MPC and ALI: their basis and their comparison

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

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

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

Threshold of toxicological concern values for non-genotoxic effects in industrial chemicals: re-evaluation of the Cramer classification.

PubMed

Kalkhof, H; Herzler, M; Stahlmann, R; Gundert-Remy, U

2012-01-01

The TTC concept employs available data from animal testing to derive a distribution of NOAELs. Taking a probabilistic view, the 5th percentile of the distribution is taken as a threshold value for toxicity. In this paper, we use 824 NOAELs from repeated dose toxicity studies of industrial chemicals to re-evaluate the currently employed TTC values, which have been derived for substances grouped according to the Cramer scheme (Cramer et al. in Food Cosm Toxicol 16:255-276, 1978) by Munro et al. (Food Chem Toxicol 34:829-867, 1996) and refined by Kroes and Kozianowski (Toxicol Lett 127:43-46, 2002), Kroes et al. 2000. In our data set, consisting of 756 NOAELs from 28-day repeated dose testing and 57 NOAELs from 90-days repeated dose testing, the experimental NOAEL had to be extrapolated to chronic TTC using regulatory accepted extrapolation factors. The TTC values derived from our data set were higher than the currently used TTC values confirming the safety of the latter. We analysed the prediction of the Cramer classification by comparing the classification by this tool with the guidance values for classification according to the Globally Harmonised System of classification and labelling of the United Nations (GHS). Nearly 90% of the chemicals were in Cramer class 3 and assumed as highly toxic compared to 22% according to the GHS. The Cramer classification does underestimate the toxicity of chemicals only in 4.6% of the cases. Hence, from a regulatory perspective, the Cramer classification scheme might be applied as it overestimates hazard of a chemical.

Impact of Genomics Platform and Statistical Filtering on Transcriptional Benchmark Doses (BMD) and Multiple Approaches for Selection of Chemical Point of Departure (PoD)

PubMed Central

Webster, A. Francina; Chepelev, Nikolai; Gagné, Rémi; Kuo, Byron; Recio, Leslie; Williams, Andrew; Yauk, Carole L.

2015-01-01

Many regulatory agencies are exploring ways to integrate toxicogenomic data into their chemical risk assessments. The major challenge lies in determining how to distill the complex data produced by high-content, multi-dose gene expression studies into quantitative information. It has been proposed that benchmark dose (BMD) values derived from toxicogenomics data be used as point of departure (PoD) values in chemical risk assessments. However, there is limited information regarding which genomics platforms are most suitable and how to select appropriate PoD values. In this study, we compared BMD values modeled from RNA sequencing-, microarray-, and qPCR-derived gene expression data from a single study, and explored multiple approaches for selecting a single PoD from these data. The strategies evaluated include several that do not require prior mechanistic knowledge of the compound for selection of the PoD, thus providing approaches for assessing data-poor chemicals. We used RNA extracted from the livers of female mice exposed to non-carcinogenic (0, 2 mg/kg/day, mkd) and carcinogenic (4, 8 mkd) doses of furan for 21 days. We show that transcriptional BMD values were consistent across technologies and highly predictive of the two-year cancer bioassay-based PoD. We also demonstrate that filtering data based on statistically significant changes in gene expression prior to BMD modeling creates more conservative BMD values. Taken together, this case study on mice exposed to furan demonstrates that high-content toxicogenomics studies produce robust data for BMD modelling that are minimally affected by inter-technology variability and highly predictive of cancer-based PoD doses. PMID:26313361

The impact of inter-fraction dose variations on biological equivalent dose (BED): the concept of equivalent constant dose.

PubMed

Zavgorodni, S

2004-12-07

Inter-fraction dose fluctuations, which appear as a result of setup errors, organ motion and treatment machine output variations, may influence the radiobiological effect of the treatment even when the total delivered physical dose remains constant. The effect of these inter-fraction dose fluctuations on the biological effective dose (BED) has been investigated. Analytical expressions for the BED accounting for the dose fluctuations have been derived. The concept of biological effective constant dose (BECD) has been introduced. The equivalent constant dose (ECD), representing the constant physical dose that provides the same cell survival fraction as the fluctuating dose, has also been introduced. The dose fluctuations with Gaussian as well as exponential probability density functions were investigated. The values of BECD and ECD calculated analytically were compared with those derived from Monte Carlo modelling. The agreement between Monte Carlo modelled and analytical values was excellent (within 1%) for a range of dose standard deviations (0-100% of the dose) and the number of fractions (2 to 37) used in the comparison. The ECDs have also been calculated for conventional radiotherapy fields. The analytical expression for the BECD shows that BECD increases linearly with the variance of the dose. The effect is relatively small, and in the flat regions of the field it results in less than 1% increase of ECD. In the penumbra region of the 6 MV single radiotherapy beam the ECD exceeded the physical dose by up to 35%, when the standard deviation of combined patient setup/organ motion uncertainty was 5 mm. Equivalently, the ECD field was approximately 2 mm wider than the physical dose field. The difference between ECD and the physical dose is greater for normal tissues than for tumours.

Assessing the reliability of dose coefficients for exposure to radioiodine by members of the public, accounting for dosimetric and risk model uncertainties.

PubMed

Puncher, M; Zhang, W; Harrison, J D; Wakeford, R

2017-06-26

Assessments of risk to a specific population group resulting from internal exposure to a particular radionuclide can be used to assess the reliability of the appropriate International Commission on Radiological Protection (ICRP) dose coefficients used as a radiation protection device for the specified exposure pathway. An estimate of the uncertainty on the associated risk is important for informing judgments on reliability; a derived uncertainty factor, UF, is an estimate of the 95% probable geometric difference between the best risk estimate and the nominal risk and is a useful tool for making this assessment. This paper describes the application of parameter uncertainty analysis to quantify uncertainties resulting from internal exposures to radioiodine by members of the public, specifically 1, 10 and 20-year old females from the population of England and Wales. Best estimates of thyroid cancer incidence risk (lifetime attributable risk) are calculated for ingestion or inhalation of 129 I and 131 I, accounting for uncertainties in biokinetic model and cancer risk model parameter values. These estimates are compared with the equivalent ICRP derived nominal age-, sex- and population-averaged estimates of excess thyroid cancer incidence to obtain UFs. Derived UF values for ingestion or inhalation of 131 I for 1 year, 10-year and 20-year olds are around 28, 12 and 6, respectively, when compared with ICRP Publication 103 nominal values, and 9, 7 and 14, respectively, when compared with ICRP Publication 60 values. Broadly similar results were obtained for 129 I. The uncertainties on risk estimates are largely determined by uncertainties on risk model parameters rather than uncertainties on biokinetic model parameters. An examination of the sensitivity of the results to the risk models and populations used in the calculations show variations in the central estimates of risk of a factor of around 2-3. It is assumed that the direct proportionality of excess thyroid cancer risk and dose observed at low to moderate acute doses and incorporated in the risk models also applies to very small doses received at very low dose rates; the uncertainty in this assumption is considerable, but largely unquantifiable. The UF values illustrate the need for an informed approach to the use of ICRP dose and risk coefficients.

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

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

A Probabilistic Approach to Uncertainty Analysis in NTPR Radiation Dose Assessments

DTIC Science & Technology

2009-11-01

Zeman, members of the Subcommittee on Dose Reconstruction of the Veterans’ Advisory Board on Dose Reconstruction (VBDR) for their critical review of...production and decay of fission products, activation products, and actinides . (It is generally assumed in these calculations that no 30 Time...histories”), and on each history selecting random values from each of the pdf’s, they were able to conduct “numerical experiments” and derive critical

Derivation of a no-significant-risk-level for tetrabromobisphenol A based on a threshold non-mutagenic cancer mode of action.

PubMed

Pecquet, Alison M; Martinez, Jeanelle M; Vincent, Melissa; Erraguntla, Neeraja; Dourson, Michael

2018-06-01

A no-significant-risk-level of 20 mg day -1 was derived for tetrabromobisphenol A (TBBPA). Uterine tumors (adenomas, adenocarcinomas, and malignant mixed Müllerian) observed in female Wistar Han rats from a National Toxicology Program 2-year cancer bioassay were identified as the critical effect. Studies suggest that TBBPA is acting through a non-mutagenic mode of action. Thus, the most appropriate approach to derivation of a cancer risk value based on US Environmental Protection Agency guidelines is a threshold approach, akin to a cancer safe dose (RfD cancer ). Using the National Toxicology Program data, we utilized Benchmark dose software to derive a benchmark dose lower limit (BMDL 10 ) as the point of departure (POD) of 103 mg kg -1  day -1 . The POD was adjusted to a human equivalent dose of 25.6 mg kg -1  day -1 using allometric scaling. We applied a composite adjustment factor of 100 to the POD to derive an RfD cancer of 0.26 mg kg -1  day -1 . Based on a human body weight of 70 kg, the RfD cancer was adjusted to a no-significant-risk-level of 20 mg day -1 . This was compared to other available non-cancer and cancer risk values, and aligns well with our understanding of the underlying biology based on the toxicology data. Overall, the weight of evidence from animal studies indicates that TBBPA has low toxicity and suggests that high doses over long exposure durations are needed to induce uterine tumor formation. Future research needs include a thorough and detailed vetting of the proposed adverse outcome pathway, including further support for key events leading to uterine tumor formation and a quantitative weight of evidence analysis. Copyright © 2018 John Wiley & Sons, Ltd.

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

Demirag, N

Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 andmore » 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics.« less

Influence of different dose calculation algorithms on the estimate of NTCP for lung complications.

PubMed

Hedin, Emma; Bäck, Anna

2013-09-06

Due to limitations and uncertainties in dose calculation algorithms, different algorithms can predict different dose distributions and dose-volume histograms for the same treatment. This can be a problem when estimating the normal tissue complication probability (NTCP) for patient-specific dose distributions. Published NTCP model parameters are often derived for a different dose calculation algorithm than the one used to calculate the actual dose distribution. The use of algorithm-specific NTCP model parameters can prevent errors caused by differences in dose calculation algorithms. The objective of this work was to determine how to change the NTCP model parameters for lung complications derived for a simple correction-based pencil beam dose calculation algorithm, in order to make them valid for three other common dose calculation algorithms. NTCP was calculated with the relative seriality (RS) and Lyman-Kutcher-Burman (LKB) models. The four dose calculation algorithms used were the pencil beam (PB) and collapsed cone (CC) algorithms employed by Oncentra, and the pencil beam convolution (PBC) and anisotropic analytical algorithm (AAA) employed by Eclipse. Original model parameters for lung complications were taken from four published studies on different grades of pneumonitis, and new algorithm-specific NTCP model parameters were determined. The difference between original and new model parameters was presented in relation to the reported model parameter uncertainties. Three different types of treatments were considered in the study: tangential and locoregional breast cancer treatment and lung cancer treatment. Changing the algorithm without the derivation of new model parameters caused changes in the NTCP value of up to 10 percentage points for the cases studied. Furthermore, the error introduced could be of the same magnitude as the confidence intervals of the calculated NTCP values. The new NTCP model parameters were tabulated as the algorithm was varied from PB to PBC, AAA, or CC. Moving from the PB to the PBC algorithm did not require new model parameters; however, moving from PB to AAA or CC did require a change in the NTCP model parameters, with CC requiring the largest change. It was shown that the new model parameters for a given algorithm are different for the different treatment types.

Monte Carlo simulations of the dose from imaging with GE eXplore 120 micro-CT using GATE

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

Bretin, Florian; Bahri, Mohamed Ali; Luxen, André

Purpose: Small animals are increasingly used as translational models in preclinical imaging studies involving microCT, during which the subjects can be exposed to large amounts of radiation. While the radiation levels are generally sublethal, studies have shown that low-level radiation can change physiological parameters in mice. In order to rule out any influence of radiation on the outcome of such experiments, or resulting deterministic effects in the subjects, the levels of radiation involved need to be addressed. The aim of this study was to investigate the radiation dose delivered by the GE eXplore 120 microCT non-invasively using Monte Carlo simulationsmore » in GATE and to compare results to previously obtained experimental values. Methods: Tungsten X-ray spectra were simulated at 70, 80, and 97 kVp using an analytical tool and their half-value layers were simulated for spectra validation against experimentally measured values of the physical X-ray tube. A Monte Carlo model of the microCT system was set up and four protocols that are regularly applied to live animal scanning were implemented. The computed tomography dose index (CTDI) inside a PMMA phantom was derived and multiple field of view acquisitions were simulated using the PMMA phantom, a representative mouse and rat. Results: Simulated half-value layers agreed with experimentally obtained results within a 7% error window. The CTDI ranged from 20 to 56 mGy and closely matched experimental values. Derived organ doses in mice reached 459 mGy in bones and up to 200 mGy in soft tissue organs using the highest energy protocol. Dose levels in rats were lower due to the increased mass of the animal compared to mice. The uncertainty of all dose simulations was below 14%. Conclusions: Monte Carlo simulations proved a valuable tool to investigate the 3D dose distribution in animals from microCT. Small animals, especially mice (due to their small volume), receive large amounts of radiation from the GE eXplore 120 microCT, which might alter physiological parameters in a longitudinal study setup.« less

Poster — Thur Eve — 15: Improvements in the stability of the tomotherapy imaging beam

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

Belec, J

2014-08-15

Use of helical TomoTherapy based MVCT imaging for adaptive planning requires the image values (HU) to remain stable over the course of treatment. In the past, the image value stability was suboptimal, which required frequent change to the image value to density calibration curve to avoid dose errors on the order of 2–4%. The stability of the image values at our center was recently improved by stabilizing the dose rate of the machine (dose control servo) and performing daily MVCT calibration corrections. In this work, we quantify the stability of the image values over treatment time by comparing patient treatmentmore » image density derived using MVCT and KVCT. The analysis includes 1) MVCT - KVCT density difference histogram, 2) MVCT vs KVCT density spectrum, 3) multiple average profile density comparison and 4) density difference in homogeneous locations. Over two months, the imaging beam stability was compromised several times due to a combination of target wobbling, spectral calibration, target change and magnetron issues. The stability of the image values were analyzed over the same period. Results show that the impact on the patient dose calculation is 0.7% +− 0.6%.« less

Mathematical optimization of high dose-rate brachytherapy—derivation of a linear penalty model from a dose-volume model

NASA Astrophysics Data System (ADS)

Morén, B.; Larsson, T.; Carlsson Tedgren, Å.

2018-03-01

High dose-rate brachytherapy is a method for cancer treatment where the radiation source is placed within the body, inside or close to a tumour. For dose planning, mathematical optimization techniques are being used in practice and the most common approach is to use a linear model which penalizes deviations from specified dose limits for the tumour and for nearby organs. This linear penalty model is easy to solve, but its weakness lies in the poor correlation of its objective value and the dose-volume objectives that are used clinically to evaluate dose distributions. Furthermore, the model contains parameters that have no clear clinical interpretation. Another approach for dose planning is to solve mixed-integer optimization models with explicit dose-volume constraints which include parameters that directly correspond to dose-volume objectives, and which are therefore tangible. The two mentioned models take the overall goals for dose planning into account in fundamentally different ways. We show that there is, however, a mathematical relationship between them by deriving a linear penalty model from a dose-volume model. This relationship has not been established before and improves the understanding of the linear penalty model. In particular, the parameters of the linear penalty model can be interpreted as dual variables in the dose-volume model.

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

PubMed

Chiu, Weihsueh A; Slob, Wout

2015-12-01

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

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 06: Investigation of an absorbed dose to water formalism for a miniature low-energy x-ray source

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

Watson, Peter; Seuntjens, Jan

Purpose: We present a formalism for calculating the absorbed dose to water from a miniature x-ray source (The INTRABEAM system, Carl Zeiss), using a parallel-plate ionization chamber calibrated in terms of air-kerma. Monte Carlo calculations were performed to derive a chamber conversion factor (C{sub Q}) from reference air-kerma to dose to water for the INTRABEAM. C{sub Q} was investigated as a function of depth in water, and compared with the manufacturer’s reported value. The effect of chamber air cavity dimension tolerance was also investigated. Methods: Air-kerma (A{sub k}) from a reference beam was calculated using the EGSnrc user code cavity.more » Using egs-chamber, a model of a PTW 34013 parallel-plate ionization chamber was created according to manufacturer specifications. The dose to the chamber air cavity (D{sub gas}) was simulated both in-air (with reference beam) and in-water (with INTRABEAM source). Dose to a small water voxel (D{sub w}) was also calculated. C{sub Q} was derived from these quantities. Results: C{sub Q} was found to vary by up to 15% (1.30 vs 1.11) between chamber dimension extremes. The agreement between chamber C{sub Q} was found to improve with increasing depth in water. However, in all cases investigated, C{sub Q} was larger than the manufacturer reported value of 1.054. Conclusions: Our results show that cavity dimension tolerance has a significant effect on C{sub Q}, with differences as large as 15%. In all cases considered, C{sub Q} was found to be larger than the reported value of 1.054. This suggests that the recommended calculation underestimates the dose to water.« less

Alternative methods for CYP2D6 phenotyping: comparison of dextromethorphan metabolic ratios from AUC, single point plasma, and urine.

PubMed

Chen, Rui; Wang, Haotian; Shi, Jun; Hu, Pei

2016-05-01

CYP2D6 is a high polymorphic enzyme. Determining its phenotype before CYP2D6 substrate treatment can avoid dose-dependent adverse events or therapeutic failures. Alternative phenotyping methods of CYP2D6 were compared to aluate the appropriate and precise time points for phenotyping after single-dose and ultiple-dose of 30-mg controlled-release (CR) dextromethorphan (DM) and to explore the antimodes for potential sampling methods. This was an open-label, single and multiple-dose study. 21 subjects were assigned to receive a single dose of CR DM 30 mg orally, followed by a 3-day washout period prior to oral administration of CR DM 30 mg every 12 hours for 6 days. Metabolic ratios (MRs) from AUC∞ after single dosing and from AUC0-12h at steady state were taken as the gold standard. The correlations of metabolic ratios of DM to dextrorphan (MRDM/DX) values based on different phenotyping methods were assessed. Linear regression formulas were derived to calculate the antimodes for potential sample methods. In the single-dose part of the study statistically significant correlations were found between MRDM/DX from AUC∞ and from serial plasma points from 1 to 30 hours or from urine (all p-values < 0.001). In the multiple-dose part, statistically significant correlations were found between MRDM/DX from AUC0-12h on day 6 and MRDM/DX from serial plasma points from 0 to 36 hours after the last dosing (all p-values < 0.001). Based on reported urinary antimode and linear regression analysis, the antimodes of AUC and plasma points were derived to profile the trend of antimodes as the drug concentrations changed. MRDM/DX from plasma points had good correlations with MRDM/DX from AUC. Plasma points from 1 to 30 hours after single dose of 30-mg CR DM and any plasma point at steady state after multiple doses of CR DM could potentially be used for phenotyping of CYP2D6.

An Empirical Method for deriving RBE values associated with Electrons, Photons and Radionuclides

DOE PAGES

Bellamy, Michael B; Puskin, J.; Eckerman, Keith F.; ...

2015-01-01

There is substantial evidence to justify using relative biological effectiveness (RBE) values greater than one for low-energy electrons and photons. But, in the field of radiation protection, radiation associated with low linear energy transfer (LET) has been assigned a radiation weighting factor w R of one. This value may be suitable for radiation protection but, for risk considerations, it is important to evaluate the potential elevated biological effectiveness of radiation to improve the quality of risk estimates. RBE values between 2 and 3 for tritium are implied by several experimental measurements. Additionally, elevated RBE values have been found for othermore » similar low-energy radiation sources. In this work, RBE values are derived for electrons based upon the fractional deposition of absorbed dose of energies less than a few keV. Using this empirical method, RBE values were also derived for monoenergetic photons and 1070 radionuclides from ICRP Publication 107 for which photons and electrons are the primary emissions.« less

Solar UV radiation exposure of seamen - Measurements, calibration and model calculations of erythemal irradiance along ship routes

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

Feister, Uwe; Meyer, Gabriele; Kirst, Ulrich

2013-05-10

Seamen working on vessels that go along tropical and subtropical routes are at risk to receive high doses of solar erythemal radiation. Due to small solar zenith angles and low ozone values, UV index and erythemal dose are much higher than at mid-and high latitudes. UV index values at tropical and subtropical Oceans can exceed UVI = 20, which is more than double of typical mid-latitude UV index values. Daily erythemal dose can exceed the 30-fold of typical midlatitude winter values. Measurements of erythemal exposure of different body parts on seamen have been performed along 4 routes of merchant vessels.more » The data base has been extended by two years of continuous solar irradiance measurements taken on the mast top of RV METEOR. Radiative transfer model calculations for clear sky along the ship routes have been performed that use satellite-based input for ozone and aerosols to provide maximum erythemal irradiance and dose. The whole data base is intended to be used to derive individual erythemal exposure of seamen during work-time.« less

Diagnostic reference levels of paediatric computed tomography examinations performed at a dedicated Australian paediatric hospital.

PubMed

Bibbo, Giovanni; Brown, Scott; Linke, Rebecca

2016-08-01

Diagnostic Reference Levels (DRL) of procedures involving ionizing radiation are important tools to optimizing radiation doses delivered to patients and in identifying cases where the levels of doses are unusually high. This is particularly important for paediatric patients undergoing computed tomography (CT) examinations as these examinations are associated with relatively high-dose. Paediatric CT studies, performed at our institution from January 2010 to March 2014, have been retrospectively analysed to determine the 75th and 95th percentiles of both the volume computed tomography dose index (CTDIvol ) and dose-length product (DLP) for the most commonly performed studies to: establish local diagnostic reference levels for paediatric computed tomography examinations performed at our institution, benchmark our DRL with national and international published paediatric values, and determine the compliance of CT radiographer with established protocols. The derived local 75th percentile DRL have been found to be acceptable when compared with those published by the Australian National Radiation Dose Register and two national children's hospitals, and at the international level with the National Reference Doses for the UK. The 95th percentiles of CTDIvol for the various CT examinations have been found to be acceptable values for the CT scanner Dose-Check Notification. Benchmarking CT radiographers shows that they follow the set protocols for the various examinations without significant variations in the machine setting factors. The derivation of DRL has given us the tool to evaluate and improve the performance of our CT service by improved compliance and a reduction in radiation dose to our paediatric patients. We have also been able to benchmark our performance with similar national and international institutions. © 2016 The Royal Australian and New Zealand College of Radiologists.

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.

INHALATION EXPOSURE-RESPONSE METHODOLOGY

EPA Science Inventory

The Inhalation Exposure-Response Analysis Methodology Document is expected to provide guidance on the development of the basic toxicological foundations for deriving reference values for human health effects, focusing on the hazard identification and dose-response aspects of the ...

Whole-body to tissue concentration ratios for use in biota dose assessments for animals.

PubMed

Yankovich, Tamara L; Beresford, Nicholas A; Wood, Michael D; Aono, Tasuo; Andersson, Pål; Barnett, Catherine L; Bennett, Pamela; Brown, Justin E; Fesenko, Sergey; Fesenko, J; Hosseini, Ali; Howard, Brenda J; Johansen, Mathew P; Phaneuf, Marcel M; Tagami, Keiko; Takata, Hyoe; Twining, John R; Uchida, Shigeo

2010-11-01

Environmental monitoring programs often measure contaminant concentrations in animal tissues consumed by humans (e.g., muscle). By comparison, demonstration of the protection of biota from the potential effects of radionuclides involves a comparison of whole-body doses to radiological dose benchmarks. Consequently, methods for deriving whole-body concentration ratios based on tissue-specific data are required to make best use of the available information. This paper provides a series of look-up tables with whole-body:tissue-specific concentration ratios for non-human biota. Focus was placed on relatively broad animal categories (including molluscs, crustaceans, freshwater fishes, marine fishes, amphibians, reptiles, birds and mammals) and commonly measured tissues (specifically, bone, muscle, liver and kidney). Depending upon organism, whole-body to tissue concentration ratios were derived for between 12 and 47 elements. The whole-body to tissue concentration ratios can be used to estimate whole-body concentrations from tissue-specific measurements. However, we recommend that any given whole-body to tissue concentration ratio should not be used if the value falls between 0.75 and 1.5. Instead, a value of one should be assumed.

Influence of CT automatic tube current modulation on uncertainty in effective dose.

PubMed

Sookpeng, S; Martin, C J; Gentle, D J

2016-01-01

Computed tomography (CT) scanners are equipped with automatic tube current modulation (ATCM) systems that adjust the current to compensate for variations in patient attenuation. CT dosimetry variables are not defined for ATCM situations and, thus, only the averaged values are displayed and analysed. The patient effective dose (E), which is derived from a weighted sum of organ equivalent doses, will be modified by the ATCM. Values for E for chest-abdomen-pelvis CT scans have been calculated using the ImPACT spreadsheet for patients on five CT scanners. Values for E resulting from the z-axis modulation under ATCM have been compared with results assessed using the same effective mAs values with constant tube currents. Mean values for E under ATCM were within ±10 % of those for fixed tube currents for all scanners. Cumulative dose distributions under ATCM have been simulated for two patient scans using single-slice dose profiles measured in elliptical and cylindrical phantoms on one scanner. Contributions to the effective dose from organs in the upper thorax under ATCM are 30-35 % lower for superficial tissues (e.g. breast) and 15-20 % lower for deeper organs (e.g. lungs). The effect on doses to organs in the abdomen depends on body shape, and they can be 10-22 % higher for larger patients. Results indicate that scan dosimetry parameters, dose-length product and effective mAs averaged over the whole scan can provide an assessment in terms of E that is sufficiently accurate to quantify relative risk for routine patient exposures under ATCM. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of realistic doses of atrazine, metolachlor, and glyphosate on lipid peroxidation and diet-derived antioxidants in caged honey bees (Apis mellifera).

PubMed

Helmer, Stephanie Hedrei; Kerbaol, Anahi; Aras, Philippe; Jumarie, Catherine; Boily, Monique

2015-06-01

The decline in the population of pollinators is a worrying phenomenon worldwide. In North America, the extensive use of herbicides in maize and soya crops may affect the health of nontarget organisms like the honey bee. In this study, caged honey bees were exposed to realistic doses of atrazine, metolachlor, and glyphosate for 10 days via contaminated syrup. Peroxidation of lipids was evaluated using the thiobarbituric acid reactive substance (TBARS) test, and diet-derived antioxidants-carotenoids, all-trans-retinol (at-ROH) and α-tocopherol-were detected and quantified using reversed-phase HPLC techniques. Significant increases in syrup consumption were observed in honey bees exposed to metolachlor, and a lower TBARS value was recorded for the highest dose. No relationship was observed between the peroxidation of lipids and the levels of antioxidants. However, β-carotene, which was found to be the most abundant carotenoid, and at-ROH (derived from β-carotene) both decreased with increasing doses of atrazine and glyphosate. In contrast, metolachlor increased levels of at-ROH without any effects on β-carotene. These results show that the honey bee carotenoid-retinoid system may be altered by sublethal field-realistic doses of herbicides.

An empirical method for deriving RBE values associated with electrons, photons and radionuclides.

PubMed

Bellamy, M; Puskin, J; Hertel, N; Eckerman, K

2015-12-01

There is substantial evidence to justify using relative biological effectiveness (RBE) values of >1 for low-energy electrons and photons. But, in the field of radiation protection, radiation associated with low linear energy transfer has been assigned a radiation weighting factor wR of 1. This value may be suitable for radiation protection but, for risk considerations, it is important to evaluate the potential elevated biological effectiveness of radiation to improve the quality of risk estimates. RBE values between 2 and 3 for tritium are implied by several experimental measurements. Additionally, elevated RBE values have been found for other similar low-energy radiation sources. In this work, RBE values are derived for electrons based upon the fractional deposition of absorbed dose of energies less than a few kiloelectron volts. Using this empirical method, RBE values were also derived for monoenergetic photons and 1070 radionuclides from ICRP Publication 107 for which photons and electrons are the primary emissions. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Determination of optimum process parameters for peroxidase-catalysed treatment of bisphenol A and application to the removal of bisphenol derivatives.

PubMed

Yamada, Kazunori; Ikeda, Naoya; Takano, Yoko; Kashiwada, Ayumi; Matsuda, Kiyomi; Hirata, Mitsuo

2010-03-01

Systematic investigations were carried out to determine the optimum process parameters such as the hydrogen peroxide (H2O2) concentration, concentration and molar mass of poly(ethylene glycol) (PEG) as an additive, pH value, temperature and enzyme dose for treatment of bisphenol A (BPA) with horseradish peroxidase (HRP). The HRP-catalysed treatment of BPA was effectively enhanced by adding PEG, and BPA was completely converted into phenoxy radicals by HRP dose of 0.10 U/cm3. The optimum conditions for HRP-catalysed treatment of BPA at 0.3 mM was determined to be 0.3 mM for H2O2 and 0.10 mg/cm3 for PEG with a molar mass of 1.0 x 10(4) in a pH 6.0 buffer at 30 degrees C. Different kinds of bisphenol derivatives were completely or effectively treated by HRP under the optimum conditions determined for treatment of BPA, although the HRP dose was further increased as necessary for some of them. The aggregation of water-insoluble oligomers generated by the enzymatic radicalization and radical coupling reaction was enhanced by decreasing the pH values to 4.0 with HCl after the enzymatic treatment, and BPA and bisphenol derivatives were removed from aqueous solutions by filtering out the oligomer precipitates.

Influence of different dose calculation algorithms on the estimate of NTCP for lung complications

PubMed Central

Bäck, Anna

2013-01-01

Due to limitations and uncertainties in dose calculation algorithms, different algorithms can predict different dose distributions and dose‐volume histograms for the same treatment. This can be a problem when estimating the normal tissue complication probability (NTCP) for patient‐specific dose distributions. Published NTCP model parameters are often derived for a different dose calculation algorithm than the one used to calculate the actual dose distribution. The use of algorithm‐specific NTCP model parameters can prevent errors caused by differences in dose calculation algorithms. The objective of this work was to determine how to change the NTCP model parameters for lung complications derived for a simple correction‐based pencil beam dose calculation algorithm, in order to make them valid for three other common dose calculation algorithms. NTCP was calculated with the relative seriality (RS) and Lyman‐Kutcher‐Burman (LKB) models. The four dose calculation algorithms used were the pencil beam (PB) and collapsed cone (CC) algorithms employed by Oncentra, and the pencil beam convolution (PBC) and anisotropic analytical algorithm (AAA) employed by Eclipse. Original model parameters for lung complications were taken from four published studies on different grades of pneumonitis, and new algorithm‐specific NTCP model parameters were determined. The difference between original and new model parameters was presented in relation to the reported model parameter uncertainties. Three different types of treatments were considered in the study: tangential and locoregional breast cancer treatment and lung cancer treatment. Changing the algorithm without the derivation of new model parameters caused changes in the NTCP value of up to 10 percentage points for the cases studied. Furthermore, the error introduced could be of the same magnitude as the confidence intervals of the calculated NTCP values. The new NTCP model parameters were tabulated as the algorithm was varied from PB to PBC, AAA, or CC. Moving from the PB to the PBC algorithm did not require new model parameters; however, moving from PB to AAA or CC did require a change in the NTCP model parameters, with CC requiring the largest change. It was shown that the new model parameters for a given algorithm are different for the different treatment types. PACS numbers: 87.53.‐j, 87.53.Kn, 87.55.‐x, 87.55.dh, 87.55.kd PMID:24036865

Early Dose Response to Yttrium-90 Microsphere Treatment of Metastatic Liver Cancer by a Patient-Specific Method Using Single Photon Emission Computed Tomography and Positron Emission Tomography

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

Campbell, Janice M.; Department of Radiation Oncology, Wayne State University, Detroit, MI; Wong, C. Oliver

2009-05-01

Purpose: To evaluate a patient-specific single photon emission computed tomography (SPECT)-based method of dose calculation for treatment planning of yttrium-90 ({sup 90}Y) microsphere selective internal radiotherapy (SIRT). Methods and Materials: Fourteen consecutive {sup 90}Y SIRTs for colorectal liver metastasis were retrospectively analyzed. Absorbed dose to tumor and normal liver tissue was calculated by partition methods with two different tumor/normal liver vascularity ratios: an average 3:1 and a patient-specific ratio derived from pretreatment technetium-99m macroaggregated albumin SPECT. Tumor response was quantitatively evaluated from fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography scans. Results: Positron emission tomography showed a significant decrease in total tumor standardizedmore » uptake value (average, 52%). There was a significant difference in the tumor absorbed dose between the average and specific methods (p = 0.009). Response vs. dose curves fit by linear and linear-quadratic modeling showed similar results. Linear fit r values increased for all tumor response parameters with the specific method (+0.20 for mean standardized uptake value). Conclusion: Tumor dose calculated with the patient-specific method was more predictive of response in liver-directed {sup 90}Y SIRT.« less

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

PubMed

Kusano, Maggie; Caldwell, Curtis B

2014-07-01

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

New Fetal Dose Estimates from 18F-FDG Administered During Pregnancy: Standardization of Dose Calculations and Estimations with Voxel-Based Anthropomorphic Phantoms.

PubMed

Zanotti-Fregonara, Paolo; Chastan, Mathieu; Edet-Sanson, Agathe; Ekmekcioglu, Ozgul; Erdogan, Ezgi Basak; Hapdey, Sebastien; Hindie, Elif; Stabin, Michael G

2016-11-01

Data from the literature show that the fetal absorbed dose from 18 F-FDG administration to the pregnant mother ranges from 0.5E-2 to 4E-2 mGy/MBq. These figures were, however, obtained using different quantification techniques and with basic geometric anthropomorphic phantoms. The aim of this study was to refine the fetal dose estimates of published as well as new cases using realistic voxel-based phantoms. The 18 F-FDG doses to the fetus (n = 19; 5-34 wk of pregnancy) were calculated with new voxel-based anthropomorphic phantoms of the pregnant woman. The image-derived fetal time-integrated activity values were combined with those of the mothers' organs from the International Commission on Radiological Protection publication 106 and the dynamic bladder model with a 1-h bladder-voiding interval. The dose to the uterus was used as a proxy for early pregnancy (up to 10 wk). The time-integrated activities were entered into OLINDA/EXM 1.1 to derive the dose with the classic anthropomorphic phantoms of pregnant women, then into OLINDA/EXM 2.0 to assess the dose using new voxel-based phantoms. The average fetal doses (mGy/MBq) with OLINDA/EXM 2.0 were 2.5E-02 in early pregnancy, 1.3E-02 in the late part of the first trimester, 8.5E-03 in the second trimester, and 5.1E-03 in the third trimester. The differences compared with the doses calculated with OLINDA/EXM 1.1 were +7%, +70%, +35%, and -8%, respectively. Except in late pregnancy, the doses estimated with realistic voxelwise anthropomorphic phantoms are higher than the doses derived from old geometric phantoms. The doses remain, however, well below the threshold for any deterministic effects. Thus, pregnancy is not an absolute contraindication of a clinically justified 18 F-FDG PET scan. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Relative bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension.

PubMed

Clemens, Pamela L; Cloyd, James C; Kriel, Robert L; Remmel, Rory P

2007-01-01

Maintenance of effective drug concentrations is essential for adequate treatment of epilepsy. Some antiepileptic drugs can be successfully administered rectally when the oral route of administration is temporarily unavailable. Oxcarbazepine is a newer antiepileptic drug that is rapidly converted to a monohydroxy derivative, the active compound. This study aimed to characterise the bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension using a randomised, crossover design in ten healthy volunteers. Two subjects received 300 mg doses of oxcarbazepine suspension via rectal and oral routes and eight received 450 mg doses. A washout period of at least 2 weeks elapsed between doses. The rectal dose was diluted 1:1 with water. Blood samples and urine were collected for 72 hours post-dose. Adverse effects were assessed at each blood collection time-point using a self-administered questionnaire. Plasma was assayed for oxcarbazepine and monohydroxy derivative; urine was assayed for monohydroxy derivative and monohydroxy derivative-glucuronide. Maximum plasma concentration (C(max)) and time to reach C(max) (t(max)) were obtained directly from the plasma concentration-time curves. The areas under the concentration-time curve (AUCs) were determined via non-compartmental analysis. Relative bioavailability was calculated and the C(max) and AUCs were compared using Wilcoxon signed-rank tests. Mean relative bioavailability calculated from plasma AUCs was 8.3% (SD 5.5%) for the monohydroxy derivative and 10.8% (SD 7.3%) for oxcarbazepine. Oxcarbazepine and monohydroxy derivative C(max) and AUC values were significantly lower following rectal administration (p < 0.01). The total amount of monohydroxy derivative excreted in the urine following rectal administration was 10 +/- 5% of the amount excreted following oral administration. Oral absorption was consistent with previous studies. The most common adverse effects were headache and fatigue with no discernible differences between routes. Monohydroxy derivative bioavailability following rectal administration of oxcarbazepine suspension is significantly lower than following oral administration, most likely because of poor oxcarbazepine water solubility. It is unlikely that adequate monohydroxy derivative concentrations can be achieved with rectal administration of diluted oxcarbazepine suspension.

A Measurement and Analysis of Buildup Region Dose for Open Field Photon Beams (Cobalt-60 through 24 MV)

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

McCullough, Edwin C.

2015-01-15

The central axis depth dose in the build-up region (surface to d{sub max}) of single open field photon beams (cobalt-60 through 24 MV) has been measured utilizing parallel plate and extrapolation chamber methodology. These data were used to derive, for a prescription dose of 100 cGy, values of surface dose, the maximum value of dose along the central axis (D{sub max}) and the depth (nearest the surface) at which 90% of the prescription dose occurs (d{sub 90}). For both single and parallel opposed pair (POP) open field configurations, data are presented at field sizes of 5 × 5, 15 ×more » 15 and 25 × 25 cm{sup 2} for prescription depths of 10, 15 and 20 cm (midplane for POP). For the treatment machines, field sizes, and prescription depths studied, it is possible to conclude that: for single open field irradiation, surface dose values (as a percentage of the prescription dose) can be either low (<10%) or comparable to the prescription dose itself; for POP open fields, surface dose values are relatively independent of photon energy and midplane depth, and range between 30% and 70% of prescription dose, being principally dependent on field size; the depth of the initial 90 cGy point for a prescription dose of 100 cGy, d{sub 90}, was larger for POP fields. For either single or POP open field treatments, d{sub 90} was always less than 22 mm, while for 6 MV or less, values of d{sub 90} were less than 4 mm; D{sub max} values can be very large (e.g., above 300 cGy) for certain treatment situations and are reduced significantly for POP treatments; for open field POP treatments, the percent reduction in D{sub max} with each increment in beam energy above 10 MV is reduced over that seen at 10 MV or less and, possibly, this further reduction may be clinically insignificant; for open field POP treatments, changes in surface dose, d{sub 90} and D{sub max} with beam energy above 10 MV do not suggest, with regard to these specific build-up curve parameters, any obvious advantage for treatment with beam energies greater than 10 MV for the specific machines and situations studied.« less

Relation between lineal energy distribution and relative biological effectiveness for photon beams according to the microdosimetric kinetic model.

