calculations of the BED distributions, the dose and BED distributions can be viewed in different projections (e.g. coronal, sagittal and transverse). The different elements of this toolkit are presented and the important steps for the execution of its calculations are illustrated. The toolkit is applied on brain, head & neck and prostate cancer patients, who received primary and boost phases in order to demonstrate its capability in calculating BED distributions, as well as measuring the inaccuracy and imprecision of the approximate BED distributions. Finally, the clinical situations in which the use of the present toolkit would have a significant clinical impact are indicated. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Whole-remnant and maximum-voxel SPECT/CT dosimetry in {sup 131}I-NaI treatments of differentiated thyroid cancer

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

Mínguez, Pablo, E-mail: pablo.minguezgabina@osakid

Purpose: To investigate the possible differences between SPECT/CT based whole-remnant and maximum-voxel dosimetry in patients receiving radio-iodine ablation treatment of differentiated thyroid cancer (DTC). Methods: Eighteen DTC patients were administered 1.11 GBq of {sup 131}I-NaI after near-total thyroidectomy and rhTSH stimulation. Two patients had two remnants, so in total dosimetry was performed for 20 sites. Three SPECT/CT scans were performed for each patient at 1, 2, and 3–7 days after administration. The activity, the remnant mass, and the maximum-voxel activity were determined from these images and from a recovery-coefficient curve derived from experimental phantom measurements. The cumulated activity was estimatedmore » using trapezoidal-exponential integration. Finally, the absorbed dose was calculated using S-values for unit-density spheres in whole-remnant dosimetry and S-values for voxels in maximum-voxel dosimetry. Results: The mean absorbed dose obtained from whole-remnant dosimetry was 40 Gy (range 2–176 Gy) and from maximum-voxel dosimetry 34 Gy (range 2–145 Gy). For any given patient, the activity concentrations for each of the three time-points were approximately the same for the two methods. The effective half-lives varied (R = 0.865), mainly due to discrepancies in estimation of the longer effective half-lives. On average, absorbed doses obtained from whole-remnant dosimetry were 1.2 ± 0.2 (1 SD) higher than for maximum-voxel dosimetry, mainly due to differences in the S-values. The method-related differences were however small in comparison to the wide range of absorbed doses obtained in patients. Conclusions: Simple and consistent procedures for SPECT/CT based whole-volume and maximum-voxel dosimetry have been described, both based on experimentally determined recovery coefficients. Generally the results from the two approaches are consistent, although there is a small, systematic difference in the absorbed dose due to differences in the S-values, and some variability due to differences in the estimated effective half-lives, especially when the effective half-life is long. Irrespective of the method used, the patient absorbed doses obtained span over two orders of magnitude.« less

Low doses of dextromethorphan attenuate morphine-induced rewarding via the sigma-1 receptor at ventral tegmental area in rats.

PubMed

Chen, Shiou-Lan; Hsu, Kuei-Ying; Huang, Eagle Yi-Kung; Lu, Ru-Band; Tao, Pao-Luh

2011-09-01

Chronic use of morphine causes rewarding and behavioral sensitization, which may lead to the development of psychological craving. In our previous study, we found that a widely used antitussive dextromethorphan (known as a low affinity NMDA receptor antagonist), at doses of 10-20 mg/kg (i.p.), effectively decreased morphine rewarding in rats. In this study, we further investigated the effects and mechanisms of low doses of DM (μg/kg range) on morphine rewarding and behavioral sensitization. A conditioned place preference test was used to determine the rewarding and a locomotor activity test was used to determine the behavioral sensitization induced by the drug(s) in rats. When a low dose of DM (3 or 10 μg/kg, i.p.) was co-administered with morphine (5 mg/kg, s.c.), the rewarding effect, but not behavioral sensitization, induced by morphine was inhibited. The inhibiting effect of DM could be blocked by systemically administering a sigma-1 receptor antagonist, BD1047 (3 mg/kg, i.p.). When BD1047 (5 nmole/site) was locally given at the VTA, it also blocked the effects of a low dose of DM in inhibiting morphine rewarding. Our findings suggest that the activation of the sigma-1 receptor at the VTA may be involved in the mechanism of low doses of DM in inhibiting the morphine rewarding effect and the possibility of using extremely low doses of DM in treatment of opioid addiction in clinics. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Protein substitute dosage in PKU: how much do young patients need?

PubMed

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-07-01

The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Reduction of the unnecessary dose from the over-range area with a spiral dynamic z-collimator: comparison of beam pitch and detector coverage with 128-detector row CT.

PubMed

Shirasaka, Takashi; Funama, Yoshinori; Hayashi, Mutsukazu; Awamoto, Shinichi; Kondo, Masatoshi; Nakamura, Yasuhiko; Hatakenaka, Masamitsu; Honda, Hiroshi

2012-01-01

Our purpose in this study was to assess the radiation dose reduction and the actual exposed scan length of over-range areas using a spiral dynamic z-collimator at different beam pitches and detector coverage. Using glass rod dosimeters, we measured the unilateral over-range scan dose between the beginning of the planned scan range and the beginning of the actual exposed scan range. Scanning was performed at detector coverage of 80.0 and 40.0 mm, with and without the spiral dynamic z-collimator. The dose-saving ratio was calculated as the ratio of the unnecessary over-range dose, with and without the spiral dynamic z-collimator. In 80.0 mm detector coverage without the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 108, 120, and 126 mm, corresponding to a beam pitch of 0.60, 0.80, and 0.99, respectively. With the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 48, 66, and 84 mm with a beam pitch of 0.60, 0.80, and 0.99, respectively. The dose-saving ratios with and without the spiral dynamic z-collimator for a beam pitch of 0.60, 0.80, and 0.99 were 35.07, 24.76, and 13.51%, respectively. With 40.0 mm detector coverage, the dose-saving ratios with and without the spiral dynamic z-collimator had the highest value of 27.23% with a low beam pitch of 0.60. The spiral dynamic z-collimator is important for a reduction in the unnecessary over-range dose and makes it possible to reduce the unnecessary dose by means of a lower beam pitch.

Methods for the isolation and identification of polycyclic aromatic hydrocarbons found in complex mixtures and the determination of their possible toxicity by means of a host mediated bioassay technique. Progress report, July 1, 1976--February 1, 1977. [Cultured mouse leumemia cell bioassay system

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

Lipsky, S.R.; Alexander, G.; McMurray, W.

1977-02-01

Techniques were developed to produce excellent high performance glass capillary columns for gas chromatographic analyses of a wide range of complex mixtures of organic compounds, including those containing a wide array of polycyclic aromatic hydrocarbons (PAH) derived from a coal liquefaction process. Work was begun to assess the potential mutogenicity and/or carcinogenicity of the various isolated PAH fractions utilizing a unique host mediated bioassay system. Preliminary results indicate that further efforts will be required to determine dose response parameters of cultured mouse leukemia cells, as well as suitable vehicles for the satisfactory introduction of certain PAH fractions into this particularmore » bioassay system.« less

[Combined use of wide-detector and adaptive statistical iterative reconstruction-V technique in abdominal CT with low radiation dose].

PubMed

Wang, H X; Lü, P J; Yue, S W; Chang, L Y; Li, Y; Zhao, H P; Li, W R; Gao, J B

2017-12-05

Objective: To investigate the image quality and radiation dose with wide-detector(80 mm) and adaptive statistical iterative reconstruction-V (ASIR-V) technique at abdominal contrast enhanced CT scan. Methods: In the first phantom experiment part, the percentage of ASIR-V for half dose of combined wide detector with ASIR-V technique as compared with standard-detector (40 mm) technique was determined. The human experiment was performed based on the phantom study, 160 patients underwent contrast-enhanced abdominal CT scan were prospectively collected and divided into the control group ( n =40) with image reconstruction using 40% ASIR (group A) and the study group ( n =120) with random number table. According to pre-ASIR-V percentage, the study group was assigned into three groups[40 cases in each group, group B: 0 pre-ASIR-V scan with image reconstruction of 0-100% post-ASIR-V (interval 10%, subgroups B0-B10); group C: 20% pre-ASIR-V with 20%, 40% and 60% post-ASIR-V (subgroups C1-C3); group D: 40%pre-ASIR-V with 40% and 60% post-ASIR-V (subgroups D1-D2)]. Image noise, CT attenuation values and CNR of the liver, pancreas, aorta and portal vein were compared by using two sample t test and One-way ANOVA. Qualitative visual parameters (overall image quality as graded on a 5-point scale) was compared by Mann-Whitney U test and Kruskal-Wallis H test. Results: The phantom experiment showed that the percentage of pre-ASIR-V for half dose was 40%. With the 40% pre-ASIR-V, radiation dose in the study group was reduced by 35.5% as compared with the control group. Image noise in the subgroups of B2-B10, C2-C3 and D1-D2 were lower ( t =-14.681--3.046, all P <0.05) while CNR in the subgroups of B4-B10, C2-3 and D1-D2 were higher( t =2.048-9.248, all P <0.05)than those in group A, except the CNR of liver in the arterial phase (AP) in C2, D1 and D2 and the CNR of pancreas in AP in D1 ( t =0.574-1.327, all P >0.05). The subjective image quality scores increased gradually in the range of 0-60% post-ASIR-V and decreased with post-ASIR-V larger than 70%. The overall image quality of subgroup B3-B8, C2-C3 and D1-D2 were higher than that in group A ( Z =-2.229--6.533, all P <0.05). Conclusion: Compared with stand-detector together with ASIR technique, wide-detector combined with 40% pre-ASIR-V technique with 60% post-ASIR-V image reconstruction can reduce radiation dose while maintain good overall image quality.

Establishment of the central radiation dose registration system for decontamination work involving radioactive fallout emitted by the Fukushima Daiichi APP accident.

PubMed

Yasui, Shojiro

2016-10-01

With respect to radiation protection for decontamination efforts involving radioactive fallout emitted by the accident at the Fukushima Daiichi Atomic Power Plant, new regulations were established and obligated employers to monitor, record, and store of workers' dose records, and to check their past dose records at the time of employment. However, cumulative doses may not be properly maintained if a worker declares incorrect values for past doses. In response, with facilitation from the Ministry of Health, Labour and Welfare, primary contractors of decontamination works decided to establish a central dose registration system. There are four major issues in the design of the system to be resolved, included the following: primary contractors (a) do not have a legal responsibility to perform dose control for subcontractors, (b) do not have the right to control decontamination sites, (c) often organize joint ventures, and (d) correspond to a wide range of ambient dose rates. To resolve the issues, requirements of the system included the following: (a) centralize the operation of radiation passbooks, which records past doses and the results of medical examinations to each worker; (b) develop a database system that could register all dose data and accept inquiry from primary contractors; (c) establish a permanent data storage system for transferred records; and (d) provide graded type of services that are appropriate to the risk of radiation exposure. The system started its operation in December 2013 and provided dose distributions in April and July 2015. The average yearly dose in 2014 was 0.7 mSv, which increased by 0.2 mSv from 0.5 mSv in 2012 and 2013. However, no cumulative dose from 2012-2014 exceeded 20 mSv, which was far below than the dose limits (100 mSv/5 years and 50 mSv/year). Although current dose distributions of decontamination workers were within appropriate levels, careful monitoring of dose distribution is necessary for preserving the proper implementation of radiation protection prescribed in the regulations.

Phthalates and heavy metals as endocrine disruptors in food: A study on pre-packed coffee products.

PubMed

De Toni, Luca; Tisato, Francesco; Seraglia, Roberta; Roverso, Marco; Gandin, Valentina; Marzano, Cristina; Padrini, Roberto; Foresta, Carlo

2017-01-01

Phthalate plasticizers and heavy metals are widely recognized to be pollutants that interfere with key developmental processes such as masculinization. We investigated the release of phthalates and heavy metals in coffee brewed from coffee packed in single-serve coffee containers made from different types of materials: metal, biodegradable and plastics. We detected with GC-MS small amounts phthalates, below the tolerated daily risks levels, in all the coffees prepared from the different types of capsules. Specifically, Di (2-ethyl-hexyl)-phthalate and DiBP: Diisobuthyl-pthalate were ubiquitously present despite the high variability among the samples (respective range 0.16-1.87 μg/mL and 0.01-0.36 μg/mL). Whereas, diethyl-phthalate (range 0.20-0.26 μg/mL) and di- n -buthyl-phthalate (range 0.02-0.14 μg/mL) were detected respectively in one and three out of the four types of capsule tested. In contrast, we detected by atomic mass spectrometry on mineralized samples heavy metals lead (Pb) and nickel (Ni), in all coffee tested. PB levels (respective range 0.32-211.57 μg/dose) accounted for 42-79%, whereas Ni levels (respective range 166.25-1950.26 μg/dose) accounted for >100% of the tolerable daily intake. These results add to the already present concerns related to the multiple pathways of human exposure and the ubiquitous presence of these pollutants in consumer products and their long-term effect on human health.

The dose-dependent effect of chronic administration of haloperidol, risperidone, and quetiapine on sexual behavior in the male rat.

PubMed

Zhang, Xiang Rong; Zhang, Zhi Jun; Jenkins, Trisha A; Cheng, Wei Rong; Reynolds, Gavin P

2011-12-01

Antipsychotic drug-induced sexual dysfunction is a common and problematic side effect, which may diminish quality of life and lead to treatment noncompliance. Up to date, there is still a scarcity of basic research regarding the chronic effects of most antipsychotic agents on sexual behavior. The present study investigated the effect of a range of doses of three antipsychotic drugs (haloperidol, risperidone, and quetiapine) on male rat sexual competence following chronic administration. Twelve groups of Sprague-Dawley rats (n = 7 each) received by gavage haloperidol (0.25, 0.5, or 1 mg/kg), risperidone (0.125, 0.25, or 0.5 mg/kg), quetiapine (10, 20, and 40 mg/kg) or vehicle (distilled water) in the corresponding control groups, respectively, once daily for 21 days. Sexual function was evaluated by the copulatory behavior test 10 hours after the last dose. The male rat behavioral parameters of copulatory test. Sexual function was widely and significantly suppressed by high dose haloperidol (1 mg/kg) after 21 days administration compared with the control group, which included both frequency and latency of intromission and ejaculation. Only ejaculation latency was significantly impaired after administration with 0.5 mg/kg haloperidol. Compared with the control group, high dose risperidone (0.5 mg/kg) significantly decreased the frequency of mounting. There were no significant changes in sexual behavior with the lower doses of either haloperidol or risperidone. Sexual behavior was not influenced by any dose of quetiapine. Haloperidol and risperidone, but not quetiapine, could impair sexual competence in a dose-related manner in male rats. © 2010 International Society for Sexual Medicine.

Wide variation in cardiopulmonary resuscitation interruption intervals among commercially available automated external defibrillators may affect survival despite high defibrillation efficacy.

PubMed

Snyder, David; Morgan, Carl

2004-09-01

Recent studies have associated interruptions of cardiopulmonary resuscitation imposed by automated external defibrillators (AEDs) with poor resuscitation outcome. In particular, the "hands-off" interval between precordial compressions and subsequent defibrillation shock has been implicated. We sought to determine the range of variation among current-generation AEDs with respect to this characteristic. Seven AEDs from six manufacturers were characterized via stopwatch and arrhythmia simulator with respect to the imposed hands-off interval. All AEDs were equipped with new batteries, and measurements were repeated five times for each AED. A wide variation in the hands-off interval between precordial compressions and shock delivery was observed, ranging from 5.2 to 28.4 secs, with only one AED achieving an interruption of <10 secs. Laboratory and clinical data suggest that this range of variation could be responsible for a more than two-fold variation in patient resuscitation success, an effect that far exceeds any defibrillation efficacy differences that may hypothetically exist. In addition to defibrillation waveform and dose, researchers should consider the hands-off cardiopulmonary resuscitation interruption interval between cardiopulmonary resuscitation and subsequent defibrillation shock to be an important covariate of outcome in resuscitation studies. Defibrillator design should minimize this interval to avoid potential adverse consequences on patient survival.

Subcutaneous Injection of Testosterone Is an Effective and Preferred Alternative to Intramuscular Injection: Demonstration in Female-to-Male Transgender Patients.

PubMed

Spratt, Daniel I; Stewart, India I; Savage, Clara; Craig, Wendy; Spack, Norman P; Chandler, Donald Walt; Spratt, Lindsey V; Eimicke, Toni; Olshan, Jerrold S

2017-07-01

Testosterone (T) is commonly administered intramuscularly to treat hypogonadal males and female-to-male (FTM) transgender patients. However, these injections can involve significant discomfort and may require arrangements for administration by others. We assessed whether T could be administered effectively and safely subcutaneously as an alternative to intramuscular (IM) injections. Retrospective cohort study. Outpatient reproductive endocrinology clinic at an academic medical center. Sixty-three FTM transgender patients aged >18 years electing to receive subcutaneous (SC) T therapy for sex transition were included. Fifty-three patients were premenopausal. Patients were administered T cypionate or enanthate weekly at an initial dose of 50 mg. Dose was adjusted if needed to achieve serum total T levels within the normal male range. Serum concentrations of free and total T and total estradiol (E2), masculinization, and surveillance for reactions at injection sites. Serum T levels within the normal male range were achieved in all 63 patients with doses of 50 to 150 mg (median, 75/80 mg). Therapy was effective across a wide range of body mass index (19.0 to 49.9 kg/m2). Minor and transient local reactions were reported in 9 out of 63 patients. Among 53 premenopausal patients, 51 achieved amenorrhea and 35 achieved serum E2 concentrations <50 pg/mL. Twenty-two patients were originally receiving IM and switched to SC therapy. All 22 had a mild (n = 2) or marked (n = 20) preference for SC injections; none preferred IM injections. Our observations indicate that SC T injections are an effective, safe, and well-accepted alternative to IM T injections. Copyright © 2017 Endocrine Society

Variation in provider vaccine purchase prices and payer reimbursement.

PubMed

Freed, Gary L; Cowan, Anne E; Gregory, Sashi; Clark, Sarah J

2009-12-01

The purpose of this work was to collect data regarding vaccine prices and reimbursements in private practices. Amid reports of physicians losing money on vaccines, there are limited supporting data to show how much private practices are paying for vaccines and how much they are being reimbursed by third-party payers. We conducted a cross-sectional survey of a convenience sample of private practices in 5 states (California, Georgia, Michigan, New York, and Texas) that purchase vaccines for administration to privately insured children/adolescents. Main outcome measures included prices paid to purchase vaccines recommended for children and adolescents and reimbursement from the 3 most common, non-Medicaid payers for vaccine purchase and administration. Detailed price and reimbursement data were provided by 76 practices. There was a considerable difference between the maximum and minimum prices paid by practices, ranging from $4 to more than $30 for specific vaccines. There was also significant variation in insurance reimbursement for vaccine purchase, with maximum and minimum reimbursements for a single vaccine differing from $8 to more than $80. Mean net yield per dose (reimbursement for vaccine purchase minus price paid per dose) varied across vaccines from a low of approximately $3 to more than $24. Reimbursement for the first dose of vaccine administered ranged from $0 to more than $26, with a mean of $16.62. There is a wide range of prices paid by practices for the same vaccine product and in the reimbursement for vaccines and administration fees by payers. This variation highlights the need for individual practices to understand their own costs and reimbursements and to seek opportunities to reduce costs and increase reimbursements.

Variation in provider vaccine purchase prices and payer reimbursement.

PubMed

Freed, Gary L; Cowan, Anne E; Gregory, Sashi; Clark, Sarah J

2008-12-01

The purpose of this work was to collect data regarding vaccine prices and reimbursements in private practices. Amid reports of physicians losing money on vaccines, there are limited supporting data to show how much private practices are paying for vaccines and how much they are being reimbursed by third-party payers. We conducted a cross-sectional survey of a convenience sample of private practices in 5 states (California, Georgia, Michigan, New York, and Texas) that purchase vaccines for administration to privately insured children/adolescents. Main outcome measures included prices paid to purchase vaccines recommended for children and adolescents and reimbursement from the 3 most common, non-Medicaid payers for vaccine purchase and administration. Detailed price and reimbursement data were provided by 76 practices. There was a considerable difference between the maximum and minimum prices paid by practices, ranging from $4 to more than $30 for specific vaccines. There was also significant variation in insurance reimbursement for vaccine purchase, with maximum and minimum reimbursements for a single vaccine differing from $8 to more than $80. Mean net yield per dose (reimbursement for vaccine purchase minus price paid per dose) varied across vaccines from a low of approximately $3 to more than $24. Reimbursement for the first dose of vaccine administered ranged from $0 to more than $26, with a mean of $16.62. There is a wide range of prices paid by practices for the same vaccine product and in the reimbursement for vaccines and administration fees by payers. This variation highlights the need for individual practices to understand their own costs and reimbursements and to seek opportunities to reduce costs and increase reimbursements.

Evaluation and Refinement of Euthanasia Methods for Xenopus laevis

PubMed Central

Torreilles, Stéphanie L; McClure, Diane E; Green, Sherril L

2009-01-01

The most common method of euthanasia for Xenopus species is by immersion in tricaine methane sulfonate solution (MS222). A wide range of doses of MS222 (0.5 to 5 g/L) have been recommended, but few reports describe dose–response testing, the time to loss of consciousness, or the reliability of euthanasia. The objective of this study is to evaluate the efficacy of immersing individual and groups of frogs in MS222 at concentrations ranging from 1 to 5 g/L for euthanasia and of 3 less-common methods: intracoelomic injection of MS222, intracoelomic injection of sodium pentobarbital with phenytoin, and ventral cutaneous application of benzocaine gel. Our results indicate that immersion for at least 1 h in a 5-g/L buffered solution of MS222, intracoelomic injection of 1100 mg/kg sodium pentobarbital with sodium phenytoin (equivalent to 0.3 mL solution per frog), or ventral cutaneous application of 182 mg/kg benzocaine (equivalent to a 2 cm × 1 mm of 20% benzocaine gel) is necessary to euthanize adult X. laevis and ensure complete cessation of the heartbeat without recovery. These doses are considerably higher than those previously recommended for this species. PMID:19807972

Polyethylene Naphthalate Scintillator: A Novel Detector for the Dosimetry of Radioactive Ophthalmic Applicators.

PubMed

Flühs, Dirk; Flühs, Andrea; Ebenau, Melanie; Eichmann, Marion

2015-09-01

Dosimetric measurements in small radiation fields with large gradients, such as eye plaque dosimetry with β or low-energy photon emitters, require dosimetrically almost water-equivalent detectors with volumes of <1 mm(3) and linear responses over several orders of magnitude. Polyvinyltoluene-based scintillators fulfil these conditions. Hence, they are a standard for such applications. However, they show disadvantages with regard to certain material properties and their dosimetric behaviour towards low-energy photons. Polyethylene naphthalate, recently recognized as a scintillator, offers chemical, physical and basic dosimetric properties superior to polyvinyltoluene. Its general applicability as a clinical dosimeter, however, has not been shown yet. To prove this applicability, extensive measurements at several clinical photon and electron radiation sources, ranging from ophthalmic plaques to a linear accelerator, were performed. For all radiation qualities under investigation, covering a wide range of dose rates, a linearity of the detector response to the dose was shown. Polyethylene naphthalate proved to be a suitable detector material for the dosimetry of ophthalmic plaques, including low-energy photon emitters and other small radiation fields. Due to superior properties, it has the potential to replace polyvinyltoluene as the standard scintillator for such applications.

Effect of heating rate on thermoluminescence output of LiF: Mg, Ti (TLD-100) in dosimetric applications

NASA Astrophysics Data System (ADS)

Singh, Ranjit; Kainth, Harpreet Singh

2018-07-01

The luminiscence characteristics of thermoluminscence dosimeter LiF: Mg, Ti (TLD-100) irradiated to X-rays from 6 MV linac have been studied for wide range of 2-50 K/s readout linear heating rates. The reproducibility of glow curves for TLDs is found to be better at lower heating rates and depreciate at higher heating rates. The glow curve spectra were analysed using deconvolution procedure based on general-order kinetics. Shift in the peak maximum temperature per unit rise in heating rate for various peaks were found to decrease with heating rate. The TLDs irradiated with same dose exhibit decreasing TL counts with increase in the heating rate, which indicate the thermal quenching effect in TLD-100. The value of activation energy for each peak within the glow curve increases with heating rate. Calibration curves plotted for the dose range 0.4-1020 cGy exhibit decreasing slope with increasing readout heating rate. Corrections for temperature lag between the heating element and the dosimeter, and the effective heating rate (βeff) across the sample estimated using formulation proposed by Kitis and Tuyn and are found to be fairly applicable.

SU-E-I-57: Evaluation and Optimization of Effective-Dose Using Different Beam-Hardening Filters in Clinical Pediatric Shunt CT Protocol

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

Gill, K; Aldoohan, S; Collier, J

Purpose: Study image optimization and radiation dose reduction in pediatric shunt CT scanning protocol through the use of different beam-hardening filters Methods: A 64-slice CT scanner at OU Childrens Hospital has been used to evaluate CT image contrast-to-noise ratio (CNR) and measure effective-doses based on the concept of CT dose index (CTDIvol) using the pediatric head shunt scanning protocol. The routine axial pediatric head shunt scanning protocol that has been optimized for the intrinsic x-ray tube filter has been used to evaluate CNR by acquiring images using the ACR approved CT-phantom and radiation dose CTphantom, which was used to measuremore » CTDIvol. These results were set as reference points to study and evaluate the effects of adding different filtering materials (i.e. Tungsten, Tantalum, Titanium, Nickel and Copper filters) to the existing filter on image quality and radiation dose. To ensure optimal image quality, the scanner routine air calibration was run for each added filter. The image CNR was evaluated for different kVps and wide range of mAs values using above mentioned beam-hardening filters. These scanning protocols were run under axial as well as under helical techniques. The CTDIvol and the effective-dose were measured and calculated for all scanning protocols and added filtration, including the intrinsic x-ray tube filter. Results: Beam-hardening filter shapes energy spectrum, which reduces the dose by 27%. No noticeable changes in image low contrast detectability Conclusion: Effective-dose is very much dependent on the CTDIVol, which is further very much dependent on beam-hardening filters. Substantial reduction in effective-dose is realized using beam-hardening filters as compare to the intrinsic filter. This phantom study showed that significant radiation dose reduction could be achieved in CT pediatric shunt scanning protocols without compromising in diagnostic value of image quality.« less

SU-E-T-129: Are Knowledge-Based Planning Dose Estimates Valid for Distensible Organs?

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

Lalonde, R; Heron, D; Huq, M

2015-06-15

Purpose: Knowledge-based planning programs have become available to assist treatment planning in radiation therapy. Such programs can be used to generate estimated DVHs and planning constraints for organs at risk (OARs), based upon a model generated from previous plans. These estimates are based upon the planning CT scan. However, for distensible OARs like the bladder and rectum, daily variations in volume may make the dose estimates invalid. The purpose of this study is to determine whether knowledge-based DVH dose estimates may be valid for distensible OARs. Methods: The Varian RapidPlan™ knowledge-based planning module was used to generate OAR dose estimatesmore » and planning objectives for 10 prostate cases previously planned with VMAT, and final plans were calculated for each. Five weekly setup CBCT scans of each patient were then downloaded and contoured (assuming no change in size and shape of the target volume), and rectum and bladder DVHs were recalculated for each scan. Dose volumes were then compared at 75, 60,and 40 Gy for the bladder and rectum between the planning scan and the CBCTs. Results: Plan doses and estimates matched well at all dose points., Volumes of the rectum and bladder varied widely between planning CT and the CBCTs, ranging from 0.46 to 2.42 for the bladder and 0.71 to 2.18 for the rectum, causing relative dose volumes to vary between planning CT and CBCT, but absolute dose volumes were more consistent. The overall ratio of CBCT/plan dose volumes was 1.02 ±0.27 for rectum and 0.98 ±0.20 for bladder in these patients. Conclusion: Knowledge-based planning dose volume estimates for distensible OARs are still valid, in absolute volume terms, between treatment planning scans and CBCT’s taken during daily treatment. Further analysis of the data is being undertaken to determine how differences depend upon rectum and bladder filling state. This work has been supported by Varian Medical Systems.« less

Critical Problems Stalling Progress in Natural Bioactive Polysaccharide Research and Development.

PubMed

Han, Quan-Bin

2018-05-09

Natural polysaccharides are attracting increasing attention from food and pharmaceutical industries for their wide range of valuable biological activities. However, the poor repeatability of the methods used in sample preparation and chemical characterization is hampering both research and product development. The unstandardized quality, in turn, undermines efforts to understand the mechanism by which they work via oral dose, which is essential to realize the full beneficial potential of polysaccharides. Some scientists believe polysaccharides work by direct gut absorption; however, increasing evidence points to the gut microbiome and intestinal Peyer's patches as holding the keys to how they work.

Life history tradeoffs in cancer evolution

PubMed Central

Boddy, Amy M.; Gatenby, Robert A.; Brown, Joel S.; Maley, Carlo C.

2014-01-01

Somatic evolution during cancer progression and therapy results in tumor cells that exhibit a wide range of phenotypes including rapid proliferation and quiescence. Evolutionary life history theory may help us understand the diversity of these phenotypes. Fast life history organisms reproduce rapidly while those with slow life histories show less fecundity and invest more resources in survival. Life history theory also provides an evolutionary framework for phenotypic plasticity with potential implications for understanding ‘cancer stem cells’. Life history theory suggests that different therapy dosing schedules could select for fast or slow life history cell phenotypes, with important clinical consequences. PMID:24213474

CMOS-Compatible SOI MESFETS for Radiation-Hardened DC-to-DC Converters

NASA Technical Reports Server (NTRS)

Thornton, Trevor; Lepkowski, William; Wilk, Seth

2013-01-01

A radiation-tolerant transistor switch has been developed that can operate between 196 and +150 C for DC-to-DC power conversion applications. A prototype buck regulator component was demonstrated to be performing well after a total ionizing dose of 300 krad(Si). The prototype buck converters showed good efficiencies at ultra-high switching speeds in the range of 1 to 10 MHz. Such high switching frequency will enable smaller, lighter buck converters to be developed as part of the next project. Switching regulators are widely used in commercial applications including portable consumer electronics.

Dosimetric characterization of GafChromic EBT film and its implication on film dosimetry quality assurance.

PubMed

Fuss, Martina; Sturtewagen, Eva; De Wagter, Carlos; Georg, Dietmar

2007-07-21

The suitability of radiochromic EBT film was studied for high-precision clinical quality assurance (QA) by identifying the dose response for a wide range of irradiation parameters typically modified in highly-conformal treatment techniques. In addition, uncertainties associated with varying irradiation conditions were determined. EBT can be used for dose assessment of absorbed dose levels as well as relative dosimetry when compared to absolute absorbed dose calibrated using ionization chamber results. For comparison, a silver halide film (Kodak EDR-2) representing the current standard in film dosimetry was included. As an initial step a measurement protocol yielding accurate and precise results was established for a flatbed transparency scanner (Epson Expression 1680 Pro) that was utilized as a film reading instrument. The light transmission measured by the scanner was found to depend on the position of the film on the scanner plate. For three film pieces irradiated with doses of 0 Gy, approximately 1 Gy and approximately 7 Gy, the pixel values measured in portrait or landscape mode differed by 4.7%, 6.2% and 10.0%, respectively. A study of 200 film pieces revealed an excellent sheet-to-sheet uniformity. On a long time scale, the optical development of irradiated EBT film consisted of a slow but steady increase of absorbance which was not observed to cease during 4 months. Sensitometric curves of EBT films obtained under reference conditions (SSD = 95 cm, FS = 5 x 5 cm(2), d = 5 cm) for 6, 10 and 25 MV photon beams did not show any energy dependence. The average separation between all curves was only 0.7%. The variation of the depth d (range 2-25 cm) in the phantom did not affect the dose response of EBT film. Also the influence of the radiation field size (range 3 x 3-40 x 40 cm(2)) on the sensitometric curve was not significant. For EDR-2 films maximum differences between the calibration curves reached 7-8% for X6MV and X25MV. Radiochromic EBT film, in combination with a flatbed scanner, presents a versatile system for high-precision dosimetry in two dimensions, provided that the intrinsic behaviour of the film reading device is taken into account. EBT film itself presents substantial improvements on formerly available models of radiographic and a radiochromic film and its dosimetric characteristics allow us to measure absorbed dose levels in a large variety of situations with a single calibration curve.