PubMed

Okamoto, Hiroyuki; Kanai, Tatsuaki; Kase, Yuki; Matsumoto, Yoshitaka; Furusawa, Yoshiya; Fujita, Yukio; Saitoh, Hidetoshi; Itami, Jun; Kohno, Toshiyuki

2011-01-01

Our cell survival data showed the obvious dependence of RBE on photon energy: The RBE value for 200 kV X-rays was approximately 10% greater than those for mega-voltage photon beams. In radiation therapy using mega-voltage photon beams, the photon energy distribution outside the field is different with that in the radiation field because of a large number of low energy scattering photons. Hence, the RBE values outside the field become greater. To evaluate the increase in RBE, the method of deriving the RBE using the Microdosimetric Kinetic model (MK model) was proposed in this study. The MK model has two kinds of the parameters, tissue-specific parameters and the dose-mean lineal energy derived from the lineal energy distributions measured with a Tissue-Equivalent Proportional Counter (TEPC). The lineal energy distributions with the same geometries of the cell irradiations for 200 kV X-rays, (60)Co γ-rays, and 6 MV X-rays were obtained with the TEPC and Monte Carlo code GEANT4. The measured lineal energy distribution for 200 kV X-rays was quite different from those for mega-voltage photon beams. The dose-mean lineal energy of 200 kV X-rays showed the greatest value, 4.51 keV/µm, comparing with 2.34 and 2.36 keV/µm for (60)Co γ-rays and 6 MV X-rays, respectively. By using the results of the TEPC and cell irradiations, the tissue-specific parameters in the MK model were determined. As a result, the RBE of the photon beams (y(D): 2~5 keV/µm) in arbitrary conditions can be derived by the measurements only or the calculations only of the dose-mean lineal energy.

Somapacitan, a once-weekly reversible albumin-binding GH derivative, in children with GH deficiency: A randomized dose-escalation trial.

PubMed

Battelino, Tadej; Rasmussen, Michael Højby; De Schepper, Jean; Zuckerman-Levin, Nehama; Gucev, Zoran; Sävendahl, Lars

2017-10-01

To evaluate the safety, local tolerability, pharmacodynamics and pharmacokinetics of escalating single doses of once-weekly somapacitan, a reversible, albumin-binding GH derivative, vs once-daily GH in children with GH deficiency (GHD). Phase 1, randomized, open-label, active-controlled, dose-escalation trial (NCT01973244). Thirty-two prepubertal GH-treated children with GHD were sequentially randomized 3:1 within each of four cohorts to a single dose of somapacitan (0.02, 0.04, 0.08 and 0.16 mg/kg; n=6 each), or once-daily Norditropin ® SimpleXx ® (0.03 mg/kg; n=2 each) for 7 days. Pharmacokinetic and pharmacodynamic profiles were assessed. Adverse events were all mild, and there were no apparent treatment-dependent patterns in type or frequency. Four mild transient injection site reactions were reported in three of 24 children treated with somapacitan. No antisomapacitan/anti-human growth hormone (hGH) antibodies were detected. Mean serum concentrations of somapacitan increased in a dose-dependent but nonlinear manner: maximum concentration ranged from 21.8 ng/mL (0.02 mg/kg dose) to 458.4 ng/mL (0.16 mg/kg dose). IGF-I and IGFBP-3, and change from baseline in IGF-I standard deviation score (SDS) and IGFBP-3 SDS, increased dose dependently; greatest changes in SDS values were seen for 0.16 mg/kg. IGF-I SDS values were between -2 and +2 SDS, except for peak IGF-I SDS with 0.08 mg/kg somapacitan. Postdosing, IGF-I SDS remained above baseline levels for at least 1 week. Single doses of once-weekly somapacitan (0.02-0.16 mg/kg) were well tolerated in children with GHD, with IGF-I profiles supporting a once-weekly treatment profile. No clinically significant safety/tolerability signals or immunogenicity concerns were identified. © 2017 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.

Eye lens dosimetry in interventional cardiology: results of staff dose measurements and link to patient dose levels.

PubMed

Antic, V; Ciraj-Bjelac, O; Rehani, M; Aleksandric, S; Arandjic, D; Ostojic, M

2013-01-01

Workers involved in interventional cardiology procedures receive high eye lens dose if protection is not used. Currently, there is no suitable method for routine use for the measurement of eye dose. Since most angiography machines are equipped with suitable patient dosemeters, deriving factors linking staff eye doses to the patient doses can be helpful. In this study the patient kerma-area product, cumulative dose at an interventional reference point and eye dose in terms of Hp(3) of the cardiologists, nurses and radiographers for interventional cardiology procedures have been measured. Correlations between the patient dose and the staff eye dose were obtained. The mean eye dose was 121 µSv for the first operator, 33 µSv for the second operator/nurse and 12 µSv for radiographer. Normalised eye lens doses per unit kerma-area product were 0.94 µSv Gy⁻¹ cm⁻² for the first operator, 0.33 µSv Gy⁻¹ cm⁻² for the second operator/nurse and 0.16 µSv Gy⁻¹ cm⁻² for radiographers. Statistical analysis indicated that there is a weak but significant (p < 0.01) correlation between the eye dose and the kerma-area product for all three staff categories. These values are based on a local practice and may provide useful reference for other studies for validation and for wider utilisation in assessing the eye dose using patient dose values.

Strengths and Weaknesses of a Planar Whole-Body Method of 153Sm Dosimetry for Patients with Metastatic Osteosarcoma and Comparison with Three-Dimensional Dosimetry

PubMed Central

Plyku, Donika; Loeb, David M.; Prideaux, Andrew R.; Baechler, Sébastien; Wahl, Richard L.; Sgouros, George

2015-01-01

Abstract Purpose: Dosimetric accuracy depends directly upon the accuracy of the activity measurements in tumors and organs. The authors present the methods and results of a retrospective tumor dosimetry analysis in 14 patients with a total of 28 tumors treated with high activities of 153Sm-ethylenediaminetetramethylenephosphonate (153Sm-EDTMP) for therapy of metastatic osteosarcoma using planar images and compare the results with three-dimensional dosimetry. Materials and Methods: Analysis of phantom data provided a complete set of parameters for dosimetric calculations, including buildup factor, attenuation coefficient, and camera dead-time compensation. The latter was obtained using a previously developed methodology that accounts for the relative motion of the camera and patient during whole-body (WB) imaging. Tumor activity values calculated from the anterior and posterior views of WB planar images of patients treated with 153Sm-EDTMP for pediatric osteosarcoma were compared with the geometric mean value. The mean activities were integrated over time and tumor-absorbed doses were calculated using the software package OLINDA/EXM. Results: The authors found that it was necessary to employ the dead-time correction algorithm to prevent measured tumor activity half-lives from often exceeding the physical decay half-life of 153Sm. Measured half-lives so long are unquestionably in error. Tumor-absorbed doses varied between 0.0022 and 0.27 cGy/MBq with an average of 0.065 cGy/MBq; however, a comparison with absorbed dose values derived from a three-dimensional analysis for the same tumors showed no correlation; moreover, the ratio of three-dimensional absorbed dose value to planar absorbed dose value was 2.19. From the anterior and posterior activity comparisons, the order of clinical uncertainty for activity and dose calculations from WB planar images, with the present methodology, is hypothesized to be about 70%. Conclusion: The dosimetric results from clinical patient data indicate that absolute planar dosimetry is unreliable and dosimetry using three-dimensional imaging is preferable, particularly for tumors, except perhaps for the most sophisticated planar methods. The relative activity and patient kinetics derived from planar imaging show a greater level of reliability than the dosimetry. PMID:26560193

Estimating human-equivalent no observed adverse-effect levels for VOCs (volatile organic compounds) based on minimal knowledge of physiological parameters. Technical paper

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

Overton, J.H.; Jarabek, A.M.

1989-01-01

The U.S. EPA advocates the assessment of health-effects data and calculation of inhaled reference doses as benchmark values for gauging systemic toxicity to inhaled gases. The assessment often requires an inter- or intra-species dose extrapolation from no observed adverse effect level (NOAEL) exposure concentrations in animals to human equivalent NOAEL exposure concentrations. To achieve this, a dosimetric extrapolation procedure was developed based on the form or type of equations that describe the uptake and disposition of inhaled volatile organic compounds (VOCs) in physiologically-based pharmacokinetic (PB-PK) models. The procedure assumes allometric scaling of most physiological parameters and that the value ofmore » the time-integrated human arterial-blood concentration must be limited to no more than to that of experimental animals. The scaling assumption replaces the need for most parameter values and allows the derivation of a simple formula for dose extrapolation of VOCs that gives equivalent or more-conservative exposure concentrations values than those that would be obtained using a PB-PK model in which scaling was assumed.« less

Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers.

PubMed

Blin, O; Jacquet, A; Callamand, S; Jouve, E; Habib, M; Gayraud, D; Durand, A; Bruguerolle, B; Pisano, P

1999-10-01

To describe the pharmacokinetic-pharmacodynamic modelling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers. This was a randomized double-blind, placebo-controlled two-way cross-over study. The effect of lorazepam was examined with the following tasks: choice reaction time, immediate and delayed cued recall of paired words and immediate and delayed free recall and recognition of pictures. The mean calculated EC50 values derived from the PK/PD modelling of the different tests ranged from 12.2 to 15.3 ng ml-1. On the basis of the statistical comparison of the EC50 values, the delayed recall trials seemed to be more impaired than the immediate recall trials; similar observations were made concerning the recognition vs recall tasks. The parameter values derived from PK/PD modelling, and especially the EC50 values, may provide sensitive indices that can be used, rather than the raw data derived from pharmacodynamic measurements, to compare CNS effects of benzodiazepines.

The U. S. Environmental Protection Agency's inhalation RfD methodology: Risk assessment for air toxics

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

Jarabek, A.M.; Menache, M.G.; Overton, J.H. Jr.

1990-10-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. This paper presents a brief background on the development of the inhalation reference dose (RfDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extra-respiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

U. S. Environmental Protection Agency's inhalation RFD methodology: Risk assessment for air toxics

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

Jarabek, A.M.; Menache, M.G.; Overton, J.H.

1989-01-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. The paper presents a brief background on the development of the inhalation reference dose (RFDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extrarespiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

Synthesis and Larvicidal and Adult Topical Activity of Some Hydrazide-Hydrazone Derivatives Against Aedes aegypti

DTIC Science & Technology

2014-01-01

anticancer, antifungal, antiviral, antitumoral, antibacterial and antimalarial activities [11-13]. Recently, our group has been investigating the...ABSTRACT A series of novel hydrazide-hydrazone derivatives were synthesized and evaluated for their larvicidal and adult topical activity against...4b) showed noteworthy larvacidal activity against Aedes aegypti. Dose-response data of compound 4b showed LC50 and LC90 values of 30.5 (15.4 – 22.7

SU-E-T-161: Characterization and Validation of CT Simulator Hounsfield Units to Relative Stopping Power Values for Proton Treatment Planning

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

Schnell, E; Ahmad, S; De La Fuente Herman, T

2015-06-15

Purpose: To develop a calibration curve that includes and minimizes the variations of Hounsfield Unit (HU) from a CT scanner to Relative Stopping Power (RSP) of tissues along the proton beam path. The variations are due to scanner and proton energy, technique, phantom size and placement, and tissue arrangement. Methods: A CIRS 062 M phantom with 10 plugs of known relative electron density (RED) was scanned through a 16 slice GE Discovery CT Simulator scanner. Three setup combinations of plug distributions and techniques clinically implemented for five treatment regions were scanned with energies of 100, 120, and 140 kV. Volumetricmore » HU values were measured for each plug and scan. The RSP values derived through the Bethe-Bloch formula are currently being verified with parallel-plate ionization chamber measurements in water using 80, 150, and 225 MeV proton beam. Typical treatment plans for treatment regions of brain, head-&-neck, chest, abdomen, and pelvis are being planned and dose delivered will be compared with film and Optically Stimulated Luminescence (OSL) measurements. Results: Percentage variations were determined for each variable. For tissues close to water, variations were <1% from any given parameter. Tissues far from water equivalence (lung and bone) showed the greatest sensitivity to change (7.4% maximum) with scanner energy and up to 5.3% with positioning of the phantom. No major variations were observed for proton energies within the treatment range. Conclusion: When deriving a calibration curve, attention should be placed to low and high HU values. A thorough verification process of calculated vs. water-phantom measured RSP values at different proton energies, followed by dose validation of planned vs. measured doses in phantom with film and OSL detectors are currently being undertaken.« less

An EGSnrc Monte Carlo study of the microionization chamber for reference dosimetry of narrow irregular IMRT beamlets.

PubMed

Capote, Roberto; Sánchez-Doblado, Francisco; Leal, Antonio; Lagares, Juan Ignacio; Arráns, Rafael; Hartmann, Günther H

2004-09-01

Intensity modulated radiation therapy (IMRT) has evolved toward the use of many small radiation fields, or "beamlets," to increase the resolution of the intensity map. The size of smaller beamlets can be typically about 1-5 cm2. Therefore small ionization chambers (IC) with sensitive volumes < or = 0.1 cm3 are generally used for dose verification of IMRT treatment. The dosimetry of these narrow photon beams pertains to the so-called nonreference conditions for beam calibration. The use of ion chambers for such narrow beams remains questionable due to the lack of electron equilibrium in most of the field. The present contribution aims to estimate, by the Monte Carlo (MC) method, the total correction needed to convert the IBA-Wellhöfer NAC007 micro IC measured charge in such radiation field to the absolute dose to water. Detailed geometrical simulation of the microionization chamber was performed. The ion chamber was always positioned at a 10 cm depth in water, parallel to the beam axis. The delivered doses to air and water cavity were calculated using the CAVRZ EGSnrc user code. The 6 MV phase-spaces for Primus Clinac (Siemens) used as an input to the CAVRZnrc code were derived by BEAM/EGS4 modeling of the treatment head of the machine along with the multileaf collimator [Sánchez-Doblado et al., Phys. Med. Biol. 48, 2081-2099 (2003)] and contrasted with experimental measurements. Dose calculations were carried out for two irradiation geometries, namely, the reference 10x10 cm2 field and an irregular (approximately 2x2 cm2) IMRT beamlet. The dose measured by the ion chamber is estimated by MC simulation as a dose averaged over the air cavity inside the ion-chamber (Dair). The absorbed dose to water is derived as the dose deposited inside the same volume, in the same geometrical position, filled and surrounded by water (Dwater) in the absence of the ionization chamber. Therefore, the Dwater/Dair dose ratio is a MC direct estimation of the total correction factor needed to convert the absorbed dose in air to absorbed dose to water. The dose ratio was calculated for several chamber positions, starting from the penumbra region around the beamlet along the two diagonals crossing the radiation field. For this quantity from 0 up to a 3% difference is observed between the dose ratio values obtained within the small irregular IMRT beamlet in comparison with the dose ratio derived for the reference 10x10 cm2 field. Greater differences from the reference value up to 9% were obtained in the penumbra region of the small IMRT beamlet.

Luminescence isochron dating: a new approach using different grain sizes.

PubMed

Zhao, H; Li, S H

2002-01-01

A new approach to isochron dating is described using different sizes of quartz and K-feldspar grains. The technique can be applied to sites with time-dependent external dose rates. It is assumed that any underestimation of the equivalent dose (De) using K-feldspar is by a factor F, which is independent of grain size (90-350 microm) for a given sample. Calibration of the beta source for different grain sizes is discussed, and then the sample ages are calculated using the differences between quartz and K-feldspar De from grains of similar size. Two aeolian sediment samples from north-eastern China are used to illustrate the application of the new method. It is confirmed that the observed values of De derived using K-feldspar underestimate the expected doses (based on the quartz De) but, nevertheless, these K-feldspar De values correlate linearly with the calculated internal dose rate contribution, supporting the assumption that the underestimation factor F is independent of grain size. The isochron ages are also compared with the results obtained using quartz De and the measured external dose rates.

SPECTRAL CORRECTION FACTORS FOR CONVENTIONAL NEUTRON DOSE METERS USED IN HIGH-ENERGY NEUTRON ENVIRONMENTS-IMPROVED AND EXTENDED RESULTS BASED ON A COMPLETE SURVEY OF ALL NEUTRON SPECTRA IN IAEA-TRS-403.

PubMed

Oparaji, U; Tsai, Y H; Liu, Y C; Lee, K W; Patelli, E; Sheu, R J

2017-06-01

This paper presents improved and extended results of our previous study on corrections for conventional neutron dose meters used in environments with high-energy neutrons (En > 10 MeV). Conventional moderated-type neutron dose meters tend to underestimate the dose contribution of high-energy neutrons because of the opposite trends of dose conversion coefficients and detection efficiencies as the neutron energy increases. A practical correction scheme was proposed based on analysis of hundreds of neutron spectra in the IAEA-TRS-403 report. By comparing 252Cf-calibrated dose responses with reference values derived from fluence-to-dose conversion coefficients, this study provides recommendations for neutron field characterization and the corresponding dose correction factors. Further sensitivity studies confirm the appropriateness of the proposed scheme and indicate that (1) the spectral correction factors are nearly independent of the selection of three commonly used calibration sources: 252Cf, 241Am-Be and 239Pu-Be; (2) the derived correction factors for Bonner spheres of various sizes (6"-9") are similar in trend and (3) practical high-energy neutron indexes based on measurements can be established to facilitate the application of these correction factors in workplaces. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Preventive or Potential Therapeutic Value of Nutraceuticals against Ionizing Radiation-Induced Oxidative Stress in Exposed Subjects and Frequent Fliers

PubMed Central

Giardi, Maria Teresa; Touloupakis, Eleftherios; Bertolotto, Delfina; Mascetti, Gabriele

2013-01-01

Humans are constantly exposed to ionizing radiation deriving from outer space sources or activities related to medical care. Absorption of ionizing radiation doses over a prolonged period of time can result in oxidative damage and cellular dysfunction inducing several diseases, especially in ageing subjects. In this report, we analyze the effects of ionizing radiation, particularly at low doses, in relation to a variety of human pathologies, including cancer, and cardiovascular and retinal diseases. We discuss scientific data in support of protection strategies by safe antioxidant formulations that can provide preventive or potential therapeutic value in response to long-term diseases that may develop following exposure. PMID:23965979

RADIOLOGICAL IMPACTS ASSESSMENT FOR WORKERS IN CERAMIC INDUSTRY IN SERBIA.

PubMed

Todorovic, Nataša; Mrda, Dušan; Hansman, Jan; Todorovic, Slavko; Nikolov, Jovana; Krmar, Miodrag

2017-11-01

Studies have been carried out to determine the natural radioactivity in some materials used in ceramic industry (zircon, zirkosil, Zircobit MO/S, zircon silicate, zirklonil frit, hematite, bentonite, wollastonite, raw kaolin, kaolinized granite, sileks ball, feldspar, pigment, white base serigraphic, engobe) and their associated radiation hazard. The external hazard index, Hex, values, radium equivalent activity, Raeq, total absorbed dose rates, D and annual effective dose, De were derived for all measured materials and compared with the recommended values to assess the external radiation hazards to workers who worked in ceramic industries in Serbia. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of biomonitoring equivalents for barium in urine and plasma for interpreting human biomonitoring data.

PubMed

Poddalgoda, Devika; Macey, Kristin; Assad, Henry; Krishnan, Kannan

2017-06-01

The objectives of the present work were: (1) to assemble population-level biomonitoring data to identify the concentrations of urinary and plasma barium across the general population; and (2) to derive biomonitoring equivalents (BEs) for barium in urine and plasma in order to facilitate the interpretation of barium concentrations in the biological matrices. In population level biomonitoring studies, barium has been measured in urine in the U.S. (NHANES study), but no such data on plasma barium levels were identified. The BE values for plasma and urine were derived from U.S. EPA's reference dose (RfD) of 0.2 mg/kg bw/d, based on a lower confidence limit on the benchmark dose (BMDL 05 ) of 63 mg/kg bw/d. The plasma BE (9 μg Ba/L) was derived by regression analysis of the near-steady-state plasma concentrations associated with the administered doses in animals exposed to barium chloride dihydrate in drinking water for 2-years in a NTP study. Using a human urinary excretion fraction of 0.023, a BE for urinary barium (0.19 mg/L or 0.25 mg/g creatinine) was derived for US EPA's RfD. The median and the 95 th percentile barium urine concentrations of the general population in U.S. are below the BE determined in this study, indicating that the population exposure to inorganic barium is expected to be below the exposure guidance value of 0.2 mg/kg bw/d. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Statistical analysis of radiation dose derived from ingestion of foods

NASA Astrophysics Data System (ADS)

Dougherty, Ward L.

2001-09-01

This analysis undertook the task of designing and implementing a methodology to determine an individual's probabilistic radiation dose from ingestion of foods utilizing Crystal Ball. A dietary intake model was determined by comparing previous existing models. Two principal radionuclides were considered-Lead210 (Pb-210) and Radium 226 (Ra-226). Samples from three different local grocery stores-Publix, Winn Dixie, and Albertsons-were counted on a gamma spectroscopy system with a GeLi detector. The same food samples were considered as those in the original FIPR database. A statistical analysis, utilizing the Crystal Ball program, was performed on the data to assess the most accurate distribution to use for these data. This allowed a determination of a radiation dose to an individual based on the above-information collected. Based on the analyses performed, radiation dose for grocery store samples was lower for Radium-226 than FIPR debris analyses, 2.7 vs. 5.91 mrem/yr. Lead-210 had a higher dose in the grocery store sample than the FIPR debris analyses, 21.4 vs. 518 mrem/yr. The output radiation dose was higher for all evaluations when an accurate estimation of distributions for each value was considered. Radium-226 radiation dose for FIPR and grocery rose to 9.56 and 4.38 mrem/yr. Radiation dose from ingestion of Pb-210 rose to 34.7 and 854 mrem/yr for FIPR and grocery data, respectively. Lead-210 was higher than initial doses for many reasons: Different peak examined, lower edge of detection limit, and minimum detectable concentration was considered. FIPR did not utilize grocery samples as a control because they calculated radiation dose that appeared unreasonably high. Consideration of distributions with the initial values allowed reevaluation of radiation does and showed a significant difference to original deterministic values. This work shows the value and importance of considering distributions to ensure that a person's radiation dose is accurately calculated. Probabilistic dose methodology was proved to be a more accurate and realistic method of radiation dose determination. This type of methodology provides a visual presentation of dose distribution that can be a vital aid in risk methodology.

Recommended approaches in the application of ...

EPA Pesticide Factsheets

ABSTRACT:Only a fraction of chemicals in commerce have been fully assessed for their potential hazards to human health due to difficulties involved in conventional regulatory tests. It has recently been proposed that quantitative transcriptomic data can be used to determine benchmark dose (BMD) and estimate a point of departure (POD). Several studies have shown that transcriptional PODs correlate with PODs derived from analysis of pathological changes, but there is no consensus on how the genes that are used to derive a transcriptional POD should be selected. Because of very large number of unrelated genes in gene expression data, the process of selecting subsets of informative genes is a major challenge. We used published microarray data from studies on rats exposed orally to multiple doses of six chemicals for 5, 14, 28, and 90 days. We evaluated eight different approaches to select genes for POD derivation and compared them to three previously proposed approaches. The relationship between transcriptional BMDs derived using these 11 approaches were compared with PODs derived from apical data that might be used in a human health risk assessment. We found that transcriptional benchmark dose values for all 11 approaches were remarkably aligned with different apical PODs, while a subset of between 3 and 8 of the approaches met standard statistical criteria across the 5-, 14-, 28-, and 90-day time points and thus qualify as effective estimates of apical PODs. Our r

SU-E-T-56: A Novel Approach to Computing Expected Value and Variance of Point Dose From Non-Gated Radiotherapy Delivery

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

Zhou, S; Zhu, X; Zhang, M

Purpose: Randomness in patient internal organ motion phase at the beginning of non-gated radiotherapy delivery may introduce uncertainty to dose received by the patient. Concerns of this dose deviation from the planned one has motivated many researchers to study this phenomenon although unified theoretical framework for computing it is still missing. This study was conducted to develop such framework for analyzing the effect. Methods: Two reasonable assumptions were made: a) patient internal organ motion is stationary and periodic; b) no special arrangement is made to start a non -gated radiotherapy delivery at any specific phase of patient internal organ motion.more » A statistical ensemble was formed consisting of patient’s non-gated radiotherapy deliveries at all equally possible initial organ motion phases. To characterize the patient received dose, statistical ensemble average method is employed to derive formulae for two variables: expected value and variance of dose received by a patient internal point from a non-gated radiotherapy delivery. Fourier Series was utilized to facilitate our analysis. Results: According to our formulae, the two variables can be computed from non-gated radiotherapy generated dose rate time sequences at the point’s corresponding locations on fixed phase 3D CT images sampled evenly in time over one patient internal organ motion period. The expected value of point dose is simply the average of the doses to the point’s corresponding locations on the fixed phase CT images. The variance can be determined by time integration in terms of Fourier Series coefficients of the dose rate time sequences on the same fixed phase 3D CT images. Conclusion: Given a non-gated radiotherapy delivery plan and patient’s 4D CT study, our novel approach can predict the expected value and variance of patient radiation dose. We expect it to play a significant role in determining both quality and robustness of patient non-gated radiotherapy plan.« less

Computer simulations and models for the performance characteristics of spectrally equivalent X-ray beams in medical diagnostic radiology

PubMed Central

Okunade, Akintunde A.

2007-01-01

In order to achieve uniformity in radiological imaging, it is recommended that the concept of equivalence in shape (quality) and size (quantity) of clinical Xray beams should be used for carrying out the comparative evaluation of image and patient dose. When used under the same irradiation geometry, X-ray beams that are strictly or relatively equivalent in terms of shape and size will produce identical or relatively identical image quality and patient dose. Simple mathematical models and software program EQSPECT.FOR were developed for the comparative evaluation of the performance characteristics in terms of contrast (C), contrast to noise ratio (CNR) and figure-of-merit (FOM = CNR2/DOSE) for spectrally equivalent beams transmitted through filter materials referred to as conventional and k-edged. At the same value of operating potential (kVp), results show that spectrally equivalent beam transmitted through conventional filter with higher atomic number (Z-value) in comparison with that transmitted through conventional filter with lower Z-value resulted in the same value of C and FOM. However, in comparison with the spectrally equivalent beam transmitted through filter of lower Z-value, the beam through filter of higher Z-value produced higher value of CNR and DOSE at equal tube loading (mAs) and kVp. Under the condition of equivalence of spectrum, at scaled (or reduced) tube loading and same kVp, filter materials of higher Z-value can produce the same values of C, CNR, DOSE and FOM as filter materials of lower Z-value. Unlike the case of comparison of spectrally equivalent beam transmitted through one conventional filter and that through another conventional filter, it is not possible to derive simple mathematical formulations for the relative performance of spectrally equivalent beam transmitted through a given conventional filter material and that through kedge filter material. PMID:21224928

Development of a chronic noncancer oral reference dose and drinking water screening level for sulfolane using benchmark dose modeling.

PubMed

Thompson, Chad M; Gaylor, David W; Tachovsky, J Andrew; Perry, Camarie; Carakostas, Michael C; Haws, Laurie C

2013-12-01

Sulfolane is a widely used industrial solvent that is often used for gas treatment (sour gas sweetening; hydrogen sulfide removal from shale and coal processes, etc.), and in the manufacture of polymers and electronics, and may be found in pharmaceuticals as a residual solvent used in the manufacturing processes. Sulfolane is considered a high production volume chemical with worldwide production around 18 000-36 000 tons per year. Given that sulfolane has been detected as a contaminant in groundwater, an important potential route of exposure is tap water ingestion. Because there are currently no federal drinking water standards for sulfolane in the USA, we developed a noncancer oral reference dose (RfD) based on benchmark dose modeling, as well as a tap water screening value that is protective of ingestion. Review of the available literature suggests that sulfolane is not likely to be mutagenic, clastogenic or carcinogenic, or pose reproductive or developmental health risks except perhaps at very high exposure concentrations. RfD values derived using benchmark dose modeling were 0.01-0.04 mg kg(-1) per day, although modeling of developmental endpoints resulted in higher values, approximately 0.4 mg kg(-1) per day. The lowest, most conservative, RfD of 0.01 mg kg(-1) per day was based on reduced white blood cell counts in female rats. This RfD was used to develop a tap water screening level that is protective of ingestion, viz. 365 µg l(-1). It is anticipated that these values, along with the hazard identification and dose-response modeling described herein, should be informative for risk assessors and regulators interested in setting health-protective drinking water guideline values for sulfolane. Copyright © 2012 John Wiley & Sons, Ltd.

The relevance of image quality indices for dose optimization in abdominal multi-detector row CT in children: experimental assessment with pediatric phantoms

NASA Astrophysics Data System (ADS)

Brisse, H. J.; Brenot, J.; Pierrat, N.; Gaboriaud, G.; Savignoni, A.; DeRycke, Y.; Neuenschwander, S.; Aubert, B.; Rosenwald, J.-C.

2009-04-01

This study assessed and compared various image quality indices in order to manage the dose of pediatric abdominal MDCT protocols and to provide guidance on dose reduction. PMMA phantoms representing average body diameters at birth, 1 year, 5 years, 10 years and 15 years of age were scanned in a four-channel MDCT with a standard pediatric abdominal CT protocol. Image noise (SD, standard deviation of CT number), noise derivative (ND, derivative of the function of noise with respect to dose) and contrast-to-noise ratio (CNR) were measured. The 'relative' low-contrast detectability (rLCD) was introduced as a new quantity to adjust LCD to the various phantom diameters on the basis of the LCD1% assessed in a Catphan® phantom and a constant central absorbed dose. The required variations of CTDIvol16 with respect to phantom size were analyzed in order to maintain each image quality index constant. The use of a fixed SD or CNR level leads to major dose ratios between extreme patient sizes (factor 22.7 to 44 for SD, 31.7 to 51.5 for CNR2.8%), whereas fixed ND and rLCD result in acceptable dose ratios ranging between factors of 2.9 and 3.9 between extreme phantom diameters. For a 5-9 mm rLCD1%, adjusted ND values range between -0.84 and -0.11 HU mGy-1. Our data provide guidance on dose reduction on the basis of patient dimensions and the required rLCD (e.g., to get a constant 7 mm rLCD1% for abdominal diameters of 10, 13, 16, 20 and 25 cm, tube current-time product should be adjusted in order to obtain CTDIvol16 values of 6.2, 7.2, 8.8, 11.6 and 17.7 mGy, respectively).

Korean anatomical reference data for adults for use in radiological protection

NASA Astrophysics Data System (ADS)

Choi, Chansoo; Yeom, Yeon Soo; Nguyen, Thang Tat; Lee, Hanjin; Han, Haegin; Shin, Bangho; Zhang, Xujia; Kim, Chan Hyeong; Chung, Beom Sun

2018-01-01

For radiological protection from exposure to ionizing radiation, in which a population-averaged dose evaluation is used, establishing a system of reference anatomical and physiological data for a specific population of interest is important. Some studies were done in the past to establish Korean reference data; however, the data provided the mass values only for a limited number of organs/tissues. In addition, the standing height and total body mass are based on 20-year-old data. In the present study, a new set of Korean reference anatomical values was established for use in the radiological protection of Korean workers and members of the public. The established Korean reference data provide the masses of 58 organs/tissues, including those needed to calculate the effective dose, which were derived by collecting and analyzing various scientific reports in the literature and data. In addition, the data provide not only standing height and total body mass, but also 131 additional anthropometric parameters; these values were derived from the most recent Korean national survey project, 7 th Size Korea. The characteristics of the data were also compared with several other population data, including the Asian and the International Commission on Radiological Protection (ICRP) reference data.

Dose verification to cochlea during gamma knife radiosurgery of acoustic schwannoma using MOSFET dosimeter.

PubMed

Sharma, Sunil D; Kumar, Rajesh; Akhilesh, Philomina; Pendse, Anil M; Deshpande, Sudesh; Misra, Basant K

2012-01-01

Dose verification to cochlea using metal oxide semiconductor field effect transistor (MOSFET) dosimeter using a specially designed multi slice head and neck phantom during the treatment of acoustic schwannoma by Gamma Knife radiosurgery unit. A multi slice polystyrene head phantom was designed and fabricated for measurement of dose to cochlea during the treatment of the acoustic schwannoma. The phantom has provision to position the MOSFET dosimeters at the desired location precisely. MOSFET dosimeters of 0.2 mm x 0.2 mm x 0.5 μm were used to measure the dose to the cochlea. CT scans of the phantom with MOSFETs in situ were taken along with Leksell frame. The treatment plans of five patients treated earlier for acoustic schwannoma were transferred to the phantom. Dose and coordinates of maximum dose point inside the cochlea were derived. The phantom along with the MOSFET dosimeters was irradiated to deliver the planned treatment and dose received by cochlea were measured. The treatment planning system (TPS) estimated and measured dose to the cochlea were in the range of 7.4 - 8.4 Gy and 7.1 - 8 Gy, respectively. The maximum variation between TPS calculated and measured dose to cochlea was 5%. The measured dose values were found in good agreement with the dose values calculated using the TPS. The MOSFET dosimeter can be a suitable choice for routine dose verification in the Gamma Knife radiosurgery.

MO-E-17A-01: BEST IN PHYSICS (IMAGING) - Calculating SSDE From CT Exams Using Size Data Available in the DICOM Header of CT Localizer Radiographs

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

McMillan, K; Bostani, M; McNitt-Gray, M

2014-06-15

Purpose: To demonstrate the feasibility of using existing data stored within the DICOM header of certain CT localizer radiographs as a patient size metric for calculating CT size-specific dose estimates (SSDE). Methods: For most Siemens CT scanners, the CT localizer radiograph (topogram) contains a private DICOM field that stores an array of numbers describing AP and LAT attenuation-based measures of patient dimension. The square root of the product of the AP and LAT size data, which provides an estimate of water-equivalent-diameter (WED), was calculated retrospectively from topogram data of 20 patients who received clinically-indicated abdomen/pelvis (n=10) and chest (n=10) scansmore » (WED-topo). In addition, slice-by-slice water-equivalent-diameter (WED-image) and effective diameter (ED-image) values were calculated from the respective image data. Using TG-204 lookup tables, size-dependent conversion factors were determined based upon WED-topo, WED-image and ED-image values. These conversion factors were used with the reported CTDIvol to calculate slice-by-slice SSDE for each method. Averaging over all slices, a single SSDE value was determined for each patient and size metric. Patientspecific SSDE and CTDIvol values were then compared with patientspecific organ doses derived from detailed Monte Carlo simulations of fixed tube current scans. Results: For abdomen/pelvis scans, the average difference between liver dose and CTDIvol, SSDE(WED-topo), SSDE(WED-image), and SSDE(ED-image) was 18.70%, 8.17%, 6.84%, and 7.58%, respectively. For chest scans, the average difference between lung dose and CTDIvol, SSDE(WED-topo), SSDE(WED-image), and SSDE(ED-image) was 25.80%, 3.33%, 4.11%, and 7.66%, respectively. Conclusion: SSDE calculated using WED derived from data in the DICOM header of the topogram was comparable to SSDE calculated using WED and ED derived from axial images; each of these estimated organ dose to within 10% for both abdomen/pelvis and chest CT examinations. The topogrambased method has the advantage that WED data are already provided and therefore available without additional post-processing of the image data. Funding Support: NIH Grant R01-EB017095; Disclosures - Michael McNitt-Gray: Institutional Research Agreement, Siemens AG; Research Support, Siemens AG; Consultant, Flaherty Sensabaugh Bonasso PLLC; Consultant, Fulbright and Jaworski; Disclosures - Cynthia McCollough: Research Grant, Siemens Healthcare.« less

The effect of dose heterogeneity on radiation risk in medical imaging.

PubMed

Samei, Ehsan; Li, Xiang; Chen, Baiyu; Reiman, Robert

2013-06-01

The current estimations of risk associated with medical imaging procedures rely on assessing the organ dose via direct measurements or simulation. The dose to each organ is assumed to be homogeneous. To take into account the differences in radiation sensitivities, the mean organ doses are weighted by a corresponding tissue-weighting coefficients provided by ICRP to calculate the effective dose, which has been used as a surrogate of radiation risk. However, those coefficients were derived under the assumption of a homogeneous dose distribution within each organ. That assumption is significantly violated in most medical-imaging procedures. In helical chest CT, for example, superficial organs (e.g. breasts) demonstrate a heterogeneous dose distribution, whereas organs on the peripheries of the irradiation field (e.g. liver) might possess a discontinuous dose profile. Projection radiography and mammography involve an even higher level of organ dose heterogeneity spanning up to two orders of magnitude. As such, mean dose or point measured dose values do not reflect the maximum energy deposited per unit volume of the organ. In this paper, the magnitude of the dose heterogeneity in both CT and projection X-ray imaging was reported, using Monte Carlo methods. The lung dose demonstrated factors of 1.7 and 2.2 difference between the mean and maximum dose for chest CT and radiography, respectively. The corresponding values for the liver were 1.9 and 3.5. For mammography and breast tomosynthesis, the difference between mean glandular dose and maximum glandular dose was 3.1. Risk models based on the mean dose were found to provide a reasonable reflection of cancer risk. However, for leukaemia, they were found to significantly under-represent the risk when the organ dose distribution is heterogeneous. A systematic study is needed to develop a risk model for heterogeneous dose distributions.

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.

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.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2003-08-01

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

Inhalation TTC values: A new integrative grouping approach considering structural, toxicological and mechanistic features.

PubMed

Tluczkiewicz, I; Kühne, R; Ebert, R-U; Batke, M; Schüürmann, G; Mangelsdorf, I; Escher, S E

2016-07-01

The present publication describes an integrative grouping concept to derive threshold values for inhalation exposure. The classification scheme starts with differences in toxicological potency and develops criteria to group compounds into two potency classes, namely toxic (T-group) or low toxic (L-group). The TTC concept for inhalation exposure is based on the TTC RepDose data set, consisting of 296 organic compounds with 608 repeated-dose inhalation studies. Initially, 21 structural features (SFs) were identified as being characteristic for compounds of either high or low NOEC values (Schüürmann et al., 2016). In subsequent analyses these SF groups were further refined by taking into account structural homogeneity, type of toxicological effect observed, differences in absorption, metabolism and mechanism of action (MoA), to better define their structural and toxicological boundaries. Differentiation of a local or systemic mode of action did not improve the classification scheme. Finally, 28 groups were discriminated: 19 T-groups and 9 L-groups. Clearly distinct thresholds were derived for the T- and L-toxicity groups, being 2 × 10(-5) ppm (2 μg/person/day) and 0.05 ppm (4260 μg/person/day), respectively. The derived thresholds and the classification are compared to the initial mainly structure driven grouping (Schüürmann et al., 2016) and to the Cramer classification. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduction of effective dose and organ dose to the eye lens in head MDCT using iterative image reconstruction and automatic tube current modulation.