Dosimetric characterization of GafChromic EBT film and its implication on film dosimetry quality assurance

NASA Astrophysics Data System (ADS)

Fuss, Martina; Sturtewagen, Eva; DeWagter, Carlos; Georg, Dietmar

2007-07-01

The suitability of radiochromic EBT film was studied for high-precision clinical quality assurance (QA) by identifying the dose response for a wide range of irradiation parameters typically modified in highly-conformal treatment techniques. In addition, uncertainties associated with varying irradiation conditions were determined. EBT can be used for dose assessment of absorbed dose levels as well as relative dosimetry when compared to absolute absorbed dose calibrated using ionization chamber results. For comparison, a silver halide film (Kodak EDR-2) representing the current standard in film dosimetry was included. As an initial step a measurement protocol yielding accurate and precise results was established for a flatbed transparency scanner (Epson Expression 1680 Pro) that was utilized as a film reading instrument. The light transmission measured by the scanner was found to depend on the position of the film on the scanner plate. For three film pieces irradiated with doses of 0 Gy, ~1 Gy and ~7 Gy, the pixel values measured in portrait or landscape mode differed by 4.7%, 6.2% and 10.0%, respectively. A study of 200 film pieces revealed an excellent sheet-to-sheet uniformity. On a long time scale, the optical development of irradiated EBT film consisted of a slow but steady increase of absorbance which was not observed to cease during 4 months. Sensitometric curves of EBT films obtained under reference conditions (SSD = 95 cm, FS = 5 × 5 cm2, d = 5 cm) for 6, 10 and 25 MV photon beams did not show any energy dependence. The average separation between all curves was only 0.7%. The variation of the depth d (range 2-25 cm) in the phantom did not affect the dose response of EBT film. Also the influence of the radiation field size (range 3 × 3-40 × 40 cm2) on the sensitometric curve was not significant. For EDR-2 films maximum differences between the calibration curves reached 7-8% for X6MV and X25MV. Radiochromic EBT film, in combination with a flatbed scanner, presents a versatile system for high-precision dosimetry in two dimensions, provided that the intrinsic behaviour of the film reading device is taken into account. EBT film itself presents substantial improvements on formerly available models of radiographic and a radiochromic film and its dosimetric characteristics allow us to measure absorbed dose levels in a large variety of situations with a single calibration curve.

Carbendazim-induced haematological, biochemical and histopathological changes to the liver and kidney of male rats.

PubMed

Selmanoglu, G; Barlas, N; Songür, S; Koçkaya, E A

2001-12-01

Carbendazim is a systemic broad-spectrum fungicide controlling a wide range of pathogens. It is also used as a preservative in paint, textile, papermaking and leather industry, as well as a preservative of fruits. In the present study, carbendazim was administered at 0, 150, 300 and 600 mg/kg per day doses orally to male rats (Rattus rattus) for 15 weeks. At the end of the experiment, blood samples, liver and kidney tissues of each animal were taken. Serum enzyme activities, and haematological and biochemical parameters were analysed. In toxicological tests, 600 mg/kg per day doses of carbendazim caused an increase of albumin, glucose, creatinine and cholesterol levels. Also, at the same doses, white blood cell and lymphocyte counts decreased. However, mean cell hemoglobin and mean cell hemoglobin concentrations increased. Histopathological examinations revealed congestion, an enlargement of the sinusoids, an increase in the number of Kupffer cells, mononuclear cell infiltration and hydropic degeneration in the liver. At the highest doses, congestion, mononuclear cell infiltration, tubular degeneration and fibrosis were observed in the kidney tissue. These results indicate that 300 and 600 mg/kg per day carbendazim affected the liver and kidney tissue and caused some changes on haematological and biochemical parameters of rats.

Positive social behaviours are induced and retained after oxytocin manipulations mimicking endogenous concentrations in a wild mammal

PubMed Central

Twiss, Sean D.; Hazon, Neil; Moss, Simon; Pomeroy, Patrick P.

2017-01-01

The neuropeptide hormone oxytocin modulates numerous social and parental behaviours across a wide range of species, including humans. We conducted manipulation experiments on wild grey seals (Halichoerus grypus) to determine whether oxytocin increases proximity-seeking behaviour, which has previously been correlated with endogenous oxytocin concentrations in wild seal populations. Pairs of seals that had never met previously were given intravenous injections of 0.41 µg kg−1 oxytocin or saline and were observed for 1 h post-manipulation. The dose was designed to mimic endogenous oxytocin concentrations during the observation period, and is one of the lowest doses used to manipulate behaviour to date. Seals given oxytocin spent significantly more time in close proximity to each other, confirming that oxytocin causes conspecifics to seek others out and remain close to one another. Aggressive and investigative behaviours also significantly fell after oxytocin manipulations. Despite using a minimal oxytocin dose, pro-social behavioural changes unexpectedly persisted for 2 days despite rapid dose clearance from circulation post-injection. This study verifies that oxytocin promotes individuals staying together, demonstrating how the hormone can form positive feedback loops of oxytocin release following conspecific stimuli, increased motivation to remain in close proximity and additional oxytocin release from stimuli received while in close proximity. PMID:28539519

Positive social behaviours are induced and retained after oxytocin manipulations mimicking endogenous concentrations in a wild mammal.

PubMed

Robinson, Kelly J; Twiss, Sean D; Hazon, Neil; Moss, Simon; Pomeroy, Patrick P

2017-05-31

The neuropeptide hormone oxytocin modulates numerous social and parental behaviours across a wide range of species, including humans. We conducted manipulation experiments on wild grey seals ( Halichoerus grypus ) to determine whether oxytocin increases proximity-seeking behaviour, which has previously been correlated with endogenous oxytocin concentrations in wild seal populations. Pairs of seals that had never met previously were given intravenous injections of 0.41 µg kg -1 oxytocin or saline and were observed for 1 h post-manipulation. The dose was designed to mimic endogenous oxytocin concentrations during the observation period, and is one of the lowest doses used to manipulate behaviour to date. Seals given oxytocin spent significantly more time in close proximity to each other, confirming that oxytocin causes conspecifics to seek others out and remain close to one another. Aggressive and investigative behaviours also significantly fell after oxytocin manipulations. Despite using a minimal oxytocin dose, pro-social behavioural changes unexpectedly persisted for 2 days despite rapid dose clearance from circulation post-injection. This study verifies that oxytocin promotes individuals staying together, demonstrating how the hormone can form positive feedback loops of oxytocin release following conspecific stimuli, increased motivation to remain in close proximity and additional oxytocin release from stimuli received while in close proximity. © 2017 The Authors.

Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

PubMed

Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

2017-06-01

Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

WE-EF-303-08: Proton Radiography Using Pencil Beam Scanning and Novel Micromegas Detectors

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

Dolney, D; Lustig, R; Teo, B

Purpose: While the energy of therapeutic proton beams can be adjusted to penetrate to any given depth in water, range uncertainties arise in patients due in part to imprecise knowledge of the stopping power of protons in human tissues. Proton radiography is one approach to reduce the beam range uncertainty, thereby allowing for a reduction in treatment margins and dose escalation. Methods: The authors have adapted a novel detector technology based on Micromesh Gaseous Structure (“Micromegas”) for proton therapy beams and have demonstrated fine spatial and time resolution of magnetically scanned proton pencil beams, as well as wide dynamic rangemore » for dosimetry. In this work, proton radiographs were obtained using Micromegas 2D planes positioned downstream of solid water assemblies. The position-sensitive monitor chambers in the IBA proton delivery nozzle provide the beam entrance position. Results: Radiography with Micromegas detectors and actively scanned beams provide spatial resolution of up to 300 µm and water-equivalent thickness (WET) resolution as good as 0.02% (60 µm out of 31 cm total thickness), with the dose delivered to the patient kept below 2 cGy. The spatial resolution as a function of sample rate and number of delivered protons is found to be near the theoretical Cramer-Rao lower bound. Using the CR bound, we argue that the imaging dose could be further lowered to 1 mGy, while still achieving sub-mm spatial resolution, by relatively simple instrumentation upgrades and beam delivery modifications. Conclusion: For proton radiography, high spatial and WET resolution can be achieved, with minimal additional dose to patient, by using magnetically scanned proton pencil beams and Micromegas detectors.« less

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.

Glyphosate in the general population and in applicators: a critical review of studies on exposures.

PubMed

Solomon, Keith R

2016-09-01

The recent classification of glyphosate as a probable human carcinogen by the International Agency for Research on Cancer (IARC) was arrived at without a detailed assessment of exposure. Glyphosate is widely used as an herbicide, which might result in exposures of the general public and applicators. Exposures were estimated from information in the open literature and unpublished reports provided by Monsanto Company. Based on the maximum measured concentration in air, an exposure dose of 1.04 × 10  -   6  mg/kg body mass (b.m.)/d was estimated. Assuming consumption of surface water without treatment, the 90th centile measured concentration would result in a consumed dose of 2.25 × 10  -   5  mg/kg b.m./d. Estimates by the Food and Agriculture Organization of the United Nations (FAO) of consumed doses in food provided a median exposure of 0.005 mg/kg b.m./d (range 0.002-0.013). Based on tolerance levels, the conservative estimate by the US Environmental Protection Agency (US EPA) for exposure of the general population via food and water was 0.088 mg/kg b.m./d (range 0.058-0.23). For applicators, 90th centiles for systemic exposures based on biomonitoring and dosimetry (normalized for penetration through the skin) were 0.0014 and 0.021 mg/kg b.m./d, respectively. All of these exposures are less than the reference dose and the acceptable daily intakes proposed by several regulatory agencies, thus supporting a conclusion that even for these highly exposed populations the exposures were within regulatory limits.

Combination of three metals for the treatment of cancer: gallium, rhenium and platinum. 1. Determination of the optimal schedule of treatment.

PubMed

Collery, Philippe; Mohsen, Ahmed; Kermagoret, Anthony; D'Angelo, Jean; Morgant, Georges; Desmaele, Didier; Tomas, Alain; Collery, Thomas; Wei, Ming; Badawi, Abdelfattah

2012-07-01

Platinum is well known for its anticancer activity, firstly used as cis-diaminedichloroplatinum (II) (CDDP), with a wide range of activity. Its main mechanism of action involves its binding to DNA. Gallium, another metal, has also demonstrated apoptotic effects on malignant cells, but through interaction with targets other than DNA, such as the membrane, cytoskeleton and proteasome, and on enzyme activities. An antitumor synergism between CDDP and both gallium and rhenium compounds has been demonstrated. For these reasons, we proposed to combine these three metals and to determine at which doses each compound could be administered without major toxicity. CDDP, tetrakis(1-octanol) tris(5-aminosalicylate)gallium(III), and a diseleno-ether rhenium(I) complex were used in this experimental study in breast cancer MCF-7 tumor-bearing mice. CDDP was administered intraperitoneally (i.p.) twice a week at the dose of 3 mg/kg. Tetrakis(1-octanol) tris(5-aminosalicylate) gallium (III) and rhenium(I) diseleno-ether complexes were administered orally, daily, five days a week for three weeks, at doses ranging from 20 to 100 mg/kg for the gallium compound and from 10 to 50 mg/kg for the rhenium compound. Doses of 10 mg/kg of rhenium(I) diseleno-ether, and 100 mg/kg of the salicylate gallium compound, in combination with CDDP induced a significant decrease of 50% of the tumor volume, by comparison with the control group. In contrast, the decrease of the tumor volume in mice treated by CDDP alone was less than 25%. Changes in the sequence of administration of the three metals will be discussed to improve the therapeutic index.

Quantifying the effect of air gap, depth, and range shifter thickness on TPS dosimetric accuracy in superficial PBS proton therapy.

PubMed

Shirey, Robert J; Wu, Hsinshun Terry

2018-01-01

This study quantifies the dosimetric accuracy of a commercial treatment planning system as functions of treatment depth, air gap, and range shifter thickness for superficial pencil beam scanning proton therapy treatments. The RayStation 6 pencil beam and Monte Carlo dose engines were each used to calculate the dose distributions for a single treatment plan with varying range shifter air gaps. Central axis dose values extracted from each of the calculated plans were compared to dose values measured with a calibrated PTW Markus chamber at various depths in RW3 solid water. Dose was measured at 12 depths, ranging from the surface to 5 cm, for each of the 18 different air gaps, which ranged from 0.5 to 28 cm. TPS dosimetric accuracy, defined as the ratio of calculated dose relative to the measured dose, was plotted as functions of depth and air gap for the pencil beam and Monte Carlo dose algorithms. The accuracy of the TPS pencil beam dose algorithm was found to be clinically unacceptable at depths shallower than 3 cm with air gaps wider than 10 cm, and increased range shifter thickness only added to the dosimetric inaccuracy of the pencil beam algorithm. Each configuration calculated with Monte Carlo was determined to be clinically acceptable. Further comparisons of the Monte Carlo dose algorithm to the measured spread-out Bragg Peaks of multiple fields used during machine commissioning verified the dosimetric accuracy of Monte Carlo in a variety of beam energies and field sizes. Discrepancies between measured and TPS calculated dose values can mainly be attributed to the ability (or lack thereof) of the TPS pencil beam dose algorithm to properly model secondary proton scatter generated in the range shifter. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Estimating radiation dose to organs of patients undergoing conventional and novel multidetector CT exams using Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Angel, Erin

Advances in Computed Tomography (CT) technology have led to an increase in the modality's diagnostic capabilities and therefore its utilization, which has in turn led to an increase in radiation exposure to the patient population. As a result, CT imaging currently constitutes approximately half of the collective exposure to ionizing radiation from medical procedures. In order to understand the radiation risk, it is necessary to estimate the radiation doses absorbed by patients undergoing CT imaging. The most widely accepted risk models are based on radiosensitive organ dose as opposed to whole body dose. In this research, radiosensitive organ dose was estimated using Monte Carlo based simulations incorporating detailed multidetector CT (MDCT) scanner models, specific scan protocols, and using patient models based on accurate patient anatomy and representing a range of patient sizes. Organ dose estimates were estimated for clinical MDCT exam protocols which pose a specific concern for radiosensitive organs or regions. These dose estimates include estimation of fetal dose for pregnant patients undergoing abdomen pelvis CT exams or undergoing exams to diagnose pulmonary embolism and venous thromboembolism. Breast and lung dose were estimated for patients undergoing coronary CTA imaging, conventional fixed tube current chest CT, and conventional tube current modulated (TCM) chest CT exams. The correlation of organ dose with patient size was quantified for pregnant patients undergoing abdomen/pelvis exams and for all breast and lung dose estimates presented. Novel dose reduction techniques were developed that incorporate organ location and are specifically designed to reduce close to radiosensitive organs during CT acquisition. A generalizable model was created for simulating conventional and novel attenuation-based TCM algorithms which can be used in simulations estimating organ dose for any patient model. The generalizable model is a significant contribution of this work as it lays the foundation for the future of simulating TCM using Monte Carlo methods. As a result of this research organ dose can be estimated for individual patients undergoing specific conventional MDCT exams. This research also brings understanding to conventional and novel close reduction techniques in CT and their effect on organ dose.

A study of dose-proportionality in the pharmacokinetics of the oral direct renin inhibitor aliskiren in healthy subjects.

PubMed

Limoges, D; Dieterich, H A; Yeh, C-M; Vaidyanathan, S; Howard, D; Dole, W P

2008-05-01

To evaluate the dose-proportionality of the pharmacokinetics of aliskiren, the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension. This was an open-label, single-center, single-dose, randomized, 4-period crossover study. Following a 21-day screening period, 32 healthy male or female subjects (ages 18 - 45 years) were randomized to 1 of 4 aliskiren dosing sequence groups (8 subjects per group): 75, 150, 300 and 600 mg. Blood samples were obtained for determination of plasma aliskiren concentrations (HPLC/MS/MS) for 96 h post dose. Log-transformed pharmacokinetic parameters AUC and C(max) were analyzed to determine dose-proportionality using the power model, parameter = A*(Dose)(beta), where A = intercept and beta = dose-proportionality coefficient. The predefined dose-proportionality criteria over the dose range 75 â 600 mg were 90% confidence intervals (CI) for beta contained within the range 0.89 - 1.11. AUC and Cmax values increased with increasing doses of aliskiren. Both AUC and C(max) were associated with high variability (coefficient of variation 55 - 64% for AUC and 59 - 117% for C(max)). The estimated proportionality coefficients (beta) for AUC(0-infiniti), AUC(0-t) and C(max) were 1.18 (90% CI 1.10, 1.25), 1.29 (90% CI 1.22, 1.36) and 1.42 (90% CI 1.31, 1.52), respectively. Dose-proportionality was, therefore, not demonstrated across the entire 8-fold dose range. For the clinical dose range of 150 â 300 mg, increases of 2.3- and 2.6-fold were observed for AUC and C(max), respectively. All doses of aliskiren were well tolerated. Exposure to aliskiren was greater than proportional over the dose range of 75 - 600 mg. Over the therapeutic dose range of 150 â 300 mg approved for the treatment of hypertension, AUC and Cmax increased by 2.3- and 2.6-fold, respectively. The pharmacokinetics of aliskiren show relatively high intersubject variability.

A Quantitative ADME-base Tool for Exploring Human ...

EPA Pesticide Factsheets

Exposure to a wide range of chemicals through our daily habits and routines is ubiquitous and largely unavoidable within modern society. The potential for human exposure, however, has not been quantified for the vast majority of chemicals with wide commercial use. Creative advances in exposure science are needed to support efficient and effective evaluation and management of chemical risks, particularly for chemicals in consumer products. The U.S. Environmental Protection Agency Office of Research and Development is developing, or collaborating in the development of, scientifically-defensible methods for making quantitative or semi-quantitative exposure predictions. The Exposure Prioritization (Ex Priori) model is a simplified, quantitative visual dashboard that provides a rank-ordered internalized dose metric to simultaneously explore exposures across chemical space (not chemical by chemical). Diverse data streams are integrated within the interface such that different exposure scenarios for “individual,” “population,” or “professional” time-use profiles can be interchanged to tailor exposure and quantitatively explore multi-chemical signatures of exposure, internalized dose (uptake), body burden, and elimination. Ex Priori has been designed as an adaptable systems framework that synthesizes knowledge from various domains and is amenable to new knowledge/information. As such, it algorithmically captures the totality of exposure across pathways. It

Impact of changing the measles vaccine vial size on Niger's vaccine supply chain: a computational model

PubMed Central

2011-01-01

Background Many countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks. Methods We developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes. Results Switching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively. Conclusions The switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child. PMID:21635774

Computational and human observer image quality evaluation of low dose, knowledge-based CT iterative reconstruction

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

Eck, Brendan L.; Fahmi, Rachid; Miao, Jun

2015-10-15

Purpose: Aims in this study are to (1) develop a computational model observer which reliably tracks the detectability of human observers in low dose computed tomography (CT) images reconstructed with knowledge-based iterative reconstruction (IMR™, Philips Healthcare) and filtered back projection (FBP) across a range of independent variables, (2) use the model to evaluate detectability trends across reconstructions and make predictions of human observer detectability, and (3) perform human observer studies based on model predictions to demonstrate applications of the model in CT imaging. Methods: Detectability (d′) was evaluated in phantom studies across a range of conditions. Images were generated usingmore » a numerical CT simulator. Trained observers performed 4-alternative forced choice (4-AFC) experiments across dose (1.3, 2.7, 4.0 mGy), pin size (4, 6, 8 mm), contrast (0.3%, 0.5%, 1.0%), and reconstruction (FBP, IMR), at fixed display window. A five-channel Laguerre–Gauss channelized Hotelling observer (CHO) was developed with internal noise added to the decision variable and/or to channel outputs, creating six different internal noise models. Semianalytic internal noise computation was tested against Monte Carlo and used to accelerate internal noise parameter optimization. Model parameters were estimated from all experiments at once using maximum likelihood on the probability correct, P{sub C}. Akaike information criterion (AIC) was used to compare models of different orders. The best model was selected according to AIC and used to predict detectability in blended FBP-IMR images, analyze trends in IMR detectability improvements, and predict dose savings with IMR. Predicted dose savings were compared against 4-AFC study results using physical CT phantom images. Results: Detection in IMR was greater than FBP in all tested conditions. The CHO with internal noise proportional to channel output standard deviations, Model-k4, showed the best trade-off between fit and model complexity according to AIC{sub c}. With parameters fixed, the model reasonably predicted detectability of human observers in blended FBP-IMR images. Semianalytic internal noise computation gave results equivalent to Monte Carlo, greatly speeding parameter estimation. Using Model-k4, the authors found an average detectability improvement of 2.7 ± 0.4 times that of FBP. IMR showed greater improvements in detectability with larger signals and relatively consistent improvements across signal contrast and x-ray dose. In the phantom tested, Model-k4 predicted an 82% dose reduction compared to FBP, verified with physical CT scans at 80% reduced dose. Conclusions: IMR improves detectability over FBP and may enable significant dose reductions. A channelized Hotelling observer with internal noise proportional to channel output standard deviation agreed well with human observers across a wide range of variables, even across reconstructions with drastically different image characteristics. Utility of the model observer was demonstrated by predicting the effect of image processing (blending), analyzing detectability improvements with IMR across dose, size, and contrast, and in guiding real CT scan dose reduction experiments. Such a model observer can be applied in optimizing parameters in advanced iterative reconstruction algorithms as well as guiding dose reduction protocols in physical CT experiments.« less

A novel biocoagulant agent from mushroom chitosan as water and wastewater therapy.

PubMed

Adnan, Oday; Abidin, Zurina Z; Idris, Azni; Kamarudin, Suryani; Al-Qubaisi, Mothanna Sadiq

2017-08-01

A new commercial cationic polyelectrolyte chitosan (CM), obtained from the waste of mushroom production, was examined using models of water and wastewater namely kaolin and palm oil mill effluent (pome). As it is biocompatible, widely available, and economically feasible, chitosan mushroom has high potential to be a suitable replacement for alum. Also, it can be a promising alternative to chitosan obtained traditionally from Crustaceans due to its higher zeta potential and homogeneity based on the raw material required for its production. A wide range of coagulant dose (5-60 mg l -1 ) and wastewater pH (2-12) were taken into account to find the optimal conditions of coagulation. The optimal doses are 10 and 20 mg l -1 at best pH (11 and 3) when treated with kaolin and palm oil mill effluent, respectively, while 1200 mg l -1 of alum was not enough to reach the efficiency of chitosan mushroom. On the other hand, the optimum dose of chitosan mushroom (20 mg l -1 ) at pH 3 of pome produced (75, 73, and 98%) removal of chemical oxygen demand (COD), biological oxygen demand (BOD), and total suspended solids (TSS), respectively. The significant potential of chitosan mushroom was proved by zeta potential measurement. Indeed, it possesses the highest zeta potential (+70 mV) as compared to the traditional chitosan produced from crustaceans. In short, chitosan mushroom as a biocoagulant is eco-friendly and it enhances water quality that meets the requirements of environmental conservatives.

Kinetic microplate bioassays for relative potency of antibiotics improved by partial Least Square (PLS) regression.

PubMed

Francisco, Fabiane Lacerda; Saviano, Alessandro Morais; Almeida, Túlia de Souza Botelho; Lourenço, Felipe Rebello

2016-05-01

Microbiological assays are widely used to estimate the relative potencies of antibiotics in order to guarantee the efficacy, safety, and quality of drug products. Despite of the advantages of turbidimetric bioassays when compared to other methods, it has limitations concerning the linearity and range of the dose-response curve determination. Here, we proposed to use partial least squares (PLS) regression to solve these limitations and to improve the prediction of relative potencies of antibiotics. Kinetic-reading microplate turbidimetric bioassays for apramacyin and vancomycin were performed using Escherichia coli (ATCC 8739) and Bacillus subtilis (ATCC 6633), respectively. Microbial growths were measured as absorbance up to 180 and 300min for apramycin and vancomycin turbidimetric bioassays, respectively. Conventional dose-response curves (absorbances or area under the microbial growth curve vs. log of antibiotic concentration) showed significant regression, however there were significant deviation of linearity. Thus, they could not be used for relative potency estimations. PLS regression allowed us to construct a predictive model for estimating the relative potencies of apramycin and vancomycin without over-fitting and it improved the linear range of turbidimetric bioassay. In addition, PLS regression provided predictions of relative potencies equivalent to those obtained from agar diffusion official methods. Therefore, we conclude that PLS regression may be used to estimate the relative potencies of antibiotics with significant advantages when compared to conventional dose-response curve determination. Copyright © 2016 Elsevier B.V. All rights reserved.

SU-E-T-105: An FMEA Survey of Intensity Modulated Radiation Therapy (IMRT) Step and Shoot Dose Delivery Failure Modes

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

Faught, J Tonigan; Johnson, J; Stingo, F

2015-06-15

Purpose: To assess the perception of TG-142 tolerance level dose delivery failures in IMRT and the application of FMEA process to this specific aspect of IMRT. Methods: An online survey was distributed to medical physicists worldwide that briefly described 11 different failure modes (FMs) covered by basic quality assurance in step- and-shoot IMRT at or near TG-142 tolerance criteria levels. For each FM, respondents estimated the worst case H&N patient percent dose error and FMEA scores for Occurrence, Detectability, and Severity. Demographic data was also collected. Results: 181 individual and three group responses were submitted. 84% were from North America.more » Most (76%) individual respondents performed at least 80% clinical work and 92% were nationally certified. Respondent medical physics experience ranged from 2.5–45 years (average 18 years). 52% of individual respondents were at least somewhat familiar with FMEA, while 17% were not familiar. Several IMRT techniques, treatment planning systems and linear accelerator manufacturers were represented. All FMs received widely varying scores ranging from 1–10 for occurrence, at least 1–9 for detectability, and at least 1–7 for severity. Ranking FMs by RPN scores also resulted in large variability, with each FM being ranked both most risky (1st ) and least risky (11th) by different respondents. On average MLC modeling had the highest RPN scores. Individual estimated percent dose errors and severity scores positively correlated (p<0.10) for each FM as expected. No universal correlations were found between the demographic information collected and scoring, percent dose errors, or ranking. Conclusion: FMs investigated overall were evaluated as low to medium risk, with average RPNs less than 110. The ranking of 11 FMs was not agreed upon by the community. Large variability in FMEA scoring may be caused by individual interpretation and/or experience, thus reflecting the subjective nature of the FMEA tool.« less

Toxicity of TiO2 nanoparticles on soil nitrification at environmentally relevant concentrations: Lack of classical dose-response relationships.

PubMed

Simonin, Marie; Martins, Jean M F; Le Roux, Xavier; Uzu, Gaëlle; Calas, Aude; Richaume, Agnès

2017-03-01

Titanium-dioxide nanoparticles (TiO 2 -NPs) are increasingly released in agricultural soils through, e.g. biosolids, irrigation or nanoagrochemicals. Soils are submitted to a wide range of concentrations of TiO 2 -NPs depending on the type of exposure. However, most studies have assessed the effects of unrealistically high concentrations, and the dose-response relationships are not well characterized for soil microbial communities. Here, using soil microcosms, we assessed the impact of TiO 2 -NPs at concentrations ranging from 0.05 to 500 mg kg -1  dry-soil, on the activity and abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB), and nitrite-oxidizing bacteria (Nitrobacter and Nitrospira). In addition, aggregation and oxidative potential of TiO 2 -NPs were measured in the spiking suspensions, as they can be important drivers of TiO 2 -NPs toxicity. After 90 days of exposure, non-classical dose-response relationships were observed for nitrifier abundance or activity, making threshold concentrations impossible to compute. Indeed, AOA abundance was reduced by 40% by TiO 2 -NPs whatever the concentration, while Nitrospira was never affected. Moreover, AOB and Nitrobacter abundances were decreased mainly at intermediate concentrations nitrification was reduced by 25% at the lowest (0.05 mg kg -1 ) and the highest (100 and 500 mg kg -1 ) TiO 2 -NPs concentrations. Path analyses indicated that TiO 2 -NPs affected nitrification through an effect on the specific activity of nitrifiers, in addition to indirect effects on nitrifier abundances. Altogether these results point out the need to include very low concentrations of NPs in soil toxicological studies, and the lack of relevance of classical dose-response tests and ecotoxicological dose metrics (EC50, IC50…) for TiO 2 -NPs impact on soil microorganisms.

Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study.

PubMed

Perera, Minoli A; Cavallari, Larisa H; Limdi, Nita A; Gamazon, Eric R; Konkashbaev, Anuar; Daneshjou, Roxana; Pluzhnikov, Anna; Crawford, Dana C; Wang, Jelai; Liu, Nianjun; Tatonetti, Nicholas; Bourgeois, Stephane; Takahashi, Harumi; Bradford, Yukiko; Burkley, Benjamin M; Desnick, Robert J; Halperin, Jonathan L; Khalifa, Sherief I; Langaee, Taimour Y; Lubitz, Steven A; Nutescu, Edith A; Oetjens, Matthew; Shahin, Mohamed H; Patel, Shitalben R; Sagreiya, Hersh; Tector, Matthew; Weck, Karen E; Rieder, Mark J; Scott, Stuart A; Wu, Alan H B; Burmester, James K; Wadelius, Mia; Deloukas, Panos; Wagner, Michael J; Mushiroda, Taisei; Kubo, Michiaki; Roden, Dan M; Cox, Nancy J; Altman, Russ B; Klein, Teri E; Nakamura, Yusuke; Johnson, Julie A

2013-08-31

VKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. We did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfarin were obtained at International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham (Birmingham, AL, USA). Patients enrolled at IWPC sites but who were not used for discovery made up the independent replication cohort. All participants were genotyped. We did a stepwise conditional analysis, conditioning first for VKORC1 -1639G→A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3. We prespecified a genome-wide significance threshold of p<5×10(-8) in the discovery cohort and p<0·0038 in the replication cohort. The discovery cohort contained 533 participants and the replication cohort 432 participants. After the prespecified conditioning in the discovery cohort, we identified an association between a novel single nucleotide polymorphism in the CYP2C cluster on chromosome 10 (rs12777823) and warfarin dose requirement that reached genome-wide significance (p=1·51×10(-8)). This association was confirmed in the replication cohort (p=5·04×10(-5)); analysis of the two cohorts together produced a p value of 4·5×10(-12). Individuals heterozygous for the rs12777823 A allele need a dose reduction of 6·92 mg/week and those homozygous 9·34 mg/week. Regression analysis showed that the inclusion of rs12777823 significantly improves warfarin dose variability explained by the IWPC dosing algorithm (21% relative improvement). A novel CYP2C single nucleotide polymorphism exerts a clinically relevant effect on warfarin dose in African Americans, independent of CYP2C9*2 and CYP2C9*3. Incorporation of this variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population. National Institutes of Health, American Heart Association, Howard Hughes Medical Institute, Wisconsin Network for Health Research, and the Wellcome Trust. Copyright © 2013 Elsevier Ltd. All rights reserved.

SU-E-T-287: Patterns of Patient Specific Dosimetry in Total Body Irradiation.

PubMed

Akino, Y; McMullen, K; Das, I

2012-06-01

Total body irradiation (TBI) is commonly used for conditioning prior to transplant in hematologic and immunologic diseases. Due to variability in body thickness, achieving dose uniformity across body within ±10% of the prescribed dose is challenging. The dose uniformity is further complicated by, techniques and beam energy used, lung shielding and selection of detector. The translational table technique for TBI could compensate for estimated delivered dose to whole body by adjusting couch speed during treatment. However, it is difficult to accurately estimate the dose by calculation and hence in vivo dosimetry (IVD) is routinely performed for TBI. The patterns of patient specific dosimetry, IVD are presented in this study. Under IRB exempt status, 161 patients who received TBI treatment between 2006 and 2011 were retrospectively analyzed using the treatment records from Cobalt-60 teletherapy unit and translational treatment couch. During treatment, IVD detectors (TLD, diode, or MOSFET) were placed on patient surface; both entrance and exit dose were recorded at the patient's head, neck, mediastinum, umbilicus, and knee. When large differences between prescribed and measured dose were observed, the dose delivery was corrected for subsequent fractions by adjustment in couch speed and/or bolus placement. Across the entire cohort, the mean (range) percent variance between calculated and measured dose were -2.3% (-66.2 - 35.3), 1.1% (-62.2 - 40.3), -1.9% (-66.4 - 46.6), -1.1% (-35.2 - 42.9), and 3.4% (-47.9 - 108.5) for head, neck, mediastinum, umbilicus, and knee, respectively. When the dose differences for multiple fractions were averaged, the compliance (±10%) between prescription and measured dose was improved as at umbilicus from 83.9% to 98.5%. Actual dose measurement analysis of TBI patients reveals a potentially wide variance from calculated dose. Dose uniformity can be significantly improved with immediate feedback after the first fraction prior to subsequent treatments. This work was supported by the JSPS Core-to-Core Program No. 23003. © 2012 American Association of Physicists in Medicine.