PubMed

Ryska, Pavel; Kvasnicka, Tomas; Jandura, Jiri; Klzo, Ludovit; Grepl, Jakub; Zizka, Jan

2014-06-01

To compare the effective and eye lens radiation dose in helical MDCT brain examinations using automatic tube current modulation in conjunction with either standard filtered back projection (FBP) technique or iterative reconstruction in image space (IRIS). Of 400 adult brain MDCT examinations, 200 were performed using FBP and 200 using IRIS with the following parameters: tube voltage 120 kV, rotation period 1 second, pitch factor 0.55, automatic tube current modulation in both transverse and longitudinal planes with reference mAs 300 (FBP) and 200 (IRIS). Doses were calculated from CT dose index and dose length product values utilising ImPACT software; the organ dose to the lens was derived from the actual tube current-time product value applied to the lens. Image quality was assessed by two independent readers blinded to the type of image reconstruction technique. The average effective scan dose was 1.47±0.26 mSv (FBP) and 0.98±0.15 mSv (IRIS), respectively (33.3% decrease). The average organ dose to the eye lens decreased from 40.0±3.3 mGy (FBP) to 26.6±2.0 mGy (IRIS, 33.5% decrease). No significant change in diagnostic image quality was noted between IRIS and FBP scans (P=0.17). Iterative reconstruction of cerebral MDCT examinations enables reduction of both effective and organ eye lens dose by one third without signficant loss of image quality.

The predictive ability of six pharmacokinetic models of rocuronium developed using a single bolus: evaluation with bolus and continuous infusion regimen.

PubMed

Sasakawa, Tomoki; Masui, Kenichi; Kazama, Tomiei; Iwasaki, Hiroshi

2016-08-01

Rocuronium concentration prediction using pharmacokinetic (PK) models would be useful for controlling rocuronium effects because neuromuscular monitoring throughout anesthesia can be difficult. This study assessed whether six different compartmental PK models developed from data obtained after bolus administration only could predict the measured plasma concentration (Cp) values of rocuronium delivered by bolus followed by continuous infusion. Rocuronium Cp values from 19 healthy subjects who received a bolus dose followed by continuous infusion in a phase III multicenter trial in Japan were used retrospectively as evaluation datasets. Six different compartmental PK models of rocuronium were used to simulate rocuronium Cp time course values, which were compared with measured Cp values. Prediction error (PE) derivatives of median absolute PE (MDAPE), median PE (MDPE), wobble, divergence absolute PE, and divergence PE were used to assess inaccuracy, bias, intra-individual variability, and time-related trends in APE and PE values. MDAPE and MDPE values were acceptable only for the Magorian and Kleijn models. The divergence PE value for the Kleijn model was lower than -10 %/h, indicating unstable prediction over time. The Szenohradszky model had the lowest divergence PE (-2.7 %/h) and wobble (5.4 %) values with negative bias (MDPE = -25.9 %). These three models were developed using the mixed-effects modeling approach. The Magorian model showed the best PE derivatives among the models assessed. A PK model developed from data obtained after single-bolus dosing can predict Cp values during bolus and continuous infusion. Thus, a mixed-effects modeling approach may be preferable in extrapolating such data.

Fluence correction factors for graphite calorimetry in a low-energy clinical proton beam: I. Analytical and Monte Carlo simulations.

PubMed

Palmans, H; Al-Sulaiti, L; Andreo, P; Shipley, D; Lühr, A; Bassler, N; Martinkovič, J; Dobrovodský, J; Rossomme, S; Thomas, R A S; Kacperek, A

2013-05-21

The conversion of absorbed dose-to-graphite in a graphite phantom to absorbed dose-to-water in a water phantom is performed by water to graphite stopping power ratios. If, however, the charged particle fluence is not equal at equivalent depths in graphite and water, a fluence correction factor, kfl, is required as well. This is particularly relevant to the derivation of absorbed dose-to-water, the quantity of interest in radiotherapy, from a measurement of absorbed dose-to-graphite obtained with a graphite calorimeter. In this work, fluence correction factors for the conversion from dose-to-graphite in a graphite phantom to dose-to-water in a water phantom for 60 MeV mono-energetic protons were calculated using an analytical model and five different Monte Carlo codes (Geant4, FLUKA, MCNPX, SHIELD-HIT and McPTRAN.MEDIA). In general the fluence correction factors are found to be close to unity and the analytical and Monte Carlo codes give consistent values when considering the differences in secondary particle transport. When considering only protons the fluence correction factors are unity at the surface and increase with depth by 0.5% to 1.5% depending on the code. When the fluence of all charged particles is considered, the fluence correction factor is about 0.5% lower than unity at shallow depths predominantly due to the contributions from alpha particles and increases to values above unity near the Bragg peak. Fluence correction factors directly derived from the fluence distributions differential in energy at equivalent depths in water and graphite can be described by kfl = 0.9964 + 0.0024·zw-eq with a relative standard uncertainty of 0.2%. Fluence correction factors derived from a ratio of calculated doses at equivalent depths in water and graphite can be described by kfl = 0.9947 + 0.0024·zw-eq with a relative standard uncertainty of 0.3%. These results are of direct relevance to graphite calorimetry in low-energy protons but given that the fluence correction factor is almost solely influenced by non-elastic nuclear interactions the results are also relevant for plastic phantoms that consist of carbon, oxygen and hydrogen atoms as well as for soft tissues.

Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents

PubMed Central

Kondratyuk, Tamara P.; Park, Eun-Jung; Yu, Rui; van Breemen, Richard B.; Asolkar, Ratnakar N.; Murphy, Brian T.; Fenical, William; Pezzuto, John M.

2012-01-01

Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were isolated and identified from the fermentation broth of a marine-derived Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1, 2 and 3 inhibited TNF-α-induced NFκB activity (IC50 values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC50 values of >48.6, 15.1, and 8.0 μM, respectively). PGE2 production was blocked with greater efficacy (IC50 values of 7.5, 0.89, and 0.63 μM, respectively), possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2. Treatment of cultured HL-60 cells led to dose-dependent accumulation in the subG1 compartment of the cell cycle, as a result of apoptosis. These data provide greater insight on the biological potential of phenazine derivatives, and some guidance on how various substituents may alter potential anti-inflammatory and anti-cancer effects. PMID:22412812

Comparison of Systemic Toxicity between Botulinum Toxin Subtypes A1 and A2 in Mice and Rats.

PubMed

Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Kozaki, Shunji; Kaji, Ryuji; Ginnaga, Akihiro

2015-06-01

The adverse events caused by botulinum toxin type A (subtype A1) product, thought to be after-effects of toxin diffusion after high-dose administration, have become serious issues. A preparation showing less diffusion in the body than existing drugs has been sought. We have attempted to produce neurotoxin derived from subtype A2 (A2NTX) with an amino acid sequence different from that of neurotoxin derived from subtype A1 (A1NTX). In this study, to investigate whether A2NTX has the potential to resolve these issues, we compared the safety of A2NTX, a progenitor toxin derived from subtype A1 (A1 progenitor toxin) and A1NTX employing the intramuscular lethal dose 50% (im LD50) in mice and rats and the compound muscle action potential (CMAP) in rats. Mouse im LD50 values for A1 progenitor toxin and A2NTX were 93 and 166 U/kg, respectively, and the rat im LD50 values were 117 and 153 U/kg, respectively. In the rat CMAP test, the dose on the contralateral side, which caused a 50% reduction in the CMAP amplitude, that is, CMAP-TD50 , was calculated as 19.0, 16.6 and 28.7 U/kg for A1 progenitor toxin, A1NTX and A2NTX, respectively. The results indicate that A2NTX is safer than A1 progenitor toxin and A1NTX. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

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

DOE PAGES

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

2015-09-01

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

Technical note: estimating absorbed doses to the thyroid in CT.

PubMed

Huda, Walter; Magill, Dennise; Spampinato, Maria V

2011-06-01

To describe a method for estimating absorbed doses to the thyroid in patients undergoing neck CT examinations. Thyroid doses in anthropomorphic phantoms were obtained for all 23 scanner dosimetry data sets in the ImPACT CT patient dosimetry calculator. Values of relative thyroid dose [R(thy)(L)], defined as the thyroid dose for a given scan length (L) divided by the corresponding thyroid dose for a whole body scan, were determined for neck CT scans. Ratios of the maximum thyroid dose to the corresponding CTDI(vol) and [D'(thy)], were obtained for two phantom diameters. The mass-equivalent water cylinder of any patient can be derived from the neck cross-sectional area and the corresponding average Hounsfield Unit, and compared to the 16.5-cm diameter water cylinder that models the ImPACT anthropomorphic phantom neck. Published values of relative doses in water cylinders of varying diameter were used to adjust thyroid doses in the anthropomorphic phantom to those of any sized patient. Relative thyroid doses R(thy)(L) increase to unity with increasing scan length and with very small difference between scanners. A 10-cm scan centered on the thyroid would result in a dose that is, nearly 90% of the thyroid dose from a whole body scan when performed using the constant radiographic techniques. At 120 kV, the average value of D'(thy) for the 16-cm diameter was 1.17 +/- 0.05 and was independent of CT vendor and year of CT scanner, and choice of x-ray tube voltage. The corresponding average value of D'(thy) in the 32-cm diameter phantom was 2.28 +/- 0.22 and showed marked variations depending on vendor, year of introduction into clinical practice as well as x-ray tube voltage. At 120 kV, a neck equivalent to a 10-cm diameter cylinder of water would have thyroid doses 36% higher than those in the ImPACT phantom, whereas a neck equivalent to a 25-cm cylinder diameter would have thyroid doses 35% lower. Patient thyroid doses can be estimated by taking into account the amount of radiation used to perform the CT examination (CTDI(vol)) and accounting for scan length and patient anatomy (i.e., neck diameter) at the thyroid location.

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

PubMed

MacVittie, Thomas J; Farese, Ann M; Jackson, William

2015-11-01

Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total body irradiation (TBI) with 250 kVp or 2 MeV x radiation, Co gamma radiation and reactor- and nuclear weapon-derived mixed gamma: neutron-radiation, delivered at various dose rates from a total body, bilateral, rotational, or unilateral exposure aspect. The DRRs established by a probit analysis vs. linear dose relationship were characterized by two main parameters or dependent variables: a slope and LD50/30. Respective LD50/30 values for studies that used 250 kVp x radiation (five primary studies combined, n = 338), 2 MeV x radiation, Co gamma radiation, and steady-state reactor-derived mixed gamma:neutron radiation for total body uniform exposures were 521 rad [498, 542], 671 rad [632, 715], 644 rad [613, 678], and 385 rad [357, 413]. The respective slopes were steep and ranged from 0.738 to 1.316. The DRR, LD50/30 values and slopes were also determined for total body, non-uniform, unilateral, pulse-rate exposures of mixed gamma:neutron radiation derived at reactor and nuclear weapon detonations. The LD50/30 values were, respectively, 395 rad [337, 432] and 412 rad [359, 460]. Secondary data sets of limited studies that did not describe a DRR were used to support the mid-to-high lethal dose range for the H-ARS and the threshold dose range for the concurrent acute GI ARS. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in young rhesus macaques exposed to 250 kVp uniform total body x radiation without the benefit of medical management. A less substantial but consistent database demonstrated the DRR for total body exposure of differing radiation quality, dose rate and non-uniform exposure. The DRR for the H-ARS is characterized by steep slopes and relative LD50/30 values that reflect the radiation quality, exposure aspect, and dose rate over a range in time from 1954-2012.

Fluorine-labeled Dasatinib Nanoformulations as Targeted Molecular Imaging Probes in a PDGFB-driven Murine Glioblastoma Model12

PubMed Central

Benezra, Miriam; Hambardzumyan, Dolores; Penate-Medina, Oula; Veach, Darren R; Pillarsetty, Nagavarakishore; Smith-Jones, Peter; Phillips, Evan; Ozawa, Tatsuya; Zanzonico, Pat B; Longo, Valerie; Holland, Eric C; Larson, Steven M; Bradbury, Michelle S

2012-01-01

Dasatinib, a new-generation Src and platelet-derived growth factor receptor (PDGFR) inhibitor, is currently under evaluation in high-grade glioma clinical trials. To achieve optimum physicochemical and/or biologic properties, alternative drug delivery vehicles may be needed. We used a novel fluorinated dasatinib derivative (F-SKI249380), in combination with nanocarrier vehicles and metabolic imaging tools (microPET) to evaluate drug delivery and uptake in a platelet-derived growth factor B (PDGFB)-driven genetically engineered mouse model (GEMM) of high-grade glioma. We assessed dasatinib survival benefit on the basis of measured tumor volumes. Using brain tumor cells derived from PDGFB-driven gliomas, dose-dependent uptake and time-dependent inhibitory effects of F-SKI249380 on biologic activity were investigated and compared with the parent drug. PDGFR receptor status and tumor-specific targeting were non-invasively evaluated in vivo using 18F-SKI249380 and 18F-SKI249380-containing micellar and liposomal nanoformulations. A statistically significant survival benefit was found using dasatinib (95 mg/kg) versus saline vehicle (P < .001) in tumor volume-matched GEMM pairs. Competitive binding and treatment assays revealed comparable biologic properties for F-SKI249380 and the parent drug. In vivo, Significantly higher tumor uptake was observed for 18F-SKI249380-containing micelle formulations [4.9 percentage of the injected dose per gram tissue (%ID/g); P = .002] compared to control values (1.6%ID/g). Saturation studies using excess cold dasatinib showed marked reduction of tumor uptake values to levels in normal brain (1.5%ID/g), consistent with in vivo binding specificity. Using 18F-SKI249380-containing micelles as radiotracers to estimate therapeutic dosing requirements, we calculated intratumoral drug concentrations (24–60 nM) that were comparable to in vitro 50% inhibitory concentration values. 18F-SKI249380 is a PDGFR-selective tracer, which demonstrates improved delivery to PDGFB-driven high-grade gliomas and facilitates treatment planning when coupled with nanoformulations and quantitative PET imaging approaches. PMID:23308046

Effects of food on the pharmacokinetics of ponatinib in healthy subjects.

PubMed

Narasimhan, N I; Dorer, D J; Niland, K; Haluska, F; Sonnichsen, Daryl

2013-12-01

Ponatinib is a potent oral tyrosine kinase inhibitor with activity against BCR-ABL, the primary driver of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia. This single-centre, single-dose, randomized, open-label, three-period crossover study evaluated the pharmacokinetics and bioavailability of a single oral dose of ponatinib (45-mg tablet) under fasting conditions and following consumption of high- and low-fat meals by healthy subjects. Subjects were randomly assigned to one of the six possible treatment sequences, each evaluating three ponatinib 45-mg treatments: administered under fasting conditions; administered after a high-fat meal; or administered after a standardized low-fat meal. The high-fat meal derived approximately 50% of its total caloric content from fat, with approximately 150, 250 and 500-600 calories derived from protein, carbohydrates and fat, respectively (total of approximately 900-1000 calories). The standardized low-fat meal derived no more than 20% of total caloric content from fat, with approximately 56, 428 and 63 calories derived from protein, carbohydrates and fat, respectively (total of approximately 547 calories). During each of the three treatment periods, blood samples were collected predose and at 13 time points over the 96-h post-dose interval. Plasma concentrations of ponatinib were measured by liquid chromatography/tandem mass spectrometry. Mixed-model analyses of variance (anova) were performed on natural log-transformed PK parameters Cmax and AUC0-∞. Geometric mean maximum plasma concentration (Cmax) values for the fasted, low-fat and high-fat regimens were 54·7, 51·6 and 51·5 ng/mL, respectively. Geometric mean area under the concentration-time curve from time zero to infinity (AUC0-∞) values for the fasted, low-fat and high-fat regimens were 1273, 1244 and 1392 h × ng/mL, respectively. All limits of the 90% CIs of the estimated geometric mean ratios for Cmax and all AUC comparisons fell within the 80%-125% margins. These results indicate that consumption of a high- or low-fat meal within 30 min prior to administration of ponatinib had no effect on the single-dose pharmacokinetics of ponatinib. Food does not affect the single-dose pharmacokinetics of ponatinib. These data demonstrate that ponatinib may be administered with or without food. © 2013 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd.

Radiation-induced change of optical property of hydroxypropyl cellulose hydrogel containing methacrylate compounds: As a basis for development of a new type of radiation dosimeter

NASA Astrophysics Data System (ADS)

Yamashita, Shinichi; Hiroki, Akihiro; Taguchi, Mitsumasa

2014-08-01

Hydrogels with matrix of a cellulose derivative, hydrogel of hydroxpropyl cellulose (HPC), containing two of methacrylate compounds (2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) dimethacrylate (9G)) were irradiated with 60Co γ-rays. The gels become white with irradiation, and thus, could be candidates of a new type of radiation dosimeter utilized in radiation therapy because the gels become white with irradiation and can be confirmed directly by human eyes even at low doses of 1-2 Gy. Radiation-induced change of optical properties, haze value and UV-vis absorption spectrum, of the irradiated gels was measured. Dose response of the white turbidity appearance was different for different compositions of the methacrylate compounds as well as for different dose rates. The degree of the radiation-induced white turbidity was quantified by measuring haze value, showing linear dose response in low dose region (<2 Gy). We also analyzed the gels with a UV-vis spectrometer and HEMA- and 9G-rich gels gave different spectral shapes, indicating that there are at least two mechanisms leading to the white turbidity. In addition, dose rate dependence was smaller for 9G-rich gels than HEMA-rich gels in the range of 0.015-1.5 Gy/min.

Preliminary results of an attempt to predict over apron occupational exposure of cardiologists from cardiac fluoroscopy procedures based on DAP (dose area product) values.

PubMed

Toossi, Mohammad Taghi Bahreyni; Mehrpouyan, Mohammad; Nademi, Hossein; Fardid, Reza

2015-03-01

This study is an effort to propose a mathematical relation between the occupational exposure measured by a dosimeter worn on a lead apron in the chest region of a cardiologist and the dose area product (DAP) recorded by a meter attached to the X-ray tube. We aimed to determine factors by which DAP values attributed to patient exposure could be converted to the over-apron entrance surface air kerma incurred by cardiologists during an angiographic procedure. A Rando phantom representing a patient was exposed by an X-ray tube from 77 pre-defined directions. DAP value for each exposure angle was recorded. Cardiologist exposure was measured by a Radcal ionization chamber 10X5-180 positioned on a second phantom representing the physician. The exposure conversion factor was determined as the quotient of over apron exposure by DAP value. To verify the validity of this method, the over-apron exposure of a cardiologist was measured using the ionization chamber while performing coronary angiography procedures on 45 patients weighing on average 75 ± 5 kg. DAP values for the corresponding procedures were also obtained. Conversion factors obtained from phantom exposure were applied to the patient DAP values to calculate physician exposure. Mathematical analysis of our results leads us to conclude that a linear relationship exists between two sets of data: (a) cardiologist exposure measured directly by Radcal & DAP values recorded by the X-ray machine system (R (2) = 0.88), (b) specialist measured and estimated exposure derived from DAP values (R (2) = 0.91). The results demonstrate that cardiologist occupational exposure can be derived from patient data accurately.

Assessment of the effects of CT dose in averaged x-ray CT images of a dose-sensitive polymer gel

NASA Astrophysics Data System (ADS)

Kairn, T.; Kakakhel, M. B.; Johnston, H.; Jirasek, A.; Trapp, J. V.

2015-01-01

The signal-to-noise ratio achievable in x-ray computed tomography (CT) images of polymer gels can be increased by averaging over multiple scans of each sample. However, repeated scanning delivers a small additional dose to the gel which may compromise the accuracy of the dose measurement. In this study, a NIPAM-based polymer gel was irradiated and then CT scanned 25 times, with the resulting data used to derive an averaged image and a "zero-scan" image of the gel. Comparison between these two results and the first scan of the gel showed that the averaged and zero-scan images provided better contrast, higher contrast-to- noise and higher signal-to-noise than the initial scan. The pixel values (Hounsfield units, HU) in the averaged image were not noticeably elevated, compared to the zero-scan result and the gradients used in the linear extrapolation of the zero-scan images were small and symmetrically distributed around zero. These results indicate that the averaged image was not artificially lightened by the small, additional dose delivered during CT scanning. This work demonstrates the broader usefulness of the zero-scan method as a means to verify the dosimetric accuracy of gel images derived from averaged x-ray CT data.

In vivo recovery of factor VIII and factor IX: intra- and interindividual variance in a clinical setting.

PubMed

Björkman, S; Folkesson, A; Berntorp, E

2007-01-01

In vivo recovery (IVR) is traditionally used as a parameter to characterize the pharmacokinetic properties of coagulation factors. It has also been suggested that dosing of factor VIII (FVIII) and factor IX (FIX) can be adjusted according to the need of the individual patient, based on an individually determined IVR value. This approach, however, requires that the individual IVR value is more reliably representative for the patient than the mean value in the population, i.e. that there is less variance within than between the individuals. The aim of this investigation was to compare intra- and interindividual variance in IVR (as U dL1 per U kg1) for FVIII and plasma-derived FIX in a cohort of non-bleeding patients with haemophilia. The data were collected retrospectively from six clinical studies, yielding 297 IVR determinations in 50 patients with haemophilia A and 93 determinations in 13 patients with haemophilia B. For FVIII, the mean variance within patients exceeded the between-patient variance. Thus, an individually determined IVR value is apparently no more informative than an average, or population, value for the dosing of FVIII. There was no apparent relationship between IVR and age of the patient (1.5-67 years). For FIX, the mean variance within patients was lower than the between-patient variance, and there was a significant positive relationship between IVR and age (13-69 years). From these data, it seems probable that using an individual IVR confers little advantage in comparison to using an age-specific population mean value. Dose tailoring of coagulation factor treatment has been applied successfully after determination of the entire single-dose curve of FVIII:C or FIX:C in the patient and calculation of the relevant pharmacokinetic parameters. However, the findings presented here do not support the assumption that dosing of FVIII or FIX can be individualized on the basis of a clinically determined IVR value.

Estimating patient dose from CT exams that use automatic exposure control: Development and validation of methods to accurately estimate tube current values.

PubMed

McMillan, Kyle; Bostani, Maryam; Cagnon, Christopher H; Yu, Lifeng; Leng, Shuai; McCollough, Cynthia H; McNitt-Gray, Michael F

2017-08-01

The vast majority of body CT exams are performed with automatic exposure control (AEC), which adapts the mean tube current to the patient size and modulates the tube current either angularly, longitudinally or both. However, most radiation dose estimation tools are based on fixed tube current scans. Accurate estimates of patient dose from AEC scans require knowledge of the tube current values, which is usually unavailable. The purpose of this work was to develop and validate methods to accurately estimate the tube current values prescribed by one manufacturer's AEC system to enable accurate estimates of patient dose. Methods were developed that took into account available patient attenuation information, user selected image quality reference parameters and x-ray system limits to estimate tube current values for patient scans. Methods consistent with AAPM Report 220 were developed that used patient attenuation data that were: (a) supplied by the manufacturer in the CT localizer radiograph and (b) based on a simulated CT localizer radiograph derived from image data. For comparison, actual tube current values were extracted from the projection data of each patient. Validation of each approach was based on data collected from 40 pediatric and adult patients who received clinically indicated chest (n = 20) and abdomen/pelvis (n = 20) scans on a 64 slice multidetector row CT (Sensation 64, Siemens Healthcare, Forchheim, Germany). For each patient dataset, the following were collected with Institutional Review Board (IRB) approval: (a) projection data containing actual tube current values at each projection view, (b) CT localizer radiograph (topogram) and (c) reconstructed image data. Tube current values were estimated based on the actual topogram (actual-topo) as well as the simulated topogram based on image data (sim-topo). Each of these was compared to the actual tube current values from the patient scan. In addition, to assess the accuracy of each method in estimating patient organ doses, Monte Carlo simulations were performed by creating voxelized models of each patient, identifying key organs and incorporating tube current values into the simulations to estimate dose to the lungs and breasts (females only) for chest scans and the liver, kidney, and spleen for abdomen/pelvis scans. Organ doses from simulations using the actual tube current values were compared to those using each of the estimated tube current values (actual-topo and sim-topo). When compared to the actual tube current values, the average error for tube current values estimated from the actual topogram (actual-topo) and simulated topogram (sim-topo) was 3.9% and 5.8% respectively. For Monte Carlo simulations of chest CT exams using the actual tube current values and estimated tube current values (based on the actual-topo and sim-topo methods), the average differences for lung and breast doses ranged from 3.4% to 6.6%. For abdomen/pelvis exams, the average differences for liver, kidney, and spleen doses ranged from 4.2% to 5.3%. Strong agreement between organ doses estimated using actual and estimated tube current values provides validation of both methods for estimating tube current values based on data provided in the topogram or simulated from image data. © 2017 American Association of Physicists in Medicine.

Organ doses for reference pediatric and adolescent patients undergoing computed tomography estimated by Monte Carlo simulation

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

Lee, Choonsik; Kim, Kwang Pyo; Long, Daniel J.

Purpose: To establish an organ dose database for pediatric and adolescent reference individuals undergoing computed tomography (CT) examinations by using Monte Carlo simulation. The data will permit rapid estimates of organ and effective doses for patients of different age, gender, examination type, and CT scanner model. Methods: The Monte Carlo simulation model of a Siemens Sensation 16 CT scanner previously published was employed as a base CT scanner model. A set of absorbed doses for 33 organs/tissues normalized to the product of 100 mAs and CTDI{sub vol} (mGy/100 mAs mGy) was established by coupling the CT scanner model with age-dependentmore » reference pediatric hybrid phantoms. A series of single axial scans from the top of head to the feet of the phantoms was performed at a slice thickness of 10 mm, and at tube potentials of 80, 100, and 120 kVp. Using the established CTDI{sub vol}- and 100 mAs-normalized dose matrix, organ doses for different pediatric phantoms undergoing head, chest, abdomen-pelvis, and chest-abdomen-pelvis (CAP) scans with the Siemens Sensation 16 scanner were estimated and analyzed. The results were then compared with the values obtained from three independent published methods: CT-Expo software, organ dose for abdominal CT scan derived empirically from patient abdominal circumference, and effective dose per dose-length product (DLP). Results: Organ and effective doses were calculated and normalized to 100 mAs and CTDI{sub vol} for different CT examinations. At the same technical setting, dose to the organs, which were entirely included in the CT beam coverage, were higher by from 40 to 80% for newborn phantoms compared to those of 15-year phantoms. An increase of tube potential from 80 to 120 kVp resulted in 2.5-2.9-fold greater brain dose for head scans. The results from this study were compared with three different published studies and/or techniques. First, organ doses were compared to those given by CT-Expo which revealed dose differences up to several-fold when organs were partially included in the scan coverage. Second, selected organ doses from our calculations agreed to within 20% of values derived from empirical formulae based upon measured patient abdominal circumference. Third, the existing DLP-to-effective dose conversion coefficients tended to be smaller than values given in the present study for all examinations except head scans. Conclusions: A comprehensive organ/effective dose database was established to readily calculate doses for given patients undergoing different CT examinations. The comparisons of our results with the existing studies highlight that use of hybrid phantoms with realistic anatomy is important to improve the accuracy of CT organ dosimetry. The comprehensive pediatric dose data developed here are the first organ-specific pediatric CT scan database based on the realistic pediatric hybrid phantoms which are compliant with the reference data from the International Commission on Radiological Protection (ICRP). The organ dose database is being coupled with an adult organ dose database recently published as part of the development of a user-friendly computer program enabling rapid estimates of organ and effective dose doses for patients of any age, gender, examination types, and CT scanner model.« less

Cathepsin B inhibitory activities of three new phthalate derivatives isolated from seahorse, Hippocampus Kuda Bleeler.

PubMed

Li, Yong; Qian, Zhong-Ji; Kim, Se-Kwon

2008-12-01

Three new phthalate acid derivatives, 2,12-diethyl-11-methylhexadecyl 2-ethyl-11-methylhexadecyl phthalate (1), 2-ethyldecyl 2-ethylundecyl phthalate (2), and bis(2-ethyldodecyl) phthalate (3), were isolated from seahorse, Hippocampus Kuda Bleeler, together with a known natural analog bis(2-ethylheptyl) phthalate (4). The structures of these compounds were elucidated mainly by means of the comprehensive analysis of their NMR spectroscopic data. The four phthalate derivatives showed dose-dependent cathepsin B inhibitions activities with IC(50) values of 0.13 mM (1), 0.21 mM (2), 0.18 mM (3), and 0.29 mM (4), respectively.

Interim methods for development of inhalation reference concentrations. Draft report

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

Blackburn, K.; Dourson, M.; Erdreich, L.

1990-08-01

An inhalation reference concentration (RfC) is an estimate of continuous inhalation exposure over a human lifetime that is unlikely to pose significant risk of adverse noncancer health effects and serves as a benchmark value for assisting in risk management decisions. Derivation of an RfC involves dose-response assessment of animal data to determine the exposure levels at which no significant increase in the frequency or severity of adverse effects between the exposed population and its appropriate control exists. The assessment requires an interspecies dose extrapolation from a no-observed-adverse-effect level (NOAEL) exposure concentration of an animal to a human equivalent NOAEL (NOAEL(HBC)).more » The RfC is derived from the NOAEL(HBC) by the application of generally order-of-magnitude uncertainty factors. Intermittent exposure scenarios in animals are extrapolated to chronic continuous human exposures. Relationships between external exposures and internal doses depend upon complex simultaneous and consecutive processes of absorption, distribution, metabolism, storage, detoxification, and elimination. To estimate NOAEL(HBC)s when chemical-specific physiologically-based pharmacokinetic models are not available, a dosimetric extrapolation procedure based on anatomical and physiological parameters of the exposed human and animal and the physical parameters of the toxic chemical has been developed which gives equivalent or more conservative exposure concentrations values than those that would be obtained with a PB-PK model.« less

Evaluation of triclosan in Minnesota lakes and rivers: Part II - human health risk assessment.

PubMed

Yost, Lisa J; Barber, Timothy R; Gentry, P Robinan; Bock, Michael J; Lyndall, Jennifer L; Capdevielle, Marie C; Slezak, Brian P

2017-08-01

Triclosan, an antimicrobial compound found in consumer products, has been detected in low concentrations in Minnesota municipal wastewater treatment plant (WWTP) effluent. This assessment evaluates potential health risks for exposure of adults and children to triclosan in Minnesota surface water, sediments, and fish. Potential exposures via fish consumption are considered for recreational or subsistence-level consumers. This assessment uses two chronic oral toxicity benchmarks, which bracket other available toxicity values. The first benchmark is a lower bound on a benchmark dose associated with a 10% risk (BMDL 10 ) of 47mg per kilogram per day (mg/kg-day) for kidney effects in hamsters. This value was identified as the most sensitive endpoint and species in a review by Rodricks et al. (2010) and is used herein to derive an estimated reference dose (RfD (Rodricks) ) of 0.47mg/kg-day. The second benchmark is a reference dose (RfD) of 0.047mg/kg-day derived from a no observed adverse effect level (NOAEL) of 10mg/kg-day for hepatic and hematopoietic effects in mice (Minnesota Department of Health [MDH] 2014). Based on conservative assumptions regarding human exposures to triclosan, calculated risk estimates are far below levels of concern. These estimates are likely to overestimate risks for potential receptors, particularly because sample locations were generally biased towards known discharges (i.e., WWTP effluent). Copyright © 2017 Elsevier Inc. All rights reserved.

Technical aspects of the integration of three-dimensional treatment planning dose parameters (GEC-ESTRO Working Group) into pre-implant planning for LDR gynecological interstitial brachytherapy.

PubMed

Chi, A; Gao, M; Nguyen, N P; Albuquerque, K

2009-06-01

This study investigates the technical feasibility of pre-implant image-based treatment planning for LDR GYN interstitial brachytherapy(IB) based on the GEC-ESTRO guidelines. Initially, a virtual plan is generated based on the prescription dose and GEC-ESTRO defined OAR dose constraints with a pre-implant CT. After the actual implant, a regular diagnostic CT was obtained and fused with our pre-implant scan/initial treatment plan in our planning software. The Flexi-needle position changes, and treatment plan modifications were made if needed. Dose values were normalized to equivalent doses in 2 Gy fractions (LQED 2 Gy) derived from the linear-quadratic model with alpha/beta of 3 for late responding tissues and alpha/beta of 10 for early responding tissues. D(90) to the CTV, which was gross tumor (GTV) at the time of brachytherapy with a margin to count for microscopic disease, was 84.7 +/- 4.9% of the prescribed dose. The OAR doses were evaluated by D(2cc) (EBRT+IB). Mean D(2cc) values (LQED(2Gy)) for the rectum, bladder, sigmoid, and small bowel were the following: 63.7 +/- 8.4 Gy, 61.2 +/- 6.9 Gy, 48.0 +/- 3.5 Gy, and 49.9 +/- 4.2 Gy. This study confirms the feasibility of applying the GEC-ESTRO recommended dose parameters in pre-implant CT-based treatment planning in GYN IB. In the process, this pre-implant technique also demonstrates a good approximation of the target volume dose coverage, and doses to the OARs.

Absolute measurement of LDR brachytherapy source emitted power: Instrument design and initial measurements.

PubMed

Malin, Martha J; Palmer, Benjamin R; DeWerd, Larry A

2016-02-01

Energy-based source strength metrics may find use with model-based dose calculation algorithms, but no instruments exist that can measure the energy emitted from low-dose rate (LDR) sources. This work developed a calorimetric technique for measuring the power emitted from encapsulated low-dose rate, photon-emitting brachytherapy sources. This quantity is called emitted power (EP). The measurement methodology, instrument design and performance, and EP measurements made with the calorimeter are presented in this work. A calorimeter operating with a liquid helium thermal sink was developed to measure EP from LDR brachytherapy sources. The calorimeter employed an electrical substitution technique to determine the power emitted from the source. The calorimeter's performance and thermal system were characterized. EP measurements were made using four (125)I sources with air-kerma strengths ranging from 2.3 to 5.6 U and corresponding EPs of 0.39-0.79 μW, respectively. Three Best Medical 2301 sources and one Oncura 6711 source were measured. EP was also computed by converting measured air-kerma strengths to EPs through Monte Carlo-derived conversion factors. The measured EP and derived EPs were compared to determine the accuracy of the calorimeter measurement technique. The calorimeter had a noise floor of 1-3 nW and a repeatability of 30-60 nW. The calorimeter was stable to within 5 nW over a 12 h measurement window. All measured values agreed with derived EPs to within 10%, with three of the four sources agreeing to within 4%. Calorimeter measurements had uncertainties ranging from 2.6% to 4.5% at the k = 1 level. The values of the derived EPs had uncertainties ranging from 2.9% to 3.6% at the k = 1 level. A calorimeter capable of measuring the EP from LDR sources has been developed and validated for (125)I sources with EPs between 0.43 and 0.79 μW.

Assessment of the anticonvulsant potency of various benzylamide derivatives in the mouse maximal electroshock-induced seizure threshold model.

PubMed

Świąder, Mariusz J; Paruszewski, Ryszard; Łuszczki, Jarogniew J

2016-04-01

The aim of this study was to assess the anticonvulsant potency of 6 various benzylamide derivatives [i.e., nicotinic acid benzylamide (Nic-BZA), picolinic acid 2-fluoro-benzylamide (2F-Pic-BZA), picolinic acid benzylamide (Pic-BZA), (RS)-methyl-alanine-benzylamide (Me-Ala-BZA), isonicotinic acid benzylamide (Iso-Nic-BZA), and (R)-N-methyl-proline-benzylamide (Me-Pro-BZA)] in the threshold for maximal electroshock (MEST)-induced seizures in mice. Electroconvulsions (seizure activity) were produced in mice by means of a current (sine-wave, 50Hz, 500V, strength from 4 to 18mA, ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Nic-BZA, 2F-Pic-BZA, Pic-BZA, Me-Ala-BZA, Iso-Nic-BZA, and Me-Pro-BZA administered systemically (ip) in a dose-dependent manner increase the threshold for maximal electroconvulsions in mice. Linear regression analysis of Nic-BZA, 2F-Pic-BZA, Pic-BZA, MeAla-BZA, IsoNic-BZA, and Me-Pro-BZA doses and their corresponding threshold increases allowed determining threshold increasing doses by 20% (TID20 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID20 values in the MEST test for Nic-BZA, 2F-Pic-BZA, Pic-BZA, Me-Ala-BZA, Iso-Nic-BZA, and Me-Pro-BZA were 7.45mg/kg, 7.72mg/kg, 8.74mg/kg, 15.11mg/kg, 21.95mg/kg and 28.06mg/kg, respectively. The studied benzylamide derivatives can be arranged with respect to their anticonvulsant potency in the MEST test as follows: Nic-BZA>2F-Pic-BZA>Pic-BZA>Me-Ala-BZA>Iso-Nic-BZA>Me-Pro-BZA. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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

PubMed Central

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

2010-01-01

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

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.

SU-E-P-57: Radiation Doses Assessment to Paediatric Patients for Some Digital Diagnostic Radiology Examination in Emergency Department in Qatar

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

Abdallah, I; Aly, A; Al Naemi, H

Purpose: The aim of this study was to evaluate radiation doses to pediatric patients undergoing standard radiographic examinations using Direct Digital Radiography (DDR) in Paediatric emergency center of Hamad General Hospital (HGH) in state of Qatar and compared with regional and international Dose Reference Levels (DRLs). Methods: Entrance Skin Dose (ESD) was measured for 2739 patients for two common X-ray examinations namely: Chest AP/PA, Abdomen. Exposure factors such as kV, mAs and Focal to Skin Distance (FSD) were recorded for each patient. Tube Output was measured for a range of selected kV values. ESD for each individual patient was calculatedmore » using the tube output and the technical exposure factors for each examination. The ESD values were compared with the some international Dose Reference Levels (DRL) for all types of examinations. Results: The most performed procedure during the time of this study was chest PA/PA (85%). The mean ESD values obtained from AP chest, PA chest and AP abdomen ranged 91–120, 80–84 and 209 – 659 µGy per radiograph for different age’s groups respectively. Two protocols have been used for chest AP and PA using different radiological parameters, and the different of ESD values for chest PA and were 41% for 1 years old child, 57% for 5 years old for chest AP. Conclusion: The mean ESD were compared with those found in literature and were found to be comparable. The radiation dose can be reduced more for Chest AP and PA examination by optimization of each investigation and hence more studies are required for this task. The results presented will serve as a baseline data needed for deriving local reference doses for pediatric X-ray examinations in this local department and hence it can be applied in the whole Qatar.« less

Analysis of activation and shutdown contact dose rate for EAST neutral beam port

NASA Astrophysics Data System (ADS)

Chen, Yuqing; Wang, Ji; Zhong, Guoqiang; Li, Jun; Wang, Jinfang; Xie, Yahong; Wu, Bin; Hu, Chundong

2017-12-01

For the safe operation and maintenance of neutral beam injector (NBI), specific activity and shutdown contact dose rate of the sample material SS316 are estimated around the experimental advanced superconducting tokamak (EAST) neutral beam port. Firstly, the neutron emission intensity is calculated by TRANSP code while the neutral beam is co-injected to EAST. Secondly, the neutron activation and shutdown contact dose rates for the neutral beam sample materials SS316 are derived by the Monte Carlo code MCNP and the inventory code FISPACT-2007. The simulations indicate that the primary radioactive nuclides of SS316 are 58Co and 54Mn. The peak contact dose rate is 8.52 × 10-6 Sv/h after EAST shutdown one second. That is under the International Thermonuclear Experimental Reactor (ITER) design values 1 × 10-5 Sv/h.

Acute toxicity of heavy metals for benthic epiphytic foraminifera Pararotalia spinigera (Le Calvez) and influence of seaweed-derived DOC

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

Bresler, V.; Yanko, V.

1995-10-01

The acute toxicity of cadmium, copper, and mercury to the benthic epiphytic foraminiferan Pararotalia spinigera (Le Calvez) was investigated using seven different vital cytophysiological and cytochemical methods. The ability to enzymatically hydrolyze the fluorogenic substrates fluorescein diacetate or fluorescein dibutyrate was the most sensitive method of LC50 value determination. The LC50 (24-h) values for cadmium, copper, and mercury determined by this assay with fluorescein diacetate was 0.56, 1.4, and 0.07 {micro}M, respectively. The content of seaweed-derived dissolved organic carbon (DOC), measured by absorbance at 436 nm, produced a dramatic increase of LC50 values for the heavy metals in a dose-dependentmore » manner. ``Intact`` epiphytic foraminifera attached to seaweeds are less sensitive to acute toxicity of cadmium, copper, and mercury than are ``detached`` foraminifera.« less

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

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

Luo, Wei, E-mail: wei.luo@uky.edu; Molloy, Janelle; Aryal, Prakash

2014-02-15

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescriptionmore » doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.« less

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

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

Luo, Wei, E-mail: wei.luo@uky.edu; Molloy, Janelle; Aryal, Prakash

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescriptionmore » doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.« less

SU-E-T-146: Reference Dosimetry for Protons and Light-Ion Beams Based on Graphite Calorimetry.

PubMed

Rossomme, S; Palmans, H; Thomas, R; Lee, N; Bailey, M; Shipley, D; Al-Sulaiti, L; Cirrone, P; Romano, F; Kacperek, A; Bertrand, D; Vynckier, S

2012-06-01

The IAEA TRS-398 code of practice can be applied for the measurement of absorbed dose to water under reference conditions with an ionization chamber. For protons, the combined relative standard uncertainty on those measurements is less than 2% while for light-ion beams, it is considerably larger, i.e. 3.2%, mainly due to the higher uncertainty contributions for the water to air stopping power ration and the W air-value on the beam quality correction factors kQ,Q 0 . To decrease this uncertainty, a quantification of kQ,Q 0 is proposed using a primary standard level graphite calorimeter. This work includes numerical and experimental determinations of dose conversion factors to derive dose to water from graphite calorimetry. It also reports on the first experimental data obtained with the graphite calorimeter in proton, alpha and carbon ion beams. Firstly, the dose conversion has been calculated with by Geant4 Monte-Carlo simulations through the determination of the water to graphite stopping power ratio and the fluence correction factor. The latter factor was also derived by comparison of measured ionization curves in graphite and water. Secondly, kQ,Q 0 was obtained by comparison of the dose response of ionization chambers with that of the calorimeter. Stopping power ratios are found to vary by no more than 0.35% up to the Bragg peak, while fluence correction factors are shown to increase slightly above unity close to the Bragg peak. The comparison of the calorimeter with ionization chambers is currently under analysis. For the modulated proton beam, preliminary results on W air confirm the value recommended in TRS-398. Data in both the non-modulated proton and light-ion beams indicate higher values but further investigation of heat loss corrections is needed. The application of graphite calorimetry to proton, alpha and carbon ion beams has been demonstrated successfully. Other experimental campaigns will be held in 2012. This work is supported by the BioWin program of the Wallon Government. © 2012 American Association of Physicists in Medicine.

Evaluation of radiation dose to anthropomorphic paediatric models from positron-emitting labelled tracers

NASA Astrophysics Data System (ADS)

Xie, Tianwu; Zaidi, Habib

2014-03-01

PET uses specific molecules labelled with positron-emitting radionuclides to provide valuable biochemical and physiological information. However, the administration of radiotracers to patients exposes them to low-dose ionizing radiation, which is a concern in the paediatric population since children are at a higher cancer risk from radiation exposure than adults. Therefore, radiation dosimety calculations for commonly used positron-emitting radiotracers in the paediatric population are highly desired. We evaluate the absorbed dose and effective dose for 19 positron-emitting labelled radiotracers in anthropomorphic paediatric models including the newborn, 1-, 5-, 10- and 15-year-old male and female. This is achieved using pre-calculated S-values of positron-emitting radionuclides of UF-NCI paediatric phantoms and published biokinetic data for various radiotracers. The influence of the type of anthropomorphic model, tissue weight factors and direct human- versus mouse-derived biokinetic data on the effective dose for paediatric phantoms was also evaluated. In the case of 18F-FDG, dosimetry calculations of reference paediatric patients from various dose regimens were also calculated. Among the considered radiotracers, 18F-FBPA and 15O-water resulted in the highest and lowest effective dose in the paediatric phantoms, respectively. The ICRP 103 updated tissue-weighting factors decrease the effective dose in most cases. Substantial differences of radiation dose were observed between direct human- versus mouse-derived biokinetic data. Moreover, the effect of using voxel- versus MIRD-type models on the calculation of the effective dose was also studied. The generated database of absorbed organ dose and effective dose for various positron-emitting labelled radiotracers using new generation computational models and the new ICRP tissue-weighting factors can be used for the assessment of radiation risks to paediatric patients in clinical practice. This work also contributes to a better understanding of the factors influencing patient-specific radiation dose calculation.

A simplified approach for exit dose in vivo measurements in radiotherapy and its clinical application.

PubMed

Banjade, D P; Shrestha, S L; Shukri, A; Tajuddin, A A; Bhat, M

2002-09-01

This is a study using LiF:Mg;Ti thermoluminescent dosimeter (TLD) rods in phantoms to investigate the effect of lack of backscatter on exit dose. Comparing the measured dose with anticipated dose calculated using tissue maximum ratio (TMR) or percentage depth dose (PDD) gives rise to a correction factor. This correction factor may be applied to in-vivo dosimetry results to derive true dose to a point within the patient. Measurements in a specially designed humanoid breast phantom as well as patients undergoing radiotherapy treatment were also been done. TLDs with reproducibility of within +/- 3% (1 SD) are irradiated in a series of measurements for 6 and 10 MV photon beams from a medical linear accelerator. The measured exit doses for the different phantom thickness for 6 MV beams are found to be lowered by 10.9 to 14.0% compared to the dose derived from theoretical estimation (normalized dose at dmax). The same measurements for 10 MV beams are lowered by 9.0 to 13.5%. The variations of measured exit dose for different field sizes are found to be within 2.5%. The exit doses with added backscatter material from 2 mm up to 15 cm, shows gradual increase and the saturated values agreed within 1.5% with the expected results for both beams. The measured exit doses in humanoid breast phantom as well as in the clinical trial on patients undergoing radiotherapy also agreed with the predicted results based on phantom measurements. The authors' viewpoint is that this technique provides sufficient information to design exit surface bolus to restore build down effect in cases where part of the exit surface is being considered as a target volume. It indicates that the technique could be translated for in vivo dose measurements, which may be a conspicuous step of quality assurance in clinical practice.

Repeatability of dose painting by numbers treatment planning in prostate cancer radiotherapy based on multiparametric magnetic resonance imaging

NASA Astrophysics Data System (ADS)

van Schie, Marcel A.; Steenbergen, Peter; Viet Dinh, Cuong; Ghobadi, Ghazaleh; van Houdt, Petra J.; Pos, Floris J.; Heijmink, Stijn W. T. J. P.; van der Poel, Henk G.; Renisch, Steffen; Vik, Torbjørn; van der Heide, Uulke A.

2017-07-01

Dose painting by numbers (DPBN) refers to a voxel-wise prescription of radiation dose modelled from functional image characteristics, in contrast to dose painting by contours which requires delineations to define the target for dose escalation. The direct relation between functional imaging characteristics and DPBN implies that random variations in images may propagate into the dose distribution. The stability of MR-only prostate cancer treatment planning based on DPBN with respect to these variations is as yet unknown. We conducted a test-retest study to investigate the stability of DPBN for prostate cancer in a semi-automated MR-only treatment planning workflow. Twelve patients received a multiparametric MRI on two separate days prior to prostatectomy. The tumor probability (TP) within the prostate was derived from image features with a logistic regression model. Dose mapping functions were applied to acquire a DPBN prescription map that served to generate an intensity modulated radiation therapy (IMRT) treatment plan. Dose calculations were done on a pseudo-CT derived from the MRI. The TP and DPBN map and the IMRT dose distribution were compared between both MRI sessions, using the intraclass correlation coefficient (ICC) to quantify repeatability of the planning pipeline. The quality of each treatment plan was measured with a quality factor (QF). Median ICC values for the TP and DPBN map and the IMRT dose distribution were 0.82, 0.82 and 0.88, respectively, for linear dose mapping and 0.82, 0.84 and 0.94 for square root dose mapping. A median QF of 3.4% was found among all treatment plans. We demonstrated the stability of DPBN radiotherapy treatment planning in prostate cancer, with excellent overall repeatability and acceptable treatment plan quality. Using validated tumor probability modelling and simple dose mapping techniques it was shown that despite day-to-day variations in imaging data still consistent treatment plans were obtained.

In Vitro Evaluations and In Vivo Toxicity and Efficacy Studies of MFM501 against MRSA.

PubMed

Johari, Saiful Azmi; Mohtar, Mastura; Syed Mohamad, Sharifah Aminah; Mohammat, Mohd Fazli; Sahdan, Rohana; Mohamed, Azman; Mohamad Ridhwan, Mohamad Jemain

2017-01-01

Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC 50 values at >625  µ g/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log 10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD 50 ) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED 50 ) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.

In Vitro Evaluations and In Vivo Toxicity and Efficacy Studies of MFM501 against MRSA

PubMed Central

Mohtar, Mastura; Syed Mohamad, Sharifah Aminah; Mohammat, Mohd Fazli; Sahdan, Rohana; Mohamed, Azman; Mohamad Ridhwan, Mohamad Jemain

2017-01-01

Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates. PMID:28536702

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

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

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

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

Patient radiation doses in interventional cardiology in the U.S.: Advisory data sets and possible initial values for U.S. reference levels

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

Miller, Donald L.; Hilohi, C. Michael; Spelic, David C.

2012-10-15

Purpose: To determine patient radiation doses from interventional cardiology procedures in the U.S and to suggest possible initial values for U.S. benchmarks for patient radiation dose from selected interventional cardiology procedures [fluoroscopically guided diagnostic cardiac catheterization and percutaneous coronary intervention (PCI)]. Methods: Patient radiation dose metrics were derived from analysis of data from the 2008 to 2009 Nationwide Evaluation of X-ray Trends (NEXT) survey of cardiac catheterization. This analysis used deidentified data and did not require review by an IRB. Data from 171 facilities in 30 states were analyzed. The distributions (percentiles) of radiation dose metrics were determined for diagnosticmore » cardiac catheterizations, PCI, and combined diagnostic and PCI procedures. Confidence intervals for these dose distributions were determined using bootstrap resampling. Results: Percentile distributions (advisory data sets) and possible preliminary U.S. reference levels (based on the 75th percentile of the dose distributions) are provided for cumulative air kerma at the reference point (K{sub a,r}), cumulative air kerma-area product (P{sub KA}), fluoroscopy time, and number of cine runs. Dose distributions are sufficiently detailed to permit dose audits as described in National Council on Radiation Protection and Measurements Report No. 168. Fluoroscopy times are consistent with those observed in European studies, but P{sub KA} is higher in the U.S. Conclusions: Sufficient data exist to suggest possible initial benchmarks for patient radiation dose for certain interventional cardiology procedures in the U.S. Our data suggest that patient radiation dose in these procedures is not optimized in U.S. practice.« less

Inverse Planning Approach for 3-D MRI-Based Pulse-Dose Rate Intracavitary Brachytherapy in Cervix Cancer

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

Chajon, Enrique; Dumas, Isabelle; Touleimat, Mahmoud B.Sc.

2007-11-01

Purpose: The purpose of this study was to evaluate the inverse planning simulated annealing (IPSA) software for the optimization of dose distribution in patients with cervix carcinoma treated with MRI-based pulsed-dose rate intracavitary brachytherapy. Methods and Materials: Thirty patients treated with a technique using a customized vaginal mold were selected. Dose-volume parameters obtained using the IPSA method were compared with the classic manual optimization method (MOM). Target volumes and organs at risk were delineated according to the Gynecological Brachytherapy Group/European Society for Therapeutic Radiology and Oncology recommendations. Because the pulsed dose rate program was based on clinical experience with lowmore » dose rate, dwell time values were required to be as homogeneous as possible. To achieve this goal, different modifications of the IPSA program were applied. Results: The first dose distribution calculated by the IPSA algorithm proposed a heterogeneous distribution of dwell time positions. The mean D90, D100, and V100 calculated with both methods did not differ significantly when the constraints were applied. For the bladder, doses calculated at the ICRU reference point derived from the MOM differed significantly from the doses calculated by the IPSA method (mean, 58.4 vs. 55 Gy respectively; p = 0.0001). For the rectum, the doses calculated at the ICRU reference point were also significantly lower with the IPSA method. Conclusions: The inverse planning method provided fast and automatic solutions for the optimization of dose distribution. However, the straightforward use of IPSA generated significant heterogeneity in dwell time values. Caution is therefore recommended in the use of inverse optimization tools with clinical relevance study of new dosimetric rules.« less

Lacrimal secretion stimulants: sigma receptors and drug implications.

PubMed

Shirolkar, S; Schoenwald, R D; Barfknecht, C F; Xia, E; Cheng, B; Iwai, Y; Ignace, C C; Vidvauns, S; Newton, R E

1993-01-01

3H-DTG (1.3-di(2-[5-3H]tolyl)guanidine) or 3H-haloperidol was added to sigma-receptors (25 nM) in the presence of 25 nM spiperone and incubated with increasing concentrations of bromhexine derivatives (phenylalkylamines; 10(-9) to 10(-2)M) in membrane homogenate suspensions. IC50 values for two derivatives ranged from 3.2 to 8.8 nM for both radioligands. A preferred derivative, 7A (N,N'-dimethyl-2-phenyl-ethylamine), yielded an IC50 of 7.8 nM for 3H-haloperidol but showed much less affinity in displacing 3H-DTG (IC50 = 900 nM). Applying the technic of Bromberg [Exp. Eye Res., 40:313-320, 1985], in vitro protein secretion rates were measured following stimulation of either lacrimal gland slices or isolated, intact lacrimocytes with the compounds. In vitro protein secretion rates exhibit a dose-response relationship with increases in protein release up to a concentration of 10(-8) to 10(-4) M for various derivatives of bromhexine and 10(-4) M for carbachol. By means of Schirmer strips, tear fluid was collected over a five minute period at 10 and 60 minutes post-dosing following the topical application (50 microliters) to the right eye of New Zealand white rabbits (n = 20-24) of 7A at various concentrations. Incubation of lacrimocytes with 7A alone (10(-4) M), with haloperidol (10(-4) M) alone or in combination show that 7A is acting as an agonist to stimulate protein release, whereas haloperidol is acting as an antagonist to inhibit release. In vivo protein secretion rates also show a dose-response curve (at both 10 and 60 minutes post-dosing) for 7A that reach a statistically significant maximum in the dosed eye at a concentration of 0.15% w/v. Analysis of protein extracts using size exclusion HPLC shows an increase in secretory proteins, particularly tear-specific prealbumin.

Investigation of mine and industry dumps in the FRG in relation to a possible release of natural radioactive elements.

PubMed

Schmitz, J

1985-10-01

More than 350 dumps of mines and industries in two federal states of the FRG were recorded, measured radiometrically, evaluated, and some of them sampled. Most of the mine dumps belonged to old and smaller residues from lead/zinc and iron ore mining, while the largest depositions contain tailings of modern ore beneficiation or flyash disposal. All mine dumps from uranium exploration in Baden-Württemberg and Bavaria were investigated. The highest doses, up to 100 mSv/a, were found on the piles of the uranium exploration. These depositions, which are supervised and licensed, are followed, in terms of surface dose, by the old uncontrolled mine dumps of silver/cobalt mining with doses up to 20 mSv/a. The numerous porphyry and granite quarries show doses between 1 and 2 mSv/a, as do flyash and slag dumps. The lowest doses were found on the dumps of the hydrothermal Pb/Zn and iron ore deposits, while the slag piles of iron ore processing showed higher thorium values. Assays for Ra-226 and Pb-210 of the materials deposited confirmed the radiometric results. Analyses of seepage waters and gallery waters showed only very few values exceeding the derived drinking water concentrations.

Evaluation of World Population-Weighted Effective Dose due to Cosmic Ray Exposure

PubMed Central

Sato, Tatsuhiko

2016-01-01

After the release of the Report of the United Nations Scientific Committee of the Effects of Atomic Radiation in 2000 (UNSCEAR2000), it became commonly accepted that the world population-weighted effective dose due to cosmic-ray exposure is 0.38 mSv, with a range from 0.3 to 2 mSv. However, these values were derived from approximate projections of altitude and geographic dependences of the cosmic-ray dose rates as well as the world population. This study hence re-evaluated the population-weighted annual effective doses and their probability densities for the entire world as well as for 230 individual nations, using a sophisticated cosmic-ray flux calculation model in tandem with detailed grid population and elevation databases. The resulting world population-weighted annual effective dose was determined to be 0.32 mSv, which is smaller than the UNSCEAR’s evaluation by 16%, with a range from 0.23 to 0.70 mSv covering 99% of the world population. These values were noted to vary with the solar modulation condition within a range of approximately 15%. All assessed population-weighted annual effective doses as well as their statistical information for each nation are provided in the supplementary files annexed to this report. These data improve our understanding of cosmic-ray radiation exposures to populations globally. PMID:27650664

Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol.

PubMed

Simons, P J; Cockshott, I D; Douglas, E J; Gordon, E A; Hopkins, K; Rowland, M

1988-04-01

1. An intravenous dose of 14C-propofol (0.47 mg/kg) administered to six male volunteers was rapidly eliminated with 88% recovered in the urine in 5 days and less than 2% in faeces. 2. The dose was cleared by metabolism with less than 0.3% excreted unchanged. The major metabolites were the glucuronic acid conjugate of propofol and the glucuronic acid and sulphate conjugates of its hydroxylated derivative, 2,6-diisopropyl-1,4-quinol. Propofol glucuronide accounted for about 53% of the urinary radioactivity and was the major metabolite in plasma from 30 min post dose. 3. The blood concentration of propofol declined in a biphasic manner from a maximum mean value of 0.44 microgram/ml, 2 min after injection. The half-lives of the first and second exponential phases, mean values 5 min and 97 min respectively, varied widely among subjects. A proportion of the dose was cleared slowly, probably due to slow release from less well perfused tissues. Propofol accounted for 94% of the total blood radioactivity at 2 min but only about 6% from 3 to 8 h post dose. 4. Propofol has a volume of distribution equivalent to about 3 to 4 times body weight, and a mean total body clearance of 2.2 1/min.

Optimisation of environmental remediation: how to select and use the reference levels.

PubMed

Balonov, M; Chipiga, L; Kiselev, S; Sneve, M; Yankovich, T; Proehl, G

2018-06-01

A number of past industrial activities and accidents have resulted in the radioactive contamination of large areas at many sites around the world, giving rise to a need for remediation. According to the International Commission on Radiological Protection (ICRP) and International Atomic Energy Agency (IAEA), such situations should be managed as existing exposure situations (ExESs). Control of exposure to the public in ExESs is based on the application of appropriate reference levels (RLs) for residual doses. The implementation of this potentially fruitful concept for the optimisation of remediation in various regions is hampered by a lack of practical experience and relevant guidance. This paper suggests a generic methodology for the selection of numeric values of relevant RLs both in terms of residual annual effective dose and derived RLs (DRLs) based on an appropriate dose assessment. The value for an RL should be selected in the range of the annual residual effective dose of 1-20 mSv, depending on the prevailing circumstances for the exposure under consideration. Within this range, RL values should be chosen by the following assessment steps: (a) assessment of the projected dose, i.e. the dose to a representative person without remedial actions by means of a realistic model as opposed to a conservative model; (b) modelling of the residual dose to a representative person following application of feasible remedial actions; and (c) selection of an RL value between the projected and residual doses, taking account of the prevailing social and economic conditions. This paper also contains some recommendations for practical implementation of the selected RLs for the optimisation of public protection. The suggested methodology used for the selection of RLs (in terms of dose) and the calculation of DRLs (in terms of activity concentration in food, ambient dose rate, etc) has been illustrated by a retrospective analysis of post-Chernobyl monitoring and modelling data from the Bryansk region, Russia, 2001. From this example, it follows that analysis of real data leads to the selection of an RL from a relatively narrow annual dose range (in this case, about 2-3 mSv), from which relevant DRLs can be calculated and directly used for optimisation of the remediation programme.

Editor's Highlight: Application of Gene Set Enrichment Analysis for Identification of Chemically Induced, Biologically Relevant Transcriptomic Networks and Potential Utilization in Human Health Risk Assessment.

PubMed

Dean, Jeffry L; Zhao, Q Jay; Lambert, Jason C; Hawkins, Belinda S; Thomas, Russell S; Wesselkamper, Scott C

2017-05-01

The rate of new chemical development in commerce combined with a paucity of toxicity data for legacy chemicals presents a unique challenge for human health risk assessment. There is a clear need to develop new technologies and incorporate novel data streams to more efficiently inform derivation of toxicity values. One avenue of exploitation lies in the field of transcriptomics and the application of gene expression analysis to characterize biological responses to chemical exposures. In this context, gene set enrichment analysis (GSEA) was employed to evaluate tissue-specific, dose-response gene expression data generated following exposure to multiple chemicals for various durations. Patterns of transcriptional enrichment were evident across time and with increasing dose, and coordinated enrichment plausibly linked to the etiology of the biological responses was observed. GSEA was able to capture both transient and sustained transcriptional enrichment events facilitating differentiation between adaptive versus longer term molecular responses. When combined with benchmark dose (BMD) modeling of gene expression data from key drivers of biological enrichment, GSEA facilitated characterization of dose ranges required for enrichment of biologically relevant molecular signaling pathways, and promoted comparison of the activation dose ranges required for individual pathways. Median transcriptional BMD values were calculated for the most sensitive enriched pathway as well as the overall median BMD value for key gene members of significantly enriched pathways, and both were observed to be good estimates of the most sensitive apical endpoint BMD value. Together, these efforts support the application of GSEA to qualitative and quantitative human health risk assessment. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the public domain in the US.

Combining uncertainty factors in deriving human exposure levels of noncarcinogenic toxicants.

PubMed

Kodell, R L; Gaylor, D W

1999-01-01

Acceptable levels of human exposure to noncarcinogenic toxicants in environmental and occupational settings generally are derived by reducing experimental no-observed-adverse-effect levels (NOAELs) or benchmark doses (BDs) by a product of uncertainty factors (Barnes and Dourson, Ref. 1). These factors are presumed to ensure safety by accounting for uncertainty in dose extrapolation, uncertainty in duration extrapolation, differential sensitivity between humans and animals, and differential sensitivity among humans. The common default value for each uncertainty factor is 10. This paper shows how estimates of means and standard deviations of the approximately log-normal distributions of individual uncertainty factors can be used to estimate percentiles of the distribution of the product of uncertainty factors. An appropriately selected upper percentile, for example, 95th or 99th, of the distribution of the product can be used as a combined uncertainty factor to replace the conventional product of default factors.

Estimating skin sensitization potency from a single dose LLNA.

PubMed

Roberts, David W

2015-04-01

Skin sensitization is an important aspect of safety assessment. The mouse local lymph node assay (LLNA) developed in the 1990 s is an in vivo test used for skin sensitization hazard identification and characterization. More recently a reduced version of the LLNA (rLLNA) has been developed as a means of identifying, but not quantifying, sensitization hazard. The work presented here is aimed at enabling rLLNA data to be used to give quantitative potency information that can be used, inter alia, in modeling and read-across approaches to non-animal based potency estimation. A probit function has been derived enabling estimation of EC3 from a single dose. This has led to development of a modified version of the rLLNA, whereby as a general principle the SI value at 10%, or at a lower concentration if 10% is not testable, is used to calculate the EC3. This version of the rLLNA has been evaluated against a selection of chemicals for which full LLNA data are available, and has been shown to give EC3 values in good agreement with those derived from the full LLNA. Copyright © 2015 Elsevier Inc. All rights reserved.

Estimation and comparison of effective dose (E) in standard chest CT by organ dose measurements and dose-length-product methods and assessment of the influence of CT tube potential (energy dependency) on effective dose in a dual-source CT.

PubMed

Paul, Jijo; Banckwitz, Rosemarie; Krauss, Bernhard; Vogl, Thomas J; Maentele, Werner; Bauer, Ralf W

2012-04-01

To determine effective dose (E) during standard chest CT using an organ dose-based and a dose-length-product-based (DLP) approach for four different scan protocols including high-pitch and dual-energy in a dual-source CT scanner of the second generation. Organ doses were measured with thermo luminescence dosimeters (TLD) in an anthropomorphic male adult phantom. Further, DLP-based dose estimates were performed by using the standard 0.014mSv/mGycm conversion coefficient k. Examinations were performed on a dual-source CT system (Somatom Definition Flash, Siemens). Four scan protocols were investigated: (1) single-source 120kV, (2) single-source 100kV, (3) high-pitch 120kV, and (4) dual-energy with 100/Sn140kV with equivalent CTDIvol and no automated tube current modulation. E was then determined following recommendations of ICRP publication 103 and 60 and specific k values were derived. DLP-based estimates differed by 4.5-16.56% and 5.2-15.8% relatively to ICRP 60 and 103, respectively. The derived k factors calculated from TLD measurements were 0.0148, 0.015, 0.0166, and 0.0148 for protocol 1, 2, 3 and 4, respectively. Effective dose estimations by ICRP 103 and 60 for single-energy and dual-energy protocols show a difference of less than 0.04mSv. Estimates of E based on DLP work equally well for single-energy, high-pitch and dual-energy CT examinations. The tube potential definitely affects effective dose in a substantial way. Effective dose estimations by ICRP 103 and 60 for both single-energy and dual-energy examinations differ not more than 0.04mSv. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Population Pharmacokinetic/Pharmacodynamic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using an Indirect Response Model to Predict Low-Density Lipoprotein Cholesterol Lowering: Support for a Biologics License Application Submission: Part II.

PubMed

Nicolas, Xavier; Djebli, Nassim; Rauch, Clémence; Brunet, Aurélie; Hurbin, Fabrice; Martinez, Jean-Marie; Fabre, David

2018-05-03

Alirocumab, a human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol levels. This analysis aimed to develop and qualify a population pharmacokinetic/pharmacodynamic model for alirocumab based on pooled data obtained from 13 phase I/II/III clinical trials. From a dataset of 2799 individuals (14,346 low-density lipoprotein-cholesterol values), individual pharmacokinetic parameters from the population pharmacokinetic model presented in Part I of this series were used to estimate alirocumab concentrations. As a second step, we then developed the current population pharmacokinetic/pharmacodynamic model using an indirect response model with a Hill coefficient, parameterized with increasing low-density lipoprotein cholesterol elimination, to relate alirocumab concentrations to low-density lipoprotein cholesterol values. The population pharmacokinetic/pharmacodynamic model allowed the characterization of the pharmacokinetic/pharmacodynamic properties of alirocumab in the target population and estimation of individual low-density lipoprotein cholesterol levels and derived pharmacodynamic parameters (the maximum decrease in low-density lipoprotein cholesterol values from baseline and the difference between baseline low-density lipoprotein cholesterol and the pre-dose value before the next alirocumab dose). Significant parameter-covariate relationships were retained in the model, with a total of ten covariates (sex, age, weight, free baseline PCSK9, total time-varying PCSK9, concomitant statin administration, total baseline PCSK9, co-administration of high-dose statins, disease status) included in the final population pharmacokinetic/pharmacodynamic model to explain between-subject variability. Nevertheless, the high number of covariates included in the model did not have a clinically meaningful impact on model-derived pharmacodynamic parameters. This model successfully allowed the characterization of the population pharmacokinetic/pharmacodynamic properties of alirocumab in its target population and the estimation of individual low-density lipoprotein cholesterol levels.

Engineering the thermal conductivity along an individual silicon nanowire by selective helium ion irradiation.

PubMed

Zhao, Yunshan; Liu, Dan; Chen, Jie; Zhu, Liyan; Belianinov, Alex; Ovchinnikova, Olga S; Unocic, Raymond R; Burch, Matthew J; Kim, Songkil; Hao, Hanfang; Pickard, Daniel S; Li, Baowen; Thong, John T L

2017-06-27

The ability to engineer the thermal conductivity of materials allows us to control the flow of heat and derive novel functionalities such as thermal rectification, thermal switching and thermal cloaking. While this could be achieved by making use of composites and metamaterials at bulk length-scales, engineering the thermal conductivity at micro- and nano-scale dimensions is considerably more challenging. In this work, we show that the local thermal conductivity along a single Si nanowire can be tuned to a desired value (between crystalline and amorphous limits) with high spatial resolution through selective helium ion irradiation with a well-controlled dose. The underlying mechanism is understood through molecular dynamics simulations and quantitative phonon-defect scattering rate analysis, where the behaviour of thermal conductivity with dose is attributed to the accumulation and agglomeration of scattering centres at lower doses. Beyond a threshold dose, a crystalline-amorphous transition was observed.

Engineering the thermal conductivity along an individual silicon nanowire by selective helium ion irradiation

PubMed Central

Zhao, Yunshan; Liu, Dan; Chen, Jie; Zhu, Liyan; Belianinov, Alex; Ovchinnikova, Olga S.; Unocic, Raymond R.; Burch, Matthew J.; Kim, Songkil; Hao, Hanfang; Pickard, Daniel S.; Li, Baowen; Thong, John T. L.

2017-01-01

The ability to engineer the thermal conductivity of materials allows us to control the flow of heat and derive novel functionalities such as thermal rectification, thermal switching and thermal cloaking. While this could be achieved by making use of composites and metamaterials at bulk length-scales, engineering the thermal conductivity at micro- and nano-scale dimensions is considerably more challenging. In this work, we show that the local thermal conductivity along a single Si nanowire can be tuned to a desired value (between crystalline and amorphous limits) with high spatial resolution through selective helium ion irradiation with a well-controlled dose. The underlying mechanism is understood through molecular dynamics simulations and quantitative phonon-defect scattering rate analysis, where the behaviour of thermal conductivity with dose is attributed to the accumulation and agglomeration of scattering centres at lower doses. Beyond a threshold dose, a crystalline-amorphous transition was observed. PMID:28653663

Engineering the thermal conductivity along an individual silicon nanowire by selective helium ion irradiation

DOE PAGES

Zhao, Yunshan; Liu, Dan; Chen, Jie; ...

2017-06-27

The ability to engineer the thermal conductivity of materials allows us to control the flow of heat and derive novel functionalities such as thermal rectification, thermal switching and thermal cloaking. While this could be achieved by making use of composites and metamaterials at bulk length-scales, engineering the thermal conductivity at micro- and nano-scale dimensions is considerably more challenging. Here, we show that the local thermal conductivity along a single Si nanowire can be tuned to a desired value (between crystalline and amorphous limits) with high spatial resolution through selective helium ion irradiation with a well-controlled dose. The underlying mechanism ismore » understood through molecular dynamics simulations and quantitative phonon-defect scattering rate analysis, where the behaviour of thermal conductivity with dose is attributed to the accumulation and agglomeration of scattering centres at lower doses. Finally, we observed threshold dose beyond a crystalline-amorphous transition.« less

Engineering the thermal conductivity along an individual silicon nanowire by selective helium ion irradiation

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

Zhao, Yunshan; Liu, Dan; Chen, Jie

The ability to engineer the thermal conductivity of materials allows us to control the flow of heat and derive novel functionalities such as thermal rectification, thermal switching and thermal cloaking. While this could be achieved by making use of composites and metamaterials at bulk length-scales, engineering the thermal conductivity at micro- and nano-scale dimensions is considerably more challenging. Here, we show that the local thermal conductivity along a single Si nanowire can be tuned to a desired value (between crystalline and amorphous limits) with high spatial resolution through selective helium ion irradiation with a well-controlled dose. The underlying mechanism ismore » understood through molecular dynamics simulations and quantitative phonon-defect scattering rate analysis, where the behaviour of thermal conductivity with dose is attributed to the accumulation and agglomeration of scattering centres at lower doses. Finally, we observed threshold dose beyond a crystalline-amorphous transition.« less

WE-DE-201-07: Measurement of Real-Time Dose for Tandem and Ovoid Brachytherapy Procedures Using a High Precision Optical Fiber Radiation Detector

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

Belley, MD; Current Address Rhode Island Hospital, Providence, RI; Faught, A

Purpose: Development of a novel on-line dosimetry tool is needed to move toward patient-specific quality assurance measurements for Ir-192 HDR brachytherapy to verify accurate dose delivery to the intended location. This work describes the development and use of a nano-crystalline yttrium oxide inorganic scintillator based optical-fiber detector capable of acquiring real-time high-precision dose measurements during tandem and ovoid (T&O) gynecological (GYN) applicator Ir-192 HDR brachytherapy procedures. Methods: An optical-fiber detector was calibrated by acquiring light output measurements in liquid water at 3, 5, 7, and 9cm radial source-detector-distances from an Ir-192 HDR source. A regression model was fit to themore » data to describe the relative light output per unit dose (TG-43 derived) as a function of source-detector-distance. Next, the optical-fiber detector was attached to a vaginal balloon fixed to a Varian Fletcher-Suit-Delclos-style applicator (to mimic clinical setup), and localized by acquiring high-resolution computed tomography (CT) images. To compare the physical point dose to the TPS calculated values (TG-43 and Acuros-BV), a phantom measurement was performed, by submerging the T&O applicator in a liquid water bath and delivering a treatment template representative of a clinical T&O procedure. The fiber detector collected scintillation signal as a function of time, and the calibration data was applied to calculate both real-time dose rate, and cumulative dose. Results: Fiber cumulative dose values were 100.0cGy, 94.3cGy, and 348.9cGy from the tandem, left ovoid, and right ovoid dwells, respectively (total of 443.2cGy). A plot of real time dose rate during the treatment was also acquired. The TPS values at the fiber location were 458.4cGy using TG-43, and 437.6cGy using Acuros-BV calculated as Dm,m (per TG-186). Conclusion: The fiber measured dose value agreement was 3% vs TG-43 and −1% vs Acuros-BV. This fiber detector opens up new possibilities for performing patient-specific quality assurance for Ir-192 HDR GYN procedures. Funding from Coulter Foundation, Duke Bio-medical Engineering. Company is being created around the detector technology. Duke holds patents on the technology.« less

WE-AB-202-02: Incorporating Regional Ventilation Function in Predicting Radiation Fibrosis After Concurrent Chemoradiotherapy for Lung Cancer

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

Lan, F; Jeudy, J; Tseng, H

Purpose: To investigate the incorporation of pre-therapy regional ventilation function in predicting radiation fibrosis (RF) in stage III non-small-cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: 37 stage III NSCLC patients were retrospectively studied. Patients received one cycle of cisplatin-gemcitabine, followed by two to three cycles of cisplatin-etoposide concurrently with involved-field thoracic radiotherapy between 46 and 66 Gy (2 Gy per fraction). Pre-therapy regional ventilation images of the lung were derived from 4DCT via a density-change-based image registration algorithm with mass correction. RF was evaluated at 6-months post-treatment using radiographic scoring based on airway dilation and volumemore » loss. Three types of ipsilateral lung metrics were studied: (1) conventional dose-volume metrics (V20, V30, V40, and mean-lung-dose (MLD)), (2) dose-function metrics (fV20, fV30, fV40, and functional mean-lung-dose (fMLD) generated by combining regional ventilation and dose), and (3) dose-subvolume metrics (sV20, sV30, sV40, and subvolume mean-lung-dose (sMLD) defined as the dose-volume metrics computed on the sub-volume of the lung with at least 60% of the quantified maximum ventilation status). Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to evaluate the predictability of these metrics for RF. Results: In predicting airway dilation, the area under the ROC curve (AUC) values for (V20, MLD), (fV20, fMLD), and (sV20, and sMLD) were (0.76, 0.70), (0.80, 0.74) and (0.82, 0.80), respectively. The logistic regression p-values were (0.09, 0.18), (0.02, 0.05) and (0.004, 0.006), respectively. With regard to volume loss, the corresponding AUC values for these metrics were (0.66, 0.57), (0.67, 0.61) and (0.71, 0.69), and p-values were (0.95, 0.90), (0.43, 0.64) and (0.08, 0.12), respectively. Conclusion: The inclusion of regional ventilation function improved predictability of radiation fibrosis. Dose-subvolume metrics provided a promising method for incorporating functional information into the conventional dose-volume parameters for outcome assessment.« less

Absorbed dose evaluation of Auger electron-emitting radionuclides: impact of input decay spectra on dose point kernels and S-values

NASA Astrophysics Data System (ADS)

Falzone, Nadia; Lee, Boon Q.; Fernández-Varea, José M.; Kartsonaki, Christiana; Stuchbery, Andrew E.; Kibédi, Tibor; Vallis, Katherine A.

2017-03-01

The aim of this study was to investigate the impact of decay data provided by the newly developed stochastic atomic relaxation model BrIccEmis on dose point kernels (DPKs - radial dose distribution around a unit point source) and S-values (absorbed dose per unit cumulated activity) of 14 Auger electron (AE) emitting radionuclides, namely 67Ga, 80mBr, 89Zr, 90Nb, 99mTc, 111In, 117mSn, 119Sb, 123I, 124I, 125I, 135La, 195mPt and 201Tl. Radiation spectra were based on the nuclear decay data from the medical internal radiation dose (MIRD) RADTABS program and the BrIccEmis code, assuming both an isolated-atom and condensed-phase approach. DPKs were simulated with the PENELOPE Monte Carlo (MC) code using event-by-event electron and photon transport. S-values for concentric spherical cells of various sizes were derived from these DPKs using appropriate geometric reduction factors. The number of Auger and Coster-Kronig (CK) electrons and x-ray photons released per nuclear decay (yield) from MIRD-RADTABS were consistently higher than those calculated using BrIccEmis. DPKs for the electron spectra from BrIccEmis were considerably different from MIRD-RADTABS in the first few hundred nanometres from a point source where most of the Auger electrons are stopped. S-values were, however, not significantly impacted as the differences in DPKs in the sub-micrometre dimension were quickly diminished in larger dimensions. Overestimation in the total AE energy output by MIRD-RADTABS leads to higher predicted energy deposition by AE emitting radionuclides, especially in the immediate vicinity of the decaying radionuclides. This should be taken into account when MIRD-RADTABS data are used to simulate biological damage at nanoscale dimensions.