Accuracy of Reduced-Dose Computed Tomography for Ureteral Stones in Emergency Department Patients

PubMed Central

Moore, Christopher L.; Daniels, Brock; Ghita, Monica; Gunabushanam, Gowthaman; Luty, Seth; Molinaro, Annette M.; Singh, Dinesh; Gross, Cary P.

2016-01-01

Study objective Reduced-dose computed tomography (CT) scans have been recommended for diagnosis of kidney stone but are rarely used in the emergency department (ED) setting. Test characteristics are incompletely characterized, particularly in obese patients. Our primary outcome is to determine the sensitivity and specificity of a reduced-dose CT protocol for symptomatic ureteral stones, particularly those large enough to require intervention, using a protocol stratified by patient size. Methods This was a prospective, blinded observational study of 201 patients at an academic medical center. Consenting subjects underwent both regular- and reduced-dose CT, stratified into a high and low body mass index (BMI) protocol based on effective abdominal diameter. Reduced-dose CT scans were interpreted by radiologists blinded to regular-dose interpretations. Follow-up for outcome and intervention was performed at 90 days. Results CT scans with both regular and reduced doses were conducted for 201 patients, with 63% receiving the high BMI reduced-dose protocol. Ureteral stone was identified in 102 patients (50.7%) of those receiving regular-dose CT, with a ureteral stone greater than 5 mm identified in 26 subjects (12.9%). Sensitivity of the reduced-dose CT for any ureteral stone was 90.2% (95% confidence interval [CI] 82.3% to 95.0%), with a specificity of 99.0% (95% CI 93.7% to 100.0%). For stones greater than 5 mm, sensitivity was 100% (95% CI 85.0% to 100.0%). Reduced-dose CT identified 96% of patients who required intervention for ureteral stone within 90 days. Mean reduction in size-specific dose estimate was 18.6 milligray (mGy), from 21.7 mGy (SD 9.7) to 3.4 mGy (SD 0.9). Conclusion CT with substantial dose reduction was 90.2% (95% CI 82.3% to 95.0%) sensitive and 98.9% (95% CI 85.0% to 100.0%) specific for ureteral stones in ED patients with a wide range of BMIs. Reduced-dose CT was 96.0% (95% CI 80.5% to 99.3%) sensitive for ureteral stones requiring intervention within 90 days. PMID:25441242

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

Lucconi, G; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Bentefour, E

Purpose: The clinical commissioning of a workflow for pre-treatment range verification/adjustment for the head treatment of pediatric medulloblastoma patients, including dose monitoring during treatment. Methods: An array of Si-diodes (DIODES Incorporated) is placed on the patient skin on the opposite side to the beam entrance. A “scout” SOBP beam, with a longer beam range to cover the diodes in its plateau, is delivered; the measured signal is analyzed and the extracted water equivalent path lengths (WEPL) are compared to the expected values, revealing if a range correction is needed. Diodes stay in place during treatment to measure dose. The workflowmore » was tested in solid water and head phantoms and validated against independent WEPL measurements. Both measured WEPL and skin doses were compared to computed values from the TPS (XiO); a Markus chamber was used for reference dose measurements. Results: The WEPL accuracy of the method was verified by comparing it with the dose extinction method. It resulted, for both solid water and head phantom, in the sub-millimeter range, with a deviation less than 1% to the value extracted from the TPS. The accuracy of dose measurements in the fall-off part of the dose profile was validated against the Markus chamber. The entire range verification workflow was successfully tested for the mock-treatment of head phantom with the standard delivery of 90 cGy per field per fraction. The WEPL measurement revealed no need for range correction. The dose measurements agreed to better than 4% with the prescription dose. The robustness of the method and workflow, including detector array, hardware set and software functions, was successfully stress-tested with multiple repetitions. Conclusion: The performance of the in-vivo range verification system and related workflow meet the clinical requirements in terms of the needed WEPL accuracy for pretreatment range verification with acceptable dose to the patient.« less

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

Son, Christina H.; Law, Ethel; Oh, Jung Hun

Purpose: Although vaginal stenosis (VS) is a recognized toxicity in women who receive pelvic radiation therapy (RT), the relationship between RT dose and the volume and extent of toxicity has not been analyzed. We modeled this relationship to identify predictors of VS. Methods and Materials: We evaluated 54 women, aged 29 to 78 years, who underwent pelvic RT for rectal or anal cancer during 2008 to 2011 and were enrolled in a prospective study evaluating vaginal dilator use. Maximum dilator size was measured before RT (baseline) and 1 month and 12 months after RT. Dilator use was initiated at 1 month. The difference (D)more » in dilator size before and after RT was recorded. Those with D ≤−1 were classified as having VS (n=35); those with D ≥0 were classified as having no VS (n=19 at 1 month). Dose-volume parameters were extracted, and the generalized equivalent uniform dose (gEUD) was used to build a predictive model. Results: The mean vaginal doses were 50.0 Gy and 36.8 Gy for anal and rectal cancer patients, respectively. One month after RT, a gEUD model using a wide range of a values suggests that sparing of vaginal volume to a low dose may be important. When gEUD (a = −1) was <35 Gy and the mean vaginal dose was <43 Gy, severe VS was reduced (P=.02). A 1-year analysis suggests increasingly negative D values with increasing mean dose. However, patients with compliance <40% were more likely to have toxicity. Conclusions: Vaginal stenosis is influenced by multiple RT dose-volume characteristics. Mean dose and gEUD constraints together may reduce the risk of severe VS. Patients receiving higher mean vaginal doses should have greater compliance with dilator therapy to minimize risk of toxicity. Further validation with independent datasets is needed.« less

Development of computational pregnant female and fetus models and assessment of radiation dose from positron-emitting tracers.

PubMed

Xie, Tianwu; Zaidi, Habib

2016-12-01

Molecular imaging using PET and hybrid (PET/CT and PET/MR) modalities nowadays plays a pivotal role in the clinical setting for diagnosis and staging, treatment response monitoring, and radiation therapy treatment planning of a wide range of oncologic malignancies. The developing embryo/fetus presents a high sensitivity to ionizing radiation. Therefore, estimation of the radiation dose delivered to the embryo/fetus and pregnant patients from PET examinations to assess potential radiation risks is highly praised. We constructed eight embryo/fetus models at various gestation periods with 25 identified tissues according to reference data recommended by the ICRP publication 89 representing the anatomy of the developing embryo/fetus. The developed embryo/fetus models were integrated into realistic anthropomorphic computational phantoms of the pregnant female and used for estimating, using Monte Carlo calculations, S-values of common positron-emitting radionuclides, organ absorbed dose, and effective dose of a number of positron-emitting labeled radiotracers. The absorbed dose is nonuniformly distributed in the fetus. The absorbed dose of the kidney and liver of the 8-week-old fetus are about 47.45 % and 44.76 % higher than the average absorbed dose of the fetal total body for all investigated radiotracers. For 18 F-FDG, the fetal effective doses are 2.90E-02, 3.09E-02, 1.79E-02, 1.59E-02, 1.47E-02, 1.40E-02, 1.37E-02, and 1.27E-02 mSv/MBq at the 8th, 10th, 15th, 20th, 25th, 30th, 35th, and 38th weeks of gestation, respectively. The developed pregnant female/fetus models matching the ICRP reference data can be exploited by dedicated software packages for internal and external dose calculations. The generated S-values will be useful to produce new standardized dose estimates to pregnant patients and embryo/fetus from a variety of positron-emitting labeled radiotracers.

Seeking Beta: Experimental Considerations and Theoretical Implications Regarding the Detection of Curvature in Dose-Response Relationships for Chromosome Aberrations.

PubMed

Shuryak, Igor; Loucas, Bradford D; Cornforth, Michael N

2017-01-01

The concept of curvature in dose-response relationships figures prominently in radiation biology, encompassing a wide range of interests including radiation protection, radiotherapy and fundamental models of radiation action. In this context, the ability to detect even small amounts of curvature becomes important. Standard (ST) statistical approaches used for this purpose typically involve least-squares regression, followed by a test on sums of squares. Because we have found that these methods are not particularly robust, we investigated an alternative information theoretic (IT) approach, which involves Poisson regression followed by information-theoretic model selection. Our first objective was to compare the performances of the ST and IT methods by using them to analyze mFISH data on gamma-ray-induced simple interchanges in human lymphocytes, and on Monte Carlo simulated data. Real and simulated data sets that contained small-to-moderate curvature were deliberately selected for this exercise. The IT method tended to detect curvature with higher confidence than the ST method. The finding of curvature in the dose response for true simple interchanges is discussed in the context of fundamental models of radiation action. Our second objective was to optimize the design of experiments aimed specifically at detecting curvature. We used Monte Carlo simulation to investigate the following parameters. Constrained by available resources (i.e., the total number of cells to be scored) these include: the optimal number of dose points to use; the best way to apportion the total number of cells among these dose points; and the spacing of dose intervals. Counterintuitively, our simulation results suggest that 4-5 radiation doses were typically optimal, whereas adding more dose points may actually prove detrimental. Superior results were also obtained by implementing unequal dose spacing and unequal distributions in the number of cells scored at each dose.

Repair-dependent cell radiation survival and transformation: an integrated theory.

PubMed

Sutherland, John C

2014-09-07

The repair-dependent model of cell radiation survival is extended to include radiation-induced transformations. The probability of transformation is presumed to scale with the number of potentially lethal damages that are repaired in a surviving cell or the interactions of such damages. The theory predicts that at doses corresponding to high survival, the transformation frequency is the sum of simple polynomial functions of dose; linear, quadratic, etc, essentially as described in widely used linear-quadratic expressions. At high doses, corresponding to low survival, the ratio of transformed to surviving cells asymptotically approaches an upper limit. The low dose fundamental- and high dose plateau domains are separated by a downwardly concave transition region. Published transformation data for mammalian cells show the high-dose plateaus predicted by the repair-dependent model for both ultraviolet and ionizing radiation. For the neoplastic transformation experiments that were analyzed, the data can be fit with only the repair-dependent quadratic function. At low doses, the transformation frequency is strictly quadratic, but becomes sigmodial over a wider range of doses. Inclusion of data from the transition region in a traditional linear-quadratic analysis of neoplastic transformation frequency data can exaggerate the magnitude of, or create the appearance of, a linear component. Quantitative analysis of survival and transformation data shows good agreement for ultraviolet radiation; the shapes of the transformation components can be predicted from survival data. For ionizing radiations, both neutrons and x-rays, survival data overestimate the transforming ability for low to moderate doses. The presumed cause of this difference is that, unlike UV photons, a single x-ray or neutron may generate more than one lethal damage in a cell, so the distribution of such damages in the population is not accurately described by Poisson statistics. However, the complete sigmodial dose-response data for neoplastic transformations can be fit using the repair-dependent functions with all parameters determined only from transformation frequency data.

Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model.

PubMed

Dropkin, Greg

2016-11-24

Analyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour. GAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 - 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy. For all solid cancer incidence, RR estimated from 0 - 100 mGy and 0 - 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 - 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort. Non-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.

SU-E-T-454: Impact of Calculation Grid Size On Dosimetry and Radiobiological Parameters for Head and Neck IMRT

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

Srivastava, S; Das, I; Indiana University Health Methodist Hospital, Indianapolis, IN

2014-06-01

Purpose: IMRT has become standard of care for complex treatments to optimize dose to target and spare normal tissues. However, the impact of calculation grid size is not widely known especially dose distribution, tumor control probability (TCP) and normal tissue complication probability (NTCP) which is investigated in this study. Methods: Ten head and neck IMRT patients treated with 6 MV photons were chosen for this study. Using Eclipse TPS, treatment plans were generated for different grid sizes in the range 1–5 mm for the same optimization criterion with specific dose-volume constraints. The dose volume histogram (DVH) was calculated for allmore » IMRT plans and dosimetric data were compared. ICRU-83 dose points such as D2%, D50%, D98%, as well as the homogeneity and conformity indices (HI, CI) were calculated. In addition, TCP and NTCP were calculated from DVH data. Results: The PTV mean dose and TCP decreases with increasing grid size with an average decrease in mean dose by 2% and TCP by 3% respectively. Increasing grid size from 1–5 mm grid size, the average mean dose and NTCP for left parotid was increased by 6.0% and 8.0% respectively. Similar patterns were observed for other OARs such as cochlea, parotids and spinal cord. The HI increases up to 60% and CI decreases on average by 3.5% between 1 and 5 mm grid that resulted in decreased TCP and increased NTCP values. The number of points meeting the gamma criteria of ±3% dose difference and ±3mm DTA was higher with a 1 mm on average (97.2%) than with a 5 mm grid (91.3%). Conclusion: A smaller calculation grid provides superior dosimetry with improved TCP and reduced NTCP values. The effect is more pronounced for smaller OARs. Thus, the smallest possible grid size should be used for accurate dose calculation especially in H and N planning.« less

Technical Note: Scanning of parallel-plate ionization chamber and diamond detector for measurements of water-dose profiles in the vicinity of a narrow x-ray microbeam.

PubMed

Nariyama, Nobuteru

2017-12-01

Scanning of dosimeters facilitates dose distribution measurements with fine spatial resolutions. This paper presents a method of conversion of the scanning results to water-dose profiles and provides an experimental verification. An Advanced Markus chamber and a diamond detector were scanned at a resolution of 6 μm near the beam edges during irradiation with a 25-μm-wide white narrow x-ray beam from a synchrotron radiation source. For comparison, GafChromic films HD-810 and HD-V2 were also irradiated. The conversion procedure for the water dose values was simulated with Monte Carlo photon-electron transport code as a function of the x-ray incidence position. This method was deduced from nonstandard beam reference-dosimetry protocols used for high-energy x-rays. Among the calculated nonstandard beam correction factors, P wall , which is the ratio of the absorbed dose in the sensitive volume of the chamber with water wall to that with a polymethyl methacrylate wall, was found to be the most influential correction factor in most conditions. The total correction factor ranged from 1.7 to 2.7 for the Advanced Markus chamber and from 1.15 to 1.86 for the diamond detector as a function of the x-ray incidence position. The water dose values obtained with the Advanced Markus chamber and the HD-810 film were in agreement in the vicinity of the beam, within 35% and 18% for the upper and lower sides of the beam respectively. The beam width obtained from the diamond detector was greater, and the doses out of the beam were smaller than the doses of the others. The comparison between the Advanced Markus chamber and HD-810 revealed that the dose obtained with the scanned chamber could be converted to the water dose around the beam by applying nonstandard beam reference-dosimetry protocols. © 2017 American Association of Physicists in Medicine.

Methamphetamine-Induced Locomotor Changes are Dependent on Age, Dose and Genotype

PubMed Central

Good, Renee L.; Radcliffe, Richard A.

2012-01-01

Adolescence is a critical age for addiction formation as a large percentage of pathological drug-seeking behaviors manifest during this time. The extent to which neurotoxic effects of drugs of abuse influence subsequent drug seeking behaviors and impulsivity is an understudied area of research. Methamphetamine (METH) is a widely abused drug that produces locomotor responses ranging from behavioral sensitization to tolerance, both of which are behaviors that may relate to risk of abuse. Here we investigated the effects of age, genotype, METH dose, including a neurotoxic dose, and METH metabolism on open-field activity (OFA) to gain insight into the complex disease of drug abuse. C57Bl/6 (B6), DBA/2 (D2), and 129S6SvEv/Tac (129) mouse strains were administered saline or either a high dose (4 × 5 mg/kg in 2h intervals for 2 days) or low dose (2 × 1 mg/kg in 24h intervals) METH pretreatment during adolescence (post natal day (PND) 40) or early adulthood (PND 80) followed by behavioral testing with a METH (1 mg/kg) or saline challenge 40 days later. Striatal concentrations of METH and AMPH were also determined. Significant findings include: 1) METH pretreated adolescent B6 mice displayed significant sensitization for horizontal locomotion due to high dose METH pretreatment; 2) METH pretreated B6 adults showed significant tolerance for the vertical activity measure caused by low dose METH pretreatment; 3) METH pretreated adult D2 mice exhibited significant sensitization for vertical activity induced by low dose METH pretreatment, and 4) 129 mice metabolized METH significantly faster than the B6 and D2 mice, but METH pretreatment did not alter metabolism. No significant behavioral responses to either METH pretreatment dose were observed for the D2 adolescent studies or either 129 age group. Our results highlight the importance of the interactions of age, strain and METH dose on locomotor behavioral outcomes. PMID:21163294

Fiber-Coupled, Time-Gated { {Al}}_{2}{ {O}}_{3} : { {C}} Radioluminescence Dosimetry Technique and Algorithm for Radiation Therapy With LINACs

NASA Astrophysics Data System (ADS)

Magne, Sylvain; Deloule, Sybelle; Ostrowsky, Aimé; Ferdinand, Pierre

2013-08-01

An original algorithm for real-time In Vivo Dosimetry (IVD) based on Radioluminescence (RL) of dosimetric-grade Al2O3:C crystals is described and demonstrated in reference conditions with 12-MV photon beams from a Saturne 43 linear accelerator (LINAC), simulating External Beam Radiation Therapy (EBRT) treatments. During the course of irradiation, a portion of electrons is trapped within the Al2O3:C crystal while another portion recombines and generates RL, recorded on-line using an optical fiber. The RL sensitivity is dose-dependent and increases in accordance with the concentration of trapped electrons. Once irradiation is completed, the Al2O3:C crystal is reset by laser light (reusable) and the resultant OSL (Optically Stimulated Luminescence) is also collected back by the remote RL-OSL reader and finally integrated to yield the absorbed dose. During irradiation, scintillation and Cerenkov lights generated within the optical fiber (“stem effect”) are removed by a time-discrimination method involving a discriminating unit and a fiber-coupled BGO scintillator placed in the irradiation room, next to the LINAC. The RL signals were then calibrated with respect to reference dose and dose rate data using an ionization chamber (IC). The algorithm relies upon the integral of the RL and provides the accumulated dose (useful to the medical physicist) at any time during irradiation, the dose rate being derived afterwards. It is tested with both step and arbitrary dose rate profiles, manually operated from the LINAC control desk. The doses measured by RL and OSL are both compared to reference doses and deviations are about ±2% and ±1% respectively, thus demonstrating the reliability of the algorithm for arbitrary profiles and wide range of dose rates. Although the calculation was done off-line, it is amenable to real-time processing during irradiation.

Clinical and pharmacokinetic results with a new ultrashort-acting calcium antagonist, clevidipine, following gradually increasing intravenous doses to healthy volunteers

PubMed Central

Ericsson, H; Fakt, C; Jolin-Mellgård, Å; Nordlander, M; Sohtell, L; Sunzel, M; Regårdh, C G

1999-01-01

Aims To investigate the tolerability and safety of clevidipine in healthy male volunteers during intravenous infusion at gradually increasing dose rates and to obtain preliminary information on the pharmacokinetics and pharmacodynamic effects of the drug. Methods Twenty-five subjects were enrolled in the study and twenty-one of them were included twice, resulting in a total of forty-six study entries encompassing 20 min infusions of clevidipine at target dose rates ranging from 0.12 to 48 nmol min−1 kg−1. Haemodynamic variables and adverse events were recorded throughout the study. Concentrations of clevidipine and its primary metabolite, H 152/81, were followed in whole blood, and the pharmacokinetics were evaluated by non-compartmental and compartmental analysis. An Emax model was fitted to the effect on mean arterial pressure (MAP) over heart rate (HR) and the corresponding blood concentrations of clevidipine. Results Clevidipine was administered up to a target dose rate of 48 nmol min−1 kg−1, where a pre-determined escape criterion was reached (HR>120 beats min−1) and the study was stopped. The most common adverse events were flush and headache, which can be directly related to the mechanism of action of clevidipine. There was a linear relationship between blood concentration and dose rate in the range studied. The median clearance value determined by non-compartmental analysis was 0.125 l min−1 kg−1. Applying the population approach to the sparse data on clevidipine concentrations, an open two compartment pharmacokinetic model was found to be the best model in describing the disposition of the drug. The population mean clearance value determined by this method was 0.121 l min−1 kg−1, and the volume of distribution at steady state was 0.56 l kg−1. The initial half-life, contributing by more than 80% to the total area under the blood concentration-time curve following i.v. bolus administration, was 1.8 min, and the terminal half-life was 9.5 min. At the highest dose rates, MAP was reduced by approximately 10%, and the HR reached the pre-determined escape criterion for this study (>120 beats min−1). Conclusions Clevidipine is well tolerated and safe in healthy volunteers at dose rates up to at least 48 nmol min−1 kg−1. The pharmacokinetics are linear over a wide dose range. Clevidipine is a high clearance drug with extremely short half-lives. The effect of clevidipine on the blood pressure was marginal, probably due to a compensatory baroreflex activation in this population of healthy volunteers. A simple Emax model adequately describes the relationship between the pharmacodynamic response (MAP/HR) and the blood concentrations of clevidipine. PMID:10336577

Quantitative evaluation of potential irradiation geometries for carbon-ion beam grid therapy.

PubMed

Tsubouchi, Toshiro; Henry, Thomas; Ureba, Ana; Valdman, Alexander; Bassler, Niels; Siegbahn, Albert

2018-03-01

Radiotherapy using grids containing cm-wide beam elements has been carried out sporadically for more than a century. During the past two decades, preclinical research on radiotherapy with grids containing small beam elements, 25 μm-0.7 mm wide, has been performed. Grid therapy with larger beam elements is technically easier to implement, but the normal tissue tolerance to the treatment is decreasing. In this work, a new approach in grid therapy, based on irradiations with grids containing narrow carbon-ion beam elements was evaluated dosimetrically. The aim formulated for the suggested treatment was to obtain a uniform target dose combined with well-defined grids in the irradiated normal tissue. The gain, obtained by crossfiring the carbon-ion beam grids over a simulated target volume, was quantitatively evaluated. The dose distributions produced by narrow rectangular carbon-ion beams in a water phantom were simulated with the PHITS Monte Carlo code. The beam-element height was set to 2.0 cm in the simulations, while the widths varied from 0.5 to 10.0 mm. A spread-out Bragg peak (SOBP) was then created for each beam element in the grid, to cover the target volume with dose in the depth direction. The dose distributions produced by the beam-grid irradiations were thereafter constructed by adding the dose profiles simulated for single beam elements. The variation of the valley-to-peak dose ratio (VPDR) with depth in water was thereafter evaluated. The separation of the beam elements inside the grids were determined for different irradiation geometries with a selection criterion. The simulated carbon-ion beams remained narrow down to the depths of the Bragg peaks. With the formulated selection criterion, a beam-element separation which was close to the beam-element width was found optimal for grids containing 3.0-mm-wide beam elements, while a separation which was considerably larger than the beam-element width was found advantageous for grids containing 0.5-mm-wide beam elements. With the single-grid irradiation setup, the VPDRs were close to 1.0 already at a distance of several cm from the target. The valley doses given to the normal tissue at 0.5 cm distance from the target volume could be limited to less than 10% of the mean target dose if a crossfiring setup with four interlaced grids was used. The dose distributions produced by grids containing 0.5- and 3.0-mm wide beam elements had characteristics which could be useful for grid therapy. Grids containing mm-wide carbon-ion beam elements could be advantageous due to the technical ease with which these beams can be produced and delivered, despite the reduced threshold doses observed for early and late responding normal tissue for beams of millimeter width, compared to submillimetric beams. The treatment simulations showed that nearly homogeneous dose distributions could be created inside the target volumes, combined with low valley doses in the normal tissue located close to the target volume, if the carbon-ion beam grids were crossfired in an interlaced manner with optimally selected beam-element separations. The formulated selection criterion was found useful for the quantitative evaluation of the dose distributions produced by the different irradiation setups. © 2018 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Analysis of a Statistical Relationship Between Dose and Error Tallies in Semiconductor Digital Integrated Circuits for Application to Radiation Monitoring Over a Wireless Sensor Network

NASA Astrophysics Data System (ADS)

Colins, Karen; Li, Liqian; Liu, Yu

2017-05-01

Mass production of widely used semiconductor digital integrated circuits (ICs) has lowered unit costs to the level of ordinary daily consumables of a few dollars. It is therefore reasonable to contemplate the idea of an engineered system that consumes unshielded low-cost ICs for the purpose of measuring gamma radiation dose. Underlying the idea is the premise of a measurable correlation between an observable property of ICs and radiation dose. Accumulation of radiation-damage-induced state changes or error events is such a property. If correct, the premise could make possible low-cost wide-area radiation dose measurement systems, instantiated as wireless sensor networks (WSNs) with unshielded consumable ICs as nodes, communicating error events to a remote base station. The premise has been investigated quantitatively for the first time in laboratory experiments and related analyses performed at the Canadian Nuclear Laboratories. State changes or error events were recorded in real time during irradiation of samples of ICs of different types in a 60Co gamma cell. From the error-event sequences, empirical distribution functions of dose were generated. The distribution functions were inverted and probabilities scaled by total error events, to yield plots of the relationship between dose and error tallies. Positive correlation was observed, and discrete functional dependence of dose quantiles on error tallies was measured, demonstrating the correctness of the premise. The idea of an engineered system that consumes unshielded low-cost ICs in a WSN, for the purpose of measuring gamma radiation dose over wide areas, is therefore tenable.

(⁹⁹m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹⁶⁶Ho-microspheres.

PubMed

Elschot, Mattijs; Nijsen, Johannes F W; Lam, Marnix G E H; Smits, Maarten L J; Prince, Jip F; Viergever, Max A; van den Bosch, Maurice A A J; Zonnenberg, Bernard A; de Jong, Hugo W A M

2014-10-01

Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization. This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with (166)Ho radioembolization. (99m)Tc-MAA-based and (166)Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after (166)Ho radioembolization. In the phantom study, (166)Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to -4.4 Gy) than (166)Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment (166)Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of (166)Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), (99m)Tc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and (99m)Tc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001). In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic (99m)Tc-MAA imaging. Pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after (166)Ho radioembolization.

Redefining the stress cortisol response to surgery.

PubMed

Khoo, Bernard; Boshier, Piers R; Freethy, Alexander; Tharakan, George; Saeed, Samerah; Hill, Neil; Williams, Emma L; Moorthy, Krishna; Tolley, Neil; Jiao, Long R; Spalding, Duncan; Palazzo, Fausto; Meeran, Karim; Tan, Tricia

2017-11-01

Cortisol levels rise with the physiological stress of surgery. Previous studies have used older, less-specific assays, have not differentiated by severity or only studied procedures of a defined type. The aim of this study was to examine this phenomenon in surgeries of varying severity using a widely used cortisol immunoassay. Euadrenal patients undergoing elective surgery were enrolled prospectively. Serum samples were taken at 8 am on surgical day, induction and 1 hour, 2 hour, 4 hour and 8 hour after. Subsequent samples were taken daily at 8 am until postoperative day 5 or hospital discharge. Total cortisol was measured using an Abbott Architect immunoassay, and cortisol-binding globulin (CBG) using a radioimmunoassay. Surgical severity was classified by POSSUM operative severity score. Ninety-three patients underwent surgery: Major/Major+ (n = 37), Moderate (n = 33) and Minor (n = 23). Peak cortisol positively correlated to severity: Major/Major+ median 680 [range 375-1452], Moderate 581 [270-1009] and Minor 574 [272-1066] nmol/L (Kruskal-Wallis test, P = .0031). CBG fell by 23%; the magnitude of the drop positively correlated to severity. The range in baseline and peak cortisol response to surgery is wide, and peak cortisol levels are lower than previously appreciated. Improvements in surgery, anaesthetic techniques and cortisol assays might explain our observed lower peak cortisols. The criteria for the dynamic testing of cortisol response may need to be reduced to take account of these factors. Our data also support a lower-dose, stratified approach to dosing of steroid replacement in hypoadrenal patients, to minimize the deleterious effects of over-replacement. © 2017 John Wiley & Sons Ltd.

Characterization of exposure and dose of man made vitreous fiber in experimental studies.

PubMed Central

Hamilton, R D; Miiller, W C; Christensen, D R; Anderson, R; Hesterberg, T W

1994-01-01

The use of fibrous test materials in in vivo experiments introduces a number of significant problems not associated with nonfibrous particulates. The key to all aspects of the experiment is the accurate characterization of the test material in terms of fiber length, diameter, particulate content, and chemistry. All data related to fiber properties must be collected in a statistically sound manner to eliminate potential bias. Procedures similar to those outlined by the National Institute of Occupational Safety and Health (NIOSH) or the World Health Organization (WHO) must be the basis of any fiber characterization. The test material to which the animal is exposed must be processed to maximize the amount of respirable fiber and to minimize particulate content. The complex relationship among the characteristics of the test material, the properties of the delivery system, and the actual dose that reaches the target tissue in the lung makes verification of dose essential. In the case of man-made vitreous fibers (MMVF), dose verification through recovery of fiber from exposed animals is a complex task. The potential for high fiber solubility makes many of the conventional techniques for tissue preservation and digestion inappropriate. Processes based on the minimum use of aggressive chemicals, such as cold storage and low temperature ashing, are potentially useful for a wide range of inorganic fibers. Any processes used to assess fiber exposure and dose must be carefully validated to establish that the chemical and physical characteristics of the fibers have not been changed and that the dose to the target tissue is completely and accurately described. PMID:7882912

Evidence that metyrapone can act as a stressor: effect on pituitary-adrenal hormones, plasma glucose and brain c-fos induction.

PubMed

Rotllant, David; Ons, Sheila; Carrasco, Javier; Armario, Antonio

2002-08-01

Metyrapone, a 11-beta steroid hydroxylase inhibitor that blocks stress-induced glucocorticoid release, is extensively used to study the physiological and behavioural roles of glucocorticoids. However, there is circumstantial evidence suggesting that metyrapone could act as a pharmacological stressor. Thus, the effects of various doses of metyrapone on two well-characterized stress markers (ACTH and glucose) were studied in male rats. Metyrapone administration, while exerting a modest effect on plasma corticosterone levels, dose-dependently increased plasma ACTH and glucose levels. Using the highest doses previously tested (200 mg/kg) we further observed, as evaluated by fos-like immunoreactivity (FLI), a strong activation of a wide range of brain areas, including the parvocellular region of the hypothalamic paraventricular nucleus (PVNp), the origin of the main ACTH secretagogues. Metyrapone-induced FLI was observed in neocortical and allocortical areas, in several limbic, thalamic and hypothalamic nuclei and, to a lesser extent, in the brainstem. In a final experiment, a dose-response study of metyrapone-induced FLI was carried out focusing on selected brain areas. The study revealed that the paraventricular thalamic nucleus and central amygdala were the areas most sensitive to metyrapone as they responded even to the lowest dose of the drug. Most areas, among them the PVNp, only showed enhanced FLI with the two highest doses, i.e. when it was associated with ACTH and glucose responses. These data suggest that some of the effects of metyrapone could be due to its stressful properties rather than its ability to inhibit glucocorticoid synthesis. The exact mechanisms involved remain to be established.

Pharmacokinetic profile of dextromethorphan hydrobromide in a syrup formulation in children and adolescents.

PubMed

Guenin, Eric; Armogida, Marianna; Riff, Dennis

2014-09-01

Dextromethorphan hydrobromide (DM) is a widely used antitussive. This study determined, for the first time, the basic pharmacokinetic profile of DM and its active metabolite, dextrorphan (DP) in children and adolescents. Thirty-eight male and female subjects at risk for developing an upper respiratory tract infection (URTI), or symptomatic with cough due to URTI, were enrolled in this single-dose, open-label study: ages 2-5 years (Group A, n = 8), 6-11 years (Group B, n = 17), 12-17 years (Group C, n = 13). Subjects were genotyped for cytochrome P450 (CYP) 2D6 polymorphisms and characterized as poor (PM) or non-poor metabolizers (non-PM). Groups A and B were dosed using an age-weight dosing schedule (DM range 7.5-24.75 mg); a 30-mg dose was used for Group C. Average exposures to total DP increased as age group increased, and average exposure to DM was highest in the adolescent group. One subject in that group was a PM. The terminal half-life (t ½) values were longer in the adolescent group due in part to the single PM subject. No relationship between body weight and pharmacokinetic parameters was noted. This is the first evaluation of the pharmacokinetic characteristics of DM in children and adolescents. A single dose of DM in this population was safe, and well tolerated at all doses tested. The data are used to model and compare pediatric DM exposures with those of adults.

Problems in evaluating radiation dose via terrestrial and aquatic pathways.

PubMed Central

Vaughan, B E; Soldat, J K; Schreckhise, R G; Watson, E C; McKenzie, D H

1981-01-01

This review is concerned with exposure risk and the environmental pathways models used for predictive assessment of radiation dose. Exposure factors, the adequacy of available data, and the model subcomponents are critically reviewed from the standpoint of absolute error propagation. Although the models are inherently capable of better absolute accuracy, a calculated dose is usually overestimated by from two to six orders of magnitude, in practice. The principal reason for so large an error lies in using "generic" concentration ratios in situations where site specific data are needed. Major opinion of the model makers suggests a number midway between these extremes, with only a small likelihood of ever underestimating the radiation dose. Detailed evaluations are made of source considerations influencing dose (i.e., physical and chemical status of released material); dispersal mechanisms (atmospheric, hydrologic and biotic vector transport); mobilization and uptake mechanisms (i.e., chemical and other factors affecting the biological availability of radioelements); and critical pathways. Examples are shown of confounding in food-chain pathways, due to uncritical application of concentration ratios. Current thoughts of replacing the critical pathways approach to calculating dose with comprehensive model calculations are also shown to be ill-advised, given present limitations in the comprehensive data base. The pathways models may also require improved parametrization, as they are not at present structured adequately to lend themselves to validation. The extremely wide errors associated with predicting exposure stand in striking contrast to the error range associated with the extrapolation of animal effects data to the human being. PMID:7037381

Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

PubMed Central

Fernandes Azevedo, Bruna; Barros Furieri, Lorena; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra; Frizera Vassallo, Paula; Ronacher Simões, Maylla; Fiorim, Jonaina; Rossi de Batista, Priscila; Fioresi, Mirian; Rossoni, Luciana; Stefanon, Ivanita; Alonso, María Jesus; Salaices, Mercedes; Valentim Vassallo, Dalton

2012-01-01

Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. PMID:22811600

Incidence of salivary gland tumors among atomic bomb survivors, 1950-1987. Evaluation of radiation-related risk

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

Land, C.E.; Saku, Takashi; Tokuoka, Shoji

1996-07-01

A wide-ranging seach for benign and malignant tumors of the major and minor salivary glands among members of the Life Span Study sample of the Radiation Effects Research Foundation identified 41 malignant and 94 benign incident tumors, including 14 malignant and 12 benign tumors of the minor salivary gland, plus 10 major gland tumors of unknown behavior. Dose-response analyses found statistically significant increases in risk with increasing A-bomb dose for both cancer and benign tumors. Estimated relative risks at 1 Sv weighted tissue kerma (RR{sub 1}Sv, with 90% confidence interval in parentheses) were 4.5 (2.5-8.5) for cancer and 1.7 (1.1-2.7)more » for benign tumors. When analyzed by histological subtype within these two broad groups, it appeared that most of the dose response for malignant tumors was provided by an exceptionally strong dose response for mucoepidermoid carcinoma [11 exposed cases with dose estimates, RR{sub 1Sv} - 9.3 (3.5-30.6)], and most or all of that for benign tumors corresponded to Warthin`s tumor [12 cases, RR{sub 1Sv} = 4.1 (1.6-11.3)]. There was a marginal dose response for malignant tumors other than mucoepidermoid carcinoma [RR{sub 1Sv} = 2.4 (0.99-5.7)] but no significant trend for benign tumors other than Warthin`s tumor [RR{sub 1Sv} = 1.3 (0.9-2.2)]. Re-examination of the original data from published studies of other irradiated populations may shed new light on the remarkable type specificity of the salivary tumor dose response observed in the present study. 33 refs., 3 figs., 7 tabs.« less

Development and reproducibility evaluation of a Monte Carlo-based standard LINAC model for quality assurance of multi-institutional clinical trials.

PubMed

Usmani, Muhammad Nauman; Takegawa, Hideki; Takashina, Masaaki; Numasaki, Hodaka; Suga, Masaki; Anetai, Yusuke; Kurosu, Keita; Koizumi, Masahiko; Teshima, Teruki

2014-11-01

Technical developments in radiotherapy (RT) have created a need for systematic quality assurance (QA) to ensure that clinical institutions deliver prescribed radiation doses consistent with the requirements of clinical protocols. For QA, an ideal dose verification system should be independent of the treatment-planning system (TPS). This paper describes the development and reproducibility evaluation of a Monte Carlo (MC)-based standard LINAC model as a preliminary requirement for independent verification of dose distributions. The BEAMnrc MC code is used for characterization of the 6-, 10- and 15-MV photon beams for a wide range of field sizes. The modeling of the LINAC head components is based on the specifications provided by the manufacturer. MC dose distributions are tuned to match Varian Golden Beam Data (GBD). For reproducibility evaluation, calculated beam data is compared with beam data measured at individual institutions. For all energies and field sizes, the MC and GBD agreed to within 1.0% for percentage depth doses (PDDs), 1.5% for beam profiles and 1.2% for total scatter factors (Scps.). Reproducibility evaluation showed that the maximum average local differences were 1.3% and 2.5% for PDDs and beam profiles, respectively. MC and institutions' mean Scps agreed to within 2.0%. An MC-based standard LINAC model developed to independently verify dose distributions for QA of multi-institutional clinical trials and routine clinical practice has proven to be highly accurate and reproducible and can thus help ensure that prescribed doses delivered are consistent with the requirements of clinical protocols. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Linear-No-Threshold Default Assumptions for Noncancer and Nongenotoxic Cancer Risks: A Mathematical and Biological Critique.

PubMed

Bogen, Kenneth T

2016-03-01

To improve U.S. Environmental Protection Agency (EPA) dose-response (DR) assessments for noncarcinogens and for nonlinear mode of action (MOA) carcinogens, the 2009 NRC Science and Decisions Panel recommended that the adjustment-factor approach traditionally applied to these endpoints should be replaced by a new default assumption that both endpoints have linear-no-threshold (LNT) population-wide DR relationships. The panel claimed this new approach is warranted because population DR is LNT when any new dose adds to a background dose that explains background levels of risk, and/or when there is substantial interindividual heterogeneity in susceptibility in the exposed human population. Mathematically, however, the first claim is either false or effectively meaningless and the second claim is false. Any dose-and population-response relationship that is statistically consistent with an LNT relationship may instead be an additive mixture of just two quasi-threshold DR relationships, which jointly exhibit low-dose S-shaped, quasi-threshold nonlinearity just below the lower end of the observed "linear" dose range. In this case, LNT extrapolation would necessarily overestimate increased risk by increasingly large relative magnitudes at diminishing values of above-background dose. The fact that chemically-induced apoptotic cell death occurs by unambiguously nonlinear, quasi-threshold DR mechanisms is apparent from recent data concerning this quintessential toxicity endpoint. The 2009 NRC Science and Decisions Panel claims and recommendations that default LNT assumptions be applied to DR assessment for noncarcinogens and nonlinear MOA carcinogens are therefore not justified either mathematically or biologically. © 2015 The Author. Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development.

PubMed

Podgorac, Jelena; Pešić, Vesna; Pavković, Željko; Martać, Ljiljana; Kanazir, Selma; Filipović, Ljupka; Sekulić, Slobodan

2016-09-15

Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities. Copyright © 2016 Elsevier B.V. All rights reserved.

Protein substitute dosage in PKU: how much do young patients need?

PubMed Central

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-01-01

Background The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). Aim To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.1 Methods In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2–10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre‐breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8–14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5–3.1 g/kg/day). Results When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre‐breakfast by 301 μmol/l (95% CI 215 to 386) and in the evening by 337 μmol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. Conclusions A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/− fat) content of the protein substitute. PMID:16547085

Comparison of patient specific dose metrics between chest radiography, tomosynthesis, and CT for adult patients of wide ranging body habitus

PubMed Central

Zhang, Yakun; Li, Xiang; Segars, W. Paul; Samei, Ehsan

2014-01-01

Purpose: Given the radiation concerns inherent to the x-ray modalities, accurately estimating the radiation doses that patients receive during different imaging modalities is crucial. This study estimated organ doses, effective doses, and risk indices for the three clinical chest x-ray imaging techniques (chest radiography, tomosynthesis, and CT) using 59 anatomically variable voxelized phantoms and Monte Carlo simulation methods. Methods: A total of 59 computational anthropomorphic male and female extended cardiac-torso (XCAT) adult phantoms were used in this study. Organ doses and effective doses were estimated for a clinical radiography system with the capability of conducting chest radiography and tomosynthesis (Definium 8000, VolumeRAD, GE Healthcare) and a clinical CT system (LightSpeed VCT, GE Healthcare). A Monte Carlo dose simulation program (PENELOPE, version 2006, Universitat de Barcelona, Spain) was used to mimic these two clinical systems. The Duke University (Durham, NC) technique charts were used to determine the clinical techniques for the radiographic modalities. An exponential relationship between CTDIvol and patient diameter was used to determine the absolute dose values for CT. The simulations of the two clinical systems compute organ and tissue doses, which were then used to calculate effective dose and risk index. The calculation of the two dose metrics used the tissue weighting factors from ICRP Publication 103 and BEIR VII report. Results: The average effective dose of the chest posteroanterior examination was found to be 0.04 mSv, which was 1.3% that of the chest CT examination. The average effective dose of the chest tomosynthesis examination was found to be about ten times that of the chest posteroanterior examination and about 12% that of the chest CT examination. With increasing patient average chest diameter, both the effective dose and risk index for CT increased considerably in an exponential fashion, while these two dose metrics only increased slightly for radiographic modalities and for chest tomosynthesis. Effective and organ doses normalized to mAs all illustrated an exponential decrease with increasing patient size. As a surface organ, breast doses had less correlation with body size than that of lungs or liver. Conclusions: Patient body size has a much greater impact on radiation dose of chest CT examinations than chest radiography and tomosynthesis. The size of a patient should be considered when choosing the best thoracic imaging modality. PMID:24506654

SU-F-T-476: Performance of the AS1200 EPID for Periodic Photon Quality Assurance

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

DeMarco, J; Fraass, B; Yang, W

2016-06-15

Purpose: To assess the dosimetric performance of a new amorphous silicon flat-panel electronic portal imaging device (EPID) suitable for high-intensity, flattening-filter-free delivery mode. Methods: An EPID-based QA suite was created with automation to periodically monitor photon central-axis output and two-dimensional beam profile constancy as a function of gantry angle and dose-rate. A Varian TrueBeamTM linear accelerator installed with Developer Mode was used to customize and deliver XML script routines for the QA suite using the dosimetry mode image acquisition for an aS1200 EPID. Automatic post-processing software was developed to analyze the resulting DICOM images. Results: The EPID was used tomore » monitor photon beam output constancy (central-axis), flatness, and symmetry over a period of 10 months for four photon beam energies (6x, 15x, 6xFFF, and 10xFFF). EPID results were consistent to those measured with a standard daily QA check device. At the four cardinal gantry angles, the standard deviation of the EPID central-axis output was <0.5%. Likewise, EPID measurements were independent for the wide range of dose rates (including up to 2400 mu/min for 10xFFF) studied with a standard deviation of <0.8% relative to the nominal dose rate for each energy. Also, profile constancy and field size measurements showed good agreement with the reference acquisition of 0° gantry angle and nominal dose rate. XML script files were also tested for MU linearity and picket-fence delivery. Using Developer Mode, the test suite was delivered in <60 minutes for all 4 photon energies with 4 dose rates per energy and 5 picket-fence acquisitions. Conclusion: Dosimetry image acquisition using a new EPID was found to be accurate for standard and high-intensity photon beams over a broad range of dose rates over 10 months. Developer Mode provided an efficient platform to customize the EPID acquisitions by using custom script files which significantly reduced the time. This work was funded in part by Varian Medical Systems.« less

Decreases in cocaine self-administration with dual inhibition of the dopamine transporter and σ receptors.

PubMed

Hiranita, Takato; Soto, Paul L; Kohut, Stephen J; Kopajtic, Theresa; Cao, Jianjing; Newman, Amy H; Tanda, Gianluigi; Katz, Jonathan L

2011-11-01

Sigma receptor (σR) antagonists attenuate many behavioral effects of cocaine but typically not its reinforcing effects in self-administration procedures. However, the σR antagonist rimcazole and its N-propylphenyl analogs, [3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]diphenylamine hydrochloride (SH 3-24) and 9-[3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]carbazole hydrobromide (SH 3-28), dose-dependently decreased the maximal rates of cocaine self-administration without affecting comparable responding maintained by food reinforcement. In contrast, a variety of σR antagonists [N-phenethylpiperidine oxalate (AC927), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine dihydrobromide (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine dihydrobromide (BD 1047), N-[2-(3,4-dichlorophenyl) ethyl]-4-methylpiperazine dihydrochloride (BD 1063), and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100)] had no effect on cocaine self-administration across the range of doses that decreased rates of food-maintained responding. Rimcazole analogs differed from selective σR antagonists in their dual affinities for σRs and the dopamine transporter (DAT) assessed with radioligand binding. Selective DAT inhibitors and σR antagonists were studied alone and in combination on cocaine self-administration to determine whether actions at both σRs and the DAT were sufficient to reproduce the effects of rimcazole analogs. Typical DAT inhibitors [2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428), methylphenidate, and nomifensine] dose-dependently shifted the cocaine dose-effect curve leftward. Combinations of DAT inhibitor and σR antagonist doses that were behaviorally inactive alone decreased cocaine self-administration without effects on food-maintained responding. In addition, whereas the DAT inhibitors were self-administered at rates similar to those of cocaine, neither rimcazole analogs nor typical σR antagonists (NE-100 and AC927) maintained responding above control levels across a wide range of doses. These findings suggest that the unique effects of rimcazole analogs are due to dual actions at the DAT and σRs and that a combined target approach may have utility in development of medical treatments for cocaine abuse.

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

Siauw, Timmy; Cunha, Adam; Berenson, Dmitry

Purpose: In this study, the authors introduce skew line needle configurations for high dose rate (HDR) brachytherapy and needle planning by integer program (NPIP), a computational method for generating these configurations. NPIP generates needle configurations that are specific to the anatomy of the patient, avoid critical structures near the penile bulb and other healthy structures, and avoid needle collisions inside the body. Methods: NPIP consisted of three major components: a method for generating a set of candidate needles, a needle selection component that chose a candidate needle subset to be inserted, and a dose planner for verifying that the finalmore » needle configuration could meet dose objectives. NPIP was used to compute needle configurations for prostate cancer data sets from patients previously treated at our clinic. NPIP took two user-parameters: a number of candidate needles, and needle coverage radius, {delta}. The candidate needle set consisted of 5000 needles, and a range of {delta} values was used to compute different needle configurations for each patient. Dose plans were computed for each needle configuration. The number of needles generated and dosimetry were analyzed and compared to the physician implant. Results: NPIP computed at least one needle configuration for every patient that met dose objectives, avoided healthy structures and needle collisions, and used as many or fewer needles than standard practice. These needle configurations corresponded to a narrow range of {delta} values, which could be used as default values if this system is used in practice. The average end-to-end runtime for this implementation of NPIP was 286 s, but there was a wide variation from case to case. Conclusions: The authors have shown that NPIP can automatically generate skew line needle configurations with the aforementioned properties, and that given the correct input parameters, NPIP can generate needle configurations which meet dose objectives and use as many or fewer needles than the current HDR brachytherapy workflow. Combined with robot assisted brachytherapy, this system has the potential to reduce side effects associated with treatment. A physical trial should be done to test the implant feasibility of NPIP needle configurations.« less

Insights into the mechanism of X-ray-induced disulfide-bond cleavage in lysozyme crystals based on EPR, optical absorption and X-ray diffraction studies

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

Sutton, Kristin A.; Black, Paul J.; Mercer, Kermit R.

2013-12-01

Electron paramagnetic resonance (EPR) and online UV–visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage, to confirm a multi-track radiation-damage process and to develop a model of that process. Electron paramagnetic resonance (EPR) and online UV–visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage. Online UV–visible spectroscopy showed that upon X-irradiation, disulfide radicalization appeared to saturate at an absorbed dose of approximately 0.5–0.8 MGy, in contrast to the saturating dose of ∼0.2 MGy observed using EPR at much lower dose rates. Themore » observations suggest that a multi-track model involving product formation owing to the interaction of two separate tracks is a valid model for radiation damage in protein crystals. The saturation levels are remarkably consistent given the widely different experimental parameters and the range of total absorbed doses studied. The results indicate that even at the lowest doses used for structural investigations disulfide bonds are already radicalized. Multi-track considerations offer the first step in a comprehensive model of radiation damage that could potentially lead to a combined computational and experimental approach to identifying when damage is likely to be present, to quantitate it and to provide the ability to recover the native unperturbed structure.« less

Toxic and hormetic-like effects of three components of citrus essential oils on adult Mediterranean fruit flies (Ceratitis capitata)

PubMed Central

Papanastasiou, Stella A.; Bali, Eleftheria-Maria D.; Ioannou, Charalampos S.; Papachristos, Dimitrios P.; Zarpas, Kostas D.

2017-01-01

Plant essential oils (EOs) and a wide range of their individual components are involved in a variety of biological interactions with insect pests including stimulatory, deterrent, toxic and even hormetic effects. Both the beneficial and toxic properties of citrus EOs on the Mediterranean fruit fly (medfly) have been experimentally evidenced over the last years. However, no information is available regarding the toxic or beneficial effects of the major components of citrus EOs via contact with the adults of the Mediterranean fruit fly. In the present study, we explored the toxicity of limonene, linalool and α-pinene (3 of the main compounds of citrus EOs) against adult medflies and identified the effects of sub-lethal doses of limonene on fitness traits in a relaxed [full diet (yeast and sugar)] and in a stressful (sugar only) feeding environment. Our results demonstrate that all three compounds inferred high toxicity to adult medflies regardless of the diet, with males being more sensitive than females. Sub-lethal doses of limonene (LD20) enhanced the lifespan of adult medflies when they were deprived of protein. Fecundity was positively affected when females were exposed to limonene sub-lethal doses. Therefore, limonene, a major constituent of citrus EOs, induces high mortality at increased doses and positive effects on life history traits of medfly adults through contact at low sub-lethal doses. A hormetic-like effect of limonene to adult medflies and its possible underlying mechanisms are discussed. PMID:28520791

Dose Response of Endotoxin on Hepatocyte and Muscle Mitochondrial Respiration In Vitro

PubMed Central

Brandt, Sebastian; Porta, Francesca; Jakob, Stephan M.; Takala, Jukka; Djafarzadeh, Siamak

2015-01-01

Introduction. Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria. Methods. Human hepatocellular carcinoma cells (HepG2) were exposed to placebo or LPS (0.1, 1, and 10 μg/mL) for 4, 8, 16, and 24 hours and primary human hepatocytes to 1 μg/mL LPS or placebo (4, 8, and 16 hours). Mitochondria from porcine skeletal muscle samples were exposed to increasing doses of LPS (0.1–100 μg/mg) for 2 and 4 hours. Respiration rates of intact and permeabilized cells and isolated mitochondria were measured by high-resolution respirometry. Results. In HepG2 cells, LPS reduced mitochondrial membrane potential and cellular ATP content but did not modify basal respiration. Stimulated complex II respiration was reduced time-dependently using 1 μg/mL LPS. In primary human hepatocytes, stimulated mitochondrial complex II respiration was reduced time-dependently using 1 μg/mL LPS. In isolated porcine skeletal muscle mitochondria, stimulated respiration decreased at high doses (50 and 100 μg/mL LPS). Conclusion. LPS reduced cellular ATP content of HepG2 cells, most likely as a result of the induced decrease in membrane potential. LPS decreased cellular and isolated mitochondrial respiration in a time-dependent, dose-dependent and complex-dependent manner. PMID:25649304

Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

PubMed Central

Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John

2018-01-01

Introduction Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED). Methods We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a period over six years (2010–2016). Primary data analyses included dosing and duration of infusion, rates of pre- and post-infusion analgesic administration, and final diagnoses. Secondary data included pre- and post-infusion pain scores and rates of side effects. Results A total of 104 patients were enrolled in the study. Average dosing of SDK infusion was 11.26 mg/hr, and the mean duration of infusion was 135.87 minutes. There was a 38% increase in patients not requiring post-infusion analgesia. The average decrease in pain score was 5.04. There were 12 reported adverse effects, with nausea being the most prevalent. Conclusion Continuous intravenous SDK infusion has a role in controlling pain of various etiologies in the ED with a potential to reduce the need for co-analgesics or rescue analgesic administration. There is a need for more robust, prospective, randomized trials that will further evaluate the analgesic efficacy and safety of this modality across a wide range of pain syndromes and different age groups in the ED. PMID:29760856

Regional deposition of nasal sprays in adults: A wide ranging computational study.

PubMed

Kiaee, Milad; Wachtel, Herbert; Noga, Michelle L; Martin, Andrew R; Finlay, Warren H

2018-05-01

The present work examines regional deposition within the nose for nasal sprays over a large and wide ranging parameter space by using numerical simulation. A set of 7 realistic adult nasal airway geometries was defined based on computed tomography images. Deposition in 6 regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location. Penetration of nasal spray particles through the airway geometries represented unintended lung exposure. Penetration was found to be relatively insensitive to injection velocity, but highly sensitive to particle size. Penetration remained at or above 30% for particles exceeding 10 μm in diameter for several airway geometries studied. Deposition in the turbinates, viewed as desirable for both local and systemic nasal drug delivery, was on average maximized for particles ranging from ~20 to 30 μm in diameter, and for low to zero injection velocity. Similar values of particle diameter and injection velocity were found to maximize deposition in the olfactory region, a potential target for nose-to-brain drug delivery. However, olfactory deposition was highly variable between airway geometries, with maximum olfactory deposition ranging over 2 orders of magnitude between geometries. This variability is an obstacle to overcome if consistent dosing between subjects is to be achieved for nose-to-brain drug delivery. Copyright © 2018 John Wiley & Sons, Ltd.

The effects of γ-ray on charging behaviour using polyimide

NASA Astrophysics Data System (ADS)

Qin, Sichen; Tu, Youping; Tan, Tian; Wang, Shaohe; Yuan, Zhikang; Wang, Cong; Li, Laifeng; Wu, Zhixiong

2018-06-01

Insulation material is a key component of electrical equipment in satellites; its electrical properties determine the reliability and lifetime of the whole satellite. High-energy radioactive rays in space affect the molecular structure of the polymeric insulating materials. Under the action of plasma, high energy particles, along with the magnetic fields experienced in orbits, electric charges get injected into and trapped by the insulating material creating distortions in the electric field and even electrostatic discharges. Polyimides have been widely used for insulation in spacecraft. Choosing Co-60 gamma ray with irradiation doses of 1 MGy and 5 MGy to simulate the radiation environment of space, we investigated the effect of radiation on charging behaviour. The thermal stimulated current (TSC) from a high electric field over a wide range of temperatures was measured from which the activation energy was calculated. These results for the two sources show that the percentage increase in total charge was 133.3% and 119.4%. The γ, β 3, and α charge peaks of specimens after an irradiation dose of 1 MGy rose. In comparison, the β 2 peak of the 5 MGy-dosed specimens was enhanced. Also, there is almost no change in the γ, β 3, and α peaks. To understand the mechanism behind the TSC changes, the resulting physicochemical characteristics of an irradiated specimen were observed employing various analyses of chemical characteristics (x-ray photoelectron spectroscopy, differential scanning calorimetry and x-ray diffraction). Compared with the non-dosed specimen, the relative content of C–N and the glass transition temperature of the 1 MGy sample decreased, and the crystallinity increased, thus increasing the γ and α peak intensities. Compared with the 1 MGy sample, only the glass transition temperature had risen, thereby enhancing the β peak intensity. With the foregoing, a theoretical base for the selection and modification of insulation materials for spacecraft is provided.

Low-dose 4D cardiac imaging in small animals using dual source micro-CT

NASA Astrophysics Data System (ADS)

Holbrook, M.; Clark, D. P.; Badea, C. T.

2018-01-01

Micro-CT is widely used in preclinical studies, generating substantial interest in extending its capabilities in functional imaging applications such as blood perfusion and cardiac function. However, imaging cardiac structure and function in mice is challenging due to their small size and rapid heart rate. To overcome these challenges, we propose and compare improvements on two strategies for cardiac gating in dual-source, preclinical micro-CT: fast prospective gating (PG) and uncorrelated retrospective gating (RG). These sampling strategies combined with a sophisticated iterative image reconstruction algorithm provide faster acquisitions and high image quality in low-dose 4D (i.e. 3D  +  Time) cardiac micro-CT. Fast PG is performed under continuous subject rotation which results in interleaved projection angles between cardiac phases. Thus, fast PG provides a well-sampled temporal average image for use as a prior in iterative reconstruction. Uncorrelated RG incorporates random delays during sampling to prevent correlations between heart rate and sampling rate. We have performed both simulations and animal studies to validate these new sampling protocols. Sampling times for 1000 projections using fast PG and RG were 2 and 3 min, respectively, and the total dose was 170 mGy each. Reconstructions were performed using a 4D iterative reconstruction technique based on the split Bregman method. To examine undersampling robustness, subsets of 500 and 250 projections were also used for reconstruction. Both sampling strategies in conjunction with our iterative reconstruction method are capable of resolving cardiac phases and provide high image quality. In general, for equal numbers of projections, fast PG shows fewer errors than RG and is more robust to undersampling. Our results indicate that only 1000-projection based reconstruction with fast PG satisfies a 5% error criterion in left ventricular volume estimation. These methods promise low-dose imaging with a wide range of preclinical applications in cardiac imaging.

Dosimetry of intracavitary placements for uterine and cervical carcinoma: results of orthogonal film, TLD, and CT-assisted techniques.

PubMed

Kapp, K S; Stuecklschweiger, G F; Kapp, D S; Hackl, A G

1992-07-01

A total of 720 192Ir high-dose-rate (HDR) applications in 331 patients with gynecological tumors were analyzed to evaluate the dose to normal tissues from brachytherapy. Based on the calculations of bladder base, bladder neck, and rectal doses derived from orthogonal films the planned tumor dose or fractionation was altered in 20.4% of intracavitary placements (ICP) for cervix carcinoma and 9.2% of ICP for treatment of the vaginal vault. In 13.8% of intracervical and 8.1% of intravaginal treatments calculated doses to both the bladder and rectum were greater than or equal to 140% of the initially planned dose fraction. Doses at the bladder base were significantly higher than at the bladder neck (p less than 0.001). In 17.5% of ICP the dose to the bladder base was at least twice as high as to the bladder neck. The ratio of bladder base dose to the bladder neck was 1.5 (+/- 1.19 SD) for intracervical and 1.46 (+/- 1.14 SD) for intravaginal applications. The comparison of calculated doses from orthogonal films with in-vivo readings showed a good correlation of rectal doses with a correlation coefficient factor of 0.9556. CT-assisted dosimetry, however, revealed that the maximum doses to bladder and rectum were generally higher than those obtained from films with ratios of 1-1.7 (average: 1.44) for the bladder neck, 1-5.4 (average: 2.42) for the bladder base, and 1.1-2.7 (average: 1.37) for the rectum. When doses to the specified reference points of bladder neck and rectum from orthogonal film dosimetry were compared with the corresponding points on CT scans, similar values were obtained for both methods with a maximum deviation of +/- 10%. Despite the determination of multiple reference points our study revealed that this information was inadequate to predict doses to the entire rectum and bladder. If conventional methods are used for dosimetry it is recommended that doses to the bladder base should be routinely calculated, since single point measurements at the bladder neck seriously underestimate the dose to the bladder. Also the rectal dose should be determined at several points over the length of the implant due to the wide range of anatomic variations possible.

A PK-PD Model of Ketamine-Induced High-Frequency Oscillations

PubMed Central

Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Fath, Amanda B.; Purdon, Patrick L.; Wilson, Matthew A.; Brown, Emery N.

2017-01-01

Objective Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a High-Frequency Oscillation (HFO) which power is modulated non-linearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PD) of ketamine and the observed HFO power. Approach In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by a high-frequency oscillation (HFO) observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent range of effects that ketamine has. PMID:26268223

Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve.

PubMed

Radak, Zsolt; Ishihara, Kazunari; Tekus, Eva; Varga, Csaba; Posa, Aniko; Balogh, Laszlo; Boldogh, Istvan; Koltai, Erika

2017-08-01

It is debated whether exercise-induced ROS production is obligatory to cause adaptive response. It is also claimed that antioxidant treatment could eliminate the adaptive response, which appears to be systemic and reportedly reduces the incidence of a wide range of diseases. Here we suggest that if the antioxidant treatment occurs before the physiological function-ROS dose-response curve reaches peak level, the antioxidants can attenuate function. On the other hand, if the antioxidant treatment takes place after the summit of the bell-shaped dose response curve, antioxidant treatment would have beneficial effects on function. We suggest that the effects of antioxidant treatment are dependent on the intensity of exercise, since the adaptive response, which is multi pathway dependent, is strongly influenced by exercise intensity. It is further suggested that levels of ROS concentration are associated with peak physiological function and can be extended by physical fitness level and this could be the basis for exercise pre-conditioning. Physical inactivity, aging or pathological disorders increase the sensitivity to oxidative stress by altering the bell-shaped dose response curve. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Comparisons of the effects of TCDD and hydrocortisone on growth factor expression provide insight into their interaction in the embryonic mouse palate

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

Abbott, B.D.; Harris, M.W.; Birnbaum, L.S.

Cleft palate (CP) can be induced in embryonic mice by a wide range of compounds, including glucocorticoids and 2,3,7,8-tyetrachlorodibenzo-p-dioxin (TCDD). Hydrocortisone (HC), a glucocorticoid, retards embryonic growth producing small palatal shelves, while TCDD exposure blocks the fusion of normally sized shelves. TCDD induction of CP involves altered differentiation of the medial epithelial cells. Recent studies indicate that growth factors such as EGF, TGF-alpha, TGF-beta1, and TGF-beta2 are involved in palatogenesis, regulating proliferation, differentiation, and extracellular matrix production. A synergism has been observed between HC and TCDD in which doses too low to induce CP alone are able to produce >90%more » incidence when coadministered. In the present study a standard teratology protocol was performed in C57BL/6N mice to examine the synergism at doses lower than those previously published. Data from the study indicate synergistic interactions at doses as low as 3 micrograms TCDD/kg + 1 mg HC/kg. This extreme sensitivity suggests the involvement of a receptor-mediated mechanism possibly resulting in altered regulation of gene expression. (Copyright (c) 1992 Wiley-Liss, Inc.)« less

Short Communication: Rheological properties of blood serum of rats after irradiation with different gamma radiation doses in vivo.

PubMed

Abdelhalim, Mohamed Anwar K; Moussa, Sherif Aa; Ms, Al-Ayed

2016-01-01

The blood serum rheological properties open the door to find suitable radio-protectors and convenient therapy for many cases of radiation exposure. The present study aimed to investigate the rheological properties of rat blood serum at wide range of shear rates after whole body irradiation with different gamma radiation doses in vivo. Healthy male rats were divided into five groups; one control group and 4 irradiated groups. The irradiation process was carried out using Co60 source with dose rate of 0.883cG/sec. Several rheological parameters were measured using Brookfield LVDV-III Programmable rheometer. A significant increase in viscosity and shear stress was observed with 25 and 50Gy corresponding to each shear rate compared with the control; while a significant decrease observed with 75 and 100Gy. The viscosity exhibited a Non-Newtonian behaviour with the shear rate while shear stress values were linearly related with shear rate. The decrease in blood viscosity might be attributed to changes in molecular weight, pH sensitivity and protein structure. The changes in rheological properties of irradiated rats' blood serum might be attributed to destruction changes in the haematological and dimensional properties of rats' blood products.

The clinical pharmacology of alkylating agents in high-dose chemotherapy.

PubMed

Huitema, A D; Smits, K D; Mathôt, R A; Schellens, J H; Rodenhuis, S; Beijnen, J H

2000-08-01

Alkylating agents are widely used in high-dose chemotherapy regimens in combination with hematological support. Knowledge about the pharmacokinetics and pharmacodynamics of these agents administered in high doses is critical for the safe and efficient use of these regimens. The aim of this review is to summarize the clinical pharmacology of the alkylating agents (including the platinum compounds) in high-dose chemotherapy. Differences between conventional and high doses will be discussed.

Optimise the microbial flora with milk and yoghurt to prevent disease.