BODY SIZE-SPECIFIC EFFECTIVE DOSE CONVERSION COEFFICIENTS FOR CT SCANS.

PubMed

Romanyukha, Anna; Folio, Les; Lamart, Stephanie; Simon, Steven L; Lee, Choonsik

2016-12-01

Effective dose from computed tomography (CT) examinations is usually estimated using the scanner-provided dose-length product and using conversion factors, also known as k-factors, which correspond to scan regions and differ by age according to five categories: 0, 1, 5, 10 y and adult. However, patients often deviate from the standard body size on which the conversion factor is based. In this study, a method for deriving body size-specific k-factors is presented, which can be determined from a simple regression curve based on patient diameter at the centre of the scan range. Using the International Commission on Radiological Protection reference paediatric and adult computational phantoms paired with Monte Carlo simulation of CT X-ray beams, the authors derived a regression-based k-factor model for the following CT scan types: head-neck, head, neck, chest, abdomen, pelvis, abdomen-pelvis (AP) and chest-abdomen-pelvis (CAP). The resulting regression functions were applied to a total of 105 paediatric and 279 adult CT scans randomly sampled from patients who underwent chest, AP and CAP scans at the National Institutes of Health Clinical Center. The authors have calculated and compared the effective doses derived from the conventional age-specific k-factors with the values computed using their body size-specific k-factor. They found that by using the age-specific k-factor, paediatric patients tend to have underestimates (up to 3-fold) of effective dose, while underweight and overweight adult patients tend to have underestimates (up to 2.6-fold) and overestimates (up to 4.6-fold) of effective dose, respectively, compared with the effective dose determined from their body size-dependent factors. The authors present these size-specific k-factors as an alternative to the existing age-specific factors. The body size-specific k-factor will assess effective dose more precisely and on a more individual level than the conventional age-specific k-factors and, hence, improve awareness of the true exposure, which is important for the clinical community to understand. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The conversion of exposures due to radon into the effective dose: the epidemiological approach.

PubMed

Beck, T R

2017-11-01

The risks and dose conversion coefficients for residential and occupational exposures due to radon were determined with applying the epidemiological risk models to ICRP representative populations. The dose conversion coefficient for residential radon was estimated with a value of 1.6 mSv year -1 per 100 Bq m -3 (3.6 mSv per WLM), which is significantly lower than the corresponding value derived from the biokinetic and dosimetric models. The dose conversion coefficient for occupational exposures with applying the risk models for miners was estimated with a value of 14 mSv per WLM, which is in good accordance with the results of the dosimetric models. To resolve the discrepancy regarding residential radon, the ICRP approaches for the determination of risks and doses were reviewed. It could be shown that ICRP overestimates the risk for lung cancer caused by residential radon. This can be attributed to a wrong population weighting of the radon-induced risks in its epidemiological approach. With the approach in this work, the average risks for lung cancer were determined, taking into account the age-specific risk contributions of all individuals in the population. As a result, a lower risk coefficient for residential radon was obtained. The results from the ICRP biokinetic and dosimetric models for both, the occupationally exposed working age population and the whole population exposed to residential radon, can be brought in better accordance with the corresponding results of the epidemiological approach, if the respective relative radiation detriments and a radiation-weighting factor for alpha particles of about ten are used.

Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer

NASA Astrophysics Data System (ADS)

Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.

2014-07-01

When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range. Presented in part at the European Society for Therapeutic Radiotherapy and Oncology Annual Meeting, April 5-8, 2014, Vienna, Austria.

Patient-specific radiation dose and cancer risk estimation in CT: Part II. Application to patients

PubMed Central

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Toncheva, Greta; Yoshizumi, Terry T.; Frush, Donald P.

2011-01-01

Purpose: Current methods for estimating and reporting radiation dose from CT examinations are largely patient-generic; the body size and hence dose variation from patient to patient is not reflected. Furthermore, the current protocol designs rely on dose as a surrogate for the risk of cancer incidence, neglecting the strong dependence of risk on age and gender. The purpose of this study was to develop a method for estimating patient-specific radiation dose and cancer risk from CT examinations. Methods: The study included two patients (a 5-week-old female patient and a 12-year-old male patient), who underwent 64-slice CT examinations (LightSpeed VCT, GE Healthcare) of the chest, abdomen, and pelvis at our institution in 2006. For each patient, a nonuniform rational B-spine (NURBS) based full-body computer model was created based on the patient’s clinical CT data. Large organs and structures inside the image volume were individually segmented and modeled. Other organs were created by transforming an existing adult male or female full-body computer model (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. A Monte Carlo program previously developed and validated for dose simulation on the LightSpeed VCT scanner was used to estimate patient-specific organ dose, from which effective dose and risks of cancer incidence were derived. Patient-specific organ dose and effective dose were compared with patient-generic CT dose quantities in current clinical use: the volume-weighted CT dose index (CTDIvol) and the effective dose derived from the dose-length product (DLP). Results: The effective dose for the CT examination of the newborn patient (5.7 mSv) was higher but comparable to that for the CT examination of the teenager patient (4.9 mSv) due to the size-based clinical CT protocols at our institution, which employ lower scan techniques for smaller patients. However, the overall risk of cancer incidence attributable to the CT examination was much higher for the newborn (2.4 in 1000) than for the teenager (0.7 in 1000). For the two pediatric-aged patients in our study, CTDIvol underestimated dose to large organs in the scan coverage by 30%–48%. The effective dose derived from DLP using published conversion coefficients differed from that calculated using patient-specific organ dose values by −57% to 13%, when the tissue weighting factors of ICRP 60 were used, and by −63% to 28%, when the tissue weighting factors of ICRP 103 were used. Conclusions: It is possible to estimate patient-specific radiation dose and cancer risk from CT examinations by combining a validated Monte Carlo program with patient-specific anatomical models that are derived from the patients’ clinical CT data and supplemented by transformed models of reference adults. With the construction of a large library of patient-specific computer models encompassing patients of all ages and weight percentiles, dose and risk can be estimated for any patient prior to or after a CT examination. Such information may aid in decisions for image utilization and can further guide the design and optimization of CT technologies and scan protocols. PMID:21361209

Patient-specific radiation dose and cancer risk estimation in CT: Part II. Application to patients

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

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

2011-01-15

Purpose: Current methods for estimating and reporting radiation dose from CT examinations are largely patient-generic; the body size and hence dose variation from patient to patient is not reflected. Furthermore, the current protocol designs rely on dose as a surrogate for the risk of cancer incidence, neglecting the strong dependence of risk on age and gender. The purpose of this study was to develop a method for estimating patient-specific radiation dose and cancer risk from CT examinations. Methods: The study included two patients (a 5-week-old female patient and a 12-year-old male patient), who underwent 64-slice CT examinations (LightSpeed VCT, GEmore » Healthcare) of the chest, abdomen, and pelvis at our institution in 2006. For each patient, a nonuniform rational B-spine (NURBS) based full-body computer model was created based on the patient's clinical CT data. Large organs and structures inside the image volume were individually segmented and modeled. Other organs were created by transforming an existing adult male or female full-body computer model (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. A Monte Carlo program previously developed and validated for dose simulation on the LightSpeed VCT scanner was used to estimate patient-specific organ dose, from which effective dose and risks of cancer incidence were derived. Patient-specific organ dose and effective dose were compared with patient-generic CT dose quantities in current clinical use: the volume-weighted CT dose index (CTDI{sub vol}) and the effective dose derived from the dose-length product (DLP). Results: The effective dose for the CT examination of the newborn patient (5.7 mSv) was higher but comparable to that for the CT examination of the teenager patient (4.9 mSv) due to the size-based clinical CT protocols at our institution, which employ lower scan techniques for smaller patients. However, the overall risk of cancer incidence attributable to the CT examination was much higher for the newborn (2.4 in 1000) than for the teenager (0.7 in 1000). For the two pediatric-aged patients in our study, CTDI{sub vol} underestimated dose to large organs in the scan coverage by 30%-48%. The effective dose derived from DLP using published conversion coefficients differed from that calculated using patient-specific organ dose values by -57% to 13%, when the tissue weighting factors of ICRP 60 were used, and by -63% to 28%, when the tissue weighting factors of ICRP 103 were used. Conclusions: It is possible to estimate patient-specific radiation dose and cancer risk from CT examinations by combining a validated Monte Carlo program with patient-specific anatomical models that are derived from the patients' clinical CT data and supplemented by transformed models of reference adults. With the construction of a large library of patient-specific computer models encompassing patients of all ages and weight percentiles, dose and risk can be estimated for any patient prior to or after a CT examination. Such information may aid in decisions for image utilization and can further guide the design and optimization of CT technologies and scan protocols.« less

Dental radiography: tooth enamel EPR dose assessment from Rando phantom measurements

NASA Astrophysics Data System (ADS)

Aragno, D.; Fattibene, P.; Onori, S.; Aragno, D.; Fattibene, P.

2000-09-01

Electron paramagnetic resonance dosimetry of tooth enamel is now established as a suitable method for individual dose reconstruction following radiation accidents. The accuracy of the method is limited by some confounding factors, among which is the dose received due to medical x-ray irradiation. In the present paper the EPR response of tooth enamel to endoral examination was experimentally evaluated using an anthropomorphic phantom. The dose to enamel for a single exposure of a typical dental examination performed with a new x-ray generation unit working at 65 kVp gave rise to a CO2- signal of intensity similar to that induced by a dose of about 2 mGy of 60Co. EPR measurements were performed on the entire tooth with no attempt to separate buccal and lingual components. Also the dose to enamel for an orthopantomography exam was estimated. It was derived from TLD measurements as equivalent to 0.2 mGy of 60Co. In view of application to risk assessment analysis, in the present work the value for the ratio of the reference dose at the phantom surface measured with TLD to the dose at the tooth measured with EPR was determined.

A review of lung-to-blood absorption rates for radon progeny.

PubMed

Marsh, J W; Bailey, M R

2013-12-01

The International Commission on Radiological Protection (ICRP) Publication 66 Human Respiratory Tract Model (HRTM) treats clearance of materials from the respiratory tract as a competitive process between absorption into blood and particle transport to the alimentary tract and lymphatics. The ICRP recommended default absorption rates for lead and polonium (Type M) in ICRP Publication 71 but stated that the values were not appropriate for short-lived radon progeny. This paper reviews and evaluates published data from volunteer and laboratory animal experiments to estimate the HRTM absorption parameter values for short-lived radon progeny. Animal studies showed that lead ions have two phases of absorption: ∼10 % absorbed with a half-time of ∼15 min, the rest with a half-time of ∼10 h. The studies also indicated that some of the lead ions were bound to respiratory tract components. Bound fractions, f(b), for lead were estimated from volunteer and animal studies and ranged from 0.2 to 0.8. Based on the evaluations of published data, the following HRTM absorption parameter values were derived for lead as a decay product of radon: f(r) = 0.1, s(r) = 100 d(-1), s(s) = 1.7 d(-1), f(b) = 0.5 and s(b) = 1.7 d(-1). Effective doses calculated assuming these absorption parameter values instead of a single absorption half-time of 10 h with no binding (as has generally been assumed) are only a few per cent higher. However, as there is some conflicting evidence on the absorption kinetics for radon progeny, dose calculations have been carried out for different sets of absorption parameter values derived from different studies. The results of these calculations are discussed.

Assessment of dose rate to terrestrial biota in the area around coal fired power plant applying ERICA tool and RESRAD BIOTA code.

PubMed

Ćujić, Mirjana; Dragović, Snežana

2018-08-01

This paper presents the environmental radiation risk assessment based on two software program approaches ERICA Tool (version 1.2) and RESRAD BIOTA (version 1.5) to estimate dose rates to terrestrial biota in the area around the largest coal fired power plant in Serbia. For dose rate assessment software's default reference animals and plants and the best estimated values of activity concentrations of 238 U, 234 U, 234 Th, 232 Th, 230 Th, 226 Ra, 210 Pb, 210 Po, 137 Cs in soil were used. Both approaches revealed the highest contribution to the internal dose rate due to 226 Ra and 210 Po, while 137 Cs contributed the most to the external dose rate. In the investigated area total dose rate to biota derived using ERICA Tool ranged from 0.3 to 14.4 μGy h -1 . The natural radionuclides exhibited significantly higher contribution to the total dose rate than the artificial one. In the investigated area, only dose rate for lichens and bryophytes exceeded ERICA Tool screening value of total dose rate of 10 μGy h -1 suggested as confident that environmental risks are negligible. The assessed total dose rates for reference animals and plants using RESRAD BIOTA were found to be 7 and 3 μGy h -1 , respectively. In RESRAD BIOTA - Level 3, 10 species (Lumbricus terrestris, Rana lessonae, Sciurus vulgaris, Anas platyrhynchos, Lepus europaeus, Vulpes vulpes, Capreolus capreolus, Suss crofa, Quercu srobur, Tilia spp.) representative for the study area were modeled. Among them the highest total dose rate (4.5 μGy h -1 ) was obtained for large mammals. Differences in the predicted dose rates to biota using the two software programs are the consequence of the difference in the values of transfer parameters used to calculate activity concentrations in biota. Doses of ionizing radiation estimated in this study will not exhibit deterministic effects at the population level. Thus, the obtained results indicate no significant radiation impact of coal fired power plant operation on terrestrial biota. This paper confirms the use ERICA Tool and RESRAD BIOTA softwares as flexible and effective means of radiation impact assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Local noise reduction for emphysema scoring in low-dose CT images

NASA Astrophysics Data System (ADS)

Schilham, Arnold; Prokop, Mathias; Gietema, Hester; van Ginneken, Bram

2005-04-01

Computed Tomography (CT) has become the new reference standard for quantification of emphysema. The most popular measure for emphysema derived from CT is the Pixel Index (PI), which expresses the fraction of the lung volume with abnormally low intensity values. As PI is calculated from a single, fixed threshold on intensity, this measure is strongly influenced by noise. This effect shows up clearly when comparing the PI score for a high-dose scan to the PI score for a low-dose (i.e. noisy) scan of the same subject. This paper presents a class of noise filters that make use of a local noise estimate to specify the filtering strength: Local Noise Variance Weighted Averaging (LNVWA). The performance of the filter is assessed by comparing high-dose and low-dose PI scores for 11 subjects. LNVWA improves the reproducibility of high-dose PI scores: For an emphysema threshold of -910 HU, the root-mean-square difference in PI score drops from 10% of the lung volume to 3.3% of the lung volume if LNVWA is used.

A reference skeletal dosimetry model for an adult male radionuclide therapy patient based on three-dimensional imaging and paired-image radiation transport

NASA Astrophysics Data System (ADS)

Shah, Amish P.

The need for improved patient-specificity of skeletal dose estimates is widely recognized in radionuclide therapy. Current clinical models for marrow dose are based on skeletal mass estimates from a variety of sources and linear chord-length distributions that do not account for particle escape into cortical bone. To predict marrow dose, these clinical models use a scheme that requires separate calculations of cumulated activity and radionuclide S values. Selection of an appropriate S value is generally limited to one of only three sources, all of which use as input the trabecular microstructure of an individual measured 25 years ago, and the tissue mass derived from different individuals measured 75 years ago. Our study proposed a new modeling approach to marrow dosimetry---the Paired Image Radiation Transport (PIRT) model---that properly accounts for both the trabecular microstructure and the cortical macrostructure of each skeletal site in a reference male radionuclide patient. The PIRT model, as applied within EGSnrc, requires two sets of input geometry: (1) an infinite voxel array of segmented microimages of the spongiosa acquired via microCT; and (2) a segmented ex-vivo CT image of the bone site macrostructure defining both the spongiosa (marrow, endosteum, and trabeculae) and the cortical bone cortex. Our study also proposed revising reference skeletal dosimetry models for the adult male cancer patient. Skeletal site-specific radionuclide S values were obtained for a 66-year-old male reference patient. The derivation for total skeletal S values were unique in that the necessary skeletal mass and electron dosimetry calculations were formulated from the same source bone site over the entire skeleton. We conclude that paired-image radiation-transport techniques provide an adoptable method by which the intricate, anisotropic trabecular microstructure of the skeletal site; and the physical size and shape of the bone can be handled together, for improved compilation of reference radionuclide S values. We also conclude that this comprehensive model for the adult male cancer patient should be implemented for use in patient-specific calculations for radionuclide dosimetry of the skeleton.

Developing new extension of GafChromic RTQA2 film to patient quality assurance field using a plan-based calibration method

NASA Astrophysics Data System (ADS)

Peng, Jiayuan; Zhang, Zhen; Wang, Jiazhou; Xie, Jiang; Chen, Junchao; Hu, Weigang

2015-10-01

GafChromic RTQA2 film is a type of radiochromic film designed for light field and radiation field alignment. The aim of this study is to extend the application of RTQA2 film to the measurement of patient specific quality assurance (QA) fields as a 2D relative dosimeter. Pre-irradiated and post-irradiated RTQA2 films were scanned in reflection mode using a flatbed scanner. A plan-based calibration (PBC) method utilized the mapping information of the calculated dose image and film grayscale image to create a dose versus pixel value calibration model. This model was used to calibrate the film grayscale image to the film relative dose image. The dose agreement between calculated and film dose images were analyzed by gamma analysis. To evaluate the feasibility of this method, eight clinically approved RapidArc cases (one abdomen cancer and seven head-and-neck cancer patients) were tested using this method. Moreover, three MLC gap errors and two MLC transmission errors were introduced to eight Rapidarc cases respectively to test the robustness of this method. The PBC method could overcome the film lot and post-exposure time variations of RTQA2 film to get a good 2D relative dose calibration result. The mean gamma passing rate of eight patients was 97.90%  ±  1.7%, which showed good dose consistency between calculated and film dose images. In the error test, the PBC method could over-calibrate the film, which means some dose error in the film would be falsely corrected to keep the dose in film consistent with the dose in the calculated dose image. This would then lead to a false negative result in the gamma analysis. In these cases, the derivative curve of the dose calibration curve would be non-monotonic which would expose the dose abnormality. By using the PBC method, we extended the application of more economical RTQA2 film to patient specific QA. The robustness of the PBC method has been improved by analyzing the monotonicity of the derivative of the calibration curve.

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

Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad

Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to testmore » the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%/3 mm for an IMRT QA plan and 3%/2 mm for a brachytherapy QA plan are passing 95% gamma function points. Conclusions: In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.« less

Phantom-derived estimation of effective dose equivalent from X rays with and without a lead apron.

PubMed

Mateya, C F; Claycamp, H G

1997-06-01

Organ dose equivalents were measured in a humanoid phantom in order to estimate effective dose equivalent (H(E)) and effective dose (E) from low-energy x rays and in the presence or absence of a protective lead apron. Plane-parallel irradiation conditions were approximated using direct x-ray beams of 76 and 104 kVp and resulting dosimetry data was adjusted to model exposures conditions in fluoroscopy settings. Values of H(E) and E estimated under-shielded conditions were compared to the results of several recent studies that used combinations of measured and calculated dosimetry to model exposures to radiologists. While the estimates of H(E) and E without the lead apron were within 0.2 to 20% of expected values, estimates based on personal monitors worn at the (phantom) waist (underneath the apron) underestimated either H(E) or E while monitors placed at the neck (above the apron) significantly overestimated both quantities. Also, the experimentally determined H(E) and E were 1.4 to 3.3 times greater than might be estimated using recently reported "two-monitor" algorithms for the estimation of effective dose quantities. The results suggest that accurate estimation of either H(E) or E from personal monitors under conditions of partial body exposures remains problematic and is likely to require the use of multiple monitors.

A Halogen-Containing Stilbene Derivative from the Leaves of Cajanus cajan that Induces Osteogenic Differentiation of Human Mesenchymal Stem Cells.

PubMed

Cai, Jia-Zhong; Tang, Rong; Ye, Gui-Fu; Qiu, Sheng-Xiang; Zhang, Nen-Ling; Hu, Ying-Jie; Shen, Xiao-Ling

2015-06-11

A new natural halogen-containing stilbene derivative was isolated from the leaves of Cajanus cajan (L.) Millsp. and identified as 3-O-(3-chloro-2-hydroxyl-propanyl)-longistylin A by comprehensive spectroscopic and chemical analysis, and named cajanstilbene H (1). It is the first halogen-containing stilbene derivative found from plants. In human mesenchymal stem cells (hMSC) from bone marrow, 1 did not promote cell proliferation, but distinctly enhanced osteogenic differentiation of hMSC in time- and dose-dependent manners. In six human cancer cell lines, 1 showed a moderate inhibitory effect on cell proliferation, with IC50 values of 21.42-25.85 μmol·L(-1).

Data and methods to estimate fetal dose from fluoroscopically guided prophylactic hypogastric artery balloon occlusion

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

Solomou, G.; Stratakis, J.; Perisinakis, K.

Purpose: To provide data for estimation of fetal radiation dose (D{sub F}) from prophylactic hypogastric artery balloon occlusion (HABO) procedures. Methods: The Monte-Carlo-N-particle (MCNP) transport code and mathematical phantoms representing a pregnant patient at the ninth month of gestation were employed. PA, RAO 20° and LAO 20° fluoroscopy projections of left and right internal iliac arteries were simulated. Projection-specific normalized fetal dose (NFD) data were produced for various beam qualities. The effects of projection angle, x-ray field location relative to the fetus, field size, maternal body size, and fetal size on NFD were investigated. Presented NFD values were compared tomore » corresponding values derived using a physical anthropomorphic phantom simulating pregnancy at the third trimester and thermoluminescence dosimeters. Results: NFD did not considerably vary when projection angle was altered by ±5°, whereas it was found to markedly depend on tube voltage, filtration, x-ray field location and size, and maternal body size. Differences in NFD < 7.5% were observed for naturally expected variations in fetal size. A difference of less than 13.5% was observed between NFD values estimated by MCNP and direct measurements. Conclusions: Data and methods provided allow for reliable estimation of radiation burden to the fetus from HABO.« less

A revised probabilistic estimate of the maternal methyl mercury intake dose corresponding to a measured cord blood mercury concentration.

PubMed

Stern, Alan H

2005-02-01

In 2001, the U.S. Environmental Protection Agency (EPA) adopted a revised reference dose (RfD) for methyl mercury (MeHg) of 0.1 microg/kg/day. The RfD is based on neurologic developmental effects measured in children associated with exposure in utero to MeHg from the maternal diet. The RfD derivation proceeded from a point of departure based on measured concentration of mercury in fetal cord blood (micrograms per liter). The RfD, however, is a maternal dose (micrograms per kilogram per day). Reconstruction of the maternal dose corresponding to this cord blood concentration, including the variability around this estimate, is a critical step in the RfD derivation. The dose reconstruction employed by the U.S. EPA using the one-compartment pharmacokinetic model contains two areas of significant uncertainty: It does not directly account for the influence of the ratio of cord blood: maternal blood Hg concentration, and it does not resolve uncertainty regarding the most appropriate central tendency estimates for pregnancy and third-trimester-specific model parameters. A probabilistic reassessment of this dose reconstruction was undertaken to address these areas of uncertainty and generally to reconsider the specification of model input parameters. On the basis of a thorough review of the literature and recalculation of the one-compartment model including sensitivity analyses, I estimated that the 95th and 99th percentiles (i.e., the lower 5th and 1st percentiles) of the maternal intake dose corresponding to a fetal cord blood Hg concentration of 58 microg/L are 0.3 and 0.2 microg/kg/day, respectively. For the 99th percentile, this is half the value previously estimated by the U.S. EPA.

Axially substituted silicon(IV) phthalocyanine and its quaternized derivative as photosensitizers towards tumor cells and bacterial pathogens.

PubMed

Ömeroğlu, İpek; Kaya, Esra Nur; Göksel, Meltem; Kussovski, Vesselin; Mantareva, Vanya; Durmuş, Mahmut

2017-10-15

Axially di-(alpha,alpha-diphenyl-4-pyridylmethoxy) silicon(IV) phthalocyanine (3) and its quaternized derivative (3Q) were synthesized and tested as photosensitizers against tumor and bacterial cells. These new phthalocyanines were characterized by elemental analysis, and different spectroscopic methods such as FT-IR, UV-Vis, MALDI-TOF and 1 H NMR. The photophysical properties such as absorption and fluorescence, and the photochemical properties such as singlet oxygen generation of both phthalocyanines were investigated in solutions. The obtained values were compared to the values obtained with unsubstituted silicon(IV) phthalocyanine dichloride (SiPcCl 2 ). The addition of two di-(alpha,alpha-diphenyl-4-pyridylmethanol) groups as axial ligands showed an improvement of the photophysical and photochemical properties and an increasement of the singlet oxygen quantum yield (Φ Δ ) from 0.15 to 0.33 was determined. The photodynamic efficacy of synthesized photosensitizers (3 and 3Q) were evaluated with promising photocytotoxicity (17% cell survival for 3 and 28% for 3Q) against the cervical cancer cell line (HeLa). The photodynamic inactivation of pathogenic bacterial strains Streptococcus mutans, Staphylococcus aureus, and Pseudomonas aeruginosa suggested a high susceptibility with quaternized derivative (3Q). The both Gram-positive bacterial strains were fully photoinactivated with 11μM 3Q and mild light dose 50J.cm -2 . In case of P. aeruginosa the effect was negligible for concentrations up to 22μM 3Q and light dose 100J.cm -2 . The results suggested that the novel axially substituted silicon(IV) phthalocyanines have promising characteristic as photosensitizer towards tumor cells. The quaternized derivative 3Q has high potential for photoinactivation of pathogenic bacterial species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of rSP-C surfactant with natural and synthetic surfactants after late treatment in a rat model of the acute respiratory distress syndrome

PubMed Central

Häfner, Dietrich; Germann, Paul-Georg; Hauschke, Dieter

1998-01-01

In a previous paper we showed that an SP-C containing surfactant preparation has similar activity as bovine-derived surfactants in a rat lung lavage model of the adult respiratory distress syndrome. In this study surfactant was given ten minutes after the last lavage (early treatment). In the present investigation we were interested how different surfactant preparations behave when they are administered 1 h after the last lavage (late treatment). Four protein containing surfactants (rSP-C surfactant, bLES, Infasurf and Survanta) were compared with three protein-free surfactants (ALEC, Exosurf and the phospholipid (PL) mixture of the rSP-C surfactant termed PL surfactant) with respect to their ability to improve gas exchange in this more stringent model when surfactant is given one hour after the last lavage. For better comparison of the surfactants the doses were related to phospholipids. The surfactants were given at doses of 25, 50 and 100 mg kg−1 body weight. The surfactants were compared to an untreated control group that was only ventilated for the whole experimental period. Tracheotomized rats (8–12 per dose and surfactant) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min−1, inspiration expiration ratio of 1 : 2, peak inspiratory pressure of 28 cmH2O at positive endexpiratory pressure (PEEP) of 8 cmH2O. Animals were ventilated for one hour after the last lavage and thereafter the surfactants were intratracheally instilled. During the whole experimental period the ventilation was not changed. Partial arterial oxygen pressures (PaO2, mmHg) at 30 min and 120 min after treatment were used for statistical comparison. All protein containing surfactants caused a dose-dependent increase of the reduced PaO2 values at 30 min after treatment. The protein-free surfactants showed only weak dose-dependent increase in PaO2 values at this time. This difference between the protein-containing and the protein-free surfactants was even more pronounced when comparing the PaO2 values at 120 min after treatment. Only rSP-C surfactant, bLES and Infasurf showed a dose-dependent increase in PaO2 at this time. With this animal model of late treatment it is possible even to differentiate between bovine derived surfactants. The differences between protein-containing and protein-free surfactants become even more pronounced. From the comparison of rSP-C surfactant with bovine-derived surfactants and the PL surfactant without rSP-C, it can be concluded that addition of rSP-C is sufficient to achieve the same activity as that of natural surfactants. PMID:9720777

RELATIVE BIOLOGICAL EFFECTIVENESS OF NEUTRONS DERIVED FROM THE EXCESS RELATIVE RISK MODEL WITH THE ATOMIC BOMB SURVIVORS DATA MANAGED BY HIROSHIMA UNIVERSITY.

PubMed

Satoh, Kenichi; Yasuda, Hiroshi; Kawakami, Hideshi; Tashiro, Satoshi

2017-09-23

According to an analysis of the Life Span Study cohort data conducted by the Radiation Effects Research Foundation in Hiroshima and Nagasaki, the sex-averaged excess relative risk (ERR) of all solid cancers was 0.42 Gy-Eq-1. On the other hand, analysis of the atomic bomb survivors (ABS) cohort data at Hiroshima University indicated the ERR value was 0.28 Gy-Eq-1 in Hiroshima. In both cases, initial radiation doses were derived from the dosimetry system DS02, in which the relative biological effectiveness (RBE) of neutrons was assumed to be a constant value of 10. To clarify the validity of the RBE, the authors investigated the possibility of different contributions of neutrons by using the ABS. Although there were no statistically significant differences among the estimated value of RBE (=65) and the ordinal value (=10), the corresponding ERR decreased by 30%, which might affect the interpretation of radiation health assessments. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

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

PubMed

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

2017-10-03

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

A new warfarin dosing algorithm including VKORC1 3730 G > A polymorphism: comparison with results obtained by other published algorithms.

PubMed

Cini, Michela; Legnani, Cristina; Cosmi, Benilde; Guazzaloca, Giuliana; Valdrè, Lelia; Frascaro, Mirella; Palareti, Gualtiero

2012-08-01

Warfarin dosing is affected by clinical and genetic variants, but the contribution of the genotype associated with warfarin resistance in pharmacogenetic algorithms has not been well assessed yet. We developed a new dosing algorithm including polymorphisms associated both with warfarin sensitivity and resistance in the Italian population, and its performance was compared with those of eight previously published algorithms. Clinical and genetic data (CYP2C9*2, CYP2C9*3, VKORC1 -1639 G > A, and VKORC1 3730 G > A) were used to elaborate the new algorithm. Derivation and validation groups comprised 55 (58.2% men, mean age 69 years) and 40 (57.5% men, mean age 70 years) patients, respectively, who were on stable anticoagulation therapy for at least 3 months with different oral anticoagulation therapy (OAT) indications. Performance of the new algorithm, evaluated with mean absolute error (MAE) defined as the absolute value of the difference between observed daily maintenance dose and predicted daily dose, correlation with the observed dose and R(2) value, was comparable with or slightly lower than that obtained using the other algorithms. The new algorithm could correctly assign 53.3%, 50.0%, and 57.1% of patients to the low (≤25 mg/week), intermediate (26-44 mg/week) and high (≥ 45 mg/week) dosing range, respectively. Our data showed a significant increase in predictive accuracy among patients requiring high warfarin dose compared with the other algorithms (ranging from 0% to 28.6%). The algorithm including VKORC1 3730 G > A, associated with warfarin resistance, allowed a more accurate identification of resistant patients who require higher warfarin dosage.

[Combined internal-external radiotherapy (CIERT) in a cell model].

PubMed

Oehme, Liane; Bartzsch, Thomas; Maucksch, Ute; Freudenberg, Robert; Wunderlich, Gerd; Kotzerke, Jörg

2018-06-01

Combined internal-external radiotherapy (CIERT) requires a unified assessment of biologic radiation effects in addition to the total dose. The concept of biological effective dose (BED) was evaluated in a cell model. The thyroid NIS-positive cell line FRTL-5 was irradiated with X-ray and the radiotracer Tc-99m pertechnetate either alone or in combination. The cellular uptake of the radionuclide during the incubation time of 24 h was controlled by the presence or absence of perchlorate. Dose calculation was performed based on measured uptake values. Cell specific radiobiologic parameters were derived from dose effect curves using the colony forming assay as biological endpoint. For the combination of the radiation qualities the sequence and time difference were varied. Cell survival was compared with the prediction of the BED model. The radiobiologic parameters from X-ray dose response were α = (0.22 ± 0.02) Gy -1 and β = (0.021 ± 0.001) Gy -2 . The half life for repair was (1.51 ± 0.21) h. These values could also explain the dose response curves for Tc-99m-irradiation with exponential decreasing dose rate. CIERT experiments showed no significant differences in cell survival regarding sequence and irradiation break. When the radionuclide uptake was not prevented the cell survival for the combination of X-ray and Tc-99m was lower than the prediction by BED calculations. The validity of the BED formalism for different dose rates and radiation qualities was verified. Supraaddive effects measured in the combination of X-ray and intracellular Tc-99m might be caused by Auger and conversion electrons, however further experiments are necessary. Schattauer GmbH.

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach.

PubMed

Lachenmeier, Dirk W; Rehm, Jürgen

2015-01-30

A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the "high risk" category with MOE < 10, the rest of the compounds except THC fall into the "risk" category with MOE < 100. On a population scale, only alcohol would fall into the "high risk" category, and cigarette smoking would fall into the "risk" category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk).

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

PubMed Central

Lachenmeier, Dirk W.; Rehm, Jürgen

2015-01-01

A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the “high risk” category with MOE < 10, the rest of the compounds except THC fall into the “risk” category with MOE < 100. On a population scale, only alcohol would fall into the “high risk” category, and cigarette smoking would fall into the “risk” category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk). PMID:25634572

Alimentary Tract Absorption (f1 Values) for Radionuclides in Local and Regional Fallout from Nuclear Tests

PubMed Central

Ibrahim, Shawki; Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold

2009-01-01

This paper presents gastrointestinal absorption fractions (f1 values) for estimating internal doses from local and regional fallout radionuclides due to nuclear tests. The choice of f1 values are based on specific circumstances of weapons test conditions and a review of reported f1 values for elements in different physical and chemical states. Special attention is given to fallout from nuclear tests conducted at the Marshall Islands. We make a distinction between the f1 values for intakes of radioactive materials immediately after deposition (acute intakes) and intakes that occur in the course of months and years after deposition, following incorporation into terrestrial and aquatic foodstuffs (chronic intakes). Multiple f1 values for different circumstances where persons are exposed to radioactive fallout (e.g. local vs. regional fallout and coral vs. continental tests) are presented when supportive information is available. In some cases, our selected f1 values are similar to those adopted by the ICRP (e.g. iodine and most actinides). However, f1 values for cesium and strontium derived from urine bioassay data of the Marshallese population are notably lower than the generic f1 values recommended by ICRP, particularly for acute intakes from local fallout (0.4 and 0.05 for Cs and Sr, respectively. The f1 values presented here form the first complete set of values relevant to realistic dose assessments for exposure to local or regional radioactive fallout. PMID:20622554

Alimentary tract absorption (f1 values) for radionuclides in local and regional fallout from nuclear tests.

PubMed

Ibrahim, Shawki A; Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold L

2010-08-01

This paper presents gastrointestinal absorption fractions (f1 values) for estimating internal doses from local and regional fallout radionuclides due to nuclear tests. The choice of f1 values are based on specific circumstances of weapons test conditions and a review of reported f1 values for elements in different physical and chemical states. Special attention is given to fallout from nuclear tests conducted at the Marshall Islands. We make a distinction between the f1 values for intakes of radioactive materials immediately after deposition (acute intakes) and intakes that occur in the course of months and years after deposition, following incorporation into terrestrial and aquatic foodstuffs (chronic intakes). Multiple f1 values for different circumstances where persons are exposed to radioactive fallout (e.g., local vs. regional fallout and coral vs. continental tests) are presented when supportive information is available. In some cases, our selected f1 values are similar to those adopted by the International Commission on Radiological Protection (ICRP) (e.g., iodine and most actinides). However, f1 values for cesium and strontium derived from urine bioassay data of the Marshallese population are notably lower than the generic f1 values recommended by ICRP, particularly for acute intakes from local fallout (0.4 and 0.05 for Cs and Sr, respectively). The f1 values presented here form the first complete set of values relevant to realistic dose assessments for exposure to local or regional radioactive fallout.

Patient- and cohort-specific dose and risk estimation for abdominopelvic CT: a study based on 100 patients

NASA Astrophysics Data System (ADS)

Tian, Xiaoyu; Li, Xiang; Segars, W. Paul; Frush, Donald P.; Samei, Ehsan

2012-03-01

The purpose of this work was twofold: (a) to estimate patient- and cohort-specific radiation dose and cancer risk index for abdominopelvic computer tomography (CT) scans; (b) to evaluate the effects of patient anatomical characteristics (size, age, and gender) and CT scanner model on dose and risk conversion coefficients. The study included 100 patient models (42 pediatric models, 58 adult models) and multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare). A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which DLP-normalized-effective dose (k factor) and DLP-normalized-risk index values (q factor) were derived. The k factor showed exponential decrease with increasing patient size. For a given gender, q factor showed exponential decrease with both increasing patient size and patient age. The discrepancies in k and q factors across scanners were on average 8% and 15%, respectively. This study demonstrates the feasibility of estimating patient-specific organ dose and cohort-specific effective dose and risk index in abdominopelvic CT requiring only the knowledge of patient size, gender, and age.

High brachytherapy doses can counteract hypoxia in cervical cancer—a modelling study

NASA Astrophysics Data System (ADS)

Lindblom, Emely; Dasu, Alexandru; Beskow, Catharina; Toma-Dasu, Iuliana

2017-01-01

Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions. To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target. By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered. It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased radioresistance caused by hypoxia if fast reoxygenation is assumed.

Experimental validation of the van Herk margin formula for lung radiation therapy

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

Ecclestone, Gillian; Heath, Emily; Bissonnette, Jean-Pierre

2013-11-15

Purpose: To validate the van Herk margin formula for lung radiation therapy using realistic dose calculation algorithms and respiratory motion modeling. The robustness of the margin formula against variations in lesion size, peak-to-peak motion amplitude, tissue density, treatment technique, and plan conformity was assessed, along with the margin formula assumption of a homogeneous dose distribution with perfect plan conformity.Methods: 3DCRT and IMRT lung treatment plans were generated within the ORBIT treatment planning platform (RaySearch Laboratories, Sweden) on 4DCT datasets of virtual phantoms. Random and systematic respiratory motion induced errors were simulated using deformable registration and dose accumulation tools available withinmore » ORBIT for simulated cases of varying lesion sizes, peak-to-peak motion amplitudes, tissue densities, and plan conformities. A detailed comparison between the margin formula dose profile model, the planned dose profiles, and penumbra widths was also conducted to test the assumptions of the margin formula. Finally, a correction to account for imperfect plan conformity was tested as well as a novel application of the margin formula that accounts for the patient-specific motion trajectory.Results: The van Herk margin formula ensured full clinical target volume coverage for all 3DCRT and IMRT plans of all conformities with the exception of small lesions in soft tissue. No dosimetric trends with respect to plan technique or lesion size were observed for the systematic and random error simulations. However, accumulated plans showed that plan conformity decreased with increasing tumor motion amplitude. When comparing dose profiles assumed in the margin formula model to the treatment plans, discrepancies in the low dose regions were observed for the random and systematic error simulations. However, the margin formula respected, in all experiments, the 95% dose coverage required for planning target volume (PTV) margin derivation, as defined by the ICRU; thus, suitable PTV margins were estimated. The penumbra widths calculated in lung tissue for each plan were found to be very similar to the 6.4 mm value assumed by the margin formula model. The plan conformity correction yielded inconsistent results which were largely affected by image and dose grid resolution while the trajectory modified PTV plans yielded a dosimetric benefit over the standard internal target volumes approach with up to a 5% decrease in the V20 value.Conclusions: The margin formula showed to be robust against variations in tumor size and motion, treatment technique, plan conformity, as well as low tissue density. This was validated by maintaining coverage of all of the derived PTVs by 95% dose level, as required by the formal definition of the PTV. However, the assumption of perfect plan conformity in the margin formula derivation yields conservative margin estimation. Future modifications to the margin formula will require a correction for plan conformity. Plan conformity can also be improved by using the proposed trajectory modified PTV planning approach. This proves especially beneficial for tumors with a large anterior–posterior component of respiratory motion.« less

Bioaccessible arsenic in the home environment in southwest England.