PubMed

Morris, James A

2018-05-01

Pathogenic bacteria, which are temporary or permanent members of our microbial flora, cause or contribute to a wide range of human disease at all ages. Conditions include Alzheimer's disease, atherosclerosis, diabetes mellitus, obesity, cancer, autoimmunity and psychosis, amongst others. The mechanism of damage is inflammation which can be chronic or acute. An optimal microbial flora includes a wide range of pathogenic bacteria in low dose. This allows specific immunity to be developed and maintained with minimal inflammatory damage. Human milk has evolved to deliver an optimal microbial flora to the infant. Cow's milk has the potential, following appropriate fortification, to maintain an optimal human microbial flora throughout life. Yoghurt is a fermented milk product in which bacteria normally present in milk convert sugars to lactic acid. The acid suppresses the growth of pathogens in the oral cavity, oropharynx and oesophagus. Thus yoghurt can restore an optimal flora in these regions in the short term. Since bacteria are transported between epithelial surfaces, yoghurt will also optimise the flora elsewhere. The judicious use of milk and yogurt could prevent a high proportion of human disease. Copyright © 2018 The Author. Published by Elsevier Ltd.. All rights reserved.

Parthenolide Selectively Sensitizes Prostate Tumor Tissue to Radiotherapy while Protecting Healthy Tissues In Vivo.

PubMed

Morel, Katherine L; Ormsby, Rebecca J; Bezak, Eva; Sweeney, Christopher J; Sykes, Pamela J

2017-05-01

Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells. Sixteen-week-old male Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) and C57BL/6J mice were treated with PTL (40 mg/kg), dimethylaminoparthenolide (DMAPT, a PTL analogue with increased bioavailability) (100 mg/kg), or vehicle control three times over one week prior to combinations of low (10 mGy) and high (6 Gy) doses of whole-body X-irradiation. Tissues were analyzed for apoptosis at a range of time points up to 72 h postirradiation. Both PTL and DMAPT protected normal tissues, but not prostate tumor tissues, from a significant proportion of high-dose-radiation-induced apoptosis. DMAPT provided superior protection compared to PTL in normal dorsolateral prostate (71.7% reduction, P = 0.026), spleen (48.2% reduction, P = 0.0001) and colorectal tissue (38.0% reduction, P = 0.0002), and doubled radiation-induced apoptosis in TRAMP prostate tumor tissue (101.3% increase, P = 0.039). Both drugs induced the greatest radiosensitivity in TRAMP prostate tissue in areas with higher grade prostatic intraepithelial neoplasia (PIN) lesions. A 10 mGy dose delivered 3 h prior to a 6 Gy dose induced a radioadaptive apoptosis response in normal C57Bl/6J prostate (28.4% reduction, P = 0.045) and normal TRAMP spleen (13.6% reduction, P = 0.047), however the low-dose-adaptive radioprotection did not significantly add to the PTL/DMAPT-induced protection in normal tissues, nor did it affect tumor kill. These results support the use of the more bioavailable DMAPT and low-dose radiation, alone or in combination as useful radioprotectors of normal tissues to alleviate radiotherapy-induced side-effects in patients. The enhanced radiosensitisation in prostate tissues displaying high-grade PIN suggests that DMAPT also holds promise for targeted therapy of advanced prostate cancer, which may go on to become metastatic. The redox mechanisms involved in the differential radioprotection observed here suggest that increased radiotherapy efficacy by DMAPT is more broadly applicable to a range of cancer types.

Estimation of dose-response models for discrete and continuous data in weed science

USDA-ARS?s Scientific Manuscript database

Dose-response analysis is widely used in biological sciences and has application to a variety of risk assessment, bioassay, and calibration problems. In weed science, dose-response methodologies have typically relied on least squares estimation under an assumption of normality. Advances in computati...

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

Poplawski, L; Li, T; Chino, J

Purpose: In brachytherapy, structures surrounding the target have the potential to move between treatments and receive unknown dose. Deformable image registration could overcome challenges through dose accumulation. This study uses two possible deformable dose summation techniques and compares the results to point dose summation currently performed in clinic. Methods: Data for ten patients treated with a Syed template was imported into the MIM software (Cleveland, OH). The deformable registration was applied to structures by masking other image data to a single intensity. The registration flow consisted of the following steps: 1) mask CTs so that each of the structures-of-interest hadmore » one unique intensity; 2) perform applicator — based rigid registration; 3) Perform deformable registration; 4) Refine registration by changing local alignments manually; 5) Repeat steps 1 to 3 until desired structure adequately deformed; 5) Transfer each deformed contours to the first CT. The deformed structure accuracy was determined by a dice similarity coefficient (DSC) comparison with the first fraction. Two dose summation techniques were investigated: a deformation and recalculation on the structure; and a dose deformation and accumulation method. Point doses were used as a comparison value. Results: The Syed deformations have DSC ranging from 0.53 to 0.97 and 0.75 and 0.95 for the bladder and rectum, respectively. For the bladder, contour deformation addition ranged from −34.8% to 0.98% and dose deformation accumulation ranged from −35% to 29.3% difference from clinical calculations. For the rectum, contour deformation addition ranged from −5.2% to 16.9% and the dose deformation accumulation ranged from −29.1% to 15.3% change. Conclusion: Deforming dose for summation leads to different volumetric doses than when dose is recalculated on deformed structures, raising concerns about the accuracy of the deformed dose. DSC alone cannot be used to establish the accuracy of a deformation for brachy dose summation purpose.« less

TH-A-19A-06: Site-Specific Comparison of Analytical and Monte Carlo Based Dose Calculations

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

Schuemann, J; Grassberger, C; Paganetti, H

2014-06-15

Purpose: To investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict dose distributions and to verify currently used uncertainty margins in proton therapy. Methods: Dose distributions predicted by an analytical pencilbeam algorithm were compared with Monte Carlo simulations (MCS) using TOPAS. 79 complete patient treatment plans were investigated for 7 disease sites (liver, prostate, breast, medulloblastoma spine and whole brain, lung and head and neck). A total of 508 individual passively scattered treatment fields were analyzed for field specific properties. Comparisons based on target coverage indices (EUD, D95, D90 and D50)more » were performed. Range differences were estimated for the distal position of the 90% dose level (R90) and the 50% dose level (R50). Two-dimensional distal dose surfaces were calculated and the root mean square differences (RMSD), average range difference (ARD) and average distal dose degradation (ADD), the distance between the distal position of the 80% and 20% dose levels (R80- R20), were analyzed. Results: We found target coverage indices calculated by TOPAS to generally be around 1–2% lower than predicted by the analytical algorithm. Differences in R90 predicted by TOPAS and the planning system can be larger than currently applied range margins in proton therapy for small regions distal to the target volume. We estimate new site-specific range margins (R90) for analytical dose calculations considering total range uncertainties and uncertainties from dose calculation alone based on the RMSD. Our results demonstrate that a reduction of currently used uncertainty margins is feasible for liver, prostate and whole brain fields even without introducing MC dose calculations. Conclusion: Analytical dose calculation algorithms predict dose distributions within clinical limits for more homogeneous patients sites (liver, prostate, whole brain). However, we recommend treatment plan verification using Monte Carlo simulations for patients with complex geometries.« less

SU-F-BRD-05: Robustness of Dose Painting by Numbers in Proton Therapy

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

Montero, A Barragan; Sterpin, E; Lee, J

Purpose: Proton range uncertainties may cause important dose perturbations within the target volume, especially when steep dose gradients are present as in dose painting. The aim of this study is to assess the robustness against setup and range errors for high heterogeneous dose prescriptions (i.e., dose painting by numbers), delivered by proton pencil beam scanning. Methods: An automatic workflow, based on MATLAB functions, was implemented through scripting in RayStation (RaySearch Laboratories). It performs a gradient-based segmentation of the dose painting volume from 18FDG-PET images (GTVPET), and calculates the dose prescription as a linear function of the FDG-uptake value on eachmore » voxel. The workflow was applied to two patients with head and neck cancer. Robustness against setup and range errors of the conventional PTV margin strategy (prescription dilated by 2.5 mm) versus CTV-based (minimax) robust optimization (2.5 mm setup, 3% range error) was assessed by comparing the prescription with the planned dose for a set of error scenarios. Results: In order to ensure dose coverage above 95% of the prescribed dose in more than 95% of the GTVPET voxels while compensating for the uncertainties, the plans with a PTV generated a high overdose. For the nominal case, up to 35% of the GTVPET received doses 5% beyond prescription. For the worst of the evaluated error scenarios, the volume with 5% overdose increased to 50%. In contrast, for CTV-based plans this 5% overdose was present only in a small fraction of the GTVPET, which ranged from 7% in the nominal case to 15% in the worst of the evaluated scenarios. Conclusion: The use of a PTV leads to non-robust dose distributions with excessive overdose in the painted volume. In contrast, robust optimization yields robust dose distributions with limited overdose. RaySearch Laboratories is sincerely acknowledged for providing us with RayStation treatment planning system and for the support provided.« less

Comparison of Individual Radiosensitivity to γ-Rays and Carbon Ions.

PubMed

Shim, Grace; Normil, Marie Delna; Testard, Isabelle; Hempel, William M; Ricoul, Michelle; Sabatier, Laure

2016-01-01

Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term "relative dose effect" (RDE). This ratio is advantageous, as it allows for simple comparison of dose-response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2-15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy.

The c-Abl signaling network in the radioadaptive response

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

Chi-Min, Yuan

2014-01-28

The radioadaptive response, or radiation hormesis, i.e. a low dose of radiation can protect cells and organisms from the effects of a subsequent higher dose, is a widely recognized phenomenon. Mechanisms underlying such radiation hormesis, however, remain largely unclear. Preliminary studies indicate an important role of c-Abl signaling in mediating the radioadaptive response. We propose to investigate how c-Abl regulates the crosstalk between p53 and NFκB in response to low doses irradiation. We found in our recent study that low dose IR induces a reciprocal p53 suppression and NFκB activation, which induces HIF-a and subsequently a metabolic reprogramming resulting inmore » a transition from oxidative phosphorylation to glycolysis. Of importance is that this glycolytic switch is essential for the radioadaptive response. This low-dose radiationinduced HIF1α activation was in sharp contrast with the high-dose IR-induced p53 activation and HIF1α inhibition. HIF1α and p53 seem to play distinct roles in mediating the radiation dose-dependent metabolic response. The induction of HIF1α-mediated glycolysis is restricted to a low dose range of radiation, which may have important implications in assessing the level of radiation exposure and its potential health risk. Our results support a dose-dependent metabolic response to IR. When IR doses are below the threshold of causing detectable DNA damage (<0.2Gy) and thus little p53 activation, HIF1α is induced resulting in induction of glycolysis and increased radiation resistance. When the radiation dose reaches levels eliciting DNA damage, p53 is activated and diminishes the activity of HIF1α and glycolysis, leading to the induction of cell death. Our work challenges the LNT model of radiation exposure risk and provides a metabolic mechanism of radioadaptive response. The study supports a need for determining the p53 and HIF1α activity as a potential reliable biological readout of radiation exposure in humans. The exquisite sensitivity of cellular metabolism to low doses of radiation could also serve as a valuable biomarker for estimating the health effects of low-level radiation exposure.« less

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

PubMed

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

2017-09-01

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

Determination of multislice computed tomography dose index (CTDI) using optically stimulated luminescence technology.

PubMed

Ruan, Chun; Yukihara, Eduardo G; Clouse, William J; Gasparian, Patricia B R; Ahmad, Salahuddin

2010-07-01

The extensive use of multislice computed tomography (MSCT) and the associated increase in patient dose calls for an accurate dose evaluation technique. Optically stimulated luminescence (OSL) dosimetry provides a potential solution to the arising concerns over patient dose. This study was intended to evaluate the feasibility and accuracy of OSL dosimeter systems in the diagnostic CT x-ray beam energy range. MSCT dose profiles were measured by irradiating OSL strips placed inside the extended PMMA head and body phantoms at different scan conditions by varying kVp settings (100, 120, and 140 kVp) and collimated beam widths (5, 10, 20, and 40 mm). All scans in this study were performed using a GE Lightspeed VCT scanner in axial mode. The exposed strips were then read out using a custom-made OSL strip reader and corrected with field-specific conversion factors. Based on the corrected OSL dose profile, the CTDI(450-OSL) and CTDI(l00-OSL) were evaluated. CTDI(100-IC) was also obtained using a 100 mm long pencil ionization chamber for accuracy verification. CTDI(100-efficiency) can be further evaluated by calculating the ratio of CTDI(100-OSL) and CTDI(450-OSL), which was compared to results from previous studies as well. The OSL detectors were found to have good sensitivity and dose response over a wide range of diagnostic CT x-ray beam energy viz. the primary beam and the scatter tail section of the dose profile. The differences between CTDI100 values obtained using the OSL strips and those obtained with 100 mm long pencil ionization chamber were < +/- 5% for all scan conditions, indicating good accuracy of the OSL system. It was also found that the CTDI(100-efficiency) did not significantly change as the beam width increased and tube voltage changed. The average CTDI(100-efficiency) at the center of the head and body phantoms were 72.6% and 56.2%, respectively. The corresponding values for the periphery of the head and body phantoms were 85.0% and 81.7%. These results agreed very well with previous results from the literature using other detection techniques or Monte Carlo simulations. The LED-based OSL system can be an accurate alternative device for CT dose evaluations. CTDI100 measurement with the use of a 100 mm pencil ionization chamber substantially underestimates the CTDIinfinity value even with 5 mm collimated beam width. The established complete set of CTDI(100-efficiency) correction factors for various scan parameters allows for accurately estimating CTDIinfinity with the current use of pencil chamber and dose phantoms. Combined with the simple calibration, it gives this work great potential to be used not only in routine clinical quality assurance checks but also as a promising tool for patient organ dose assessment.

Gender differences in the behavioral effects of methamphetamine.

PubMed

Schindler, Charles W; Bross, Joshua G; Thorndike, Eric B

2002-05-10

The effects of methamphetamine were tested in male and female rats on two different behavioral tasks. Following habituation to a locomotor activity chamber, female rats were more sensitive to the locomotor activating effect of i.p. methamphetamine (0.1-3.0 mg/kg) than were male rats. A similar effect has been observed for other psychomotor stimulants, including cocaine and amphetamine. However, males and females did not differ on methamphetamine-induced place preference following eight conditioning trials with a wide range of doses (0.1-5.6 mg/kg). These results suggest that males and females differ in their response to methamphetamine for only some behavioral tasks.

Adverse Effects of Nonsystemic Steroids (Inhaled, Intranasal, and Cutaneous): a Review of the Literature and Suggested Monitoring Tool.

PubMed

Gupta, Ratika; Fonacier, Luz S

2016-06-01

Inhaled, intranasal, and cutaneous steroids are prescribed by physicians for a plethora of disease processes including asthma and rhinitis. While the high efficacy of this class of medication is well known, the wide range of adverse effects, both local and systemic, is not well elucidated. It is imperative to monitor total steroid burden in its varied forms as well as tracking for possible side effects that may be caused by a high cumulative dose of steroids. This review article highlights the adverse effects of different steroid modalities as well as suggests a monitoring tool to determine steroid totality and side effects.

Excitatory amino acids in epilepsy and potential novel therapies.

PubMed

Meldrum, B S

1992-07-01

Evidence that an abnormality of excitatory neurotransmission may contribute to the epileptic phenomena in various animal and human syndromes is reviewed. Altered glutamate transport or metabolism may be a contributory factor in some genetic syndromes and enhanced responsiveness to activation of NMDA receptors may be significant in various acquired forms of epilepsy. Decreasing glutamatergic neurotransmission provides a rational therapeutic approach to epilepsy. Potent anticonvulsant effects are seen with the acute administration of NMDA antagonists in a wide range of animal models. Some competitive antagonists acting at the NMDA/glutamate site show prolonged anticonvulsant activity following oral administration at doses free of motor side effects and appear suitable for clinical trial.

[Evaluation of the mutagenicity of detergents by tests on bacteria, plant cells and human leucocytes.].

PubMed

Feretti, Donatella; Pedrazzani, Roberta; Ceretti, Elisabetta; Zerbini, Ilaria; Gozio, Eleonora; Belotti, Caterina; Alias, Carlotta; Donato, Francesco; Gelatti, Umberto

2009-01-01

The aim of this study was to evaluate the mutagenicity of several traditional detergents and that of newer more biodegradable detergents, by using a bacterial test (Ames test), a plant cell test (Allium cepa micronuclei test) and a human leucocyte test (Comet test). All tests were conducted using a wide range of doses (1-2000 mg/l). None of the examined detergents induced mutations in S.typhimurium. One traditional detergent showed a genotoxic effect with the A. cepa test, while all newer detergents and one traditional detergent were shown by the Comet test to be capable of inducing DNA damage.

SU-F-T-587: Quality Assurance of Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT) for Patient Specific Plans: A Comparison Between MATRIXX and Delta4 QA Devices

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

Tsai, YC; Lu, SH; Chen, LH

2016-06-15

Purpose: Patient-specific quality assurance (QA) is necessary to accurately deliver high dose radiation to the target, especially for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). Unlike previous 2 dimensional (D) array QA devices, Delta{sup 4} can verify the dose delivery in 3D. In this study, the difference between calculated and measured dose distribution was compared with two QA devices (MATRIXX and Delta{sup 4}) to evaluate the delivery accuracy. Methods: Twenty-seven SRS/SBRT plans with VMAT were verified with point-dose and dose-map analysis. We use an ion chamber (A1SL, 0.053cc) for point-dose measurement. For verification of the dose map, themore » differences between the calculated and measured doses were analyzed with a gamma index using MATRIXX and Delta{sup 4} devices. The passing criteria for gamma evaluation were set at 3 mm for distance-to-agreement (DTA) and 3% for dose-difference. A gamma index less than 1 was defined as the verification passing the criteria and satisfying at least 95% of the points. Results: The mean prescribed dose and fraction was 40 ± 14.41 Gy (range: 16–60) and 10 ± 2.35 fractions (range: 1–8), respectively. In point dose analysis, the differences between the calculated and measured doses were all less than 5% (mean: 2.12 ± 1.13%; range: −0.55% to 4.45%). In dose-map analysis, the average passing rates were 99.38 ± 0.96% (range: 95.31–100%) and 100 ± 0.12% (range: 99.5%–100%) for MATRIXX and Delta{sup 4}, respectively. Even using criteria of 2%/2 mm, the passing rate of Delta{sup 4} was still more than 95% (mean: 99 ± 1.08%; range: 95.6%–100%). Conclusion: Both MATRIXX and Delta{sup 4} offer accurate and efficient verification for SRS/SBRT plans. The results measured by MATRIXX and Delta{sup 4} dosimetry systems are similar for SRS/SBRT performed with the VMAT technique.« less

Polycystic kidney disease induced in F(1) Sprague-Dawley rats fed para-nonylphenol in a soy-free, casein-containing diet.

PubMed

Latendresse, J R; Newbold, R R; Weis, C C; Delclos, K B

2001-07-01

para-Nonylphenol (NP; CAS #84852-15-3), an alkylphenol with a 9-carbon olefin side chain, is widely used in the manufacture of nonionic surfactants, lubricant additives, polymer stabilizers, and antioxidants. Due to its wide commercial use and putative endocrine activity in humans and wildlife, the NTP elected to assess its effects on reproduction in multigenerational studies. To avoid known estrogenic activity of phytoestrogens in soy and alfalfa, a soy- and alfalfa-free, casein-containing diet was used in a range-finding study to determine the doses of NP to be tested further. NP was administered to Sprague-Dawley rats in the diet at 0, 5, 25, 200, 500, 1000, or 2000 ppm to F(0) dams beginning on gestation-day 7. The F(1) pups were weaned at postnatal day (PND) 21, and their exposure via diet was continued at the same dose level as their respective dams. Pup weights from birth through weaning were not significantly different from controls in any dose group, but the average weight of both sexes was significantly less compared to controls, beginning with the PND 28 weighing. The F(1) rats were sacrificed on PND 50 (n = 15, 3 pups of each sex from 5 litters for all dose groups). Terminal body weights of males and females in the 2000-ppm dose group were 74% and 85% of controls, respectively. Severe polycystic kidney disease (PKD) was present in 100% of the 2000 ppm-exposed male and female rats. At 1000 ppm, 67% of males and 53% of females had mild to moderate PKD versus none of either sex in the control and lower-dose groups. The no-adverse-effect level (NOAEL) for PKD was determined to be 500 ppm. Previous studies with comparable duration and route of exposure, but using soy-containing diets, reported either no or only mild PKD at 2000 ppm NP. We conclude that the renal toxicity of NP is highly dependent on the diet on which the animals are maintained. The potential interaction of diet and test compounds on nonreproductive as well as reproductive endpoints should be considered when contemplating the use of special diets formulated to minimize exogenous "hormone" content for the study of the effects of putative endocrine disruptive chemicals.

Influence of solar flare X-rays on the habitability on the Mars

NASA Astrophysics Data System (ADS)

Jain, Rajmal; Awasthi, Arun K.; Tripathi, Sharad C.; Bhatt, Nipa J.; Khan, Parvaiz A.

2012-08-01

We probe the lethality of X-rays from solar flares to organisms on Mars based on the observations of 10 solar flares. We, firstly, estimate the doses produced by the strong flares observed by the RHESSI and GOES missions during the descending phase of sunspot cycle 23. Next, in order to realize the dependence of dose on flux and steepness of spectra, we model the incident spectra over a wide range of spectral index to estimate dose values and compare them with the observed doses. We calculate the distribution of surficial spectra visible to organisms on the martian surface by employing attenuation of X-rays due to CO2 column densities distribution over the South Pole. The surficial flux distribution after folding with the opacity of water enables us to estimate the dose distribution over the South Pole. The dose measured from the surficial spectrum produced by the observed 10 flares corresponding to the latitudes 50-60°, 60-70°, 70-80° and 80-90°S varies in the range of 6.39 × 10-9-1.80 × 10-6; 4.89 × 10-10-5.21 × 10-8; 5.10 × 10-11-5.20 × 10-9 and 4.42 × 10-10-4.89 × 10-12 gray (1 gray = 104 erg/g) respectively. Comparing the measured as well as the modeled doses with those proposed to be lethal for various organisms by Smith and Scalo (Smith, D.S., Scalo, J. [2007]. Planet. Space Sci. 55, 517-527); we report that the habitability of life on the South Pole remains unaffected even by the strongest solar flare occurred during descending phase of solar cycle 23. Further, the monthly integrated energy released by the solar flares in the most productive month viz. October 2003 and January 2005 from the GOES soft X-ray observations is estimated to be 8.43 and 3.32 × 1032 ergs respectively, which is almost equal in order to the typical energy released by a single strong X-class flare. Therefore, we propose the life near the South Pole region on the Mars remain uninfluenced by X-ray emission even during monster phenomena of energy release on the Sun and/or Star.

Opioid analgesics: does potency matter?

PubMed

Passik, Steven D; Webster, Lynn

2014-01-01

Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

Availability and dose response of phytophenols from a wheat bran rich cereal product in healthy human volunteers.

PubMed

Neacsu, Madalina; McMonagle, Jolene; Fletcher, Reg J; Hulshof, Toine; Duncan, Sylvia H; Scobbie, Lorraine; Duncan, Gary J; Cantlay, Louise; Horgan, Graham; de Roos, Baukje; Duthie, Garry G; Russell, Wendy R

2017-03-01

Phytophenols present in cereals are metabolised to compounds that could be partly responsible for the reduced risk of chronic diseases and all-cause mortality associated with fibre-rich diets. The bioavailability, form and in vivo concentrations of these metabolites require to be established. Eight healthy volunteers consumed a test meal containing a recommended dose (40 g) and high dose (120 g) of ready-to-eat wheat bran cereal and the systemic and colonic metabolites determined quantitatively by LC-MS. Analysis of the systemic metabolomes demonstrated that a wide range of phytophenols were absorbed/excreted (43 metabolites) within 5 h of consumption. These included 16 of the 21 major parent compounds identified in the intervention product and several of these were also found to be significantly increased in the colon. Not all of the metabolites were increased with the higher dose, suggesting some limitation in absorption due to intrinsic factors and/or the food matrix. Many compounds identified (e.g. ferulic acid and major metabolites) exhibit anti-inflammatory activity and impact on redox pathways. The combination of postprandial absorption and delivery to the colon, as well as hepatic recycling of the metabolites at these concentrations, is likely to be beneficial to both systemic and gut health. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In Vivo Subacute Toxicity and Antidiabetic Effect of Aqueous Extract of Nigella sativa

PubMed Central

Kacimi, Ghouti; Haffaf, El-Mehdi; Aouichat-Bouguerra, Souhila

2017-01-01

Context. Nigella sativa seeds are usually used as traditional medicine for a wide range of therapeutic purposes. Objective. To investigate the subacute toxicity of NS aqueous extract and select its lowest dose to study its antidiabetic effect. Methods. 5 AqE.NS doses (2, 6.4, 21, 33, and 60 g/Kg) were daily administered to mice by gavage. Biochemical parameters measurements and histological study of the liver and the kidney were performed after 6 weeks of supplementation. Thereafter, and after inducing diabetes by alloxan, rats were treated by 2 g/Kg of AqE.NS during 8 weeks. Metabolic parameters were measured on sera. A horizontal electrophoresis of plasmatic lipoprotein was conducted. Glycogen, total lipids, and triglycerides were measured in the liver. TBARS were evaluated on adipose tissue, liver, and pancreas. Results. AqE.NS showed no variation in urea and albumin at the 5 doses, but hepatotoxicity from 21 g/Kg was confirmed by histopathological observations of the liver. In diabetic rats, AqE.NS significantly decreased glycemia, TG, T-cholesterol, LDL-c, and TBARS and showed a restored insulinemia and a significant increase in HDL-c. Results on the liver indicated a decrease in lipids and a possible glycogenogenesis. Conclusion. AqE.NS showed its safety at low doses and its evident antihyperglycemic, antihyperlipidemic, and antioxidant effect. PMID:29479371

Acute radiation risk models

NASA Astrophysics Data System (ADS)

Smirnova, Olga

Biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems) in acutely/chronically irradiated humans are developed. These models are implemented as systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is shown that the developed models are capable of reproducing clinical data on the dynamics of these systems in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the "lethal" dose rates of chronic irradiation evaluated within models of these four major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the major human hematopoietic lineages for a vast pattern of irradiation scenarios. In particular, these models could be applied for the radiation risk assessment for health of astronauts exposed to space radiation during long-term space missions, such as voyages to Mars or Lunar colonies, as well as for health of people exposed to acute/chronic irradiation due to environmental radiological events.

SU-F-I-33: Estimating Radiation Dose in Abdominal Fat Quantitative CT

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

Li, X; Yang, K; Liu, B

Purpose: To compare size-specific dose estimate (SSDE) in abdominal fat quantitative CT with another dose estimate D{sub size,L} that also takes into account scan length. Methods: This study complied with the requirements of the Health Insurance Portability and Accountability Act. At our institution, abdominal fat CT is performed with scan length = 1 cm and CTDI{sub vol} = 4.66 mGy (referenced to body CTDI phantom). A previously developed CT simulation program was used to simulate single rotation axial scans of 6–55 cm diameter water cylinders, and dose integral of the longitudinal dose profile over the central 1 cm length wasmore » used to predict the dose at the center of one-cm scan range. SSDE and D{sub size,L} were assessed for 182 consecutive abdominal fat CT examinations with mean water-equivalent diameter (WED) of 27.8 cm ± 6.0 (range, 17.9 - 42.2 cm). Patient age ranged from 18 to 75 years, and weight ranged from 39 to 163 kg. Results: Mean SSDE was 6.37 mGy ± 1.33 (range, 3.67–8.95 mGy); mean D{sub size,L} was 2.99 mGy ± 0.85 (range, 1.48 - 4.88 mGy); and mean D{sub size,L}/SSDE ratio was 0.46 ± 0.04 (range, 0.40 - 0.55). Conclusion: The conversion factors for size-specific dose estimate in AAPM Report No. 204 were generated using 15 - 30 cm scan lengths. One needs to be cautious in applying SSDE to small length CT scans. For abdominal fat CT, SSDE was 80–150% higher than the dose of 1 cm scan length.« less

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

PubMed

KuKanich, Butch; Warner, Matt; Hahn, Kevin

2017-02-01

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

Calcium intake and colorectal adenoma risk: dose-response meta-analysis of prospective observational studies.

PubMed

Keum, NaNa; Lee, Dong Hoon; Greenwood, Darren C; Zhang, Xuehong; Giovannucci, Edward L

2015-04-01

Evidence from randomized controlled trials suggests that calcium may protect against recurrence of colorectal adenomas, which could lead to the subsequent prevention of cancer. Yet the trials used only a large single dose and were of small sizes, and thus, knowledge of the dose-response relationship and influence on high-risk adenomas is limited. To address these issues, we conducted linear and nonlinear dose-response meta-analyses primarily based on prospective observational studies published up to July 2014 identified from PubMed and Embase. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated for total and supplemental calcium intake, respectively, using a random-effects model. For total calcium intake, summary RR for each 300 mg/day increase was 0.95 (95% CI = 0.92-0.98; I(2)  = 45%; eight studies with 11,005 cases; range of intake = 333-2,229 mg/day). Evidence of nonlinearity was indicated: approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.92 (95% CI = 0.89-0.94) at 1,000 mg/day and 0.87 (95% CI = 0.84-0.90) at 1,450 mg/day (pnonlinearity  < 0.01). Associations were stronger for high-risk adenomas (≥1 cm in diameter, (tubulo)villous histology, dysplasia, or multiplicity): approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.77 (95% CI = 0.74-0.81) at 1,000 mg/day and reduced to 0.69 (95% CI = 0.66-0.73) at 1,450 mg/da (pnonlinearity  < 0.01). For supplemental calcium intake, summary RR of total adenoma risk for each 300 mg/day increase was 0.96 (95% CI = 0.93-0.99; I(2)  = 0%; three studies with 4,548 cases; range of supplementation = 0-1,366 mg/day). In conclusion, calcium intake may continue to decrease the risk of adenomas, particularly high-risk adenomas, over a wide range of calcium intake. © 2014 UICC.

Modeling the dose effects of soybean oil in salad dressing on carotenoid and fat-soluble vitamin bioavailability in salad vegetables.

PubMed

White, Wendy S; Zhou, Yang; Crane, Agatha; Dixon, Philip; Quadt, Frits; Flendrig, Leonard M

2017-10-01

Background: Previously, we showed that vegetable oil is necessary for carotenoid absorption from salad vegetables. Research is needed to better define the dose effect and its interindividual variation for carotenoids and fat-soluble vitamins. Objective: The objective was to model the dose-response relation between the amount of soybean oil in salad dressing and the absorption of 1 ) carotenoids, phylloquinone, and tocopherols in salad vegetables and 2 ) retinyl palmitate formed from the provitamin A carotenoids. Design: Women ( n = 12) each consumed 5 vegetable salads with salad dressings containing 0, 2, 4, 8, or 32 g soybean oil. Blood was collected at selected time points. The outcome variables were the chylomicron carotenoid and fat-soluble vitamin area under the curve (AUC) and maximum content in the plasma chylomicron fraction ( C max ). The individual-specific and group-average dose-response relations were investigated by fitting linear mixed-effects random coefficient models. Results: Across the entire 0-32-g range, soybean oil was linearly related to the chylomicron AUC and C max values for α-carotene, lycopene, phylloquinone, and retinyl palmitate. Across 0-8 g of soybean oil, there was a linear increase in the chylomicron AUC and C max values for β-carotene. Across a more limited 0-4-g range of soybean oil, there were minor linear increases in the chylomicron AUC for lutein and α- and total tocopherol. Absorption of all carotenoids and fat-soluble vitamins was highest with 32 g oil ( P < 0.002). For 32 g oil, the interindividual rank order of the chylomicron AUCs was consistent across the carotenoids and fat-soluble vitamins ( P < 0.0001). Conclusions: Within the linear range, the average absorption of carotenoids and fat-soluble vitamins could be largely predicted by the soybean oil effect. However, the effect varied widely, and some individuals showed a negligible response. There was a global soybean oil effect such that those who absorbed more of one carotenoid and fat-soluble vitamin also tended to absorb more of the others. This trial was registered at clinicaltrials.gov as NCT02867488. © 2017 American Society for Nutrition.

Body-wide anatomy recognition in PET/CT images

NASA Astrophysics Data System (ADS)

Wang, Huiqian; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Zhao, Liming; Torigian, Drew A.

2015-03-01

With the rapid growth of positron emission tomography/computed tomography (PET/CT)-based medical applications, body-wide anatomy recognition on whole-body PET/CT images becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem and seldom studied due to unclear anatomy reference frame and low spatial resolution of PET images as well as low contrast and spatial resolution of the associated low-dose CT images. We previously developed an automatic anatomy recognition (AAR) system [15] whose applicability was demonstrated on diagnostic computed tomography (CT) and magnetic resonance (MR) images in different body regions on 35 objects. The aim of the present work is to investigate strategies for adapting the previous AAR system to low-dose CT and PET images toward automated body-wide disease quantification. Our adaptation of the previous AAR methodology to PET/CT images in this paper focuses on 16 objects in three body regions - thorax, abdomen, and pelvis - and consists of the following steps: collecting whole-body PET/CT images from existing patient image databases, delineating all objects in these images, modifying the previous hierarchical models built from diagnostic CT images to account for differences in appearance in low-dose CT and PET images, automatically locating objects in these images following object hierarchy, and evaluating performance. Our preliminary evaluations indicate that the performance of the AAR approach on low-dose CT images achieves object localization accuracy within about 2 voxels, which is comparable to the accuracies achieved on diagnostic contrast-enhanced CT images. Object recognition on low-dose CT images from PET/CT examinations without requiring diagnostic contrast-enhanced CT seems feasible.

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.

Survey of external cephalic version for breech presentation and neuraxial blockade use.

PubMed

Weiniger, Carolyn F; Sultan, Pervez; Dunn, Ashley; Carvalho, Brendan

2016-11-01

Neuraxial blockade may increase external cephalic version (ECV) success rates. This survey aimed to assess the frequency and characteristics of neuraxial blockade used to facilitate ECV. We surveyed Society for Obstetric Anesthesia and Perinatology members regarding ECV practice using a 15-item survey developed by 3 obstetric anesthesiologists and tested for face validity. The survey was e-mailed in January 2015 and again in February 2015 to the 1056 Society of Obstetric Anesthesiology and Perinatology members. We present descriptive statistics of responses. Our survey response rate was 322 of 1056 (30.5%). Neuraxial blockade was used for ECV always by 18 (5.6%), often by 52 (16.1%), sometimes by 98 (30.4%), rarely by 78 (24.2%), and never by 46 (14.3%) of respondents. An anesthetic sensory block target was selected by 141 (43.8%) respondents, and analgesic by 102 (31.7%) respondents. Epidural drug doses ranged widely, including sufentanil 5-25 μg; lidocaine 1% or 2% 10-20 mL, bupivacaine 0.0625% to 0.5% 6-15 mL, and ropivacaine 0.2% 20 mL. Intrathecal bupivacaine was used by 182 (56.5%) respondents; the most frequent doses were 2.5 mg used by 24 (7.5%), 7.5 mg used by 35 (10.9%), and 12 mg used by 30 (9.3%). Neuraxial blockade is not universally offered to facilitate ECV, and there is wide variability in neuraxial blockade techniques, in drugs and doses administered, and in the sensory blockade (anesthetic or analgesic) targeted. Future studies need to evaluate and remove barriers to allow for more widespread use of neuraxial blockade for pain relief and to optimize ECV success rates. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation and comparison of absorbed dose for electron beams by LiF and diamond dosimeters

NASA Astrophysics Data System (ADS)

Mosia, G. J.; Chamberlain, A. C.

2007-09-01

The absorbed dose response of LiF and diamond thermoluminescent dosimeters (TLDs), calibrated in 60Co γ-rays, has been determined using the MCNP4B Monte Carlo code system in mono-energetic megavoltage electron beams from 5 to 20 MeV. Evaluation of the dose responses was done against the dose responses of published works by other investigators. Dose responses of both dosimeters were compared to establish if any relation exists between them. The dosimeters were irradiated in a water phantom with the centre of their top surfaces (0.32×0.32 cm 2), placed at dmax perpendicular to the radiation beam on the central axis. For LiF TLD, dose responses ranged from 0.945±0.017 to 0.997±0.011. For the diamond TLD, the dose response ranged from 0.940±0.017 to 1.018±0.011. To correct for dose responses by both dosimeters, energy correction factors were generated from dose response results of both TLDs. For LiF TLD, these correction factors ranged from 1.003 up to 1.058 and for diamond TLD the factors ranged from 0.982 up to 1.064. The results show that diamond TLDs can be used in the place of the well-established LiF TLDs and that Monte Carlo code systems can be used in dose determinations for radiotherapy treatment planning.

Polyethylene Naphthalate Scintillator: A Novel Detector for the Dosimetry of Radioactive Ophthalmic Applicators

PubMed Central

Flühs, Dirk; Flühs, Andrea; Ebenau, Melanie; Eichmann, Marion

2015-01-01

Background Dosimetric measurements in small radiation fields with large gradients, such as eye plaque dosimetry with β or low-energy photon emitters, require dosimetrically almost water-equivalent detectors with volumes of <1 mm3 and linear responses over several orders of magnitude. Polyvinyltoluene-based scintillators fulfil these conditions. Hence, they are a standard for such applications. However, they show disadvantages with regard to certain material properties and their dosimetric behaviour towards low-energy photons. Purpose, Materials and Methods Polyethylene naphthalate, recently recognized as a scintillator, offers chemical, physical and basic dosimetric properties superior to polyvinyltoluene. Its general applicability as a clinical dosimeter, however, has not been shown yet. To prove this applicability, extensive measurements at several clinical photon and electron radiation sources, ranging from ophthalmic plaques to a linear accelerator, were performed. Results For all radiation qualities under investigation, covering a wide range of dose rates, a linearity of the detector response to the dose was shown. Conclusion Polyethylene naphthalate proved to be a suitable detector material for the dosimetry of ophthalmic plaques, including low-energy photon emitters and other small radiation fields. Due to superior properties, it has the potential to replace polyvinyltoluene as the standard scintillator for such applications. PMID:27171681

Preparation and Evaluation of Titanium-Based Xerogel as a Promising Coagulant for Water/Wastewater Treatment.

PubMed

Wang, Xiaomeng; Li, Minghui; Song, Xiaojie; Chen, Zhihao; Wu, Bingdang; Zhang, Shujuan

2016-09-06

The nontoxicity of titanium (Ti) and the potential to produce valuable photocatalysts from the final coagulated sludge constitute the main advantages of Ti-based coagulants over conventional ones. However, the low effluent pH and the too-fast hydrolysis limit the wide application of Ti-salt coagulants. Prehydrolysis, to some extent, is helpful to improve the coagulation performance of Ti-salt coagulants. However, the prehydrolyzed polytitanium chloride (PTC) still suffers from narrow applicable dose/pH range. A novel and efficient Ti-based coagulant, denoted as titanium xerogel coagulant (TXC), was successfully prepared by the sol-gel method with TiCl4 as the precursor and acetylacetone as a modifying agent. Compared with TiCl4, a PTC, and a commercial polyferric sulfate, the resulting TXC possessed a larger floc size, better settling property, and wider applicable coagulant dose/pH range. Moreover, the effluent pH after TXC coagulation was not significantly reduced, avoiding the corrosion problem sometimes caused by the low effluent pH. TXC exhibited good coagulation performance for several real wastewaters, especially for the wastewaters of low turbidity. These results demonstrate that gelation was a more effective strategy than prehydrolysis to overcome the inherent weaknesses of Ti salts as a type of promising coagulants.

Site-specific range uncertainties caused by dose calculation algorithms for proton therapy

NASA Astrophysics Data System (ADS)

Schuemann, J.; Dowdell, S.; Grassberger, C.; Min, C. H.; Paganetti, H.

2014-08-01

The purpose of this study was to assess the possibility of introducing site-specific range margins to replace current generic margins in proton therapy. Further, the goal was to study the potential of reducing margins with current analytical dose calculations methods. For this purpose we investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict the range of proton fields. Dose distributions predicted by an analytical pencil-beam algorithm were compared with those obtained using Monte Carlo (MC) simulations (TOPAS). A total of 508 passively scattered treatment fields were analyzed for seven disease sites (liver, prostate, breast, medulloblastoma-spine, medulloblastoma-whole brain, lung and head and neck). Voxel-by-voxel comparisons were performed on two-dimensional distal dose surfaces calculated by pencil-beam and MC algorithms to obtain the average range differences and root mean square deviation for each field for the distal position of the 90% dose level (R90) and the 50% dose level (R50). The average dose degradation of the distal falloff region, defined as the distance between the distal position of the 80% and 20% dose levels (R80-R20), was also analyzed. All ranges were calculated in water-equivalent distances. Considering total range uncertainties and uncertainties from dose calculation alone, we were able to deduce site-specific estimations. For liver, prostate and whole brain fields our results demonstrate that a reduction of currently used uncertainty margins is feasible even without introducing MC dose calculations. We recommend range margins of 2.8% + 1.2 mm for liver and prostate treatments and 3.1% + 1.2 mm for whole brain treatments, respectively. On the other hand, current margins seem to be insufficient for some breast, lung and head and neck patients, at least if used generically. If no case specific adjustments are applied, a generic margin of 6.3% + 1.2 mm would be needed for breast, lung and head and neck treatments. We conclude that the currently used generic range uncertainty margins in proton therapy should be redefined site specific and that complex geometries may require a field specific adjustment. Routine verifications of treatment plans using MC simulations are recommended for patients with heterogeneous geometries.

Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

NASA Astrophysics Data System (ADS)

Mahmood, M.; Xu, Y.; Dantuluri, V.; Mustafa, T.; Zhang, Y.; Karmakar, A.; Casciano, D.; Ali, S.; Biris, A.

2013-02-01

Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells.

Thermoluminescence properties of Yb-Tb-doped SiO2 optical fiber subject to 6 and 10 MV photon irradiation

NASA Astrophysics Data System (ADS)

Sahini, M. H.; Wagiran, H.; Hossain, I.; Saeed, M. A.; Ali, H.

2014-08-01

This paper reports thermoluminescence characteristics of thermoluminescence dosimetry 100 chips and Yb-Tb-doped optical fibers irradiated with 6 and 10 MV photons. Thermoluminescence response of both dosimeters increases over a wide photon dose range from 0.5 to 4 Gy. Yb-Tb-doped optical fibers demonstrate useful thermoluminescence properties and represent a good candidate for thermoluminescence dosimetry application with ionizing radiation. The results of this fiber have been compared with those of commercially available standard thermoluminescence dosimetry-100 media. Commercially available Yb-Tb-doped optical fibers and said standard media are found to yield a linear relationship between dose- and thermoluminescence signal, although Yb-Tb-doped optical fibers provide only 10 % of the sensitivity of thermoluminescence dosimetry-100. With better thermoluminescence characteristics such as small size (125 μm diameter), high flexibility, easy of handling and low cost, as compared to other thermoluminescence materials, indicate that commercial Yb-Tb-doped optical fiber is a promising thermoluminescence material for variety of applications.

EPR and photoluminescence study of irradiated anion-defective alumina single crystals

NASA Astrophysics Data System (ADS)

Kortov, V. S.; Ananchenko, D. V.; Konev, S. F.; Pustovarov, V. A.

2017-09-01

Electron paramagnetic resonance (EPR) and photoluminescence (PL) spectra of anion-defective alumina single crystals were measured. Exposure to a dose 10 Gy-1 kGy causes isotropic EPR signal of a complex form, this signal contains narrow and broad components. At the same time, in the PL spectrum alongside with a band of F+-centers (3.8 eV) an additional emission band with the maximum of 2.25 eV is registered. This band corresponds to aggregate F22+-centers which were create under irradiation. By comparing measurements in EPR and PL spectra with further stepped annealing in the temperature range of 773-1473 K of the samples exposed to the same doses, we were able to conclude that a narrow component of isotropic EPR signal is associated with the formation of paramagnetic F22+-centers under irradiation. A wide component can be caused by deep hole traps which are created by a complex defect (VAl2- - F+) with a localized hole.

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

Leichner, P.K.

This report summarizes research in beta-particle dosimetry, quantitative single-photon emission computed tomography (SPECT), the clinical implementation of these two areas of research in radioimmunotherapy (RIT), and postgraduate training provided since the inception of this grant on July 15, 1989. To improve beta-particle dosimetry, a point source function was developed that is valid for a wide range of beta emitters. Analytical solutions for beta-particle dose rates within out outside slabs of finite thickness were validated in experimental tumors and are now being used in clinical RIT. Quantitative SPECT based on the circular harmonic transform (CHT) algorithm was validated in phantom, experimental,more » and clinical studies. This has led to improved macrodosimetry in clinical RIT. In dosimetry at the multi-cellular level studies were made of the HepG2 human hepatoblastoma grown subcutaneously in nude mice. Histologic sections and autoradiographs were prepared to quantitate activity distributions of radiolabeled antibodies. Absorbed-dose calculations are being carried out for {sup 131}I and {sup 90}Y beta particles for these antibody distributions.« less

Bisphenol A and Risk Management Ethics

PubMed Central

Resnik, David B.; Elliot, Kevin C.

2013-01-01

It is widely recognized that endocrine disrupting compounds, such as Bisphenol A, pose challenges for traditional paradigms in toxicology, insofar as these substances appear to have a wider range of low-dose effects than previously recognized. These compounds also pose challenges for ethics and policymaking. When a chemical does not have significant low-dose effects, regulators can allow it to be introduced into commerce or the environment, provided that procedures and rules are in place to keep exposures below an acceptable level. This option allows society to maximize the benefits from the use of the chemical while minimizing risks to human health or the environment, and it represents a compromise between competing values. When it is not possible to establish acceptable exposure levels for chemicals that pose significant health or environmental risks, the most reasonable options for risk management may be to enact either partial or complete bans on their use. These options create greater moral conflict than other risk management strategies, leaving policymakers difficult choices between competing values. PMID:24471646

Bisphenol A and risk management ethics.

PubMed

Resnik, David B; Elliott, Kevin C

2015-03-01

It is widely recognized that endocrine disrupting compounds, such as Bisphenol A, pose challenges for traditional paradigms in toxicology, insofar as these substances appear to have a wider range of low-dose effects than previously recognized. These compounds also pose challenges for ethics and policymaking. When a chemical does not have significant low-dose effects, regulators can allow it to be introduced into commerce or the environment, provided that procedures and rules are in place to keep exposures below an acceptable level. This option allows society to maximize the benefits from the use of the chemical while minimizing risks to human health or the environment, and it represents a compromise between competing values. When it is not possible to establish acceptable exposure levels for chemicals that pose significant health or environmental risks, the most reasonable options for risk management may be to enact either partial or complete bans on their use. These options create greater moral conflict than other risk management strategies, leaving policymakers difficult choices between competing values. © 2014 John Wiley & Sons Ltd.

Effect of thermal annealing on the thermoluminescent properties of nano-calcium fluoride and its dose-response characteristics.

PubMed

Mundupuzhakal, J K; Biswas, R H; Chauhan, S; Varma, V; Acharya, Y B; Chakrabarty, B S

2015-12-01

Nano-CaF2, prepared by the co-precipitation method, was annealed under different annealing conditions to improve its thermoluminescence (TL) characteristics. Different annealing parameters, such as temperature (400-700°C), duration (1-4 h) and environment (vacuum and air), were explored. The effect on TL sensitivity, peak position (Tm) and full-width at half-maximum (FWHM) with respect to the different annealing conditions are discussed as they are the measure of crystallinity of the material. Annealing temperature of 500°C with annealing duration of two and a half hours in vacuum provided the highest luminescence response (i.e. maximum sensitivity, minimum peak temperature and FWHM). Wide detectable dose range (5 mGy to 2 kGy), absence of thermal quenching and sufficient activation energy (1.04 eV) of this phosphor make it suitable for dosimetric applications. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effect of gamma irradiation on rice protein aqueous solution

NASA Astrophysics Data System (ADS)

Baccaro, Stefania; Bal, Oya; Cemmi, Alessia; Di Sarcina, Ilaria

2018-05-01

The use of proteins as natural biopolymers are sensibly increasing in several application fields such as food industry, packaging and environment protection. In particular, rice proteins (RP) present good nutritional, hypoallergenic and healthful properties very interesting for human consumption. Since ionizing radiation can be successfully applied on protein containing systems involved in different industrial processes, this work aims to determine the effect of gamma radiation on 5 wt%-7.5 wt% RP aqueous solutions in a wide range of absorbed doses up to around 40 kGy. The changes of RP secondary and tertiary structures and their chemical composition were followed by UV-VIS absorbance spectroscopy, luminescence analysis and pH measurements. The experimental data showed the occurrence of the unfolding of RP chains with the increase of the absorbed dose and the formation of new molecules, due to the reaction among tryptophane and tyrosine amino acids and the radical species induced by gamma radiation. The results are also confirmed by the modification of the pH values measured for the irradiated solutions.

Calculated Energy Deposits from the Decay of Tritium and Other Radioisotopes Incorporated into Bacteria

PubMed Central

Bockrath, Richard; Person, Stanley; Funk, Fred

1968-01-01

Transmutation of the radioisotope tritium occurs with the production of a low energy electron, having a range in biological material similar to the dimensions of a bacterium. A computer program was written to determine the radiation dose distributions which may be expected within a bacterium as a result of tritium decay, when the isotope has been incorporated into specific regions of the bacterium. A nonspherical model bacterium was used, represented by a cylinder with hemispherical ends. The energy distributions resulting from a wide variety of simulated labeled regions were determined; the results suggested that the nuclear region of a bacterium receives on the average significantly different per decay doses, if the labeled regions were those conceivably produced by the incorporation of thymidine-3H, uracil-3H, or 3H-amino acids. Energy distributions in the model bacterium were also calculated for the decay of incorporated 14carbon, 35sulfur, and 32phosphorous. PMID:5678319

Research on ion implantation in MEMS device fabrication by theory, simulation and experiments

NASA Astrophysics Data System (ADS)

Bai, Minyu; Zhao, Yulong; Jiao, Binbin; Zhu, Lingjian; Zhang, Guodong; Wang, Lei

2018-06-01

Ion implantation is widely utilized in microelectromechanical systems (MEMS), applied for embedded lead, resistors, conductivity modifications and so forth. In order to achieve an expected device, the principle of ion implantation must be carefully examined. The elementary theory of ion implantation including implantation mechanism, projectile range and implantation-caused damage in the target were studied, which can be regarded as the guidance of ion implantation in MEMS device design and fabrication. Critical factors including implantations dose, energy and annealing conditions are examined by simulations and experiments. The implantation dose mainly determines the dopant concentration in the target substrate. The implantation energy is the key factor of the depth of the dopant elements. The annealing time mainly affects the repair degree of lattice damage and thus the activated elements’ ratio. These factors all together contribute to ions’ behavior in the substrates and characters of the devices. The results can be referred to in the MEMS design, especially piezoresistive devices.

Formulated Beta-Cyfluthrin Shows Wide Divergence in Toxicity among Bird Species

PubMed Central

Addy-Orduna, Laura M.; Zaccagnini, María-Elena; Canavelli, Sonia B.; Mineau, Pierre

2011-01-01

It is generally assumed that the toxicity of pyrethroid insecticides to birds is negligible, though few species have been tested. The oral acute toxicity of formulated beta-cyfluthrin was determined for canaries (Serinus sp.), shiny cowbirds (Molothrus bonariensis), and eared doves (Zenaida auriculata). Single doses were administered to adults by gavage. Approximate lethal doses 50 (LD50) and their confidence intervals were determined by approximate D-optimal design. Canaries were found to be substantially more sensitive to formulated beta-cyfluthrin (LD50 = (170 ± 41) mg/kg) than the other two species tested (LD50 = (2234 ± 544) mg/kg and LD50 = (2271 ± 433) mg/kg, resp.). The LD50 obtained for canaries was also considerably lower than typical toxicity values available in the literature for pyrethroids. This study emphasizes the need for testing a broader range of species with potentially toxic insecticides, using modern up and down test designs with minimal numbers of birds. PMID:21584255

Single and compound effects of radiation and microgravity responses in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Wang, Wei; Sun, Yeqing; Xu, Dan; Yang, Jun; Luo, Yajing

2016-07-01

Space radiation and microgravity are main factors of spaceflight which could cause effects on organism. However, studies on the combined effects of microgravity and radiation have had conflicting results. For further elucidate the single factor effects of radiation or microgravity and the compound factor effects of them, the wild-type strain (Bristol N2) and muscle repair defective strain (dys-1) of Caenorhabditis elegansin dauer larvae were treated by ground simulated radiation in different doses (0.2Gy,2Gy) and/or 16.5-day simulated microgravity. The locomotory capacity assay and proteomic analysis were processed after the recovery of dauer larvae to adult. Locomotory capacity assay showed that the N2 nematodes were susceptible to simulated microgravity while dys-1 nematodes were susceptible to simulation radiation especially in high dose radiation (2Gy). The compound factor of microgravity and radiation has different influences to different strains. Proteomic results indicated that a wide range but different biological processes were involved in responding to radiation and/or microgravity.

Iodine-131 in sewage sludge from a small water pollution control plant serving a thyroid cancer treatment facility.

PubMed

Rose, Paula S; Swanson, R Lawrence

2013-08-01

Iodine-131 (half-life = 8.04 d) is the most widely used radionuclide in medicine for therapeutic purposes. It is excreted by patients and is discharged directly to sewer systems. Despite considerable dilution in waste water and the relatively short half-life of I, it is readily measured in sewage. This work presents I concentrations in sewage sludge from three water pollution control plants (WPCPs) on Long Island, NY. Iodine-131 concentrations ranged from 0.027 ± 0.002 to 148 ± 4 Bq g dry weight. The highest concentrations were measured in the Stony Brook WPCP, a relatively small plant (average flow = 6.8 × 10 L d) serving a regional thyroid cancer treatment facility in Stony Brook, NY. Preliminary radiation dose calculations suggested further evaluation of dose to treatment plant workers in the Stony Brook WPCP based on the recommendations of the Interagency Steering Committee on Radiation Standards.

Valerian for sleep: a systematic review and meta-analysis.

PubMed

Bent, Stephen; Padula, Amy; Moore, Dan; Patterson, Michael; Mehling, Wolf

2006-12-01

Insomnia affects approximately one-third of the adult population and contributes to increased rates of absenteeism, health care use, and social disability. Extracts of the roots of valerian (Valeriana officinalis) are widely used for inducing sleep and improving sleep quality. A systematic review of randomized, placebo-controlled trials of valerian for improving sleep quality is presented. An extensive literature search identified 16 eligible studies examining a total of 1093 patients. Most studies had significant methodologic problems, and the valerian doses, preparations, and length of treatment varied considerably. A dichotomous outcome of sleep quality (improved or not) was reported by 6 studies and showed a statistically significant benefit (relative risk of improved sleep = 1.8, 95% confidence interval, 1.2-2.9), but there was evidence of publication bias in this summary measure. The available evidence suggests that valerian might improve sleep quality without producing side effects. Future studies should assess a range of doses of standardized preparations of valerian and include standard measures of sleep quality and safety.

Valerian for Sleep: A Systematic Review and Meta-Analysis

PubMed Central

Bent, Stephen; Padula, Amy; Moore, Dan; Patterson, Michael; Mehling, Wolf

2014-01-01

Insomnia affects approximately one-third of the adult population and contributes to increased rates of absenteeism, health care use, and social disability. Extracts of the roots of valerian (Valeriana officinalis) are widely used for inducing sleep and improving sleep quality. A systematic review of randomized, placebo-controlled trials of valerian for improving sleep quality is presented. An extensive literature search identified 16 eligible studies examining a total of 1093 patients. Most studies had significant methodologic problems, and the valerian doses, preparations, and length of treatment varied considerably. A dichotomous outcome of sleep quality (improved or not) was reported by 6 studies and showed a statistically significant benefit (relative risk of improved sleep = 1.8, 95% confidence interval, 1.2-2.9), but there was evidence of publication bias in this summary measure. The available evidence suggests that valerian might improve sleep quality without producing side effects. Future studies should assess a range of doses of standardized preparations of valerian and include standard measures of sleep quality and safety. PMID:17145239

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

Formulated Beta-Cyfluthrin Shows Wide Divergence in Toxicity among Bird Species.

PubMed

Addy-Orduna, Laura M; Zaccagnini, María-Elena; Canavelli, Sonia B; Mineau, Pierre

2011-01-01

It is generally assumed that the toxicity of pyrethroid insecticides to birds is negligible, though few species have been tested. The oral acute toxicity of formulated beta-cyfluthrin was determined for canaries (Serinus sp.), shiny cowbirds (Molothrus bonariensis), and eared doves (Zenaida auriculata). Single doses were administered to adults by gavage. Approximate lethal doses 50 (LD(50)) and their confidence intervals were determined by approximate D-optimal design. Canaries were found to be substantially more sensitive to formulated beta-cyfluthrin (LD(50) = (170 ± 41) mg/kg) than the other two species tested (LD(50) = (2234 ± 544) mg/kg and LD(50) = (2271 ± 433) mg/kg, resp.). The LD(50) obtained for canaries was also considerably lower than typical toxicity values available in the literature for pyrethroids. This study emphasizes the need for testing a broader range of species with potentially toxic insecticides, using modern up and down test designs with minimal numbers of birds.

Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

PubMed

Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

2010-08-01

The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

Dose density in adjuvant chemotherapy for breast cancer.

PubMed

Citron, Marc L

2004-01-01

Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer. The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity. Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are significantly greater than with conventional schedules (q21d). The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.

Oxygen beams for therapy: advanced biological treatment planning and experimental verification

NASA Astrophysics Data System (ADS)

Sokol, O.; Scifoni, E.; Tinganelli, W.; Kraft-Weyrather, W.; Wiedemann, J.; Maier, A.; Boscolo, D.; Friedrich, T.; Brons, S.; Durante, M.; Krämer, M.

2017-10-01

Nowadays there is a rising interest towards exploiting new therapeutical beams beyond carbon ions and protons. In particular, 16 O ions are being widely discussed due to their increased LET distribution. In this contribution, we report on the first experimental verification of biologically optimized treatment plans, accounting for different biological effects, generated with the TRiP98 planning system with 16 O beams, performed at HIT and GSI. This implies the measurements of 3D profiles of absorbed dose as well as several biological measurements. The latter includes the measurements of relative biological effectiveness along the range of linear energy transfer values from  ≈20 up to  ≈750 keV μ m-1 , oxygen enhancement ratio values and the verification of the kill-painting approach, to overcome hypoxia, with a phantom imitating an unevenly oxygenated target. With the present implementation, our treatment planning system is able to perform a comparative analysis of different ions, according to any given condition of the target. For the particular cases of low target oxygenation, 16 O ions demonstrate a higher peak-to-entrance dose ratio for the same cell killing in the target region compared to 12 C ions. Based on this phenomenon, we performed a short computational analysis to reveal the potential range of treatment plans, where 16 O can benefit over lighter modalities. It emerges that for more hypoxic target regions (partial oxygen pressure of  ≈0.15% or lower) and relatively low doses (≈4 Gy or lower) the choice of 16 O over 12 C or 4 He may be justified.

Hepatitis C treatment among racial and ethnic groups in the IDEAL trial.

PubMed

Muir, A J; Hu, K-Q; Gordon, S C; Koury, K; Boparai, N; Noviello, S; Albrecht, J K; Sulkowski, M S; McCone, J

2011-04-01

Previous studies of chronic hepatitis C virus (HCV) treatment have demonstrated variations in response among racial and ethnic groups including poorer efficacy rates among African American and Hispanic patients. The individualized dosing efficacy vs flat dosing to assess optimaL pegylated interferon therapy (IDEAL) trial enrolled 3070 patients from 118 United States centres to compare treatment with peginterferon (PEG-IFN) alfa-2a and ribavirin (RBV) and two doses of PEG-IFN alfa-2b and RBV. This analysis examines treatment response among the major racial and ethnic groups in the trial. Overall, sustained virologic response (SVR) rates were 44% for white, 22% for African American, 38% for Hispanic and 59% for Asian American patients. For patients with undetectable HCV RNA at treatment week 4, the positive predictive value of SVR was 86% for white, 92% for African American, 83% for Hispanic and 89% for Asian American patients. The positive predictive values of SVR in those with undetectable HCV RNA at treatment week 12 ranged from 72% to 81%. Multivariate regression analysis using baseline characteristics demonstrated that treatment regimen was not a predictor of SVR. Despite wide-ranging SVR rates among the different racial and ethnic groups, white and Hispanic patients had similar SVR rates. In all groups, treatment response was largely determined by antiviral activity in the first 12 weeks of treatment. Therefore, decisions regarding HCV treatment should consider the predictive value of the early on-treatment response, not just baseline characteristics, such as race and ethnicity. © 2010 Blackwell Publishing Ltd.

Ten-year results of treatment of ductal carcinoma in situ (DCIS) of the breast with conservative surgery and radiotherapy.

PubMed

Amichetti, M; Caffo, O; Richetti, A; Zini, G; Rigon, A; Antonello, M; Arcicasa, M; Coghetto, F; Valdagni, R; Maluta, S; Di Marco, A

1997-09-01

The optimal treatment of ductal carcinoma in situ (DCIS) of the breast has not yet been established. The effectiveness of adjuvant postoperative radiotherapy after conservative surgery is debated. Few data are available in Italy on the combined treatment. A collaborative multi-institutional study on this issue in 10 radiation oncology departments of the north-east of Italy was conducted. One hundred and thirty nine women with DCIS of the breast were treated between 1980 and 1990. Age ranged between 28 and 88 years (median 50 years). Surgical procedures were: quadrantectomy in 108, lumpectomy in 22 and wide excision in 9 cases. The axilla was surgically staged in 97 cases: all the patients were node-negative. Radiation therapy was delivered with 60Co units (78%) or 6 MV linear accelerators (22%) for a median total dose to the entire breast of 50 Gy (mean 49.48 Gy; range 45-60 Gy). The tumour bed was boosted in 109 cases (78%) at a dose of 4-30 Gy (median 10 Gy) for a minimum tumour dose of 58 Gy. Median follow-up was 81 months. Thirteen local recurrences were recorded, 7 intraductal and 6 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease. Actuarial overall, cause-specific and recurrence-free survival at 10 years are of 93%, 100% and 86%, respectively. The results of this retrospective multicentric study substantiate the favourable data reported in the literature and confirm the efficacy of the breast-conserving treatment of DCIS employing conservative surgery and adjuvant radiation therapy.

Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements

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

Bentefour, El H., E-mail: hassan.bentefour@iba-group.com; Prieels, Damien; Tang, Shikui

Purpose: In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. Methods: An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification inmore » the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. Results: Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. Conclusions: Time-resolved dose measurement method satisfies the two basic requirements, WEPL accuracy and minimum dose, necessary for clinical use, thus, its potential for in-vivo protons range verification. Further development is needed, namely, devising a workflow that takes into account the limits imposed by proton range mixing and the susceptibility of the comparison of measured and expected WEPLs to errors on the detector positions. The methods may also be used for in-vivo dosimetry and could benefit various proton therapy treatments.« less

Determination of gonad doses during robotic stereotactic radiosurgery for various tumor sites

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

Zorlu, Faruk; Dugel, Gozde; Ozyigit, Gokhan

Purpose: The authors evaluated the absorbed dose received by the gonads during robotic stereotactic radiosurgery (SRS) for the treatment of different tumor localizations. Methods: The authors measured the gonad doses during the treatment of head and neck, thoracic, abdominal, or pelvic tumors in both RANDO phantom and actual patients. The computerized tomography images were transferred to the treatment planning system. The contours of tumor and critical organs were delineated on each slice, and treatment plans were generated. Measurements for gonad doses were taken from the geometric projection of the ovary onto the skin for female patients, and from the scrotalmore » skin for male patients by attaching films and Thermoluminescent dosimeters (TLDs). SRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA). Results: The median gonadal doses with TLD and film dosimeter in actual patients were 0.19 Gy (range, 0.035-2.71 Gy) and 0.34 Gy (range, 0.066-3.18 Gy), respectively. In the RANDO phantom, the median ovarian doses with TLD and film dosimeter were 0.08 Gy (range, 0.03-0.159 Gy) and 0.05 Gy (range, 0.015-0.13 Gy), respectively. In the RANDO phantom, the median testicular doses with TLD and film dosimeter were 0.134 Gy (range 0.056-1.97 Gy) and 0.306 Gy (range, 0.065-2.25 Gy). Conclusions: Gonad doses are below sterility threshold in robotic SRS for different tumor localizations. However, particular attention should be given to gonads during robotic SRS for pelvic tumors.« less

Dependency of EBT2 film calibration curve on postirradiation time

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

Chang, Liyun, E-mail: liyunc@isu.edu.tw; Ding, Hueisch-Jy; Ho, Sheng-Yow

2014-02-15

Purpose: The Ashland Inc. product EBT2 film model is a widely used quality assurance tool, especially for verification of 2-dimensional dose distributions. In general, the calibration film and the dose measurement film are irradiated, scanned, and calibrated at the same postirradiation time (PIT), 1-2 days after the films are irradiated. However, for a busy clinic or in some special situations, the PIT for the dose measurement film may be different from that of the calibration film. In this case, the measured dose will be incorrect. This paper proposed a film calibration method that includes the effect of PIT. Methods: Themore » dose versus film optical density was fitted to a power function with three parameters. One of these parameters was PIT dependent, while the other two were found to be almost constant with a standard deviation of the mean less than 4%. The PIT-dependent parameter was fitted to another power function of PIT. The EBT2 film model was calibrated using the PDD method with 14 different PITs ranging from 1 h to 2 months. Ten of the fourteen PITs were used for finding the fitting parameters, and the other four were used for testing the model. Results: The verification test shows that the differences between the delivered doses and the film doses calculated with this modeling were mainly within 2% for delivered doses above 60 cGy, and the total uncertainties were generally under 5%. The errors and total uncertainties of film dose calculation were independent of the PIT using the proposed calibration procedure. However, the fitting uncertainty increased with decreasing dose or PIT, but stayed below 1.3% for this study. Conclusions: The EBT2 film dose can be modeled as a function of PIT. For the ease of routine calibration, five PITs were suggested to be used. It is recommended that two PITs be located in the fast developing period (1∼6 h), one in 1 ∼ 2 days, one around a week, and one around a month.« less

Comparison of Individual Radiosensitivity to γ-Rays and Carbon Ions

PubMed Central

Shim, Grace; Normil, Marie Delna; Testard, Isabelle; Hempel, William M.; Ricoul, Michelle; Sabatier, Laure

2016-01-01

Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term “relative dose effect” (RDE). This ratio is advantageous, as it allows for simple comparison of dose–response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2–15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy. PMID:27379201

Preoperative single fraction partial breast radiotherapy for early-stage breast cancer.