PubMed

Rieuwerts, J S; Searle, P; Buck, R

2006-12-01

Samples of household dust and garden soil were collected from twenty households in the vicinity of an ex-mining site in southwest England and from nine households in a control village. All samples were analysed by ICP-MS for pseudo-total arsenic (As) concentrations and the results show clearly elevated levels, with maximum As concentrations of 486 microg g(-1) in housedusts and 471 microg g(-1) in garden soils (and mean concentrations of 149 microg g(-1) and 262 microg g(-1), respectively). Arsenic concentrations in all samples from the mining area exceeded the UK Soil Guideline Value (SGV) of 20 microg g(-1). No significant correlation was observed between garden soil and housedust As concentrations. Bioaccessible As concentrations were determined in a small subset of samples using the Physiologically Based Extraction Test (PBET). For the stomach phase of the PBET, bioaccessibility percentages of 10-20% were generally recorded. Higher percentages (generally 30-45%) were recorded in the intestine phases with a maximum value (for one of the housedusts) of 59%. Data from the mining area were used, together with default values for soil ingestion rates and infant body weights from the Contaminated Land Exposure Assessment (CLEA) model, to derive estimates of As intake for infants and small children (0-6 years old). Dose estimates of up to 3.53 microg kg(-1) bw day(-1) for housedusts and 2.43 microg kg(-1) bw day(-1) for garden soils were calculated, compared to the index dose used for the derivation of the SGV of 0.3 microg kg(-1) bw day(-1) (based on health risk assessments). The index dose was exceeded by 75% (18 out of 24) of the estimated As doses that were calculated for children aged 0-6 years, a group which is particularly at risk from exposure via soil and dust ingestion. The results of the present study support the concerns expressed by previous authors about the significant As contamination in southwest England and the potential implications for human health.

SITE SPECIFIC REFERENCE PERSON PARAMETERS AND DERIVED CONCENTRATION STANDARDS FOR THE SAVANNAH RIVER SITE

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

Jannik, T.

2013-03-14

The purpose of this report is twofold. The first is to develop a set of behavioral parameters for a reference person specific for the Savannah River Site (SRS) such that the parameters can be used to determine dose to members of the public in compliance with Department of Energy (DOE) Order 458.1 “Radiation Protection of the Public and the Environment.” A reference person is a hypothetical, gender and age aggregation of human physical and physiological characteristics arrived at by international consensus for the purpose of standardizing radiation dose calculations. DOE O 458.1 states that compliance with the annual dose limitmore » of 100 mrem (1 mSv) to a member of the public may be demonstrated by calculating the dose to the maximally exposed individual (MEI) or to a representative person. Historically, for dose compliance, SRS has used the MEI concept, which uses adult dose coefficients and adult male usage parameters. Beginning with the 2012 annual site environmental report, SRS will be using the representative person concept for dose compliance. The dose to a representative person will be based on 1) the SRS-specific reference person usage parameters at the 95th percentile of appropriate national or regional data, which are documented in this report, 2) the reference person (gender and age averaged) ingestion and inhalation dose coefficients provided in DOE Derived Concentration Technical Standard (DOE-STD-1196-2011), and 3) the external dose coefficients provided in the DC_PAK3 toolbox. The second purpose of this report is to develop SRS-specific derived concentration standards (DCSs) for all applicable food ingestion pathways, ground shine, and water submersion. The DCS is the concentration of a particular radionuclide in water, in air, or on the ground that results in a member of the public receiving 100 mrem (1 mSv) effective dose following continuous exposure for one year. In DOE-STD-1196-2011, DCSs were developed for the ingestion of water, inhalation of air and submersion in air pathways, only. These DCSs are required by DOE O 458.1 to be used at all DOE sites in the design and conduct of radiological environmental protection programs. In this report, DCSs for the following additional pathways were considered and documented: ingestion of meat, dairy, grains, produce (fruits and vegetables), seafood, submersion in water and ground shine. These additional DCSs were developed using the same methods as in DOE-STD-1196-2011 and will be used at SRS, where appropriate, as screening and reference values.« less

Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

PubMed Central

Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

2017-01-01

Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blood, urine, feces and bile, as well as carcasses, were collected through 168 hours after dosing. Samples were analyzed for total radioactivity content by liquid scintillation counting, and carcasses were analyzed by quantitative whole-body autoradiography. Results [14C]APX001-derived radioactivity was rapidly and extensively absorbed and extensively distributed to most tissues for both routes of administration in both species. In rats, tissues with the highest radioactivity Cmax values included bile, abdominal fat, reproductive fat, subcutaneous fat, and liver, but radioactivity was also detected in tissues associated with IFI, including lung, brain and eye. In monkeys, the highest Cmax values were in bile, urine, uveal tract, bone marrow, abdominal fat, liver, and kidney cortex. Liver and kidney were the tissues with highest radioactivity, but as in the rat, radioactivity was also detected in lung, brain and eye tissues. In pigmented rats, radiocarbon was densely distributed into pigmented tissue and more slowly cleared than from other tissues. Mean recovery of radioactivity in rats was approximately 95–100%. In bile duct-intact rats, >90% of radioactivity was recovered in feces. In cannulated rats, biliary excretion of radioactivity was the major route of elimination and accounted for 88.8% of the dose, whereas urinary and fecal excretion of radioactivity was minor and accounted for 2.56% and 5.42% of the dose, respectively. In monkeys, the overall recovery of radioactivity was 87.6%, and was eliminated in feces (49.8% of dose) and to a lesser extent in urine (20.6% of dose). Conclusion Together, the results indicate that APX001-related radioactivity is extensively distributed to major tissues (including tissues relevant to IFI) in both rats and monkeys and cleared primarily by biliary/fecal excretion. Disclosures R. Mansbach, Amplyx Pharmaceuticals Inc.: Consultant, Consulting fee; K. J. Shaw, Amplyx Pharmaceuticals Inc.: Employee, Salary; M. R. Hodges, Amplyx Pharmaceuticals: Employee, Salary; S. Coleman, Covance Laboratories: Employee, Salary; M. E. Fitzsimmons, Covance Laboratories: Employee, Salary

Comparison of capnovolumetry-derived dead space parameters with pulmonary function test in normal adults using histamine provocation.

PubMed

Sun, Xiaoli; Zhang, Yan; Yang, Wenlan; Liu, Jinming

2015-04-01

This study in healthy adults was conducted to explore the clinical application of capnovolumetric indices as compared to lung function parameters using histamine provocation. Forty healthy subjects received aerosol histamine or salbutamol in an automatic stimulation system with escalating doses of histamine. Dead space volumes of capnovolumetry and lung function parameters were examined with increased concentrations of histamine at a fixed time interval. The doses of histamine were selected from 0.0562 mg-2.2 mg and 0.1 mg salbutamol was inhaled when a maximal dose of histamine was reached. Baseline values in each group were calculated prior to histamine inhalation. Fowler dead space (VDF), Wolff dead space (VDW), threshold dead space (VDT), Bohr dead space (VDB), forced expiratory volume in 1 s (FEV1 ) and peak expiratory flow (PEF) showed a dose-dependent reduction following histamine provocation, but there were no statistical differences in the measurements at baseline and post S6 provocation. The value of dC3/DV at the maximal dose was significantly increased over its baseline value (P < 0.05). VDF, VDT and VDW were significantly increased after bronchodilator use (P < 0.05 or <0.01). The changes in capnovolumetry did not correspond with the results of lung function test. The dC3/DV and airway dead spaces of capnovolumetry in healthy adults are significantly increased compared to lung function parameters before or after bronchodilator use, suggesting that capnovolumetry is feasible in diagnostic evaluation of airway reactivity, especially for persons who are unable to undertake lung function test. © 2014 John Wiley & Sons Ltd.

Adapting radiotherapy to hypoxic tumours

NASA Astrophysics Data System (ADS)

Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

2006-10-01

In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields and step-and-shoot intensity levels). Simulated random and systematic errors in the pO2-related images reduced the TCP for the non-uniform dose prescription. In conclusion, improved tumour control of hypoxic tumours by dose redistribution may be expected following hypoxia imaging, tumour control predictions, inverse treatment planning and IMRT.

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

NASA Astrophysics Data System (ADS)

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

2006-12-01

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

Irradiation of Anastrepha fraterculus (Diptera: Tephritidae) Eggs to Inhibit Fly Emergence in the Mass-Rearing of Diachasmimorpha longicaudata (Hymenoptera: Braconidae)

PubMed Central

Costa, M. L. Z.; Pacheco, M. G.; Lopes, L. A.; Botteon, V. W.; Mastrangelo, T.

2016-01-01

As the incidence of Anastrepha fraterculus (Wiedemann) has increased in Southern Brazil in the past 3 yr, an initiative to release sterile flies and parasitoids has started. In order to make feasible the mass-rearing of the parasitoid Diachasmimorpha longicaudata (Ashmed), this study investigated the suitability of A. fraterculus larvae derived from irradiated eggs as host for D. longicaudata. Two different ages of A. fraterculus eggs (24 and 48 h old) were analyzed for hatchability after the exposure to a range of radiation doses. The hatchability of 48-h-old eggs was not affected by radiation, and no fly emerged at doses higher than 27.5 Gy. The larvae derived from irradiated eggs proved to be suitable hosts for the parasitoid development, with observed parasitism rates higher than 70% and sex ratio values above 0.6. The parasitism capability and longevity of D. longicaudata reared on larvae derived from irradiated eggs were also assessed. During the 10 d of parasitism evaluated, D. longicaudata from the treatments were able to parasitize nonirradiated larvae similarly as the parasitoids from controls and the laboratory colony. The longevity of D. longicaudata from the treatments was not affected either, with survival rates higher than 80% after 20 d of evaluation. The age of 48 h and a dose of 30 Gy could be considered the best age and dose for A. fraterculus eggs to be used in the mass-rearing of D. longicaudata. The results of this study will decrease the costs of mass-rearing D. longicaudata on A. fraterculus. PMID:27638956

Screening-Level Risk Assessment for Styrene-Acrylonitrile (SAN) Trimer Detected in Soil and Groundwater

PubMed Central

Kirman, C. R.; Gargas, M. L.; Collins, J. J.; Rowlands, J. C.

2012-01-01

A screening-level risk assessment was conducted for styrene-acrylonitrile (SAN) Trimer detected at the Reich Farm Superfund site in Toms River, NJ. Consistent with a screening-level approach, on-site and off-site exposure scenarios were evaluated using assumptions that are expected to overestimate actual exposures and hazards at the site. Environmental sampling data collected for soil and groundwater were used to estimate exposure point concentrations. Several exposure scenarios were evaluated to assess potential on-site and off-site exposures, using parameter values for exposures to soil (oral, inhalation of particulates, and dermal contact) and groundwater (oral, dermal contact) to reflect central tendency exposure (CTE) and reasonable maximum exposure (RME) conditions. Three reference dose (RfD) values were derived for SAN Trimer for short-term, subchronic, and chronic exposures, based upon its effects on the liver in exposed rats. Benchmark (BMD) methods were used to assess the relationship between exposure and response, and to characterize appropriate points of departure (POD) for each RfD. An uncertainty factor of 300 was applied to each POD to yield RfD values of 0.1, 0.04, and 0.03 mg/kg-d for short-term, subchronic, and chronic exposures, respectively. Because a chronic cancer bioassay for SAN Trimer in rats (NTP 2011a) does not provide evidence of carcinogenicity, a cancer risk assessment is not appropriate for this chemical. Potential health hazards to human health were assessed using a hazard index (HI) approach, which considers the ratio of exposure dose (i.e., average daily dose, mg/kg-d) to toxicity dose (RfD, mg/kg-d) for each scenario. All CTE and RME HI values are well below 1 (where the average daily dose is equivalent to the RfD), indicating that there is no concern for potential noncancer effects in exposed populations even under the conservative assumptions of this screening-level assessment. PMID:23030654

Antidiabetic Activity of Self Nanoemulsifying Drug Delivery System from Bay Leaves (Eugenia polyantha Wight) Ethyl Acetate Fraction

NASA Astrophysics Data System (ADS)

Prihapsara, F.; Harini, M.; Widiyani, T.; Artanti, A. N.; Ani, I. L.

2017-02-01

Insulin resistance is caused by inability of target tissues to insulin response. Bay leaves (Eugenia polyantha Wight) fraction or extract have been used for the treatment of antidibetic mellitus type-2 resistance insulin (ADMRI) but it has low solubility and bioavailability. To overcome these problems, ethyl acetate fraction of bay leaves was formulated into self nanoemulsifying drug delivery system (SNEDDS) using Virgin Coconut Oil (VCO) as a carrier oil. This study aims to produce nanoherbal medicine, determine effect of nanoherbal preparation derived from bay leaves as an anti-ADMRI. The results showed that the optimum SNEDDS formula was tween 80 : PEG 400 : Virgin Coconut Oil (30% : 60% : 10%) in 5 mL. It has emulsification time 13.00 seconds with the average of droplet size value 84.5 nanometer and zeta potential value ± 0.2 mV. Morphological observation showed the nanoemulsion particles has spherical shaped and stable in different pH media. Hypoglycaemic effect of single dose metformin, SNEDDS, combination a-half dose of SNEEDS with metformin value is 28.3%; 15.6%; 34.6% respectively.

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

PubMed

Balderson, Michael J; Kirkby, Charles

2015-01-01

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

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

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

Bender, Edward T.

Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when comparedmore » the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.« less

The influence of electron beam radiation in the nutritional value, chemical composition and bioactivities of edible flowers of Bauhinia variegata L. var. candida alba Buch.-Ham from Brazil.

PubMed

Villavicencio, Anna L C H; Heleno, Sandrina A; Calhelha, Ricardo C; Santos-Buelga, Celestino; Barros, Lillian; Ferreira, Isabel C F R

2018-02-15

As edible flowers are highly perishable, irradiation technology can be applied to increase their shelf life, as also for phytosanitary purposes. Herein, flowers of Bauhinia variegata L. var. candida alba Buch.-Ham were submitted to electron beam irradiation at the doses of 0.5, 0.8 and 1kGy, to study the effects in the nutritional and chemical profiles, and also in antioxidant, cytotoxic and anti-inflammatory activities. The petals of white flowers revealed interesting bioactive properties being kaempferol derivatives the most abundant compounds, especially kaempferol-3-O-rutinoside. The applied irradiation doses did not highly affect the nutritional profile. No changes were produced in cytotoxicity, but the anti-inflammatory activity slightly decreased. However, the antioxidant activity was increased, especially in the dose of 0.5kGy, in agreement with the higher content in phenolic compounds found at this dose. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiological Modeling for Determination of Derived Concentration Levels of an Area with Uranium Residual Material - 13533

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

Perez-Sanchez, Danyl

As a result of a pilot project developed at the old Spanish 'Junta de Energia Nuclear' to extract uranium from ores, tailings materials were generated. Most of these residual materials were sent back to different uranium mines, but a small amount of it was mixed with conventional building materials and deposited near the old plant until the surrounding ground was flattened. The affected land is included in an area under institutional control and used as recreational area. At the time of processing, uranium isotopes were separated but other radionuclides of the uranium decay series as Th-230, Ra-226 and daughters remainmore » in the residue. Recently, the analyses of samples taken at different ground's depths confirmed their presence. This paper presents the methodology used to calculate the derived concentration level to ensure that the reference dose level of 0.1 mSv y-1 used as radiological criteria. In this study, a radiological impact assessment was performed modeling the area as recreational scenario. The modelization study was carried out with the code RESRAD considering as exposure pathways, external irradiation, inadvertent ingestion of soil, inhalation of resuspended particles, and inhalation of radon (Rn-222). As result was concluded that, if the concentration of Ra-226 in the first 15 cm of soil is lower than, 0.34 Bq g{sup -1}, the dose would not exceed the reference dose. Applying this value as a derived concentration level and comparing with the results of measurements on the ground, some areas with a concentration of activity slightly higher than latter were found. In these zones the remediation proposal has been to cover with a layer of 15 cm of clean material. This action represents a reduction of 85% of the dose and ensures compliance with the reference dose. (authors)« less

Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms

PubMed Central

Scheerans, Christian; Heinig, Roland; Mueck, Wolfgang

2015-01-01

Recently, the European Medicines Agency (EMA) published the new draft guideline on the pharmacokinetic and clinical evaluation of modified release (MR) formulations. The draft guideline contains the new requirement of performing multiple dose (MD) bioequivalence studies, in the case when the MR formulation is expected to show ‘relevant’ drug accumulation at steady state (SS). This new requirement reveals three fundamental issues, which are discussed in the current work: first, measurement for the extent of drug accumulation (MEDA) predicted from single dose (SD) study data; second, its relationship with the percentage residual area under the plasma concentration–time curve (AUC) outside the dosing interval (τ) after SD administration, %AUC(τ-∞)SD; and third, the rationale for a threshold of %AUC(τ-∞)SD that predicts ‘relevant’ drug accumulation at SS. This work revealed that the accumulation ratio RA,AUC, derived from the ratio of the time-averaged plasma concentrations during τ at SS and after SD administration, respectively, is the ‘preferred’ MEDA for MR formulations. A causal relationship was derived between %AUC(τ-∞)SD and RA,AUC, which is valid for any drug (product) that shows (dose- and time-) linear pharmacokinetics regardless of the shape of the plasma concentration–time curve. Considering AUC thresholds from other guidelines together with the causal relationship between %AUC(τ-∞)SD and RA,AUC indicates that values of %AUC(τ-∞)SD ≤ 20%, resulting in RA,AUC ≤ 1.25, can be considered as leading to non-relevant drug accumulation. Hence, the authors suggest that 20% for %AUC(τ-∞)SD is a reasonable threshold and selection criterion between SD or MD study designs for bioequivalence studies of new MR formulations. © 2014 The Authors Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd. PMID:25327367

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

DOEpatents

Horn, Kevin M.

2013-07-09

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

Radiation protection issues in galactic cosmic ray risk assessment

NASA Technical Reports Server (NTRS)

Sinclair, W. K.

1994-01-01

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

Radiation protection issues in galactic cosmic ray risk assessment.

PubMed

Sinclair, W K

1994-01-01

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

Automatic exposure control systems designed to maintain constant image noise: effects on computed tomography dose and noise relative to clinically accepted technique charts.

PubMed

Favazza, Christopher P; Yu, Lifeng; Leng, Shuai; Kofler, James M; McCollough, Cynthia H

2015-01-01

To compare computed tomography dose and noise arising from use of an automatic exposure control (AEC) system designed to maintain constant image noise as patient size varies with clinically accepted technique charts and AEC systems designed to vary image noise. A model was developed to describe tube current modulation as a function of patient thickness. Relative dose and noise values were calculated as patient width varied for AEC settings designed to yield constant or variable noise levels and were compared to empirically derived values used by our clinical practice. Phantom experiments were performed in which tube current was measured as a function of thickness using a constant-noise-based AEC system and the results were compared with clinical technique charts. For 12-, 20-, 28-, 44-, and 50-cm patient widths, the requirement of constant noise across patient size yielded relative doses of 5%, 14%, 38%, 260%, and 549% and relative noises of 435%, 267%, 163%, 61%, and 42%, respectively, as compared with our clinically used technique chart settings at each respective width. Experimental measurements showed that a constant noise-based AEC system yielded 175% relative noise for a 30-cm phantom and 206% relative dose for a 40-cm phantom compared with our clinical technique chart. Automatic exposure control systems that prescribe constant noise as patient size varies can yield excessive noise in small patients and excessive dose in obese patients compared with clinically accepted technique charts. Use of noise-level technique charts and tube current limits can mitigate these effects.

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

PubMed

van Dillen, Teun; van Dijk, Arjan

2018-06-12

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

Response functions for computing absorbed dose to skeletal tissues from photon irradiation—an update

NASA Astrophysics Data System (ADS)

Johnson, Perry B.; Bahadori, Amir A.; Eckerman, Keith F.; Lee, Choonsik; Bolch, Wesley E.

2011-04-01

A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues—active and total shallow marrow—within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R2 = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.

Response functions for computing absorbed dose to skeletal tissues from photon irradiation--an update.

PubMed

Johnson, Perry B; Bahadori, Amir A; Eckerman, Keith F; Lee, Choonsik; Bolch, Wesley E

2011-04-21

A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues-active and total shallow marrow-within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R(2) = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.

Fluence-to-dose conversion coefficients for heavy ions calculated using the PHITS code and the ICRP/ICRU adult reference computational phantoms.

PubMed

Sato, Tatsuhiko; Endo, Akira; Niita, Koji

2010-04-21

The fluence to organ-absorbed-dose and effective-dose conversion coefficients for heavy ions with atomic numbers up to 28 and energies from 1 MeV/nucleon to 100 GeV/nucleon were calculated using the PHITS code coupled to the ICRP/ICRU adult reference computational phantoms, following the instruction given in ICRP Publication 103 (2007 (Oxford: Pergamon)). The conversion coefficients for effective dose equivalents derived using the radiation quality factors of both Q(L) and Q(y) relationships were also estimated, utilizing the functions for calculating the probability densities of absorbed dose in terms of LET (L) and lineal energy (y), respectively, implemented in PHITS. The calculation results indicate that the effective dose can generally give a conservative estimation of the effective dose equivalent for heavy-ion exposure, although it is occasionally too conservative especially for high-energy lighter-ion irradiations. It is also found from the calculation that the conversion coefficients for the Q(y)-based effective dose equivalents are generally smaller than the corresponding Q(L)-based values because of the conceptual difference between LET and y as well as the numerical incompatibility between the Q(L) and Q(y) relationships. The calculated data of these dose conversion coefficients are very useful for the dose estimation of astronauts due to cosmic-ray exposure.

Effects of low doses and low dose rates of external ionizing radiation: Cancer mortality among nuclear industry workers in three countries

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

Cardis, E.; Kato, I.; Lave, C.

Studies of the mortality among nuclear industry workforces have been carried out, and nationally combined analyses performed, in the U.S., the UK and Canada. This paper presents the results of internationally combined analyses of mortality data on 95,673 workers (85.4% men) monitored for external exposure to ionizing radiation and employed for 6 months or longer in the nuclear industry of one of the three countries. These analyses were undertaken to obtain a more precise direct assessment of the carcinogenic effects of protracted low-level exposure to external, predominantly {gamma}, radiation. The combination of the data from the various studies increases themore » power to study associations between radiation dose and mortality from all causes or from all cancers. Mortality from leukemia, excluding chronic lymphocytic leukemia (CLL)-the cause of death most strongly and consistently related to radiation dose in studies of atomic bomb survivors and other populations exposed at high dose rates-was significantly associated with cumulative external radiation dose (one-sided P value = 0.046; 119 deaths). Among the 31 other specific types of cancer studied, a significant association was observed only for multiple myeloma (one-sided P value = 0.037; 44 deaths), and this was attributable primarily to the associations reported previously between this disease and radiation dose in the Hanford (U.S.) and Sellafield (UK) cohorts. The excess relative risk (ERR) estimates for all cancers excluding leukemia, and leukemia excluding CLL, the two main groupings of causes of death for which risk estimates have been derived from studies of atomic bomb survivors, were -0.07 per Sv [90% confidence interval (CI):-0.4,0.3] and 2.18 per Sv (90% CI:0.1,5.7), respectively. These values correspond to a relative risk of 0.99 for all cancers excluding leukemia and 1.22 for leukemia excluding CLL for a cumulative protracted dose of 100 mSv compared to O mSv. 53 refs., 1 fig., 8 tabs.« less

γH2AX assay in ex vivo irradiated tumour specimens: A novel method to determine tumour radiation sensitivity in patient-derived material.

PubMed

Menegakis, Apostolos; von Neubeck, Cläre; Yaromina, Ala; Thames, Howard; Hering, Sandra; Hennenlotter, Joerg; Scharpf, Marcus; Noell, Susan; Krause, Mechthild; Zips, Daniel; Baumann, Michael

2015-09-01

To establish a clinically applicable protocol for quantification of residual γH2AX foci in ex vivo irradiated tumour samples and to apply this method in a proof-of-concept feasibility study to patient-derived tumour specimens. Evaluation of γH2AX foci formation and disappearance in excised FaDu tumour specimens after (a) different incubation times in culture medium, 4Gy irradiation and fixation after 24h (cell recovery), (b) 10h medium incubation, 4Gy irradiation and fixation after various time points (double strand break repair kinetics), and (c) 10h medium incubation, irradiation with graded single radiation doses and fixation after 24h (dose-response). The optimised protocol was applied to patient-derived samples of seminoma, prostate cancer and glioblastoma multiforme. Post excision or biopsy, tumour tissues showed stable radiation-induced γH2AX foci values in oxic cells after >6h of recovery in medium. Kinetics of foci disappearance indicated a plateau of residual foci after >12h following ex vivo irradiation. Fitting the dose-response of residual γH2AX foci yielded slopes comparable with in situ irradiation of FaDu tumours. Significant differences in the slopes of ex vivo irradiated patient-derived tumour samples were found. A novel clinically applicable method to quantify residual γH2AX foci in ex vivo irradiated tumour samples was established. The first clinical results suggest that this method allows to distinguish between radiosensitive and radioresistant tumour types. These findings support further translational evaluation of this assay to individualise radiation therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

Prediction of terrestrial gamma dose rate based on geological formations and soil types in the Johor State, Malaysia.

PubMed

Saleh, Muneer Aziz; Ramli, Ahmad Termizi; bin Hamzah, Khaidzir; Alajerami, Yasser; Moharib, Mohammed; Saeed, Ismael

2015-10-01

This study aims to predict and estimate unmeasured terrestrial gamma dose rate (TGDR) using statistical analysis methods to derive a model from the actual measurement based on geological formation and soil type. The measurements of TGDR were conducted in the state of Johor with a total of 3873 measured points which covered all geological formations, soil types and districts. The measurements were taken 1 m above the soil surface using NaI [Ti] detector. The measured gamma dose rates ranged from 9 nGy h(-1) to 1237 nGy h(-1) with a mean value of 151 nGy h(-1). The data have been normalized to fit a normal distribution. Tests of significance were conducted among all geological formations and soil types, using the unbalanced one way ANOVA. The results indicated strong significant differences due to the different geological formations and soil types present in Johor State. Pearson Correlation was used to measure the relations between gamma dose rate based on geological formation and soil type (D(G,S)) with the gamma dose rate based on geological formation (D(G)) or soil type (D(s)). A very good correlation was found between D(G,S) and D(G) or D(G,S) and D(s). A total of 118 pairs of geological formations and soil types were used to derive the statistical contribution of geological formations and soil types to gamma dose rates. The contribution of the gamma dose rate from geological formation and soil type were found to be 0.594 and 0.399, respectively. The null hypotheses were accepted for 83% of examined data, therefore, the model could be used to predict gamma dose rates based on geological formation and soil type information. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2008-08-01

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

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

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

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

2008-08-07

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

Should regional ventilation function be considered during radiation treatment planning to prevent radiation-induced complications?

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

Lan, Fujun; Jeudy, Jean; D’Souza, Warren

Purpose: To investigate the incorporation of pretherapy regional ventilation function in predicting radiation fibrosis (RF) in stage III nonsmall cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: Thirty-seven patients with stage III NSCLC were retrospectively studied. Patients received one cycle of cisplatin–gemcitabine, followed by two to three cycles of cisplatin–etoposide concurrently with involved-field thoracic radiotherapy (46–66 Gy; 2 Gy/fraction). Pretherapy regional ventilation images of the lung were derived from 4D computed tomography via a density change–based algorithm with mass correction. In addition to the conventional dose–volume metrics (V{sub 20}, V{sub 30}, V{sub 40}, and mean lung dose),more » dose–function metrics (fV{sub 20}, fV{sub 30}, fV{sub 40}, and functional mean lung dose) were generated by combining regional ventilation and radiation dose. A new class of metrics was derived and referred to as dose–subvolume metrics (sV{sub 20}, sV{sub 30}, sV{sub 40}, and subvolume mean lung dose); these were defined as the conventional dose–volume metrics computed on the functional lung. Area under the receiver operating characteristic curve (AUC) values and logistic regression analyses were used to evaluate these metrics in predicting hallmark characteristics of RF (lung consolidation, volume loss, and airway dilation). Results: AUC values for the dose–volume metrics in predicting lung consolidation, volume loss, and airway dilation were 0.65–0.69, 0.57–0.70, and 0.69–0.76, respectively. The respective ranges for dose–function metrics were 0.63–0.66, 0.61–0.71, and 0.72–0.80 and for dose–subvolume metrics were 0.50–0.65, 0.65–0.75, and 0.73–0.85. Using an AUC value = 0.70 as cutoff value suggested that at least one of each type of metrics (dose–volume, dose–function, dose–subvolume) was predictive for volume loss and airway dilation, whereas lung consolidation cannot be accurately predicted by any of the metrics. Logistic regression analyses showed that dose–function and dose–subvolume metrics were significant (P values ≤ 0.02) in predicting volume airway dilation. Likelihood ratio test showed that when combining dose–function and/or dose–subvolume metrics with dose–volume metrics, the achieved improvements of prediction accuracy on volume loss and airway dilation were significant (P values ≤ 0.04). Conclusions: The authors’ results demonstrated that the inclusion of regional ventilation function improved accuracy in predicting RF. In particular, dose–subvolume metrics provided a promising method for preventing radiation-induced pulmonary complications.« less

Dosimetric and radiobiological consequences of computed tomography-guided adaptive strategies for intensity modulated radiation therapy of the prostate.

PubMed

Battista, Jerry J; Johnson, Carol; Turnbull, David; Kempe, Jeff; Bzdusek, Karl; Van Dyk, Jacob; Bauman, Glenn

2013-12-01

To examine a range of scenarios for image-guided adaptive radiation therapy of prostate cancer, including different schedules for megavoltage CT imaging, patient repositioning, and dose replanning. We simulated multifraction dose distributions with deformable registration using 35 sets of megavoltage CT scans of 13 patients. We computed cumulative dose-volume histograms, from which tumor control probabilities and normal tissue complication probabilities (NTCPs) for rectum were calculated. Five-field intensity modulated radiation therapy (IMRT) with 18-MV x-rays was planned to achieve an isocentric dose of 76 Gy to the clinical target volume (CTV). The differences between D95, tumor control probability, V70Gy, and NTCP for rectum, for accumulated versus planned dose distributions, were compared for different target volume sizes, margins, and adaptive strategies. The CTV D95 for IMRT treatment plans, averaged over 13 patients, was 75.2 Gy. Using the largest CTV margins (10/7 mm), the D95 values accumulated over 35 fractions were within 2% of the planned value, regardless of the adaptive strategy used. For tighter margins (5 mm), the average D95 values dropped to approximately 73.0 Gy even with frequent repositioning, and daily replanning was necessary to correct this deficit. When personalized margins were applied to an adaptive CTV derived from the first 6 treatment fractions using the STAPLE (Simultaneous Truth and Performance Level Estimation) algorithm, target coverage could be maintained using a single replan 1 week into therapy. For all approaches, normal tissue parameters (rectum V(70Gy) and NTCP) remained within acceptable limits. The frequency of adaptive interventions depends on the size of the CTV combined with target margins used during IMRT optimization. The application of adaptive target margins (<5 mm) to an adaptive CTV determined 1 week into therapy minimizes the need for subsequent dose replanning. Copyright © 2013 Elsevier Inc. All rights reserved.

α-Glucosidase inhibition and antihyperglycemic activity of flavonoids from Ampelopsis grossedentata and the flavonoid derivatives.

PubMed

Chen, Jia; Wu, Yuechan; Zou, Jianwei; Gao, Kun

2016-04-01

The dried leaves and stems of Ampelopsis grossedentata have been used as a health tea and herbal medicine for hundreds of years in China. The study was aimed at searching for novel α-glucosidase inhibitors among the richest components of A. grossedentata and their derivatives. Three known major components (1-3) were isolated by recrystallization process and six new derivatives (4-9) were obtained by etherification of the bioactive flavonoid. All compounds were evaluated for their inhibitory activities against α-glucosidase (from Saccharomyces cerevisiae). As a result, compound 9 showed a significant α-glucosidase inhibitory activity with IC50 value of 9.3 μM and acted as a competitive inhibitor with the value of the inhibition constant (Ki) being 10.3 μM. The oral administration of compound 9 at a dose of 50mg/kg significantly reduced the post prandial blood glucose levels of normal and streptozotocin (STZ)-induced diabetic mice. Furthermore, compound 9 significantly decreased the fasting blood glucose levels in STZ-induced diabetic mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

A radiobiology-based inverse treatment planning method for optimisation of permanent l-125 prostate implants in focal brachytherapy.

PubMed

Haworth, Annette; Mears, Christopher; Betts, John M; Reynolds, Hayley M; Tack, Guido; Leo, Kevin; Williams, Scott; Ebert, Martin A

2016-01-07

Treatment plans for ten patients, initially treated with a conventional approach to low dose-rate brachytherapy (LDR, 145 Gy to entire prostate), were compared with plans for the same patients created with an inverse-optimisation planning process utilising a biologically-based objective. The 'biological optimisation' considered a non-uniform distribution of tumour cell density through the prostate based on known and expected locations of the tumour. Using dose planning-objectives derived from our previous biological-model validation study, the volume of the urethra receiving 125% of the conventional prescription (145 Gy) was reduced from a median value of 64% to less than 8% whilst maintaining high values of TCP. On average, the number of planned seeds was reduced from 85 to less than 75. The robustness of plans to random seed displacements needs to be carefully considered when using contemporary seed placement techniques. We conclude that an inverse planning approach to LDR treatments, based on a biological objective, has the potential to maintain high rates of tumour control whilst minimising dose to healthy tissue. In future, the radiobiological model will be informed using multi-parametric MRI to provide a personalised medicine approach.

A radiobiology-based inverse treatment planning method for optimisation of permanent l-125 prostate implants in focal brachytherapy

NASA Astrophysics Data System (ADS)

Haworth, Annette; Mears, Christopher; Betts, John M.; Reynolds, Hayley M.; Tack, Guido; Leo, Kevin; Williams, Scott; Ebert, Martin A.

2016-01-01

Treatment plans for ten patients, initially treated with a conventional approach to low dose-rate brachytherapy (LDR, 145 Gy to entire prostate), were compared with plans for the same patients created with an inverse-optimisation planning process utilising a biologically-based objective. The ‘biological optimisation’ considered a non-uniform distribution of tumour cell density through the prostate based on known and expected locations of the tumour. Using dose planning-objectives derived from our previous biological-model validation study, the volume of the urethra receiving 125% of the conventional prescription (145 Gy) was reduced from a median value of 64% to less than 8% whilst maintaining high values of TCP. On average, the number of planned seeds was reduced from 85 to less than 75. The robustness of plans to random seed displacements needs to be carefully considered when using contemporary seed placement techniques. We conclude that an inverse planning approach to LDR treatments, based on a biological objective, has the potential to maintain high rates of tumour control whilst minimising dose to healthy tissue. In future, the radiobiological model will be informed using multi-parametric MRI to provide a personalised medicine approach.

Volatile profile, lipid oxidation and protein oxidation of irradiated ready-to-eat cured turkey meat products

NASA Astrophysics Data System (ADS)

Feng, Xi; Ahn, Dong Uk

2016-10-01

Irradiation had little effects on the thiobarbituric acid reactive substances (TBARS) values in ready-to-eat (RTE) turkey meat products, while it increased protein oxidation at 4.5 kGy. The volatile profile analyses indicated that the amount of sulfur compounds increased linearly as doses increased in RTE turkey meat products. By correlation analysis, a positive correlation was found between benzene/ benzene derivatives and alcohols with lipid oxidation, while aldehydes, ketones and alkane, alkenes and alkynes were positively correlated with protein oxidation. Principle component analysis showed that irradiated meat samples can be discriminated by two categories of volatile compounds: Strecker degradation products and radiolytic degradation products. The cluster analysis of volatile data demonstrated that low-dose irradiation had minor effects on the volatile profile of turkey sausages (<1.5 kGy). However, as the doses increased, the differences between the irradiated and non-irradiated cured turkey products became significant.

Development of probabilistic internal dosimetry computer code

NASA Astrophysics Data System (ADS)

Noh, Siwan; Kwon, Tae-Eun; Lee, Jai-Ki

2017-02-01

Internal radiation dose assessment involves biokinetic models, the corresponding parameters, measured data, and many assumptions. Every component considered in the internal dose assessment has its own uncertainty, which is propagated in the intake activity and internal dose estimates. For research or scientific purposes, and for retrospective dose reconstruction for accident scenarios occurring in workplaces having a large quantity of unsealed radionuclides, such as nuclear power plants, nuclear fuel cycle facilities, and facilities in which nuclear medicine is practiced, a quantitative uncertainty assessment of the internal dose is often required. However, no calculation tools or computer codes that incorporate all the relevant processes and their corresponding uncertainties, i.e., from the measured data to the committed dose, are available. Thus, the objective of the present study is to develop an integrated probabilistic internal-dose-assessment computer code. First, the uncertainty components in internal dosimetry are identified, and quantitative uncertainty data are collected. Then, an uncertainty database is established for each component. In order to propagate these uncertainties in an internal dose assessment, a probabilistic internal-dose-assessment system that employs the Bayesian and Monte Carlo methods. Based on the developed system, we developed a probabilistic internal-dose-assessment code by using MATLAB so as to estimate the dose distributions from the measured data with uncertainty. Using the developed code, we calculated the internal dose distribution and statistical values ( e.g. the 2.5th, 5th, median, 95th, and 97.5th percentiles) for three sample scenarios. On the basis of the distributions, we performed a sensitivity analysis to determine the influence of each component on the resulting dose in order to identify the major component of the uncertainty in a bioassay. The results of this study can be applied to various situations. In cases of severe internal exposure, the causation probability of a deterministic health effect can be derived from the dose distribution, and a high statistical value ( e.g., the 95th percentile of the distribution) can be used to determine the appropriate intervention. The distribution-based sensitivity analysis can also be used to quantify the contribution of each factor to the dose uncertainty, which is essential information for reducing and optimizing the uncertainty in the internal dose assessment. Therefore, the present study can contribute to retrospective dose assessment for accidental internal exposure scenarios, as well as to internal dose monitoring optimization and uncertainty reduction.