PubMed

Palta, Manisha; Yoo, Sua; Adamson, Justus D; Prosnitz, Leonard R; Horton, Janet K

2012-01-01

Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A "virtual plan" was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. The median breast volume was 1,713 cm(3) (range: 1,014-2,140), and the median clinical target volume was 44 cm(3) (range: 26-73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42) and 53% (range: 24-65) in the institutional historical controls treated with postoperative external beam PBI (p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm(3) of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing. Copyright © 2012 Elsevier Inc. All rights reserved.

Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

PubMed

Eapen, Alex K; de Cock, Peter; Crincoli, Christine M; Means, Charlotte; Wismer, Tina; Pappas, Christopher

2017-07-01

Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose-Range Dependency of Radio-Biological Parameters.

PubMed

Troeller, A; Soehn, M; Yan, D

2012-06-01

Introducing an extended, phenomenological, generalized equivalent uniform dose (eEUD) that incorporates multiple volume-effect parameters for different dose-ranges. The generalized EUD (gEUD) was introduced as an estimate of the EUD that incorporates a single, tissue-specific parameter - the volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its radio-biological equivalency to a given inhomogeneous dose distribution is not a priori clear and mechanistic models based on radio-biological parameters are assumed to better resemble the underlying biology. However, for normal organs mechanistic models are hard to derive, since the structural organization of the tissue plays a significant role. Consequently, phenomenological approaches might be especially useful in order to describe dose-response for normal tissues. However, the single parameter used to estimate the gEUD may not suffice in accurately representing more complex biological effects that have been discussed in the literature. For instance, radio-biological parameters and hence the effects of fractionation are known to be dose-range dependent. Therefore, we propose an extended phenomenological eEUD formula that incorporates multiple VEPs accounting for dose-range dependency. The eEUD introduced is a piecewise polynomial expansion of the gEUD formula. In general, it allows for an arbitrary number of VEPs, each valid for a certain dose-range. We proved that the formula fulfills required mathematical and physical criteria such as invertibility of the underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD as a special case, if all VEPs are equal to 'a' from the gEUD model. The eEUD is a concept that expands the gEUD such that it can theoretically represent dose-range dependent effects. Its practicality, however, remains to be shown. As a next step, this will be done by estimating the eEUD from patient data using maximum-likelihood based NTCP modelling in the same way it is commonly done for the gEUD. © 2012 American Association of Physicists in Medicine.

IMRT QA: Selecting gamma criteria based on error detection sensitivity.

PubMed

Steers, Jennifer M; Fraass, Benedick A

2016-04-01

The gamma comparison is widely used to evaluate the agreement between measurements and treatment planning system calculations in patient-specific intensity modulated radiation therapy (IMRT) quality assurance (QA). However, recent publications have raised concerns about the lack of sensitivity when employing commonly used gamma criteria. Understanding the actual sensitivity of a wide range of different gamma criteria may allow the definition of more meaningful gamma criteria and tolerance limits in IMRT QA. We present a method that allows the quantitative determination of gamma criteria sensitivity to induced errors which can be applied to any unique combination of device, delivery technique, and software utilized in a specific clinic. A total of 21 DMLC IMRT QA measurements (ArcCHECK®, Sun Nuclear) were compared to QA plan calculations with induced errors. Three scenarios were studied: MU errors, multi-leaf collimator (MLC) errors, and the sensitivity of the gamma comparison to changes in penumbra width. Gamma comparisons were performed between measurements and error-induced calculations using a wide range of gamma criteria, resulting in a total of over 20 000 gamma comparisons. Gamma passing rates for each error class and case were graphed against error magnitude to create error curves in order to represent the range of missed errors in routine IMRT QA using 36 different gamma criteria. This study demonstrates that systematic errors and case-specific errors can be detected by the error curve analysis. Depending on the location of the error curve peak (e.g., not centered about zero), 3%/3 mm threshold = 10% at 90% pixels passing may miss errors as large as 15% MU errors and ±1 cm random MLC errors for some cases. As the dose threshold parameter was increased for a given %Diff/distance-to-agreement (DTA) setting, error sensitivity was increased by up to a factor of two for select cases. This increased sensitivity with increasing dose threshold was consistent across all studied combinations of %Diff/DTA. Criteria such as 2%/3 mm and 3%/2 mm with a 50% threshold at 90% pixels passing are shown to be more appropriately sensitive without being overly strict. However, a broadening of the penumbra by as much as 5 mm in the beam configuration was difficult to detect with commonly used criteria, as well as with the previously mentioned criteria utilizing a threshold of 50%. We have introduced the error curve method, an analysis technique which allows the quantitative determination of gamma criteria sensitivity to induced errors. The application of the error curve method using DMLC IMRT plans measured on the ArcCHECK® device demonstrated that large errors can potentially be missed in IMRT QA with commonly used gamma criteria (e.g., 3%/3 mm, threshold = 10%, 90% pixels passing). Additionally, increasing the dose threshold value can offer dramatic increases in error sensitivity. This approach may allow the selection of more meaningful gamma criteria for IMRT QA and is straightforward to apply to other combinations of devices and treatment techniques.

A dose-volume analysis of magnetic resonance imaging-aided high-dose-rate image-based interstitial brachytherapy for uterine cervical cancer.

PubMed

Yoshida, Ken; Yamazaki, Hideya; Takenaka, Tadashi; Kotsuma, Tadayuki; Yoshida, Mineo; Furuya, Seiichi; Tanaka, Eiichi; Uegaki, Tadaaki; Kuriyama, Keiko; Matsumoto, Hisanobu; Yamada, Shigetoshi; Ban, Chiaki

2010-07-01

To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2)). The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results. (c) 2010 Elsevier Inc. All rights reserved.

Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions.

PubMed

Elmore, E; Lao, X-Y; Kapadia, R; Redpath, J L

2009-06-01

Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has been examined. The data indicate a threshold-type dose-response curve with no increase in transformation frequency until doses above 20 cGy. At doses <10 cGy, not all exposed cells receive a direct traversal of an iron-ion track core, but all exposed cells receive up to several mGy of low-LET radiation associated with the delta-ray penumbra. It is proposed that the threshold-type response seen is a consequence of an adaptive response associated with the delta-ray exposure. For comparison purposes, the dose response for (137)Cs gamma rays over the same dose range was examined using the same experimental procedure. As we have shown previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron ions were 1.5 to 1.7 times more biologically effective than the gamma radiation over the dose range examined.

Light delivery over extended time periods enhances the effectiveness of photodynamic therapy.

PubMed

Seshadri, Mukund; Bellnier, David A; Vaughan, Lurine A; Spernyak, Joseph A; Mazurchuk, Richard; Foster, Thomas H; Henderson, Barbara W

2008-05-01

The rate of energy delivery is a principal factor determining the biological consequences of photodynamic therapy (PDT). In contrast to conventional high-irradiance treatments, recent preclinical and clinical studies have focused on low-irradiance schemes. The objective of this study was to investigate the relationship between irradiance, photosensitizer dose, and PDT dose with regard to treatment outcome and tumor oxygenation in a rat tumor model. Using the photosensitizer HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide), a wide range of PDT doses that included clinically relevant photosensitizer concentrations was evaluated. Magnetic resonance imaging and oxygen tension measurements were done along with the Evans blue exclusion assay to assess vascular response, oxygenation status, and tumor necrosis. In contrast to high-incident laser power (150 mW), low-power regimens (7 mW) yielded effective tumor destruction. This was largely independent of PDT dose (drug-light product), with up to 30-fold differences in photosensitizer dose and 15-fold differences in drug-light product. For all drug-light products, the duration of light treatment positively influenced tumor response. Regimens using treatment times of 120 to 240 min showed marked reduction in signal intensity in T2-weighted magnetic resonance images at both low (0.1 mg/kg) and high (3 mg/kg) drug doses compared with short-duration (6-11 min) regimens. Significantly greater reductions in pO(2) were observed with extended exposures, which persisted after completion of treatment. These results confirm the benefit of prolonged light exposure, identify vascular response as a major contributor, and suggest that duration of light treatment (time) may be an important new treatment variable.

Light Delivery Over Extended Time Periods Enhances the Effectiveness of Photodynamic Therapy

PubMed Central

Seshadri, Mukund; Bellnier, David A.; Vaughan, Lurine A.; Spernyak, Joseph A.; Mazurchuk, Richard; Foster, Thomas H.; Henderson, Barbara W.

2009-01-01

Purpose The rate of energy delivery is a principal factor determining the biological consequences of photodynamic therapy (PDT). In contrast to conventional high irradiance treatments, recent preclinical and clinical studies have focused on low irradiance schemes. The objective of this study was to investigate the relationship between irradiance, photosensitizer dose and PDT dose with regard to treatment outcome and tumor oxygenation in a rat tumor model. Experimental Design Using the photosensitizer HPPH (2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide), a wide range of PDT doses that included clinically relevant photosensitizer concentrations were evaluated. Magnetic resonance imaging (MRI) and oxygen tension measurements were performed along with the Evans blue exclusion assay to assess vascular response, oxygenation status and tumor necrosis. Results In contrast to high incident laser power (150 mW), low power regimens (7 mW) yielded effective tumor destruction. This was largely independent of PDT dose (drug-light product), with up to 30-fold differences in photosensitizer dose and 15-fold differences in drug-light product. For all drug-light products, the duration of light treatment positively influenced tumor response. Regimens utilizing treatment times of 120–240 mins showed marked reduction in signal intensity in T2-weighted MR images at both low (0.1 mg/kg) and high (3 mg/kg) drug doses compared to short duration (6–11 mins) regimens. Significantly greater reductions in pO2 were observed with extended exposures, which persisted after completion of treatment. Conclusions These results confirm the benefit of prolonged light exposure, identify vascular response as a major contributor and suggest that duration of light treatment (time) may be an important new treatment parameter. PMID:18451247

Modulation of distinct asthmatic phenotypes in mice by dose-dependent inhalation of microbial products.

PubMed

Whitehead, Gregory S; Thomas, Seddon Y; Cook, Donald N

2014-01-01

Humans with asthma display considerable heterogeneity with regard to T helper (Th) 2-associated eosinophilic and Th17-associated neutrophilic inflammation, but the impact of the environment on these different forms of asthma is poorly understood. We studied the nature and longevity of asthma-like responses triggered by inhalation of allergen together with environmentally relevant doses of inhaled lipopolysaccharide (LPS). Ovalbumin (OVA) was instilled into the airways of mice together with a wide range of LPS doses. Following a single OVA challenge, or multiple challenges, animals were assessed for pulmonary cytokine production, airway inflammation, and airway hyperresponsiveness (AHR). Mice instilled with OVA together with very low doses (≤10⁻³ μg) of LPS displayed modest amounts of Th2 cytokines, with associated airway eosinophilia and AHR after a single challenge, and these responses were sustained after multiple OVA challenges. When the higher but still environmentally relevant dose of 10⁻¹ μg LPS was used, mice initially displayed similar Th2 responses, as well as Th17-associated neutrophilia. After multiple OVA challenges, however, the 10⁻¹ μg LPS animals also accumulated large numbers of allergen-specific T regulatory (Treg) cells with high levels of inducible co-stimulatory molecule (ICOS). As a result, asthma-like features in these mice were shorter-lived than in mice sensitized using lower doses of LPS. The nature and longevity of Th2, Th17, and Treg immune responses to inhaled allergen are dependent on the quantity of LPS inhaled at the time of allergic sensitization. These findings might account in part for the heterogeneity of inflammatory infiltrates seen in lungs of asthmatics.

Influence of high dose tumescent local anaesthesia with prilocaine on systemic interleukin (IL)-6, IL-8 and tumour necrosis factor-α.

PubMed

Schmittner, M D; Faulhaber, J; Kemler, B; Koenen, W; Thumfart, J O; Weiss, C; Neumaier, M; Beck, G C

2010-12-01

Tumescent local anaesthesia (TLA) with high prilocaine doses leads to formation of methemoglobin (MHb) which is known to be a potent activator of pro-inflammatory endothelial cell response in vitro. As TLA is widely used for large dermatological resections, the aim of this study was to investigate the effects of high prilocaine doses on the systemic inflammatory response in vivo and its clinical relevance. This prospective study examines the influence of MHb on serum interleukin (IL)-6, IL-8 and tumour necrosis tumour necrosis (TNF)-α levels up to 72 h after application of TLA with prilocaine in doses higher than 600 mg. A total of 30 patients received prilocaine in a median dose of 1500 mg (range: 880-4160 mg) for large resections. Peak prilocaine serum concentration was reached 4 h (0.72 ± 0.07 μg/mL), the maximum concentration of MHb (7.43 ± 0.87%) and IL-6 (28.4 ± 4.1 U/L) 12 h after TLA application. TNF-α and IL-8 release were not found significantly increased. Three patients developed MHb concentrations >15%. This clinical study shows for the first time that a high prilocaine serum concentration leads in vivo to elevated systemic levels of IL-6 but not of IL-8 and TNF-α because of initial high MHb levels. Because of possible and unpredictable high MHb concentrations, TLA should only be performed with prilocaine in doses of 2.5 mg/kg. In general, new solutions of TLA are necessary to achieve adequate anaesthesia for large dermatological resections to decrease the risk of methemoglobinaemia. © 2010 The Authors. Journal compilation © 2010 European Academy of Dermatology and Venereology.

Sirolimus and everolimus clearance in maintenance kidney and liver transplant recipients: Diagnostic efficiency of the concentration/dose ratio for the prediction of trough steady-state concentrations

PubMed Central

Bouzas, Lorena; Hermida, Jesús

2010-01-01

Objectives Therapeutic monitoring of sirolimus and everolimus is necessary in order to minimize adverse side-effects and to ensure effective immunosuppression. A sirolimus-dosing model using the concentration/dose ratio has been previously proposed for kidney transplant patients, and the aim of our study was the evaluation of this single model for the prediction of trough sirolimus and everolimus concentrations. Methods Trough steady-state sirolimus concentrations were determined in several blood samples from each of 7 kidney and 9 liver maintenance transplant recipients, and everolimus concentrations from 20 kidney, 17 liver, and 3 kidney/liver maintenance transplant recipients. Predicted sirolimus and everolimus concentrations (Css), corresponding to the doses (D), were calculated using the measured concentrations (Css0) and corresponding doses (D0) on starting the study: Css = (Css0)(D)/D0. Results The diagnostic efficiency of the predicting model for the correct classification as subtherapeutic, therapeutic, and supratherapeutic values with respect to the experimentally obtained concentrations was 91.3% for sirolimus and 81.4% for everolimus in the kidney transplant patients. In the liver transplant patients the efficiency was 69.2% for sirolimus and 72.6% for everolimus, and in the kidney/liver transplant recipients the efficiency for everolimus was 67.9%. Conclusions The model has an acceptable diagnostic efficiency (>80%) for the prediction of sirolimus and everolimus concentrations in kidney transplant recipients, but not in liver transplant recipients. However, considering the wide ranges found for the prediction error of sirolimus and everolimus concentrations, the clinical relevance of this dosing model is weak. PMID:19943816

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

PubMed

Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

2013-01-15

We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

PubMed Central

2013-01-01

Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. Trial registration ClinicalTrials.gov number:NCT00978211 PMID:23320604

Development of an objective dose distribution analysis method for OSL dating and pilot studies for planetary applications

NASA Astrophysics Data System (ADS)

Lepper, Kenneth Errol

Scope and method of study. Part I: In its simplest expression a luminescence age is the natural absorbed radiation dose (De) divided by the in-situ dose rate. The experimental techniques of Optically Stimulated Luminescence (OSL) dating have evolved to the point were hundreds of Des, and therefore depositional ages can be quickly and conveniently determined for a single sediment sample. The first major objective of this research was to develop an objective analysis method for analyzing dose distribution data and selecting an age-representative dose (Dp). The analytical method was developed based on dose data sets collected from 3 eolian and 3 fluvial sediment samples from Central Oklahoma. Findings and conclusions. Part I: An objective method of presenting the dose distribution data, and a mathematically rigorous means of determining the Dp, as well as a statistically meaningful definition of the uncertainty in Dp have been proposed. The concept of experimental error deconvolution was introduced. In addition a set of distribution shape parameters to facilitate comparison among samples have been defined. These analytical techniques hold the potential to greatly enhance the accuracy and utility of OSL dating for young fluvial sediments. Scope and method of study. Part II: The second major objective of this research was to propose the application of luminescence dating to sediments on Mars. A set of fundamental luminescence dating properties was evaluated for a martian surface materials analog and a polar deposit contextual analog. Findings and conclusions. Part II: The luminescence signals measured from the analogs were found to have a wide dynamic dose response range with no unusual or prohibitive short-term instabilities and were readily reset by exposure to sunlight. These properties form a stable base for continued investigations toward the development of luminescence dating instruments and procedures for Mars.

Population pharmacokinetics of ϵ-aminocaproic acid in adolescents undergoing posterior spinal fusion surgery.

PubMed

Stricker, P A; Gastonguay, M R; Singh, D; Fiadjoe, J E; Sussman, E M; Pruitt, E Y; Goebel, T K; Zuppa, A F

2015-04-01

Despite demonstrated efficacy of ϵ-aminocaproic acid (EACA) in reducing blood loss in adolescents undergoing spinal fusion, there are no population-specific pharmacokinetic data to guide dosing. The aim of this study was to determine the pharmacokinetics of EACA in adolescents undergoing spinal fusion surgery and make dosing recommendations. Twenty children ages 12-17 years were enrolled, with 10 children in each of two groups based on diagnosis (idiopathic scoliosis or non-idiopathic scoliosis). Previously reported data from infants undergoing craniofacial surgery were included in the model to enable dosing recommendations over a wide range of weights, ages, and diagnoses. A population non-linear mixed effects modelling approach was used to characterize EACA pharmacokinetics. Population pharmacokinetic parameters were estimated using a two-compartment disposition model with allometrically scaled weight and an age effect on clearance. Pharmacokinetic parameters for the typical patient were a plasma clearance of 153 ml min(-1) 70 kg(-1) (6.32 ml min(-1) kg(-0.75)), intercompartmental clearance of 200 ml min(-1) 70 kg(-1) (8.26 ml min(-1) kg(-0.75)), central volume of distribution of 8.78 litre 70 kg(-1) (0.13 litre kg(-1)), and peripheral volume of distribution of 15.8 litre 70 kg(-1) (0.23 litre kg(-1)). Scoliosis aetiology did not have a clinically significant effect on drug pharmacokinetics. The following dosing schemes are recommended according to patient weight: weight <25 kg, 100 mg kg(-1) loading dose and 40 mg kg(-1) h(-1) infusion; weight ≤25 kg-<50 kg, 100 mg kg(-1) loading dose and 35 mg kg(-1) h(-1) infusion; and weight ≥50 kg, 100 mg kg(-1) loading dose and 30 mg kg(-1) h(-1) infusion. An efficacy trial employing this dosing strategy is warranted. NCT01408823. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Population pharmacokinetics of ϵ-aminocaproic acid in adolescents undergoing posterior spinal fusion surgery

PubMed Central

Stricker, P. A.; Gastonguay, M. R.; Singh, D.; Fiadjoe, J. E.; Sussman, E. M.; Pruitt, E. Y.; Goebel, T. K.; Zuppa, A. F.

2015-01-01

Background Despite demonstrated efficacy of ϵ-aminocaproic acid (EACA) in reducing blood loss in adolescents undergoing spinal fusion, there are no population-specific pharmacokinetic data to guide dosing. The aim of this study was to determine the pharmacokinetics of EACA in adolescents undergoing spinal fusion surgery and make dosing recommendations. Methods Twenty children ages 12–17 years were enrolled, with 10 children in each of two groups based on diagnosis (idiopathic scoliosis or non-idiopathic scoliosis). Previously reported data from infants undergoing craniofacial surgery were included in the model to enable dosing recommendations over a wide range of weights, ages, and diagnoses. A population non-linear mixed effects modelling approach was used to characterize EACA pharmacokinetics. Results Population pharmacokinetic parameters were estimated using a two-compartment disposition model with allometrically scaled weight and an age effect on clearance. Pharmacokinetic parameters for the typical patient were a plasma clearance of 153 ml min−1 70 kg−1 (6.32 ml min−1 kg−0.75), intercompartmental clearance of 200 ml min−1 70 kg−1 (8.26 ml min−1 kg−0.75), central volume of distribution of 8.78 litre 70 kg−1 (0.13 litre kg−1), and peripheral volume of distribution of 15.8 litre 70 kg−1 (0.23 litre kg−1). Scoliosis aetiology did not have a clinically significant effect on drug pharmacokinetics. Conclusions The following dosing schemes are recommended according to patient weight: weight <25 kg, 100 mg kg−1 loading dose and 40 mg kg−1 h−1 infusion; weight ≤25 kg–<50 kg, 100 mg kg−1 loading dose and 35 mg kg−1 h−1 infusion; and weight ≥50 kg, 100 mg kg−1 loading dose and 30 mg kg−1 h−1 infusion. An efficacy trial employing this dosing strategy is warranted. Clinical trial registration NCT01408823. PMID:25586726

SU-G-BRC-08: Evaluation of Dose Mass Histogram as a More Representative Dose Description Method Than Dose Volume Histogram in Lung Cancer Patients

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

Liu, J; Eldib, A; Ma, C

2016-06-15

Purpose: Dose-volume-histogram (DVH) is widely used for plan evaluation in radiation treatment. The concept of dose-mass-histogram (DMH) is expected to provide a more representative description as it accounts for heterogeneity in tissue density. This study is intended to assess the difference between DVH and DMH for evaluating treatment planning quality. Methods: 12 lung cancer treatment plans were exported from the treatment planning system. DVHs for the planning target volume (PTV), the normal lung and other structures of interest were calculated. DMHs were calculated in a similar way as DVHs expect that the voxel density converted from the CT number wasmore » used in tallying the dose histogram bins. The equivalent uniform dose (EUD) was calculated based on voxel volume and mass, respectively. The normal tissue complication probability (NTCP) in relation to the EUD was calculated for the normal lung to provide quantitative comparison of DVHs and DMHs for evaluating the radiobiological effect. Results: Large differences were observed between DVHs and DMHs for lungs and PTVs. For PTVs with dense tumor cores, DMHs are higher than DVHs due to larger mass weighing in the high dose conformal core regions. For the normal lungs, DMHs can either be higher or lower than DVHs depending on the target location within the lung. When the target is close to the lower lung, DMHs show higher values than DVHs because the lower lung has higher density than the central portion or the upper lung. DMHs are lower than DVHs for targets in the upper lung. The calculated NTCPs showed a large range of difference between DVHs and DMHs. Conclusion: The heterogeneity of lung can be well considered using DMH for evaluating target coverage and normal lung pneumonitis. Further studies are warranted to quantify the benefits of DMH over DVH for plan quality evaluation.« less

Estimation of the radiation dose from radiotherapy for skin haemangiomas in childhood: the ICTA software for epidemiology

NASA Astrophysics Data System (ADS)

Shamsaldin, A.; Lundell, M.; Diallo, I.; Ligot, L.; Chavaudra, J.; de Vathaire, F.

2000-12-01

Radium applicators and pure beta emitters have been widely used in the past to treat skin haemangioma in early childhood. A well defined relationship between the low doses received from these applicators and radiation-induced cancers requires accurate dosimetry. A human-based CT scan phantom has been used to simulate every patient and treatment condition and then to calculate the source-target distance when radium and pure beta applicators were used. The effective transmission factor ϕ(r) for the gamma spectrum emitted by the radium sources applied on the skin surface was modelled using Monte Carlo simulations. The well-known quantization approach was used to calculate gamma doses delivered from radium applicators to various anatomical points. For 32P, 90Sr/90Y applicators and 90Y needles we have used the apparent exponential attenuation equation. The dose calculation algorithm was integrated into the ICTA software (standing for a model that constructs an Individualized phantom based on CT slices and Auxological data), which has been developed for epidemiological studies of cohorts of patients who received radium and beta-treatments for skin haemangioma. The ϕ(r) values obtained for radium skin applicators are in good agreement with the available values in the first 10 cm but higher at greater distances. Gamma doses can be calculated with this algorithm at 165 anatomical points throughout the body of patients treated with radium applicators. Lung heterogeneity and air crossed by the gamma rays are considered. Comparison of absorbed doses in water from a 10 mg equivalent radium source simulated by ICTA with those measured at the Radiumhemmet, Karolinska Hospital (RAH) showed good agreement, but ICTA estimation of organ doses did not always correspond those estimated at the RAH. Beta doses from 32P, 90Sr/90Y applicators and 90Y needles are calculated up to the maximum beta range (11 mm).

No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

PubMed

Yu, Rosie Z; Gunawan, Rudy; Li, Zhaoyang; Mittleman, Robert S; Mahmood, Asif; Grundy, John S; Singleton, Walter; Geary, Richard; Wang, Yanfeng

2016-03-01

The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

Dynamic Collimator Angle Adjustments During Volumetric Modulated Arc Therapy to Account for Prostate Rotations

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

Boer, Johan de; Wolf, Anne Lisa; Szeto, Yenny Z.

2015-04-01

Purpose: Rotations of the prostate gland induce considerable geometric uncertainties in prostate cancer radiation therapy. Collimator and gantry angle adjustments can correct these rotations in intensity modulated radiation therapy. Modern volumetric modulated arc therapy (VMAT) treatments, however, include a wide range of beam orientations that differ in modulation, and corrections require dynamic collimator rotations. The aim of this study was to implement a rotation correction strategy for VMAT dose delivery and validate it for left-right prostate rotations. Methods and Materials: Clinical VMAT treatment plans of 5 prostate cancer patients were used. Simulated left-right prostate rotations between +15° and −15° weremore » corrected by collimator rotations. We compared corrected and uncorrected plans by dose volume histograms, minimum dose (D{sub min}) to the prostate, bladder surface receiving ≥78 Gy (S78) and rectum equivalent uniform dose (EUD; n=0.13). Each corrected plan was delivered to a phantom, and its deliverability was evaluated by γ-evaluation between planned and delivered dose, which was reconstructed from portal images acquired during delivery. Results: On average, clinical target volume minimum dose (D{sub min}) decreased up to 10% without corrections. Negative left-right rotations were corrected almost perfectly, whereas D{sub min} remained within 4% for positive rotations. Bladder S78 and rectum EUD of the corrected plans matched those of the original plans. The average pass rate for the corrected plans delivered to the phantom was 98.9% at 3% per 3 mm gamma criteria. The measured dose in the planning target volume approximated the original dose, rotated around the simulated left-right angle, well. Conclusions: It is feasible to dynamically adjust the collimator angle during VMAT treatment delivery to correct for prostate rotations. This technique can safely correct for left-right prostate rotations up to 15°.« less

Estimating thyroid dose in pediatric CT exams from surface dose measurement

NASA Astrophysics Data System (ADS)

Al-Senan, Rani; Mueller, Deborah L.; Hatab, Mustapha R.

2012-07-01

The purpose of this study was to investigate the possibility of estimating pediatric thyroid doses from CT using surface neck doses. Optically stimulated luminescence dosimeters were used to measure the neck surface dose of 25 children ranging in ages between one and three years old. The neck circumference for each child was measured. The relationship between obtained surface doses and thyroid dose was studied using acrylic phantoms of various sizes and with holes of different depths. The ratios of hole-to-surface doses were used to convert patients' surface dose to thyroid dose. ImPACT software was utilized to calculate thyroid dose after applying the appropriate age correction factors. A paired t-test was performed to compare thyroid doses from our approach and ImPACT. The ratio of thyroid to surface dose was found to be 1.1. Thyroid doses ranged from 20 to 80 mGy. Comparison showed no statistical significance (p = 0.18). In addition, the average of surface dose variation along the z-axis in helical scans was studied and found to range between 5% (in 10 cm diameter phantom/24 mm collimation/pitch 1.0) and 8% (in 16 cm diameter phantom/12 mm collimation/pitch 0.7). We conclude that surface dose is an acceptable predictor for pediatric thyroid dose from CT. The uncertainty due to surface dose variability may be reduced if narrower collimation is used with a pitch factor close to 1.0. Also, the results did not show any effect of thyroid depth on the measured dose.

Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

NASA Astrophysics Data System (ADS)

Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

2015-02-01

In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5-20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10-2, 1.48×10-2, 4.14×10-2, and 6.03×10-2, 9.44×10-2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose.

Organ dose measurements from multiple-detector computed tomography using a commercial dosimetry system and tomographic, physical phantoms

NASA Astrophysics Data System (ADS)

Lavoie, Lindsey K.

The technology of computed tomography (CT) imaging has soared over the last decade with the use of multi-detector CT (MDCT) scanners that are capable of performing studies in a matter of seconds. While the diagnostic information obtained from MDCT imaging is extremely valuable, it is important to ensure that the radiation doses resulting from these studies are at acceptably safe levels. This research project focused on the measurement of organ doses resulting from modern MDCT scanners. A commercially-available dosimetry system was used to measure organ doses. Small dosimeters made of optically-stimulated luminescent (OSL) material were analyzed with a portable OSL reader. Detailed verification of this system was performed. Characteristics studied include energy, scatter, and angular responses; dose linearity, ability to erase the exposed dose and ability to reuse dosimeters multiple times. The results of this verification process were positive. While small correction factors needed to be applied to the dose reported by the OSL reader, these factors were small and expected. Physical, tomographic pediatric and adult phantoms were used to measure organ doses. These phantoms were developed from CT images and are composed of tissue-equivalent materials. Because the adult phantom is comprised of numerous segments, dosimeters were placed in the phantom at several organ locations, and doses to select organs were measured using three clinical protocols: pediatric craniosynostosis, adult brain perfusion and adult cardiac CT angiography (CTA). A wide-beam, 320-slice, volumetric CT scanner and a 64-slice, MDCT scanner were used for organ dose measurements. Doses ranged from 1 to 26 mGy for the pediatric protocol, 1 to 1241 mGy for the brain perfusion protocol, and 2-100 mGy for the cardiac protocol. In most cases, the doses measured on the 64-slice scanner were higher than those on the 320-slice scanner. A methodology to measure organ doses with OSL dosimeters received from CT imaging has been presented. These measurements are especially important in keeping with the ALARA (as low as reasonably achievable) principle. While diagnostic information from CT imaging is valuable and necessary, the dose to patients is always a consideration. This methodology aids in this important task. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)

Dose coefficients in pediatric and adult abdominopelvic CT based on 100 patient models.