Dose Rationalization of Pembrolizumab and Nivolumab Using Pharmacokinetic Modeling and Simulation and Cost Analysis.

PubMed

Ogungbenro, Kayode; Patel, Alkesh; Duncombe, Robert; Nuttall, Richard; Clark, James; Lorigan, Paul

2018-04-01

Pembrolizumab and nivolumab are highly selective anti-programmed cell death 1 (PD-1) antibodies approved for the treatment of advanced malignancies. Variable exposure and significant wastage have been associated with body size dosing of monoclonal antibodies (mAbs). The following dosing strategies were evaluated using simulations: body weight, dose banding, fixed dose, and pharmacokinetic (PK)-based methods. The relative cost to body weight dosing for band, fixed 150 mg and 200 mg, and PK-derived strategies were -15%, -25%, + 7%, and -16% for pembrolizumab and -8%, -6%, and -10% for band, fixed, and PK-derived strategies for nivolumab, respectively. Relative to mg/kg doses, the median exposures were -1.0%, -4.6%, + 27.1%, and +3.0% for band, fixed 150 mg, fixed 200 mg, and PK-derived strategies, respectively, for pembrolizumab and -3.1%, + 1.9%, and +1.4% for band, fixed 240 mg, and PK-derived strategies, respectively, for nivolumab. Significant wastage can be reduced by alternative dosing strategies without compromising exposure and efficacy. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Shielding application of perturbation theory to determine changes in neutron and gamma doses due to changes in shield layers

NASA Technical Reports Server (NTRS)

Fieno, D.

1972-01-01

Perturbation theory formulas were derived and applied to determine changes in neutron and gamma-ray doses due to changes in various radiation shield layers for fixed sources. For a given source and detector position, the perturbation method enables dose derivatives with respect to density, or equivalently thickness, for every layer to be determined from one forward and one inhomogeneous adjoint calculation. A direct determination without the perturbation approach would require two forward calculations to evaluate the dose derivative due to a change in a single layer. Hence, the perturbation method for obtaining dose derivatives requires fewer computations for design studies of multilayer shields. For an illustrative problem, a comparison was made of the fractional change in the dose per unit change in the thickness of each shield layer in a two-layer spherical configuration as calculated by perturbation theory and by successive direct calculations; excellent agreement was obtained between the two methods.

A system of equations to approximate the pharmacokinetic parameters of lacosamide at steady state from one plasma sample.

PubMed

Cawello, Willi; Schäfer, Carina

2014-08-01

Frequent plasma sampling to monitor pharmacokinetic (PK) profile of antiepileptic drugs (AEDs), is invasive, costly and time consuming. For drugs with a well-defined PK profile, such as AED lacosamide, equations can accurately approximate PK parameters from one steady-state plasma sample. Equations were derived to approximate steady-state peak and trough lacosamide plasma concentrations (Cpeak,ss and Ctrough,ss, respectively) and area under concentration-time curve during dosing interval (AUCτ,ss) from one plasma sample. Lacosamide (ka: ∼2 h(-1); ke: ∼0.05 h(-1), corresponding to half-life of 13 h) was calculated to reach Cpeak,ss after ∼1 h (tmax,ss). Equations were validated by comparing approximations to reference PK parameters obtained from single plasma samples drawn 3-12h following lacosamide administration, using data from double-blind, placebo-controlled, parallel-group PK study. Values of relative bias (accuracy) between -15% and +15%, and root mean square error (RMSE) values≤15% (precision) were considered acceptable for validation. Thirty-five healthy subjects (12 young males; 11 elderly males, 12 elderly females) received lacosamide 100mg/day for 4.5 days. Equation-derived PK values were compared to reference mean Cpeak,ss, Ctrough,ss and AUCτ,ss values. Equation-derived PK data had a precision of 6.2% and accuracy of -8.0%, 2.9%, and -0.11%, respectively. Equation-derived versus reference PK values for individual samples obtained 3-12h after lacosamide administration showed correlation (R2) range of 0.88-0.97 for AUCτ,ss. Correlation range for Cpeak,ss and Ctrough,ss was 0.65-0.87. Error analyses for individual sample comparisons were independent of time. Derived equations approximated lacosamide Cpeak,ss, Ctrough,ss and AUCτ,ss using one steady-state plasma sample within validation range. Approximated PK parameters were within accepted validation criteria when compared to reference PK values. Copyright © 2014 Elsevier B.V. All rights reserved.

Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

PubMed

O'Brien, J; Renwick, A G; Constable, A; Dybing, E; Müller, D J G; Schlatter, J; Slob, W; Tueting, W; van Benthem, J; Williams, G M; Wolfreys, A

2006-10-01

The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

In-vivo singlet oxygen threshold doses for PDT

PubMed Central

Zhu, Timothy C.; Kim, Michele M.; Liang, Xing; Finlay, Jarod C.; Busch, Theresa M.

2015-01-01

Objective Dosimetry of singlet oxygen (1O2) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [1O2]rx,sh, for PDT was developed. Material and methods An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [1O2]rx,sh. Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature. Results The mean values (standard deviation) of the in-vivo [1O2]rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×107 and 4.6×107 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g, β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses. Discussion In comparison, the [1O2]rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×108 per cell per 1/e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/e to in-vivo singlet oxygen threshold dose (in mM). The sensitivity of threshold singlet oxygen dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanisms on the singlet oxygen threshold dose is discussed by comparing [1O2]rx,sh for BPD with 3 hr and 15 min drug-light-intervals, with the later being known to have a dominantly vascular effect. Conclusions The experimental results of threshold singlet oxygen concentration in an in-vivo RIF tumor model for Photofrin®, BPD, and mTHPC are about 20 times smaller than those observed in vitro. These results are consistent with knowledge that factors other than singlet oxygen-mediated tumor cell killing can contribute to PDT damage in-vivo. PMID:25927018

In-vivo singlet oxygen threshold doses for PDT.

PubMed

Zhu, Timothy C; Kim, Michele M; Liang, Xing; Finlay, Jarod C; Busch, Theresa M

2015-02-01

Dosimetry of singlet oxygen ( 1 O 2 ) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [ 1 O 2 ] rx,sh , for PDT was developed. An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [ 1 O 2 ] rx,sh . Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin ® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature. The mean values (standard deviation) of the in-vivo [ 1 O 2 ] rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×10 7 and 4.6×10 7 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin ® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g , β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses. In comparison, the [ 1 O 2 ] rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×10 8 per cell per 1/ e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/ e to in-vivo singlet oxygen threshold dose (in mM). The sensitivity of threshold singlet oxygen dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanisms on the singlet oxygen threshold dose is discussed by comparing [ 1 O 2 ] rx,sh for BPD with 3 hr and 15 min drug-light-intervals, with the later being known to have a dominantly vascular effect. The experimental results of threshold singlet oxygen concentration in an in-vivo RIF tumor model for Photofrin ® , BPD, and mTHPC are about 20 times smaller than those observed in vitro . These results are consistent with knowledge that factors other than singlet oxygen-mediated tumor cell killing can contribute to PDT damage in-vivo .

An interspecies correlation model to predict acute dermal toxicity of plant protection products to terrestrial life stages of amphibians using fish acute toxicity and bioconcentration data.

PubMed

Weltje, Lennart; Janz, Philipp; Sowig, Peter

2017-12-01

This paper presents a model to predict acute dermal toxicity of plant protection products (PPPs) to terrestrial amphibian life stages from (regulatory) fish data. By combining existing concepts, including interspecies correlation estimation (ICE), allometric relations, lethal body burden (LBB) and bioconcentration modelling, an equation was derived that predicts the amphibian median lethal dermal dose (LD 50 ) from standard acute toxicity values (96-h LC 50 ) for fish and bioconcentration factors (BCF) in fish. Where possible, fish BCF values were corrected to 5% lipid, and to parent compound. Then, BCF values were adjusted to an exposure duration of 96 h, in case steady state took longer to be achieved. The derived correlation equation is based on 32 LD 50 values from acute dermal toxicity experiments with 15 different species of anuran amphibians, comprising 15 different PPPs. The developed ICE model can be used in a screening approach to estimate the acute risk to amphibian terrestrial life stages from dermal exposures to PPPs with organic active substances. This has the potential to reduce unnecessary testing of vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

THERMOLUMINESCENT DOSIMETRY IN THE EVALUATION OF NATURAL RADIOACTIVITY INDOOR OF HOMES NEAR THE URANIUM DEPOSIT OF PARAÍBA, BRAZIL.

PubMed

Bezerra, Jairo Dias; Dos Santos Júnior, José Araújo; Dos Santos Amaral, Romilton; Menezes, Rômulo Simões Cezar; Fernández, Zahily Herrero; do Nascimento Santos, Josineide Marques; da Silva, Arykerne Nascimento Casado; Rojas, Lino Angel Valcárcel

2018-06-01

High levels of primordial radionuclides have been reported in soils and rocks of São José de Espinharas, in the state of Paraiba, Brazil. These radionuclides are derived from high concentrations of natural uranium and thorium from a mine in the region. Thus, there is a need for a dosimetric evaluation in the area near the mine and the surrounding cities. In this study, the annual effective dose was analyzed in 178 points of five cities. The measurements were performed using thermoluminescent dosimetry with LiF:Mg, Ti (TLD-100). The annual effective dose from environmental exposure varied from 0.71 to 2.07 mSv, with an arithmetic mean of 0.99 mSv. This average is more than twice the estimated value for indoor environments adopted by the UNSCEAR, which is 0.41 mSv. These results will allow establishing reference values for background radiation of the region and criteria to infer a stochastic risk for the local population.

Dosimetric and microdosimetric analyses for blood exposed to reactor-derived thermal neutrons.

PubMed

Ali, F; Atanackovic, J; Boyer, C; Festarini, A; Kildea, J; Paterson, L C; Rogge, R; Stuart, M; Richardson, R B

2018-06-06

Thermal neutrons are found in reactor, radiotherapy, aircraft, and space environments. The purpose of this study was to characterise the dosimetry and microdosimetry of thermal neutron exposures, using three simulation codes, as a precursor to quantitative radiobiological studies using blood samples. An irradiation line was designed employing a pyrolytic graphite crystal or-alternatively-a super mirror to expose blood samples to thermal neutrons from the National Research Universal reactor to determine radiobiological parameters. The crystal was used when assessing the relative biological effectiveness for dicentric chromosome aberrations, and other biomarkers, in lymphocytes over a low absorbed dose range of 1.2-14 mGy. Higher exposures using a super mirror will allow the additional quantification of mitochondrial responses. The physical size of the thermal neutron fields and their respective wavelength distribution was determined using the McStas Monte Carlo code. Spinning the blood samples produced a spatially uniform absorbed dose as determined from Monte Carlo N-Particle version 6 simulations. The major part (71%) of the total absorbed dose to blood was determined to be from the 14 N(n,p) 14 C reaction and the remainder from the 1 H(n,γ) 2 H reaction. Previous radiobiological experiments at Canadian Nuclear Laboratories involving thermal neutron irradiation of blood yielded a relative biological effectiveness of 26 ± 7. Using the Particle and Heavy Ion Transport Code System, a similar value of ∼19 for the quality factor of thermal neutrons initiating the 14 N(n,p) 14 C reaction in soft tissue was determined by microdosimetric simulations. This calculated quality factor is of similar high value to the experimentally-derived relative biological effectiveness, and indicates the potential of thermal neutrons to induce deleterious health effects in superficial organs such as cataracts of the eye lens.

Dose to 'water-like' media or dose to tissue in MV photons radiotherapy treatment planning: still a matter of debate.

PubMed

Andreo, Pedro

2015-01-07

The difference between Monte Carlo Treatment Planning (MCTP) based on the assumption of 'water-like' tissues with densities obtained from CT procedures, or on tissue compositions derived from CT-determined densities, have been investigated. Stopping powers and electron fluences have been calculated for a range of media and body tissues for 6 MV photon beams, including changes in their physical data (density and stopping powers). These quantities have been used to determine absorbed doses using cavity theory. It is emphasized that tissue compositions given in ICRU or ICRP reports should not be given the standing of physical constants as they correspond to average values obtained for a limited number of human-body samples. It has been shown that mass stopping-power ratios to water are more dependent on patient-to-patient composition differences, and therefore on their mean excitation energies (I-values), than on mass density. Electron fluence in different media are also more dependent on media composition (and their I-values) than on density. However, as a consequence of the balance between fluence and stopping powers, doses calculated from their product are more constant than what the independent stopping powers and fluence variations suggest. Additionally, cancelations in dose ratios minimize the differences between the 'water-like' and 'tissue' approaches, yielding practically identical results except for bone, and to a lesser extent for adipose tissue. A priori, changing from one approach to another does not seem to be justified considering the large number of approximations and uncertainties involved throughout the treatment planning tissue segmentation and dose calculation procedures. The key issue continues to be the composition of tissues and their I-values, and as these cannot be obtained for individual patients, whatever approach is selected does not lead to significant differences from a water reference dose, the maximum of these being of the order of 5% for bone tissues. Considering, however, current developments in advanced dose calculation methods, planning in terms of dose-to-tissue should be the preferred choice, under the expectancy that progress in the field will gradually improve some of the crude approximations included in MCTP and numerical transport methods. The small differences obtained also show that a retrospective conversion from dose-to-tissue to dose-to-water, based on a widely used approach, would mostly increase the final uncertainty of the treatment planning process. It is demonstrated that, due to the difference between electron fluence distributions in water and in body tissues, the conversion requires an additional fluence correction that has so far been neglected. An improved expression for the conversion and data for the fluence correction factor are provided. These will be necessary even in a dose-to-tissue environment, for the normalization of the treatment plan to the reference dosimetry of the treatment unit, always calibrated in terms of absorbed dose to water.

Dose to ‘water-like’ media or dose to tissue in MV photons radiotherapy treatment planning: still a matter of debate

NASA Astrophysics Data System (ADS)

Andreo, Pedro

2015-01-01

The difference between Monte Carlo Treatment Planning (MCTP) based on the assumption of ‘water-like’ tissues with densities obtained from CT procedures, or on tissue compositions derived from CT-determined densities, have been investigated. Stopping powers and electron fluences have been calculated for a range of media and body tissues for 6 MV photon beams, including changes in their physical data (density and stopping powers). These quantities have been used to determine absorbed doses using cavity theory. It is emphasized that tissue compositions given in ICRU or ICRP reports should not be given the standing of physical constants as they correspond to average values obtained for a limited number of human-body samples. It has been shown that mass stopping-power ratios to water are more dependent on patient-to-patient composition differences, and therefore on their mean excitation energies (I-values), than on mass density. Electron fluence in different media are also more dependent on media composition (and their I-values) than on density. However, as a consequence of the balance between fluence and stopping powers, doses calculated from their product are more constant than what the independent stopping powers and fluence variations suggest. Additionally, cancelations in dose ratios minimize the differences between the ‘water-like’ and ‘tissue’ approaches, yielding practically identical results except for bone, and to a lesser extent for adipose tissue. A priori, changing from one approach to another does not seem to be justified considering the large number of approximations and uncertainties involved throughout the treatment planning tissue segmentation and dose calculation procedures. The key issue continues to be the composition of tissues and their I-values, and as these cannot be obtained for individual patients, whatever approach is selected does not lead to significant differences from a water reference dose, the maximum of these being of the order of 5% for bone tissues. Considering, however, current developments in advanced dose calculation methods, planning in terms of dose-to-tissue should be the preferred choice, under the expectancy that progress in the field will gradually improve some of the crude approximations included in MCTP and numerical transport methods. The small differences obtained also show that a retrospective conversion from dose-to-tissue to dose-to-water, based on a widely used approach, would mostly increase the final uncertainty of the treatment planning process. It is demonstrated that, due to the difference between electron fluence distributions in water and in body tissues, the conversion requires an additional fluence correction that has so far been neglected. An improved expression for the conversion and data for the fluence correction factor are provided. These will be necessary even in a dose-to-tissue environment, for the normalization of the treatment plan to the reference dosimetry of the treatment unit, always calibrated in terms of absorbed dose to water.

X-ray-induced debromination of nucleic acids at the Br K absorption edge and implications for MAD phasing.

PubMed

Ennifar, E; Carpentier, P; Ferrer, J L; Walter, P; Dumas, P

2002-08-01

Multi-wavelength anomalous dispersion (MAD) using brominated derivatives is considered a common and convenient technique for solving chemically synthesized nucleic acid structures. Here, it is shown that a relatively moderate X-ray dose (of the order of 5 x 10(15) photons mm(-2)) can induce sufficient debromination to prevent structure determination. The decrease in bromine occupancy with radiation dose can be accounted for by a simple exponential, with an estimated rate constant at the absorption-peak wavelength, 7.4 (0.8) MGy, that is not significantly different from its value at the absorption-edge wavelength, 9.2 (2.6) MGy (the given e.s.d.s assess the relative closeness of the two values, not their absolute accuracy, which is probably worse). Chemically, these results (and others) are consistent with bromine cleavage resulting from direct photodissociation and/or from the action of free electrons, rather than from the action of hydroxyl radicals originating from water dissociation. The free bromine species (Br(-)) diffuse too quickly, even in amorphous ice around 100 K, to allow the determination of a diffusion coefficient. From a practical point of view, it is suggested that a single data collection with a crystal consisting of iodinated instead of brominated derivatives could provide both anomalous scattering and SIR phase information by the progressive cleavage of iodine.

Mammography dosimetry using an in-house developed polymethyl methacrylate phantom.

PubMed

Sharma, Reena; Sharma, Sunil Dutt; Mayya, Y S; Chourasiya, G

2012-08-01

Phantom-based measurements in mammography are well-established for quality assurance (QA) and quality control (QC) procedures involving equipment performance and comparisons of X-ray machines. Polymethyl methacrylate (PMMA) is among the best suitable materials for simulation of the breast. For carrying out QA/QC exercises in India, a mammographic PMMA phantom with engraved slots for keeping thermoluminescence dosemeters (TLD) has been developed. The radiation transmission property of the developed phantom was compared with the commercially available phantoms for verifying its suitability for mammography dosimetry. The breast entrance exposure (BEE), mean glandular dose (MGD), percentage depth dose (PDD), percentage surface dose distribution (PSDD), calibration testing of automatic exposure control (AEC) and density control function of a mammography machine were measured using this phantom. MGD was derived from the measured BEE following two different methodologies and the results were compared. The PDD and PSDD measurements were carried out using LiF: Mg, Cu, P chips. The in-house phantom was found comparable with the commercially available phantoms. The difference in the MGD values derived using two different methods were found in the range of 17.5-32.6 %. Measured depth ranges in the phantom lie between 0.32 and 0.40 cm for 75 % depth dose, 0.73 and 0.92 cm for 50 % depth dose, and 1.54 and 1.78 cm for 25 % depth dose. Higher PSDD value was observed towards chest wall edge side of the phantom, which is due to the orientation of cathode-anode axis along the chest wall to the nipple direction. Results obtained for AEC configuration testing shows that the observed mean optical density (O.D) of the phantom image was 1.59 and O.D difference for every successive increase in thickness of the phantom was within±0.15 O.D. Under density control function testing, at -2 and -1 density settings, the variation in film image O.D was within±0.15 O.D of the normal density setting '0' and at +2 and +1 density setting, it was observed to be within±0.30 O.D. This study indicates that the locally made PMMA TLD slot phantom can be used to measure various mammography QC parameters which are essentially required for better outcomes in mammography.

Dose-dependent bioavailability indicators for curcumin and two of its novel derivatives.

PubMed

Abd el Aziz, Mohamed; El-Asmer, Mohamed; Rezq, Ameen; Al-Malki, Abdulrahman; Kumosani, Taha; Fouad, Hanan; Ahmed, Hanan; Taha, Fatma; Hassouna, Amira; Hafez, Hafez

2014-01-01

Novel water-soluble curcumin derivatives have been developed to overcome low in vivo bioavailability of curcumin. The aim of this work is to assess the potential utility of certain downstream targets as bioavailability indicators of systemic activity of pure curcumin and two novel water-soluble curcumin derivatives (NCD) by constructing dose-dependent response curves and to prove whether this novel curcumin derivatives retained, improved, or abolished biological activity of pure curcumin when applied in vivo. Pure curcumin (CUR), curcumin-carboxy derivative (NCD-1), and curcumin protein conjugate (NCD-2) were administered orally to rats at escalating doses: 37, 74, 148, and 296 μM/kg body weight, respectively. Plasma levels of GST activity, cavernous tissue levels of cGMP, and enzymatic activity of both HO-1 and GST were assessed one and half and 24 hours after oral administration of curcumin formulae. This study showed that there was a progressive elevation of cavernous tissue levels of cGMP and enzymatic activity of both HO-1 and GST in a dose-dependent manner that was maintained for 24 h with CUR, NCD-1, and NCD-2. Plasma GST activity was decreased by the lowest doses on the curve. The three dose-dependent bioavailability indicators as surrogates of curcumin and two of its novel derivatives are valid in the studied range of concentration and extended time. The novel curcumin derivatives still conserve with improvement the biological activity of natural curcumin when applied in vivo. © 2013 International Union of Biochemistry and Molecular Biology.

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

Moura, Eduardo S., E-mail: emoura@wisc.edu; Micka, John A.; Hammer, Cliff G.

Purpose: This work presents the development of a phantom to verify the treatment planning system (TPS) algorithms used for high-dose-rate (HDR) brachytherapy. It is designed to measure the relative dose in a heterogeneous media. The experimental details used, simulation methods, and comparisons with a commercial TPS are also provided. Methods: To simulate heterogeneous conditions, four materials were used: Virtual Water™ (VM), BR50/50™, cork, and aluminum. The materials were arranged in 11 heterogeneity configurations. Three dosimeters were used to measure the relative response from a HDR {sup 192}Ir source: TLD-100™, Gafchromic{sup ®} EBT3 film, and an Exradin™ A1SL ionization chamber. Tomore » compare the results from the experimental measurements, the various configurations were modeled in the PENELOPE/penEasy Monte Carlo code. Images of each setup geometry were acquired from a CT scanner and imported into BrachyVision™ TPS software, which includes a grid-based Boltzmann solver Acuros™. The results of the measurements performed in the heterogeneous setups were normalized to the dose values measured in the homogeneous Virtual Water™ setup and the respective differences due to the heterogeneities were considered. Additionally, dose values calculated based on the American Association of Physicists in Medicine-Task Group 43 formalism were compared to dose values calculated with the Acuros™ algorithm in the phantom. Calculated doses were compared at the same points, where measurements have been performed. Results: Differences in the relative response as high as 11.5% were found from the homogeneous setup when the heterogeneous materials were inserted into the experimental phantom. The aluminum and cork materials produced larger differences than the plastic materials, with the BR50/50™ material producing results similar to the Virtual Water™ results. Our experimental methods agree with the PENELOPE/penEasy simulations for most setups and dosimeters. The TPS relative differences with the Acuros™ algorithm were similar in both experimental and simulated setups. The discrepancy between the BrachyVision™, Acuros™, and TG-43 dose responses in the phantom described by this work exceeded 12% for certain setups. Conclusions: The results derived from the phantom measurements show good agreement with the simulations and TPS calculations, using Acuros™ algorithm. Differences in the dose responses were evident in the experimental results when heterogeneous materials were introduced. These measurements prove the usefulness of the heterogeneous phantom for verification of HDR treatment planning systems based on model-based dose calculation algorithms.« less

WE-DE-201-05: Evaluation of a Windowless Extrapolation Chamber Design and Monte Carlo Based Corrections for the Calibration of Ophthalmic Applicators

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

Hansen, J; Culberson, W; DeWerd, L

Purpose: To test the validity of a windowless extrapolation chamber used to measure surface dose rate from planar ophthalmic applicators and to compare different Monte Carlo based codes for deriving correction factors. Methods: Dose rate measurements were performed using a windowless, planar extrapolation chamber with a {sup 90}Sr/{sup 90}Y Tracerlab RA-1 ophthalmic applicator previously calibrated at the National Institute of Standards and Technology (NIST). Capacitance measurements were performed to estimate the initial air gap width between the source face and collecting electrode. Current was measured as a function of air gap, and Bragg-Gray cavity theory was used to calculate themore » absorbed dose rate to water. To determine correction factors for backscatter, divergence, and attenuation from the Mylar entrance window found in the NIST extrapolation chamber, both EGSnrc Monte Carlo user code and Monte Carlo N-Particle Transport Code (MCNP) were utilized. Simulation results were compared with experimental current readings from the windowless extrapolation chamber as a function of air gap. Additionally, measured dose rate values were compared with the expected result from the NIST source calibration to test the validity of the windowless chamber design. Results: Better agreement was seen between EGSnrc simulated dose results and experimental current readings at very small air gaps (<100 µm) for the windowless extrapolation chamber, while MCNP results demonstrated divergence at these small gap widths. Three separate dose rate measurements were performed with the RA-1 applicator. The average observed difference from the expected result based on the NIST calibration was −1.88% with a statistical standard deviation of 0.39% (k=1). Conclusion: EGSnrc user code will be used during future work to derive correction factors for extrapolation chamber measurements. Additionally, experiment results suggest that an entrance window is not needed in order for an extrapolation chamber to provide accurate dose rate measurements for a planar ophthalmic applicator.« less

Rational design of biaryl pharmacophore inserted noscapine derivatives as potent tubulin binding anticancer agents.

PubMed

Santoshi, Seneha; Manchukonda, Naresh Kumar; Suri, Charu; Sharma, Manya; Sridhar, Balasubramanian; Joseph, Silja; Lopus, Manu; Kantevari, Srinivas; Baitharu, Iswar; Naik, Pradeep Kumar

2015-03-01

We have strategically designed a series of noscapine derivatives by inserting biaryl pharmacophore (a major structural constituent of many of the microtubule-targeting natural anticancer compounds) onto the scaffold structure of noscapine. Molecular interaction of these derivatives with α,β-tubulin heterodimer was investigated by molecular docking, molecular dynamics simulation, and binding free energy calculation. The predictive binding affinity indicates that the newly designed noscapinoids bind to tubulin with a greater affinity. The predictive binding free energy (ΔG(bind, pred)) of these derivatives (ranging from -5.568 to -5.970 kcal/mol) based on linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model showed improved binding affinity with tubulin compared to the lead compound, natural α-noscapine (-5.505 kcal/mol). Guided by the computational findings, these new biaryl type α-noscapine congeners were synthesized from 9-bromo-α-noscapine using optimized Suzuki reaction conditions for further experimental evaluation. The derivatives showed improved inhibition of the proliferation of human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human lung adenocarcinoma cells (A549), compared to natural noscapine. The cell cycle analysis in MCF-7 further revealed that these compounds alter the cell cycle profile and cause mitotic arrest at G2/M phase more strongly than noscapine. Tubulin binding assay revealed higher binding affinity to tubulin, as suggested by dissociation constant (Kd) of 126 ± 5.0 µM for 5a, 107 ± 5.0 µM for 5c, 70 ± 4.0 µM for 5d, and 68 ± 6.0 µM for 5e compared to noscapine (Kd of 152 ± 1.0 µM). In fact, the experimentally determined value of ΔG(bind, expt) (calculated from the Kd value) are consistent with the predicted value of ΔG(bind, pred) calculated based on LIE-SGB. Based on these results, one of the derivative 5e of this series was used for further toxicological evaluation. Treatment of mice with a daily dose of 300 mg/kg and a single dose of 600 mg/kg indicates that the compound does not induce detectable pathological abnormalities in normal tissues. Also there were no significant differences in hematological parameters between the treated and untreated groups. Hence, the newly designed noscapinoid, 5e is an orally bioavailable, safe and effective anticancer agent with a potential for the treatment of cancer and might be a candidate for clinical evaluation.

Rational design of biaryl pharmacophore inserted noscapine derivatives as potent tubulin binding anticancer agents

NASA Astrophysics Data System (ADS)

Santoshi, Seneha; Manchukonda, Naresh Kumar; Suri, Charu; Sharma, Manya; Sridhar, Balasubramanian; Joseph, Silja; Lopus, Manu; Kantevari, Srinivas; Baitharu, Iswar; Naik, Pradeep Kumar

2015-03-01

We have strategically designed a series of noscapine derivatives by inserting biaryl pharmacophore (a major structural constituent of many of the microtubule-targeting natural anticancer compounds) onto the scaffold structure of noscapine. Molecular interaction of these derivatives with α,β-tubulin heterodimer was investigated by molecular docking, molecular dynamics simulation, and binding free energy calculation. The predictive binding affinity indicates that the newly designed noscapinoids bind to tubulin with a greater affinity. The predictive binding free energy (ΔGbind, pred) of these derivatives (ranging from -5.568 to -5.970 kcal/mol) based on linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model showed improved binding affinity with tubulin compared to the lead compound, natural α-noscapine (-5.505 kcal/mol). Guided by the computational findings, these new biaryl type α-noscapine congeners were synthesized from 9-bromo-α-noscapine using optimized Suzuki reaction conditions for further experimental evaluation. The derivatives showed improved inhibition of the proliferation of human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human lung adenocarcinoma cells (A549), compared to natural noscapine. The cell cycle analysis in MCF-7 further revealed that these compounds alter the cell cycle profile and cause mitotic arrest at G2/M phase more strongly than noscapine. Tubulin binding assay revealed higher binding affinity to tubulin, as suggested by dissociation constant (Kd) of 126 ± 5.0 µM for 5a, 107 ± 5.0 µM for 5c, 70 ± 4.0 µM for 5d, and 68 ± 6.0 µM for 5e compared to noscapine (Kd of 152 ± 1.0 µM). In fact, the experimentally determined value of ΔGbind, expt (calculated from the Kd value) are consistent with the predicted value of ΔGbind, pred calculated based on LIE-SGB. Based on these results, one of the derivative 5e of this series was used for further toxicological evaluation. Treatment of mice with a daily dose of 300 mg/kg and a single dose of 600 mg/kg indicates that the compound does not induce detectable pathological abnormalities in normal tissues. Also there were no significant differences in hematological parameters between the treated and untreated groups. Hence, the newly designed noscapinoid, 5e is an orally bioavailable, safe and effective anticancer agent with a potential for the treatment of cancer and might be a candidate for clinical evaluation.

Risk of solid cancer in low dose-rate radiation epidemiological studies and the dose-rate effectiveness factor.

PubMed

Shore, Roy; Walsh, Linda; Azizova, Tamara; Rühm, Werner

2017-10-01

Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy -1 ) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta-analyses that included only cohorts in which the mean dose was <100 mGy yielded a risk ratio of 1.06 (95% CI 0.30, 1.83) for solid cancer mortality and 0.58 (95% CI 0.10, 1.06) for mortality + incidence data. The interpretation of a best estimate for a value of the DREF depends on the appropriateness of including the Mayak study. This study indicates a range of uncertainty in the value of DREF between 1 and about 2 after protracted radiation exposure. The LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the LSS risk estimates used for radiation protection purposes.

Effects of ferumoxytol on quantitative PET measurements in simultaneous PET/MR whole-body imaging: a pilot study in a baboon model.

PubMed

Borra, Ronald Jh; Cho, Hoon-Sung; Bowen, Spencer L; Attenberger, Ulrike; Arabasz, Grae; Catana, Ciprian; Josephson, Lee; Rosen, Bruce R; Guimaraes, Alexander R; Hooker, Jacob M

2015-12-01

Simultaneous PET/MR imaging depends on MR-derived attenuation maps (mu-maps) for accurate attenuation correction of PET data. Currently, these maps are derived from gradient-echo-based MR sequences, which are sensitive to susceptibility changes. Iron oxide magnetic nanoparticles have been used in the measurement of blood volume, tumor microvasculature, tumor-associated macrophages, and characterizing lymph nodes. Our aim in this study was to assess whether the susceptibility effects associated with iron oxide nanoparticles can potentially affect measured (18)F-FDG PET standardized uptake values (SUV) through effects on MR-derived attenuation maps. The study protocol was approved by the Institutional Animal Care and Use Committee. Using a Siemens Biograph mMR PET/MR scanner, we evaluated the effects of increasing concentrations of ferumoxytol and ferumoxytol aggregates on MR-derived mu-maps using an agarose phantom. In addition, we performed a baboon experiment evaluating the effects of a single i.v. ferumoxytol dose (10 mg/kg) on the liver, spleen, and pancreas (18)F-FDG SUV at baseline (ferumoxytol-naïve), within the first hour and at 1, 3, 5, and 11 weeks. Phantom experiments showed mu-map artifacts starting at ferumoxytol aggregate concentrations of 10 to 20 mg/kg. The in vivo baboon data demonstrated a 53% decrease of observed (18)F-FDG SUV compared to baseline within the first hour in the liver, persisting at least 11 weeks. A single ferumoxytol dose can affect measured SUV for at least 3 months, which should be taken into account when administrating ferumoxytol in patients needing sequential PET/MR scans. Advances in knowledge 1. Ferumoxytol aggregates, but not ferumoxytol alone, produce significant artifacts in MR-derived attenuation correction maps at approximate clinical dose levels of 10 mg/kg. 2. When performing simultaneous whole-body (18)F-FDG PET/MR, a single dose of ferumoxytol can result in observed SUV decreases up to 53%, depending on the amount of ferumoxytol aggregates in the studied tissue. Implications for patient care Administration of a single, clinically relevant, dose of ferumoxytol can potentially result in changes in observed SUV for a prolonged period of time in the setting of simultaneous PET/MR. These potential changes should be considered in particular when administering ferumoxytol to patients with expected future PET/MR studies, as ferumoxytol-induced SUV changes might interfere with therapy assessment.

Correlation between prescribed daily dose, seizure freedom and defined daily dose in antiepileptic drug treatment.

PubMed

Horváth, László; Fekete, Klára; Márton, Sándor; Fekete, István

2017-04-01

Background Although defined daily doses (DDD) for antiepileptic drugs (AED) have been assigned only in combination therapy, based on the literature, most patients take them in monotherapy. Furthermore, discrepancies between DDD and prescribed daily dose (PDD) were observed. Objective First, to determine PDDs of AEDs and to reveal PDD/DDD ratio among seizure free versus not seizure free patients in everyday clinical practice. Second, to test the applicability of 75% cut-off of DDD to achieve seizure freedom. Furthermore, to find out what factors might influence PDD. Setting Outpatient data files at a Hungarian university hospital were studied. Methods A retrospective, 20-year cross-sectional database was compiled from 1282 epileptic outpatients' files. Main outcome measure Seizure freedom and PDD were used as outcome measures. Results The mean DDD% of all prescribed AEDs increased steadily from monotherapy, through bitherapy towards polytherapy (p < 0.0001). Most seizure free patients took AEDs in doses in the range of ≤75% of DDDs in monotherapy and bitherapy. Older AEDs (carbamazepine and valproate) were given in a significantly higher mean dose in bitherapy in the seizure free group. Among the newer types, only levetiracetam and lamotrigine had a significantly higher DDD% in mono-, bi-, and polytherapy. Confirmed by logistic regression analysis, gender, age, type of epilepsy, and number of AEDs had a significant impact on the value of 75% DDD. Conclusion No significant unfavourable impact of the lower ratio of PDD/DDD on the outcome of achieving seizure freedom has been confirmed. As a measure of seizure freedom, 75% of DDD may be used, although individual therapy must be emphasised. Precisely quantified DDD would provide a more accurate calculation of other derived values.

Out-of-Field Dose Equivalents Delivered by Passively Scattered Therapeutic Proton Beams for Clinically Relevant Field Configurations

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

Wroe, Andrew; Centre for Medical Radiation Physics, University of Wollongong, Wollongong; Clasie, Ben

2009-01-01

Purpose: Microdosimetric measurements were performed at Massachusetts General Hospital, Boston, MA, to assess the dose equivalent external to passively delivered proton fields for various clinical treatment scenarios. Methods and Materials: Treatment fields evaluated included a prostate cancer field, cranial and spinal medulloblastoma fields, ocular melanoma field, and a field for an intracranial stereotactic treatment. Measurements were completed with patient-specific configurations of clinically relevant treatment settings using a silicon-on-insulator microdosimeter placed on the surface of and at various depths within a homogeneous Lucite phantom. The dose equivalent and average quality factor were assessed as a function of both lateral displacement frommore » the treatment field edge and distance downstream of the beam's distal edge. Results: Dose-equivalent value range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral displacement) for the ocular melanoma field. Measurements of external field dose equivalent for the stereotactic field case showed differences as high as 50% depending on the modality of beam collimation. Average quality factors derived from this work ranged from 2-7, with the value dependent on the position within the phantom in relation to the primary beam. Conclusions: This work provides a valuable and clinically relevant comparison of the external field dose equivalents for various passively scattered proton treatment fields.« less

Bronchodilatory and Anti-Inflammatory Effects of ASM-024, a Nicotinic Receptor Ligand, Developed for the Treatment of Asthma

PubMed Central

Assayag, Evelyne Israël; Beaulieu, Marie-Josée; Cormier, Yvon

2014-01-01

Conventional asthma and COPD treatments include the use of bronchodilators, mainly β2-adrenergic agonists, muscarinic receptor antagonists and corticosteroids or leukotriene antagonists as anti-inflammatory agents. These active drugs are administered either separately or given as a fixed-dose combination medication into a single inhaler. ASM-024, a homopiperazinium compound, derived from the structural modification of diphenylmethylpiperazinium (DMPP), has been developed to offer an alternative mechanism of action that could provide symptomatic control through combined anti-inflammatory and bronchodilator properties in a single entity. A dose-dependent inhibition of cellular inflammation in bronchoalveolar lavage fluid was observed in ovalbumin-sensitized mice, subsequently treated for 3 days by nose-only exposure with aerosolized ASM-024 at doses up to 3.8 mg/kg (ED50 = 0.03 mg/kg). The methacholine ED250 values indicated that airway hyperresponsivenness (AHR) to methacholine decreased following ASM-024 administration by inhalation at a dose of 1.5 mg/kg, with a value of 0.145±0.032 mg/kg for ASM 024-treated group as compared to 0.088±0.023 mg/kg for untreated mice. In in vitro isometric studies, ASM-024 elicited dose-dependent relaxation of isolated mouse tracheal, human, and dog bronchial preparations contracted with methacholine and guinea pig tracheas contracted with histamine. ASM-024 showed also a dose and time dependant protective effect on methacholine-induced contraction. Overall, with its combined anti-inflammatory, bronchodilating and bronchoprotective properties, ASM-024 may represent a new class of drugs with a novel pharmacological approach that could prove useful for the chronic maintenance treatment of asthma and, possibly, COPD. PMID:24465890

Bronchodilatory and anti-inflammatory effects of ASM-024, a nicotinic receptor ligand, developed for the treatment of asthma.