PubMed

Tian, Xiaoyu; Li, Xiang; Segars, W Paul; Frush, Donald P; Paulson, Erik K; Samei, Ehsan

2013-12-21

Recent studies have shown the feasibility of estimating patient dose from a CT exam using CTDI(vol)-normalized-organ dose (denoted as h), DLP-normalized-effective dose (denoted as k), and DLP-normalized-risk index (denoted as q). However, previous studies were limited to a small number of phantom models. The purpose of this work was to provide dose coefficients (h, k, and q) across a large number of computational models covering a broad range of patient anatomy, age, size percentile, and gender. The study consisted of 100 patient computer models (age range, 0 to 78 y.o.; weight range, 2-180 kg) including 42 pediatric models (age range, 0 to 16 y.o.; weight range, 2-80 kg) and 58 adult models (age range, 18 to 78 y.o.; weight range, 57-180 kg). Multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare) were included. A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which h, k, and q were derived. The relationships between h, k, and q and patient characteristics (size, age, and gender) were ascertained. The differences in conversion coefficients across the scanners were further characterized. CTDI(vol)-normalized-organ dose (h) showed an exponential decrease with increasing patient size. For organs within the image coverage, the average differences of h across scanners were less than 15%. That value increased to 29% for organs on the periphery or outside the image coverage, and to 8% for distributed organs, respectively. The DLP-normalized-effective dose (k) decreased exponentially with increasing patient size. For a given gender, the DLP-normalized-risk index (q) showed an exponential decrease with both increasing patient size and patient age. The average differences in k and q across scanners were 8% and 10%, respectively. This study demonstrated that the knowledge of patient information and CTDIvol/DLP values may be used to estimate organ dose, effective dose, and risk index in abdominopelvic CT based on the coefficients derived from a large population of pediatric and adult patients.

Feasibility of RACT for 3D dose measurement and range verification in a water phantom.

PubMed

Alsanea, Fahed; Moskvin, Vadim; Stantz, Keith M

2015-02-01

The objective of this study is to establish the feasibility of using radiation-induced acoustics to measure the range and Bragg peak dose from a pulsed proton beam. Simulation studies implementing a prototype scanner design based on computed tomographic methods were performed to investigate the sensitivity to proton range and integral dose. Derived from thermodynamic wave equation, the pressure signals generated from the dose deposited from a pulsed proton beam with a 1 cm lateral beam width and a range of 16, 20, and 27 cm in water using Monte Carlo methods were simulated. The resulting dosimetric images were reconstructed implementing a 3D filtered backprojection algorithm and the pressure signals acquired from a 71-transducer array with a cylindrical geometry (30 × 40 cm) rotated over 2π about its central axis. Dependencies on the detector bandwidth and proton beam pulse width were performed, after which, different noise levels were added to the detector signals (using 1 μs pulse width and a 0.5 MHz cutoff frequency/hydrophone) to investigate the statistical and systematic errors in the proton range (at 20 cm) and Bragg peak dose (of 1 cGy). The reconstructed radioacoustic computed tomographic image intensity was shown to be linearly correlated to the dose within the Bragg peak. And, based on noise dependent studies, a detector sensitivity of 38 mPa was necessary to determine the proton range to within 1.0 mm (full-width at half-maximum) (systematic error < 150 μm) for a 1 cGy Bragg peak dose, where the integral dose within the Bragg peak was measured to within 2%. For existing hydrophone detector sensitivities, a Bragg peak dose of 1.6 cGy is possible. This study demonstrates that computed tomographic scanner based on ionizing radiation-induced acoustics can be used to verify dose distribution and proton range with centi-Gray sensitivity. Realizing this technology into the clinic has the potential to significantly impact beam commissioning, treatment verification during particle beam therapy and image guided techniques.

Dose coefficients in pediatric and adult abdominopelvic CT based on 100 patient models

NASA Astrophysics Data System (ADS)

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

2013-12-01

Recent studies have shown the feasibility of estimating patient dose from a CT exam using CTDIvol-normalized-organ dose (denoted as h), DLP-normalized-effective dose (denoted as k), and DLP-normalized-risk index (denoted as q). However, previous studies were limited to a small number of phantom models. The purpose of this work was to provide dose coefficients (h, k, and q) across a large number of computational models covering a broad range of patient anatomy, age, size percentile, and gender. The study consisted of 100 patient computer models (age range, 0 to 78 y.o.; weight range, 2-180 kg) including 42 pediatric models (age range, 0 to 16 y.o.; weight range, 2-80 kg) and 58 adult models (age range, 18 to 78 y.o.; weight range, 57-180 kg). Multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare) were included. A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which h, k, and q were derived. The relationships between h, k, and q and patient characteristics (size, age, and gender) were ascertained. The differences in conversion coefficients across the scanners were further characterized. CTDIvol-normalized-organ dose (h) showed an exponential decrease with increasing patient size. For organs within the image coverage, the average differences of h across scanners were less than 15%. That value increased to 29% for organs on the periphery or outside the image coverage, and to 8% for distributed organs, respectively. The DLP-normalized-effective dose (k) decreased exponentially with increasing patient size. For a given gender, the DLP-normalized-risk index (q) showed an exponential decrease with both increasing patient size and patient age. The average differences in k and q across scanners were 8% and 10%, respectively. This study demonstrated that the knowledge of patient information and CTDIvol/DLP values may be used to estimate organ dose, effective dose, and risk index in abdominopelvic CT based on the coefficients derived from a large population of pediatric and adult patients.

DSC studies on gamma irradiated poly(vinylidene fluoride) applied to high gamma dose dosimetry

NASA Astrophysics Data System (ADS)

Batista, Adriana S. M.; Faria, Luiz O.

2017-11-01

Poly(vinylidene fluoride) homopolymer (PVDF) was investigated for use on high gamma dose dosimetry. Samples were irradiated with gamma doses ranging from 100 kGy to 3000 kGy. Differential scanning calorimetry (DSC) was used to construct an unambiguous relationship between the melting transition latent heat (LM) and the absorbed dose (D). DSC thermograms were taken immediately, 1, 2 and 8 months after the irradiation process revealing that the LMx D relationship presented no change for doses ranging from 100 to 2750 kGy. FTIR and UV-Vis spectroscopy data revealed the radio-induction of C˭O and C˭C bonds. These radio-induced bonds were responsible by the chain stiffening and chain oxidation, respectively. SEM microscopy demonstrates that the spherulitic large crystalline structures present in pristine PVDF are destroyed with doses as low as 100 kGy. The DRX analysis revealed that the main effect of high gamma doses in the crystalline structure of PVDF is to provoke a change from the pristine PVDF α-phase to the γ-phase. Both the ability to detect gamma doses in a large dose range and the low fading features make PVDF homopolymers good candidates to be investigated as high gamma dose dosimeters.

Entrance radiation doses during paediatric cardiac catheterisations performed for diagnosis or the treatment of congenital heart disease.

PubMed

Papadopoulou, D; Yakoumakis, Em; Sandilos, P; Thanopoulos, V; Makri, Tr; Gialousis, G; Houndas, D; Yakoumakis, N; Georgiou, Ev

2005-01-01

The purpose of this study was to estimate the radiation exposure of children, during cardiac catheterisations for the diagnosis or treatment of congenital heart disease. Radiation doses were estimated for 45 children aged from 1 d to 13 y old. Thermoluminescent dosemeters (TLDs) were used to estimate the posterior entrance dose (DP), the lateral entrance dose (DLAT), the thyroid dose and the gonads dose. A dose-area product (DAP) meter was also attached externally to the tube of the angiographic system and gave a direct value in mGy cm2 for each procedure. Posterior and lateral entrance dose values during cardiac catheterisations ranged from 1 to 197 mGy and from 1.1 to 250.3 mGy, respectively. Radiation exposure to the thyroid and the gonads ranged from 0.3 to 8.4 mGy to 0.1 and 0.7 mGy, respectively. Finally, the DAP meter values ranged between 360 and 33,200 mGy cm2. Radiation doses measured in this study are comparable with those reported to previous studies. Moreover, strong correlation was found between the DAP values and the entrance radiation dose measured with TLDs.

Dosimetric characterization and organ dose assessment in digital breast tomosynthesis: Measurements and Monte Carlo simulations using voxel phantoms

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

Baptista, Mariana, E-mail: marianabaptista@ctn.ist.utl.pt; Di Maria, Salvatore; Barros, Sílvia

2015-07-15

Purpose: Due to its capability to more accurately detect deep lesions inside the breast by removing the effect of overlying anatomy, digital breast tomosynthesis (DBT) has the potential to replace the standard mammography technique in clinical screening exams. However, the European Guidelines for DBT dosimetry are still a work in progress and there are little data available on organ doses other than to the breast. It is, therefore, of great importance to assess the dosimetric performance of DBT with respect to the one obtained with standard digital mammography (DM) systems. The aim of this work is twofold: (i) to studymore » the dosimetric properties of a combined DBT/DM system (MAMMOMAT Inspiration Siemens{sup ®}) for a tungsten/rhodium (W/Rh) anode/filter combination and (ii) to evaluate organs doses during a DBT examination. Methods: For the first task, measurements were performed in manual and automatic exposure control (AEC) modes, using two homogeneous breast phantoms: a PMMA slab phantom and a 4 cm thick breast-shaped rigid phantom, with 50% of glandular tissue in its composition. Monte Carlo (MC) simulations were performed using Monte Carlo N-Particle eXtended v.2.7.0. A MC model was implemented to mimic DM and DBT acquisitions for a wide range of x-ray spectra (24 –34 kV). This was used to calculate mean glandular dose (MGD) and to compute series of backscatter factors (BSFs) that could be inserted into the DBT dosimetric formalism proposed by Dance et al. Regarding the second aim of the study, the implemented MC model of the clinical equipment, together with a female voxel phantom (“Laura”), was used to calculate organ doses considering a typical DBT acquisition. Results were compared with a standard two-view mammography craniocaudal (CC) acquisition. Results: Considering the AEC mode, the acquisition of a single CC view results in a MGD ranging from 0.53 ± 0.07 mGy to 2.41 ± 0.31 mGy in DM mode and from 0.77 ± 0.11 mGy to 2.28 ± 0.32 mGy in DBT mode. Regarding the BSF, the results achieved may lead to a MGD correction of about 6%, contributing to the improvement of the current guidelines used in these applications. Finally, considering the MC results obtained for the organ dose study, the radiation doses found for the tissues of the body other than the breast were in the range of tens of μSv, and are in part comparable to the ones obtained in standard DM. Nevertheless, in a single DBT examination, some organs (such as lung and thyroid) receive higher doses (of about 9% and 21%, respectively) with respect to the CC DM acquisition. Conclusions: Taking into account an average breast with a thickness of 4.5 cm, the MGDs for DM and DBT acquisitions were below the achievable value (2.0 mGy) defined by the European protocol. Additionally, in the case of a fusion imaging study (DM + DBT), the MGD for a 4.5 cm thick breast is of the order of 1.88 ± 0.36 mGy. Finally, organ dose evaluations underline the need to improve awareness concerning dose estimation of DBT exams for some organs, especially when radiation risk is assessed by using the effective dose.« less

PROBABILISTIC SAFETY ASSESSMENT OF OPERATIONAL ACCIDENTS AT THE WASTE ISOLATION PILOT PLANT

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

Rucker, D.F.

2000-09-01

This report presents a probabilistic safety assessment of radioactive doses as consequences from accident scenarios to complement the deterministic assessment presented in the Waste Isolation Pilot Plant (WIPP) Safety Analysis Report (SAR). The International Council of Radiation Protection (ICRP) recommends both assessments be conducted to ensure that ''an adequate level of safety has been achieved and that no major contributors to risk are overlooked'' (ICRP 1993). To that end, the probabilistic assessment for the WIPP accident scenarios addresses the wide range of assumptions, e.g. the range of values representing the radioactive source of an accident, that could possibly have beenmore » overlooked by the SAR. Routine releases of radionuclides from the WIPP repository to the environment during the waste emplacement operations are expected to be essentially zero. In contrast, potential accidental releases from postulated accident scenarios during waste handling and emplacement could be substantial, which necessitates the need for radiological air monitoring and confinement barriers (DOE 1999). The WIPP Safety Analysis Report (SAR) calculated doses from accidental releases to the on-site (at 100 m from the source) and off-site (at the Exclusive Use Boundary and Site Boundary) public by a deterministic approach. This approach, as demonstrated in the SAR, uses single-point values of key parameters to assess the 50-year, whole-body committed effective dose equivalent (CEDE). The basic assumptions used in the SAR to formulate the CEDE are retained for this report's probabilistic assessment. However, for the probabilistic assessment, single-point parameter values were replaced with probability density functions (PDF) and were sampled over an expected range. Monte Carlo simulations were run, in which 10,000 iterations were performed by randomly selecting one value for each parameter and calculating the dose. Statistical information was then derived from the 10,000 iteration batch, which included 5%, 50%, and 95% dose likelihood, and the sensitivity of each assumption to the calculated doses. As one would intuitively expect, the doses from the probabilistic assessment for most scenarios were found to be much less than the deterministic assessment. The lower dose of the probabilistic assessment can be attributed to a ''smearing'' of values from the high and low end of the PDF spectrum of the various input parameters. The analysis also found a potential weakness in the deterministic analysis used in the SAR, a detail on drum loading was not taken into consideration. Waste emplacement operations thus far have handled drums from each shipment as a single unit, i.e. drums from each shipment are kept together. Shipments typically come from a single waste stream, and therefore the curie loading of each drum can be considered nearly identical to that of its neighbor. Calculations show that if there are large numbers of drums used in the accident scenario assessment, e.g. 28 drums in the waste hoist failure scenario (CH5), then the probabilistic dose assessment calculations will diverge from the deterministically determined doses. As it is currently calculated, the deterministic dose assessment assumes one drum loaded to the maximum allowable (80 PE-Ci), and the remaining are 10% of the maximum. The effective average of drum curie content is therefore less in the deterministic assessment than the probabilistic assessment for a large number of drums. EEG recommends that the WIPP SAR calculations be revisited and updated to include a probabilistic safety assessment.« less

Measured and Calculated Neutron Spectra and Dose Equivalent Rates at High Altitudes; Relevance to SST Operations and Space Research

NASA Technical Reports Server (NTRS)

Foelsche, T.; Mendell, R. B.; Wilson, J. W.; Adams, R. R.

1974-01-01

Results of the NASA Langley-New York University high-altitude radiation study are presented. Measurements of the absorbed dose rate and of secondary fast neutrons (1 to 10 MeV energy) during the years 1965 to 1971 are used to determine the maximum radiation exposure from galactic and solar cosmic rays of supersonic transport (SST) and subsonic jet occupants. The maximum dose equivalent rates that the SST crews might receive turn out to be 13 to 20 percent of the maximum permissible dose rate (MPD) for radiation workers (5 rem/yr). The exposure of passengers encountering an intense giant-energy solar particle event could exceed the MPD for the general population (0.5 rem/yr), but would be within these permissible limits if in such rare cases the transport descends to subsonic altitude; it is in general less than 12 percent of the MPD. By Monte Carlo calculations of the transport and buildup of nucleons in air for incident proton energies E of 0.02 to 10 GeV, the measured neutron spectra were extrapolated to lower and higher energies and for galactic cosmic rays were found to continue with a relatively high intensity to energies greater than 400 MeV, in a wide altitude range. This condition, together with the measured intensity profiles of fast neutrons, revealed that the biologically important fast and energetic neutrons penetrate deep into the atmosphere and contribute approximately 50 percent of the dose equivalant rates at SST and present subsonic jet altitudes.

Animal model of methylphenidate's long-term memory-enhancing effects.

PubMed

Carmack, Stephanie A; Howell, Kristin K; Rasaei, Kleou; Reas, Emilie T; Anagnostaras, Stephan G

2014-01-16

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01-10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1-10 mg/kg, i.p.), bupropion (0.5-20 mg/kg, i.p.), and citalopram (0.01-10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development.

Animal model of methylphenidate's long-term memory-enhancing effects

PubMed Central

Carmack, Stephanie A.; Howell, Kristin K.; Rasaei, Kleou; Reas, Emilie T.; Anagnostaras, Stephan G.

2014-01-01

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01–10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1–10 mg/kg, i.p.), bupropion (0.5–20 mg/kg, i.p.), and citalopram (0.01–10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development. PMID:24434869

A Characterization of the Radiation from a Rod-Pinch Diode

NASA Astrophysics Data System (ADS)

Swanekamp, Stephen B.; Allen, Raymond J.; Hinshelwood, David D.; Mosher, David; Schumer, Joseph W.

2002-12-01

Coupled PIC-Monte-Carlo simulations of the electron-flow and radiation production in a rod-pinch diode show that multiple scatterings in the rod produce incident electron energies that ranging from zero to slightly higher than the applied voltage. It is speculated that those electrons that gain energy do so by remaining in phase with a rapidly varying electric field near the tip of the rod. The simulations also show that multiple passes in the rod produce a wide spread in incident electron angles. For diode voltages of V=2 MV, the angular distribution of electrons incident on the rod is broad and peaked near 90° to the axis of the rod with a larger fraction of electrons striking the rod at angles less than 90°. The electron angular distribution for V=4 MV is narrower and peaked at 105° with a larger fraction of electrons incident on the rod with angles greater than 90°. The photon distributions are peaked along the direction of the high-energy electrons. For V=2 MV the dose filtered through 21/4-cm thick Plexiglas is peaked at 90° and is 1.8 times higher than the forward-directed [0°] dose. For V=4 MV the dose filtered through 21/4-cm thick Plexiglas is peaked at 120° and is 2.3 times higher than the forward-directed dose. Similar angular variation of the dose has been observed on the 4-MV Asterix accelerator [2] and on 1-2 MV accelerators at the Atomic Weapons Establishment [8].

Comparison of patient specific dose metrics between chest radiography, tomosynthesis, and CT for adult patients of wide ranging body habitus

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

Zhang, Yakun; Li, Xiang; Segars, W. Paul

2014-02-15

Purpose: Given the radiation concerns inherent to the x-ray modalities, accurately estimating the radiation doses that patients receive during different imaging modalities is crucial. This study estimated organ doses, effective doses, and risk indices for the three clinical chest x-ray imaging techniques (chest radiography, tomosynthesis, and CT) using 59 anatomically variable voxelized phantoms and Monte Carlo simulation methods. Methods: A total of 59 computational anthropomorphic male and female extended cardiac-torso (XCAT) adult phantoms were used in this study. Organ doses and effective doses were estimated for a clinical radiography system with the capability of conducting chest radiography and tomosynthesis (Definiummore » 8000, VolumeRAD, GE Healthcare) and a clinical CT system (LightSpeed VCT, GE Healthcare). A Monte Carlo dose simulation program (PENELOPE, version 2006, Universitat de Barcelona, Spain) was used to mimic these two clinical systems. The Duke University (Durham, NC) technique charts were used to determine the clinical techniques for the radiographic modalities. An exponential relationship between CTDI{sub vol} and patient diameter was used to determine the absolute dose values for CT. The simulations of the two clinical systems compute organ and tissue doses, which were then used to calculate effective dose and risk index. The calculation of the two dose metrics used the tissue weighting factors from ICRP Publication 103 and BEIR VII report. Results: The average effective dose of the chest posteroanterior examination was found to be 0.04 mSv, which was 1.3% that of the chest CT examination. The average effective dose of the chest tomosynthesis examination was found to be about ten times that of the chest posteroanterior examination and about 12% that of the chest CT examination. With increasing patient average chest diameter, both the effective dose and risk index for CT increased considerably in an exponential fashion, while these two dose metrics only increased slightly for radiographic modalities and for chest tomosynthesis. Effective and organ doses normalized to mAs all illustrated an exponential decrease with increasing patient size. As a surface organ, breast doses had less correlation with body size than that of lungs or liver. Conclusions: Patient body size has a much greater impact on radiation dose of chest CT examinations than chest radiography and tomosynthesis. The size of a patient should be considered when choosing the best thoracic imaging modality.« less

Comparison of Acuros (AXB) and Anisotropic Analytical Algorithm (AAA) for dose calculation in treatment of oesophageal cancer: effects on modelling tumour control probability.

PubMed

Padmanaban, Sriram; Warren, Samantha; Walsh, Anthony; Partridge, Mike; Hawkins, Maria A

2014-12-23

To investigate systematic changes in dose arising when treatment plans optimised using the Anisotropic Analytical Algorithm (AAA) are recalculated using Acuros XB (AXB) in patients treated with definitive chemoradiotherapy (dCRT) for locally advanced oesophageal cancers. We have compared treatment plans created using AAA with those recalculated using AXB. Although the Anisotropic Analytical Algorithm (AAA) is currently more widely used in clinical routine, Acuros XB (AXB) has been shown to more accurately calculate the dose distribution, particularly in heterogeneous regions. Studies to predict clinical outcome should be based on modelling the dose delivered to the patient as accurately as possible. CT datasets from ten patients were selected for this retrospective study. VMAT (Volumetric modulated arc therapy) plans with 2 arcs, collimator rotation ± 5-10° and dose prescription 50 Gy / 25 fractions were created using Varian Eclipse (v10.0). The initial dose calculation was performed with AAA, and AXB plans were created by re-calculating the dose distribution using the same number of monitor units (MU) and multileaf collimator (MLC) files as the original plan. The difference in calculated dose to organs at risk (OAR) was compared using dose-volume histogram (DVH) statistics and p values were calculated using the Wilcoxon signed rank test. The potential clinical effect of dosimetric differences in the gross tumour volume (GTV) was evaluated using three different TCP models from the literature. PTV Median dose was apparently 0.9 Gy lower (range: 0.5 Gy - 1.3 Gy; p < 0.05) for VMAT AAA plans re-calculated with AXB and GTV mean dose was reduced by on average 1.0 Gy (0.3 Gy -1.5 Gy; p < 0.05). An apparent difference in TCP of between 1.2% and 3.1% was found depending on the choice of TCP model. OAR mean dose was lower in the AXB recalculated plan than the AAA plan (on average, dose reduction: lung 1.7%, heart 2.4%). Similar trends were seen for CRT plans. Differences in dose distribution are observed with VMAT and CRT plans recalculated with AXB particularly within soft tissue at the tumour/lung interface, where AXB has been shown to more accurately represent the true dose distribution. AAA apparently overestimates dose, particularly the PTV median dose and GTV mean dose, which could result in a difference in TCP model parameters that reaches clinical significance.

Sizes of particles formed during municipal wastewater treatment.

PubMed

Lech, Smoczynski; Marta, Kosobucka; Michal, Smoczynski; Harsha, Ratnaweera; Krystyna, Pieczulis-Smoczynska

2017-02-01

Volumetric diameters Dv and specific surface area SpS of sludge particles formed during chemical coagulation and electrocoagulation of sewage were determined. The obtained aggregate-flocs differed substantially in both Dv and SpS values. The differences in Dv and SpS values of the analyzed particles were interpreted based on theoretical models for expanding aggregates. The most uniform particles were formed under exposure to: (a) optimal and maximal doses of PIX, (b) optimal doses of PAX, (c) maximal doses of the Al electro-coagulant. The lowest PIX dose produced the least uniform particles. Sludge aggregates-particles produced under exposure to minimal doses of PIX and the Al electro-coagulant were characterized by the lowest SpS values. Sludge particles coagulated by PAX and the particles formed at higher doses of PIX and the Al electro-coagulant had higher SpS values. The particles formed at all doses of the applied coagulants and electro-coagulants were generally classified into two size ranges: the main range and the secondary range. Most particles belonged to the main size range. An increase in the percentage of colloidal hydroxide particles in sewage sludge increased SpS.

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

PubMed

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

SU-F-T-170: Patient Surface Dose Measurements Using Optically Stimulated Luminescence Dosimeters in Scanning Proton Beam Therapy for Breast Cancer

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

Yu, J; Strauss, D; Langner, U

Purpose: To establish patient surface dose dosimetry for scanning proton beam therapy (SPBT) for breast cancer using optically stimulated luminescence dosimeters (OSLD). Methods: OSLDs were calibrated with SPB under the similar conditions as the treatments for breast cancer. A range shifter (RS) of 5 cm water equivalent thickness (WET) was used. The air gap from the surface of the range shifter to the surface of the phantom was 15 cm. A uniform planar dose generated by nominal energy of 118 MeV was delivered. The range of 118 MeV proton beam after the 5cm RS is approximately 5 cm in water,more » which is the common range for breast treatments. The OSLDs were placed on the surface of high density polyethylene slabs, and a bolus of 1.06 cm WET was used for buildup. A variety of dose levels in the range of 0.5 to 8 Gy were delivered. Under the same condition, an ADCL calibrated parallel plate (PP) chamber was used to measure the reference dose. The correlation between the output signals of OSLDs and the reference doses was established. The calibration of OSLD was verified against the PP chamber measurements for two SPBT breast plans calculated for two patients. Results: the least squares fitting for the OSLD calibration curve was a polynomial function to the order of 2 in the range of 0.5 to 8 Gy (RBE). The differences between the dose measured with OSLDs and PP chamber were within 3% for the two breast proton plans. Conclusion: the calibrated OSLDs under the similar conditions as the treatments can be used for patient surface dose measurements.« less

Verification of Pharmacogenetics-Based Warfarin Dosing Algorithms in Han-Chinese Patients Undertaking Mechanic Heart Valve Replacement

PubMed Central

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

Objective To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. Methods We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. Results A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88–4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. Conclusions All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement. PMID:24728385

Verification of pharmacogenetics-based warfarin dosing algorithms in Han-Chinese patients undertaking mechanic heart valve replacement.

PubMed

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88-4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement.

Subclinical ductal carcinoma in situ of the breast: treatment with conservative surgery and radiotherapy.

PubMed

Amichetti, M; Caffo, O; Richetti, A; Zini, G; Rigon, A; Antonello, M; Roncadin, M; Coghetto, F; Valdagni, R; Fasan, S; Maluta, S; Di Marco, A; Neri, S; Vidali, C; Panizzoni, G; Aristei, C

1999-01-01

In spite of the fact that ductal carcinoma in situ (DCIS) of the breast is a frequently encountered clinical problem, there is no consensus about the optimal treatment of clinically occult (i.e., mammographic presentation only) DCIS. Interest in breast conservation therapy has recently increased. Few data are available in Italy on the conservative treatment with surgery and adjuvant postoperative radiotherapy. A retrospective multi-institutional study was performed in 15 Radiation Oncology Departments in northern Italy involving 112 women with subclinical DCIS of the breast treated between 1982 and 1993. Age of the patients ranged between 32 and 72 years (median, 50 years). All of them underwent conservative surgery: quadrantectomy in 89, tumorectomy in 11, and wide excision in 12 cases. The most common histologic subtype was comedocarcinoma (37%). The median pathologic size was 10 mm (range 1 to 55 mm). Axillary dissection was performed in 83 cases: all the patients were node negative. All the patients received adjunctive radiation therapy with 60Co units (77%) or 6 MV linear accelerators (23%) for a median total dose to the entire breast of 50 Gy (mean, 49.48 Gy; range, 45-60 Gy). Seventy-six cases (68%) received a boost to the tumor bed at a dose of 8-20 Gy (median 10 Gy) for a minimum tumor dose of 58 Gy. At a median follow-up of 66 months, 8 local recurrences were observed, 4 intraductal and 4 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease at this writing. The 10-year actuarial overall, cause-specific, and recurrence-free survival was of 98.8%, 100%, and 91%, respectively. The retrospective multicentric study, with a local control rate of more than 90% at 10 years with 100% cause-specific survival, showed that conservative surgery and adjuvant radiation therapy is a safe and efficacious treatment for patients with occult, non-palpable DCIS.

Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.

PubMed

Krösser, S; Tillner, J; Fluck, M; Ungethüm, W; Wolna, P; Kovar, A

2007-05-01

Sarizotan is a 5-HTIA receptor agonist with high affinity for D3 and D4 receptors. Here we report the pharmacokinetic and tolerability results from four Phase 1 studies. Two single-dose (5 -25 mg, n = 25, 0.5 - 5 mg, n = 16) and two multiple-dose (10 and 20 mg b.i.d., n = 30, 5 mg b.i.d., n = 12) studies with orally administered sarizotan HCl were carried out in healthy subjects. Plasma sarizotan HCl concentrations were measured using a validated HPLC method and fluorescence or MS/MS detection. Pharmacokinetic parameters were obtained using standard non-compartmental methods. Sarizotan was rapidly absorbed, group-median times to reach maximum concentration (tmax) ranged from 0.5 -2.25 h after single doses and during steady state. Maximum plasma concentration (Cmax) and tmax were slightly dependent on formulation and food intake, whereas area under the curve (AUC) was unaffected by these factors. AUC and Cmax increased dose-proportionally over the tested dose range. Independently of dose and time, sarizotan HCl plasma concentrations declined polyexponentially with a terminal elimination half-life (t1/2) of 5 - 7 h. Accumulation factors corresponded to t1/2 values, and steady state was reached within 24 h. Plasma metabolite concentrations were considerably lower than those of the parent drug. The ratio metabolite AUC : parent drug AUC was time- and dose-independent for all three metabolites suggesting that the metabolism of sarizotan is non-saturable in the tested dose range. The pharmacokinetics of sarizotan were dose-proportional and time-independent for the dose range 0.5 -25 mg). The drug was well-tolerated by healthy subjects up to a single dose of 20 mg.

Radiation dose and magnification in pelvic X-ray: EOS™ imaging system versus plain radiographs.

PubMed

Chiron, P; Demoulin, L; Wytrykowski, K; Cavaignac, E; Reina, N; Murgier, J

2017-12-01

In plain pelvic X-ray, magnification makes measurement unreliable. The EOS™ (EOS Imaging, Paris France) imaging system is reputed to reproduce patient anatomy exactly, with a lower radiation dose. This, however, has not been assessed according to patient weight, although both magnification and irradiation are known to vary with weight. We therefore conducted a prospective comparative study, to compare: (1) image magnification and (2) radiation dose between the EOS imaging system and plain X-ray. The EOS imaging system reproduces patient anatomy exactly, regardless of weight, unlike plain X-ray. A single-center comparative study of plain pelvic X-ray and 2D EOS radiography was performed in 183 patients: 186 arthroplasties; 104 male, 81 female; mean age 61.3±13.7years (range, 24-87years). Magnification and radiation dose (dose-area product [DAP]) were compared between the two systems in 186 hips in patients with a mean body-mass index (BMI) of 27.1±5.3kg/m 2 (range, 17.6-42.3kg/m 2 ), including 7 with morbid obesity. Mean magnification was zero using the EOS system, regardless of patient weight, compared to 1.15±0.05 (range, 1-1.32) on plain X-ray (P<10 -5 ). In patients with BMI<25, mean magnification on plain X-ray was 1.15±0.05 (range, 1-1.25) and, in patients with morbid obesity, 1.22±0.06 (range, 1.18-1.32). The mean radiation dose was 8.19±2.63dGy/cm 2 (range, 1.77-14.24) with the EOS system, versus 19.38±12.37dGy/cm 2 (range, 4.77-81.75) with plain X-ray (P<10 -4 ). For BMI >40, mean radiation dose was 9.36±2.57dGy/cm 2 (range, 7.4-14.2) with the EOS system, versus 44.76±22.21 (range, 25.2-81.7) with plain X-ray. Radiation dose increased by 0.20dGy with each extra BMI point for the EOS system, versus 0.74dGy for plain X-ray. Magnification did not vary with patient weight using the EOS system, unlike plain X-ray, and radiation dose was 2.5-fold lower. 3, prospective case-control study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluation of aqueous and ethanol extract of bioactive medicinal plant, Cassia didymobotrya (Fresenius) Irwin & Barneby against immature stages of filarial vector, Culex quinquefasciatus Say (Diptera: Culicidae).

PubMed

Nagappan, Raja

2012-09-01

To evaluate aqueous and ethanol extract of Cassia didymobotrya leaves against immature stages of Culex quinquefasciatus. The mortality rate of immature mosquitoes was tested in wide and narrow range concentration of the plant extract based on WHO standard protocol. The wide range concentration tested in the present study was 10 000, 1 000, 100, 10 and 1 mg/L and narrow range concentration was 50, 100, 150, 200 and 250 mg/L. 2nd instar larvae exposed to 100 mg/L and above concentration of ethanol extract showed 100% mortality. Remaining stages such as 3rd, 4th and pupa, 100% mortality was observed at 1 000 mg/L and above concentration after 24 h exposure period. In aqueous extract all the stages 100% mortality was recorded at 1 000 mg/L and above concentration. In narrow range concentration 2nd instar larvae 100% mortality was observed at 150 mg/L and above concentration of ethanol extract. The remaining stages 100% mortality was recorded at 250 mg/L. In aqueous extract all the tested immature stages 100% mortality was observed at 250 mg/L concentration after 24 h exposure period. The results clearly indicate that the rate of mortality was based dose of the plant extract and stage of the mosquitoes. From this study it is confirmed and concluded that Cassia didymobotrya is having active principle which is responsible for controlling Culex quinquefasciatus. The isolation of bioactive molecules and development of simple formulation technique is important for large scale implementation.