PubMed

Assayag, Evelyne Israël; Beaulieu, Marie-Josée; Cormier, Yvon

2014-01-01

Conventional asthma and COPD treatments include the use of bronchodilators, mainly β2-adrenergic agonists, muscarinic receptor antagonists and corticosteroids or leukotriene antagonists as anti-inflammatory agents. These active drugs are administered either separately or given as a fixed-dose combination medication into a single inhaler. ASM-024, a homopiperazinium compound, derived from the structural modification of diphenylmethylpiperazinium (DMPP), has been developed to offer an alternative mechanism of action that could provide symptomatic control through combined anti-inflammatory and bronchodilator properties in a single entity. A dose-dependent inhibition of cellular inflammation in bronchoalveolar lavage fluid was observed in ovalbumin-sensitized mice, subsequently treated for 3 days by nose-only exposure with aerosolized ASM-024 at doses up to 3.8 mg/kg (ED50 = 0.03 mg/kg). The methacholine ED250 values indicated that airway hyperresponsivenness (AHR) to methacholine decreased following ASM-024 administration by inhalation at a dose of 1.5 mg/kg, with a value of 0.145 ± 0.032 mg/kg for ASM 024-treated group as compared to 0.088 ± 0.023 mg/kg for untreated mice. In in vitro isometric studies, ASM-024 elicited dose-dependent relaxation of isolated mouse tracheal, human, and dog bronchial preparations contracted with methacholine and guinea pig tracheas contracted with histamine. ASM-024 showed also a dose and time dependant protective effect on methacholine-induced contraction. Overall, with its combined anti-inflammatory, bronchodilating and bronchoprotective properties, ASM-024 may represent a new class of drugs with a novel pharmacological approach that could prove useful for the chronic maintenance treatment of asthma and, possibly, COPD.

Automatic Exposure Control Systems Designed to Maintain Constant Image Noise: Effects on Computed Tomography Dose and Noise Relative to Clinically Accepted Technique Charts

PubMed Central

Favazza, Christopher P.; Yu, Lifeng; Leng, Shuai; Kofler, James M.; McCollough, Cynthia H.

2015-01-01

Objective To compare computed tomography dose and noise arising from use of an automatic exposure control (AEC) system designed to maintain constant image noise as patient size varies with clinically accepted technique charts and AEC systems designed to vary image noise. Materials and Methods A model was developed to describe tube current modulation as a function of patient thickness. Relative dose and noise values were calculated as patient width varied for AEC settings designed to yield constant or variable noise levels and were compared to empirically derived values used by our clinical practice. Phantom experiments were performed in which tube current was measured as a function of thickness using a constant-noise-based AEC system and the results were compared with clinical technique charts. Results For 12-, 20-, 28-, 44-, and 50-cm patient widths, the requirement of constant noise across patient size yielded relative doses of 5%, 14%, 38%, 260%, and 549% and relative noises of 435%, 267%, 163%, 61%, and 42%, respectively, as compared with our clinically used technique chart settings at each respective width. Experimental measurements showed that a constant noise–based AEC system yielded 175% relative noise for a 30-cm phantom and 206% relative dose for a 40-cm phantom compared with our clinical technique chart. Conclusions Automatic exposure control systems that prescribe constant noise as patient size varies can yield excessive noise in small patients and excessive dose in obese patients compared with clinically accepted technique charts. Use of noise-level technique charts and tube current limits can mitigate these effects. PMID:25938214

Dosimetry during intramedullary nailing of the tibia.

PubMed

Kirousis, George; Delis, Harry; Megas, Panagiotis; Lambiris, Elias; Panayiotakis, George

2009-10-01

Intramedullary nailing under fluoroscopic guidance is a common operation. We studied the intraoperative radiation dose received by both the patient and the personnel. 25 intramedullary nailing procedures of the tibia were studied. All patients suffered from tibial fractures and were treated using the Grosse-Kempf intramedullary nail, with free-hand technique for fixation of the distal screws, under fluoroscopic guidance. The exposure, at selected positions, was recorded using an ion chamber, while the dose area product (DAP) was measured with a DAP meter, attached to the tube head. Thermoluminescent dosimeters (TLDs) were used to derive the occupational dose to the personnel, and also to monitor the surface dose on the gonads of some of the patients. The mean operation time was 101 (48-240) min, with a mean fluoroscopic time of 72 seconds and a mean DAP value of 75 cGy x cm(2). The surface dose to the gonads of the patients was less than 8.8 mGy during any procedure, and thus cannot be considered to be a contraindication for the use of this technique. Occupational dose differed substantially between members of the operating personnel, the maximum dose recorded being to the operator of the fluoroscopic equipment (0.11 mSv). Our findings underscore the care required by the primary operator not to exceed the dose constraint of 10 mSv per year. The rest of the operating personnel, although they do not receive very high doses, should focus on the dose optimization of the technique.

Comparison of PDR brachytherapy and external beam radiation therapy in the case of breast cancer

NASA Astrophysics Data System (ADS)

Teymournia, L.; Berger, D.; Kauer-Dorner, D.; Poljanc, K.; Seitz, W.; Aiginger, H.; Kirisits, C.

2009-04-01

Pulsed dose rate brachytherapy (PDR) was compared to external beam radiation therapy (EBRT) in the case of breast cancer. The benefits were figured out by evaluation of dosimetric parameters and calculating the normal tissue complication probability (NTCP). PDR plans were set up for five randomly chosen left-sided breast cancer patients delivering a total dose of 50.4 Gy to the target (dose rate 0.8 Gy h-1). For EBRT five left-sided breast cancer patients were planned using 3D-conformal tangential photon beams with a prescribed total dose of 50 Gy (2 Gy/fraction) to the total breast volume. For plan ranking and NTCP calculation the physical dose was first converted into the biologically effective dose (BED) and then into the normalized total dose (NTD) using the linear quadratic model with an α/β ratio of 3 Gy. In PDR the relative effectiveness (RE) was calculated for each dose bin of the differential dose volume histogram to get the BED. NTCPs were calculated for the ipsilateral lung and the heart as contoured on CT slices based on the Lyman model and the Kutcher reduction scheme. Dosimetric parameters as Vth (percentage of the total volume exceeding a threshold dose) and Jackson's fdam (fraction of the organ damaged) were also used to figure out the benefits. The comparison of calculated NTCPs in PDR and EBRT showed no difference between these two modalities. All values were below 0.01%. fdam derived from EBRT was always higher (mean value 8.95% versus 1.21% for the lung). The mean V10 and V20 of the lung related to BED were 6.32% and 1.72% for PDR versus 11.72% and 9.59% for EBRT. When using dosimetric parameters as Vth and fdam, PDR was mostly superior to EBRT in respect of sparing normal tissues. NTCP calculation as a single method of modality ranking showed a lack of information, especially when normal tissue was exposed to low radiation doses.

SU-F-I-01: Normalized Mean Glandular Dose Values for Dedicated Breast CT Using Realistic Breast-Shaped Phantoms

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

Hernandez, A; Boone, J

Purpose: To estimate normalized mean glandular dose values for dedicated breast CT (DgN-CT) using breast CT-derived phantoms and compare to estimations using cylindrical phantoms. Methods: Segmented breast CT (bCT) volume data sets (N=219) were used to measure effective diameter profiles and were grouped into quintiles by volume. The profiles were averaged within each quintile to represent the range of breast sizes found clinically. These profiles were then used to generate five voxelized computational phantoms (V1, V2, V3, V4, V5 for the small to large phantom sizes, respectively), and loaded into the MCNP6 lattice geometry to simulate normalized mean glandular dosemore » coefficients (DgN-CT) using the system specifications of the Doheny-prototype bCT scanner in our laboratory. The DgN-CT coefficients derived from the bCT-derived breast-shaped phantoms were compared to those generated using a simpler cylindrical phantom using a constant volume, and the following constraints: (1) Length=1.5*radius; (2) radius determined at chest wall (Rcw), and (3) radius determined at the phantom center-of-mass (Rcm). Results: The change in Dg-NCT coefficients averaged across all phantom sizes, was - 0.5%, 19.8%, and 1.3%, for constraints 1–3, respectively. This suggests that the cylindrical assumption is a good approximation if the radius is taken at the breast center-of-mass, but using the radius at the chest wall results in an underestimation of the glandular dose. Conclusion: The DgN-CT coefficients for bCT-derived phantoms were compared against the assumption of a cylindrical phantom and proved to be essentially equivalent when the cylinder radius was set to r=1.5/L or Rcm. While this suggests that for dosimetry applications a patient’s breast can be approximated as a cylinder (if the correct radius is applied), this assumes a homogenous composition of breast tissue and the results may be different if the realistic heterogeneous distribution of glandular tissue is considered. Research reported in this paper was supported in part by the National Cancer Institute of the National Institutes of Health under award R01CA181081. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institue of Health.« less

Independent calculation of monitor units for VMAT and SPORT

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

Chen, Xin; Bush, Karl; Ding, Aiping

Purpose: Dose and monitor units (MUs) represent two important facets of a radiation therapy treatment. In current practice, verification of a treatment plan is commonly done in dose domain, in which a phantom measurement or forward dose calculation is performed to examine the dosimetric accuracy and the MU settings of a given treatment plan. While it is desirable to verify directly the MU settings, a computational framework for obtaining the MU values from a known dose distribution has yet to be developed. This work presents a strategy to calculate independently the MUs from a given dose distribution of volumetric modulatedmore » arc therapy (VMAT) and station parameter optimized radiation therapy (SPORT). Methods: The dose at a point can be expressed as a sum of contributions from all the station points (or control points). This relationship forms the basis of the proposed MU verification technique. To proceed, the authors first obtain the matrix elements which characterize the dosimetric contribution of the involved station points by computing the doses at a series of voxels, typically on the prescription surface of the VMAT/SPORT treatment plan, with unit MU setting for all the station points. An in-house Monte Carlo (MC) software is used for the dose matrix calculation. The MUs of the station points are then derived by minimizing the least-squares difference between doses computed by the treatment planning system (TPS) and that of the MC for the selected set of voxels on the prescription surface. The technique is applied to 16 clinical cases with a variety of energies, disease sites, and TPS dose calculation algorithms. Results: For all plans except the lung cases with large tissue density inhomogeneity, the independently computed MUs agree with that of TPS to within 2.7% for all the station points. In the dose domain, no significant difference between the MC and Eclipse Anisotropic Analytical Algorithm (AAA) dose distribution is found in terms of isodose contours, dose profiles, gamma index, and dose volume histogram (DVH) for these cases. For the lung cases, the MC-calculated MUs differ significantly from that of the treatment plan computed using AAA. However, the discrepancies are reduced to within 3% when the TPS dose calculation algorithm is switched to a transport equation-based technique (Acuros™). Comparison in the dose domain between the MC and Eclipse AAA/Acuros calculation yields conclusion consistent with the MU calculation. Conclusions: A computational framework relating the MU and dose domains has been established. The framework does not only enable them to verify the MU values of the involved station points of a VMAT plan directly in the MU domain but also provide a much needed mechanism to adaptively modify the MU values of the station points in accordance to a specific change in the dose domain.« less

SU-G-IeP3-04: Effective Dose Measurements in Fast Kvp Switch Dual Energy Computed Tomography

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

Raudabaugh, J; Moore, B; Nguyen, G

2016-06-15

Purpose: The objective of this study was two-fold: (a) to test a new approach to approximating organ dose by using the effective energy of the combined 80kV/140kV beam in dual-energy (DE) computed tomography (CT), and (b) to derive the effective dose (ED) in the abdomen-pelvis protocol in DECT. Methods: A commercial dual energy CT scanner was employed using a fast-kV switch abdomen/pelvis protocol alternating between 80 kV and 140 kV. MOSFET detectors were used for organ dose measurements. First, an experimental validation of the dose equivalency between MOSFET and ion chamber (as a gold standard) was performed using a CTDImore » phantom. Second, the ED of DECT scans was measured using MOSFET detectors and an anthropomorphic phantom. For ED calculations, an abdomen/pelvis scan was used using ICRP 103 tissue weighting factors; ED was also computed using the AAPM Dose Length Product (DLP) method and compared to the MOSFET value. Results: The effective energy was determined as 42.9 kV under the combined beam from half-value layer (HVL) measurement. ED for the dual-energy scan was calculated as 16.49 ± 0.04 mSv by the MOSFET method and 14.62 mSv by the DLP method. Conclusion: Tissue dose in the center of the CTDI body phantom was 1.71 ± 0.01 cGy (ion chamber) and 1.71 ± 0.06 (MOSFET) respectively; this validated the use of effective energy method for organ dose estimation. ED from the abdomen-pelvis scan was calculated as 16.49 ± 0.04 mSv by MOSFET and 14.62 mSv by the DLP method; this suggests that the DLP method provides a reasonable approximation to the ED.« less

A Comparison of Four Indices for Combining Distance and Dose Differences

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

Thomas, Simon J., E-mail: simon.thomas@addenbrookes.nhs.uk; Cowley, Ian R.

2012-04-01

Purpose: When one is comparing two dose distributions, a number of methods have been published to combine dose difference and distance to agreement into a single measure. Some have been defined as pass/fail indices and some as numeric indices. We show that the pass/fail indices can all be used to derive numeric indices, and we compare the results of using these indices to evaluate one-dimensional (1D) and three-dimensional (3D) dose distributions, with the aim of selecting the most appropriate index for use in different circumstances. Methods and Materials: The indices compared are the gamma index, the kappa index, the indexmore » in International Commission on Radiation Units and Measurements Report 83, and a box index. Comparisons are made for 1D and 3D distributions. The 1D distribution is chosen to have a variety of dose gradients. The 3D distribution is taken from a clinical treatment plan. The effect of offsetting distributions by known distances and doses is studied. Results: The International Commission on Radiation Units and Measurements Report 83 index causes large discontinuities unless the dose gradient cutoff is set to equal the ratio of the dose tolerance to the distance tolerance. If it is so set, it returns identical results to the kappa index. Where the gradient is very high or very low, all the indices studied in this article give similar results for the same tolerance values. For moderate gradients, they differ, with the box index being the least strict, followed by the gamma index, and with the kappa index being the most strict. Conclusions: If the clinical tolerances are much greater than the uncertainties of the measuring system, the kappa index should be used, with tolerance values determined by the clinical tolerances. In cases where the uncertainties of the measuring system dominate, the box index will be best able to determine errors in the delivery system.« less

Cost-effectiveness of the Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults.

PubMed

Le, Phuc; Rothberg, Michael B

2018-02-01

The live attenuated herpes zoster vaccine (ZVL) is recommended for immunocompetent adults 60 years or older, but the efficacy wanes with age and over time. A new adjuvanted herpes zoster subunit vaccine (HZ/su) has higher efficacy but might be more expensive. The choice of vaccines depends on their relative values. To assess the cost-effectiveness of HZ/su. Markov decision model with transition probabilities based on the US medical literature. Participants were immunocompetent adults 60 years or older. Data were derived from participant groups ranging in number from less than 100 to more than 30 000 depending on the variable assessed. The study dates were July 1 to 31, 2017. No vaccination, ZVL (single dose), and HZ/su (2-dose series) vaccine administered at different ages. Total costs and quality-adjusted life-years (QALYs) were estimated. Based on randomized clinical trial data, at a price of $280 per series ($140 per dose), HZ/su was more effective and less expensive than ZVL at all ages. The incremental cost-effectiveness ratios compared with no vaccination ranged from $20 038 to $30 084 per QALY, depending on vaccination age. The finding was insensitive to variations in most model inputs other than the vaccine price and certain combinations of low adherence rate with a second dose and low efficacy of a single dose of HZ/su. At the current ZVL price ($213 per dose), HZ/su had lower overall costs than ZVL up to a price of $350 per 2-dose series. In probabilistic sensitivity analysis, HZ/su had 73% probability of being cost-effective for 60-year-olds at $50 000 per QALY. Under conservative assumptions, at a price of $280 per series ($140 per dose), HZ/su would cost less than ZVL and has a high probability of offering good value.

Do changes in biomarkers from space radiation reflect dose or risk?

NASA Astrophysics Data System (ADS)

Brooks, A.

The space environment is made up of many different kinds of radiation so that the proper use of biomarkers is essential to estimate radiation risk. This presentation will evaluate differences between biomarkers of dose and risk and demonstrate why they should not be confused following radiation exposures in deep space. Dose is a physical quantity, while risk is a biological quantity. Many examples exist w ereh dose or changes in biomarkers of dose are inappropriately used as predictors of risk. Without information on the biology of the system, the biomarkers of dose provide little help in predicting risk in tissues or radiation exposure types where no excess risk can be demonstrated. Many of these biomarkers of dose only reflect changes in radiation dose or exposure. However, these markers are often incorrectly used to predict risk. For example, exposure of the trachea or of the deep lung to high-LET alpha particles results in similar changes in the biomarker chromosome damage in these two tissues. Such an observation would predict that the risk for cancer induction would be similar in these two tissues. It has been noted , however, that there has never been a tracheal tumor observed in rats that inhaled radon, but with the same exposure, large numbers of tumors were produced in the deep lung. The biology of the different tissues is the major determinant of the risk rather than the radiation dose. Recognition of this fact has resulted in the generation of tissue weighting factors for use in radiation protection. When tissue weighting factors are used the values derived are still called "dose". It is important to recognize that tissue specific observations have been corrected to reflect risk, and therefore should no longer be viewed as dose. The relative biological effectiveness (RBE) is also used to estimate radiation risk. The use of biomarkers to derive RBE is a difficult since it involves the use of a biological response to a standard low-LET reference radiation. Following low-LET radiation exposure, the biological response often does not increase as a linear function of dose. Thus, the RBE and the subsequent risk predicted is dependent on the dose where the two radiation types are compared. To avoid this problem the standard procedure is to use the dose and dose-rate response and compare the linear components of the two r diation exposures. Important riska comparisons are often done at very low doses, where the reference radiation may either increase or decrease as a function of dose. Since the low-LET exposure often does not produce a significant change above the background level of damage, the derived RBE factors can become very large.Studies using micronuclei as biomarkers following exposure to mono-energetic neutrons, x-rays and gamma rays delivered at very low doses (up to 0.10 Gy) demonstrated the differences in the shape of each dose-response relationship and the problems associated with the RBE. These studies show that RBE may not accurately reflect the hazards or risk associated with space radiation exposure. As additional measures of biological change are developed, it may become possible to base risk on biological change and not on changes in radiation doses. Research funded through grants # DE-FG03-99ER62787 from DOE Office of Biological and Environmental Research and RO1 CA74053-01 from NIH/NASA to Washington State University Tri-Cities.

Lipophilicity plays a major role in modulating the inhibition of monoamine oxidase B by 7-substituted coumarins.

PubMed

Carotti, Angelo; Altomare, Cosimo; Catto, Marco; Gnerre, Carmela; Summo, Luciana; De Marco, Agostino; Rose, Sarah; Jenner, Peter; Testa, Bernard

2006-02-01

A series of coumarin derivatives (1-22), bearing at the 7-position ether, ketone, ester, carbamate, or amide functions of varying size and lipophilicity, were synthesized and investigated for their in vitro monoamine oxidase-A and -B (MAO-A and -B) inhibitory activities. Most of the compounds acted preferentially as MAO-B inhibitors, with IC(50) values in the micromolar to low-nanomolar range. A structure-activity-relationship (SAR) study highlighted lipophilicity as an important property modulating the MAO-B inhibition potency of 7-substituted coumarins, as shown by a linear correlation (n=20, r(2)=0.72) between pIC(50) and calculated log P values. The stability of ester-containing coumarin derivatives in rat plasma provided information on factors that either favor (lipophilicity) or decrease (steric hindrance) esterase-catalyzed hydrolysis. Two compounds (14 and 22) were selected to investigate how lipophilicity and enzymatic stability may affect in vivo MAO activities, as assayed ex vivo in rat. The most-potent and -selective MAO-B inhibitor 22 (=7-[(3,4-difluorobenzyl)oxy]-3,4-dimethyl-1-benzopyran-2(2H)-one) within the examined series significantly inhibited (>60%) ex vivo rat-liver and striatal MAO-B activities 1 h after intraperitoneal administration of high doses (100 and 300 mumol kg(-1)), revealing its ability to cross the blood-brain barrier. At the same doses, liver and striatum MAO-A was less inhibited in vivo, somehow reflecting MAO-B selectivity, as assessed in vitro. In contrast, the metabolically less stable derivative 14, bearing an isopropyl ester in the lateral chain, had a weak effect on hepatic MAO-B activity in vivo, and none on striatal MAO-B, but, surprisingly, displayed inhibitory effects on MAO-A in both peripheral and brain tissues.

Ir-192 HDR transit dose and radial dose function determination using alanine/EPR dosimetry

NASA Astrophysics Data System (ADS)

Guzmán Calcina, Carmen S.; de Almeida, Adelaide; Oliveira Rocha, José R.; Abrego, Felipe Chen; Baffa, Oswaldo

2005-03-01

Source positioning close to the tumour in high dose rate (HDR) brachytherapy is not instantaneous. An increment of dose will be delivered during the movement of the source in the trajectory to its static position. This increment is the transit dose, often not taken into account in brachytherapeutic treatment planning. The transit dose depends on the prescribed dose, number of treatment fractions, velocity and activity of the source. Combining all these factors, the transit dose can be 5% higher than the prescribed absorbed dose value (Sang-Hyun and Muller-Runkel, 1994 Phys. Med. Biol. 39 1181 8, Nath et al 1995 Med. Phys. 22 209 34). However, it cannot exceed this percentage (Nath et al 1995). In this work, we use the alanine-EPR (electron paramagnetic resonance) dosimetric system using analysis of the first derivative of the signal. The transit dose was evaluated for an HDR system and is consistent with that already presented for TLD dosimeters (Bastin et al 1993 Int. J. Radiat. Oncol. Biol. Phys. 26 695 702). Also using the same dosimetric system, the radial dose function, used to evaluate the geometric dose degradation around the source, was determined and its behaviour agrees better with those obtained by Monte Carlo simulations (Nath et al 1995, Williamson and Nath 1991 Med. Phys. 18 434 48, Ballester et al 1997 Med. Phys. 24 1221 8, Ballester et al 2001 Phys. Med. Biol. 46 N79 90) than with TLD measurements (Nath et al 1990 Med. Phys. 17 1032 40).

Ir-192 HDR transit dose and radial dose function determination using alanine/EPR dosimetry.

PubMed

Calcina, Carmen S Guzmán; de Almeida, Adelaide; Rocha, José R Oliveira; Abrego, Felipe Chen; Baffa, Oswaldo

2005-03-21

Source positioning close to the tumour in high dose rate (HDR) brachytherapy is not instantaneous. An increment of dose will be delivered during the movement of the source in the trajectory to its static position. This increment is the transit dose, often not taken into account in brachytherapeutic treatment planning. The transit dose depends on the prescribed dose, number of treatment fractions, velocity and activity of the source. Combining all these factors, the transit dose can be 5% higher than the prescribed absorbed dose value (Sang-Hyun and Muller-Runkel, 1994 Phys. Med. Biol. 39 1181-8, Nath et al 1995 Med. Phys. 22 209-34). However, it cannot exceed this percentage (Nath et al 1995). In this work, we use the alanine-EPR (electron paramagnetic resonance) dosimetric system using analysis of the first derivative of the signal. The transit dose was evaluated for an HDR system and is consistent with that already presented for TLD dosimeters (Bastin et al 1993 Int. J. Radiat. Oncol. Biol. Phys. 26 695-702). Also using the same dosimetric system, the radial dose function, used to evaluate the geometric dose degradation around the source, was determined and its behaviour agrees better with those obtained by Monte Carlo simulations (Nath et al 1995, Williamson and Nath 1991 Med. Phys. 18 434-48, Ballester et al 1997 Med. Phys. 24 1221-8, Ballester et al 2001 Phys. Med. Biol. 46 N79-90) than with TLD measurements (Nath et al 1990 Med. Phys. 17 1032-40).

Effective radiation dose and eye lens dose in dental cone beam CT: effect of field of view and angle of rotation.

PubMed

Pauwels, R; Zhang, G; Theodorakou, C; Walker, A; Bosmans, H; Jacobs, R; Bogaerts, R; Horner, K

2014-10-01

To quantify the effect of field of view (FOV) and angle of rotation on radiation dose in dental cone beam CT (CBCT) and to define a preliminary volume-dose model. Organ and effective doses were estimated using 148 thermoluminescent dosemeters placed in an anthropomorphic phantom. Dose measurements were undertaken on a 3D Accuitomo 170 dental CBCT unit (J. Morita, Kyoto, Japan) using six FOVs as well as full-rotation (360°) and half-rotation (180°) protocols. For the 360° rotation protocols, effective dose ranged between 54 µSv (4 × 4 cm, upper canine) and 303 µSv (17 × 12 cm, maxillofacial). An empirical relationship between FOV dimension and effective dose was derived. The use of a 180° rotation resulted in an average dose reduction of 45% compared with a 360° rotation. Eye lens doses ranged between 95 and 6861 µGy. Significant dose reduction can be achieved by reducing the FOV size, particularly the FOV height, of CBCT examinations to the actual region of interest. In some cases, a 180° rotation can be preferred, as it has the added value of reducing the scan time. Eye lens doses should be reduced by decreasing the height of the FOV rather than using inferior FOV positioning, as the latter would increase the effective dose considerably. The effect of the FOV and rotation angle on the effective dose in dental CBCT was quantified. The dominant effect of FOV height was demonstrated. A preliminary model has been proposed, which could be used to predict effective dose as a function of FOV size and position.

Chernobyl Doses. Volume 2. Conifer Stress near Chernobyl Derived from Landsat Imagery

DTIC Science & Technology

1992-12-01

Defense Nuclear Agency Alexandria, VA 22310-3398 AD-A259 085 S.... IiilII|IlH~l D.A-TR-92-3,,.v2 Chernobyl Doses Volume 2-Conifer Stress Near... Chernobyl Derived from Landsat Imagery Gene E. McClellan Terrence H. Hemmer Ronald N. DeWitt Pacific-Sierra Research Corporation 12340 Santa Monica Boulevard...870929 - 920228 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Chernobyl Doses C - DNA 001-87-C-0104 Volume 2- Conifer Stress Near Chernobyl Derived from

Chernobyl accident: reconstruction of thyroid dose for inhabitants of the Republic of Belarus.

PubMed

Gavrilin, Y I; Khrouch, V T; Shinkarev, S M; Krysenko, N A; Skryabin, A M; Bouville, A; Anspaugh, L R

1999-02-01

The Chernobyl accident in April 1986 resulted in widespread contamination of the environment with radioactive materials, including (131)I and other radioiodines. This environmental contamination led to substantial radiation doses in the thyroids of many inhabitants of the Republic of Belarus. The reconstruction of thyroid doses received by Belarussians is based primarily on exposure rates measured against the neck of more than 200,000 people in the more contaminated territories; these measurements were carried out within a few weeks after the accident and before the decay of (131)I to negligible levels. Preliminary estimates of thyroid dose have been divided into 3 classes: Class 1 ("measured" doses), Class 2 (doses "derived by affinity"), and Class 3 ("empirically-derived" doses). Class 1 doses are estimated directly from the measured thyroidal (131)I content of the person considered, plus information on lifestyle and dietary habits. Such estimates are available for about 130,000 individuals from the contaminated areas of the Gomel and Mogilev Oblasts and from the city of Minsk. Maximum individual doses are estimated to range up to about 60 Gy. For every village with a sufficient number of residents with Class 1 doses, individual thyroid dose distributions are determined for several age groups and levels of milk consumption. These data are used to derive Class 2 thyroid dose estimates for unmeasured inhabitants of these villages. For any village where the number of residents with Class 1 thyroid doses is small or equal to zero, individual thyroid doses of Class 3 are derived from the relationship obtained between the mean adult thyroid dose and the deposition density of (131)I or 137Cs in villages with Class 2 thyroid doses presenting characteristics similar to those of the village considered. In order to improve the reliability of the Class 3 thyroid doses, an extensive program of measurement of (129)I in soils is envisaged.

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

PubMed

Anagnostopoulos, Georgios; Andrássy, Michael; Baltas, Dimos

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

Derivation of Human Lethal Doses

DTIC Science & Technology

2006-01-19

1956; Blair, 1961; Mason et al., 1965; Clarke , 1969; Cretney, 1976; Gray et al., 1985). Gordon reported blood level of 5 mg/100ml in a victim. The...LD50 ( Clark et al., 1979). This is a primary source for the value. No LD50 for mouse Clinical Management of Poisoning and Drug Overdose 100 mL...Verschueren (2001) lists an oral LD50 range in various mammalian species as 30-112 mg/kg based on Clark et al., (1966 as cited in Verschueren, 2001

Radiation exposure in interventional radiology

NASA Astrophysics Data System (ADS)

Pinto, N. G. V.; Braz, D.; Vallim, M. A.; Filho, L. G. P.; Azevedo, F. S.; Barroso, R. C.; Lopes, R. T.

2007-09-01

The aim of this study is to evaluate dose values in patients and staff involved in some interventional radiology procedures. Doses have been measured using thermoluminescent dosemeters for single procedures (such as renal and cerebral arteriography, transjungular intrahepatic portasystemic shunt (TIPS) and chemoembolization). The magnitude of doses through the hands of interventional radiologists has been studied. Dose levels were evaluated in three points for patients (eye, thyroid and gonads). The dose-area product (DAP) was also investigated using a Diamentor (PTW-M2). The dose in extremities was estimated for a professional who generally performed one TIPS, two chemoembolizations, two cerebral arteriographies and two renal arteriographies in a week. The estimated annual radiation dose was converted to effective dose as suggested by the 453-MS/Brazil norm The annual dose values were 137.25 mSv for doctors, 40.27 mSv for nurses and 51.95 mSv for auxiliary doctors, and all these annual dose values are below the limit established. The maximum values of the dose obtained for patients were 6.91, 10.92 and 15.34 mGy close to eye, thyroid and gonads, respectively. The DAP values were evaluated for patients in the same interventional radiology procedures. The dose and DAP values obtained are in agreement with values encountered in the literature.

Diagnostic x-ray dosimetry using Monte Carlo simulation.

PubMed

Ioppolo, J L; Price, R I; Tuchyna, T; Buckley, C E

2002-05-21

An Electron Gamma Shower version 4 (EGS4) based user code was developed to simulate the absorbed dose in humans during routine diagnostic radiological procedures. Measurements of absorbed dose using thermoluminescent dosimeters (TLDs) were compared directly with EGS4 simulations of absorbed dose in homogeneous, heterogeneous and anthropomorphic phantoms. Realistic voxel-based models characterizing the geometry of the phantoms were used as input to the EGS4 code. The voxel geometry of the anthropomorphic Rando phantom was derived from a CT scan of Rando. The 100 kVp diagnostic energy x-ray spectra of the apparatus used to irradiate the phantoms were measured, and provided as input to the EGS4 code. The TLDs were placed at evenly spaced points symmetrically about the central beam axis, which was perpendicular to the cathode-anode x-ray axis at a number of depths. The TLD measurements in the homogeneous and heterogenous phantoms were on average within 7% of the values calculated by EGS4. Estimates of effective dose with errors less than 10% required fewer numbers of photon histories (1 x 10(7)) than required for the calculation of dose profiles (1 x 10(9)). The EGS4 code was able to satisfactorily predict and thereby provide an instrument for reducing patient and staff effective dose imparted during radiological investigations.

Diagnostic x-ray dosimetry using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Ioppolo, J. L.; Price, R. I.; Tuchyna, T.; Buckley, C. E.

2002-05-01

An Electron Gamma Shower version 4 (EGS4) based user code was developed to simulate the absorbed dose in humans during routine diagnostic radiological procedures. Measurements of absorbed dose using thermoluminescent dosimeters (TLDs) were compared directly with EGS4 simulations of absorbed dose in homogeneous, heterogeneous and anthropomorphic phantoms. Realistic voxel-based models characterizing the geometry of the phantoms were used as input to the EGS4 code. The voxel geometry of the anthropomorphic Rando phantom was derived from a CT scan of Rando. The 100 kVp diagnostic energy x-ray spectra of the apparatus used to irradiate the phantoms were measured, and provided as input to the EGS4 code. The TLDs were placed at evenly spaced points symmetrically about the central beam axis, which was perpendicular to the cathode-anode x-ray axis at a number of depths. The TLD measurements in the homogeneous and heterogenous phantoms were on average within 7% of the values calculated by EGS4. Estimates of effective dose with errors less than 10% required fewer numbers of photon histories (1 × 107) than required for the calculation of dose profiles (1 × 109). The EGS4 code was able to satisfactorily predict and thereby provide an instrument for reducing patient and staff effective dose imparted during radiological investigations.

Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships

PubMed Central

Blumberg, Jeffrey B.; Vita, Joseph A.; Chen, C. -Y. Oliver

2015-01-01

Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD), blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL) to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages. PMID:26633488

Alternative chitosan-based EPR dosimeter applicable for a relatively wide range of gamma radiation doses

NASA Astrophysics Data System (ADS)

Piroonpan, Thananchai; Katemake, Pichayada; Panritdam, Eagkapong; Pasanphan, Wanvimol

2017-12-01

Chitosan biopolymer is proposed as an alternative EPR dosimeter. Its ability to be EPR dosimeter was studied in comparison with the conventional alanine, sugars (i.e., glucose and sucrose), formate derivatives (i.e., lithium (Li), magnesium (Mg), and calcium (Ca) formate). Ethylene vinyl acetate (EVA) and paraffin were used as binder for the preparation of composite EPR dosimeter. Dose responses of all materials were investigated in a wide dose range of radiation doses, i.e., low-level (0-1 kGy), medium-level (1-10 kGy) and high-level (10-100 kGy). The EPR dosimeter properties were studied under different parameters, i.e., microwave power, materials contents, absorbed doses, storage conditions and post-irradiation effects. Li-formate showed a simple EPR spectrum and exhibited superior radiation response for low-dose range; whereas chitosan and sucrose exhibited linear dose response in all studied dose ranges. The EPR signals of chitosan exhibited similar stability as glucose, Li-formate and alanine at ambient temperature after irradiation as long as a year. All EPR signals of the studied materials were affected post-irradiation temperature and humidity after gamma irradiation. The EPR signal of chitosan exhibited long-term stability and it was not sensitive to high storage temperatures and humidity values after irradiation. Chitosan has a good merit as the alternative bio-based material for a stable EPR dosimeter in a wide range of radiation-absorbed doses.

Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

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

Gillmann, Clarissa, E-mail: clarissa.gillmann@med.uni-heidelberg.de; Jäkel, Oliver; Heidelberg Ion Beam Therapy Center

2014-04-01

Purpose: To compare the relative biological effectiveness (RBE)–weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials: In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time ofmore » 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm³ (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cm³ with the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results: The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD{sub 5}) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions: LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a comparable photon-treated collective using the same dosimetric variable as in the present study.« less

A Comparison of Dose-Response Models for the Parotid Gland in a Large Group of Head-and-Neck Cancer Patients

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

Houweling, Antonetta C., E-mail: A.Houweling@umcutrecht.n; Philippens, Marielle E.P.; Dijkema, Tim

2010-03-15

Purpose: The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose-response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose-volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulatedmore » salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose-threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC). Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD{sub 50} in these models was approximately 39 Gy. Conclusions: The mean dose model was preferred for describing the dose-response relationship of the parotid gland.« less

Structure-based design, synthesis and biological evaluation of β-glucuronidase inhibitors

NASA Astrophysics Data System (ADS)

Khan, Khalid M.; Ambreen, Nida; Taha, Muhammad; Halim, Sobia A.; Zaheer-ul-Haq; Naureen, Shagufta; Rasheed, Saima; Perveen, Shahnaz; Ali, Sajjad; Choudhary, Mohammad Iqbal

2014-05-01

Using structure-based virtual screening approach, a coumarin derivative ( 1) was identified as β-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of β-glucuronidase with IC50 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC50 = 9.9-352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e, 1k, 1n and 1p exhibited more potency than the standard inhibitor with IC50 values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent.

Structure-based design, synthesis and biological evaluation of β-glucuronidase inhibitors.

PubMed

Khan, Khalid M; Ambreen, Nida; Taha, Muhammad; Halim, Sobia A; Zaheer-ul-Haq; Naureen, Shagufta; Rasheed, Saima; Perveen, Shahnaz; Ali, Sajjad; Choudhary, Mohammad Iqbal

2014-05-01

Using structure-based virtual screening approach, a coumarin derivative (1) was identified as β-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of β-glucuronidase with IC50 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC50 = 9.9-352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e, 1k, 1n and 1p exhibited more potency than the standard inhibitor with IC50 values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent.

A systematic evaluation of the potential effects of trichloroethylene exposure on cardiac development.

PubMed

Makris, Susan L; Scott, Cheryl Siegel; Fox, John; Knudsen, Thomas B; Hotchkiss, Andrew K; Arzuaga, Xabier; Euling, Susan Y; Powers, Christina M; Jinot, Jennifer; Hogan, Karen A; Abbott, Barbara D; Hunter, E Sidney; Narotsky, Michael G

2016-10-01

The 2011 EPA trichloroethylene (TCE) IRIS assessment, used developmental cardiac defects from a controversial drinking water study in rats (Johnson et al. [51]), along with several other studies/endpoints to derive reference values. An updated literature search of TCE-related developmental cardiac defects was conducted. Study quality, strengths, and limitations were assessed. A putative adverse outcome pathway (AOP) construct was developed to explore key events for the most commonly observed cardiac dysmorphologies, particularly those involved with epithelial-mesenchymal transition (EMT) of endothelial origin (EndMT); several candidate pathways were identified. A hypothesis-driven weight-of-evidence analysis of epidemiological, toxicological, in vitro, in ovo, and mechanistic/AOP data concluded that TCE has the potential to cause cardiac defects in humans when exposure occurs at sufficient doses during a sensitive window of fetal development. The study by Johnson et al. [51] was reaffirmed as suitable for hazard characterization and reference value derivation, though acknowledging study limitations and uncertainties. Published by Elsevier Inc.

Site-Specific Reference Person Parameters and Derived Concentration Standards for the Savannah River Site

DOE PAGES

Stone, Daniel K.; Higley, Kathryn A.; Jannik, G. Timothy

2014-05-01

The U.S. Department of Energy Order 458.1 states that the compliance with the 1 mSv annual dose constraint to a member of the public may be demonstrated by calculating dose to the maximally exposed individual (MEI) or to a representative person. Historically, the MEI concept was used for dose compliance at the Savannah River Site (SRS) using adult dose coefficients and adult male usage parameters. For future compliance, SRS plans to use the representative person concept for dose estimates to members of the public. The representative person dose will be based on the reference person dose coefficients from the U.S.more » DOE Derived Concentration Technical Standard and on usage parameters specific to SRS for the reference and typical person. Usage parameters and dose coefficients were determined for inhalation, ingestion and external exposure pathways. The parameters for the representative person were used to calculate and tabulate SRS-specific derived concentration standards (DCSs) for the pathways not included in DOE-STD-1196-2011.« less

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

Novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one derivatives as potential inhibitors of chorismate mutase.

PubMed

Mallikarjuna Rao, V; Mahesh Kumar, P; Rambabu, D; Kapavarapu, Ravikumar; Shobha Rani, S; Misra, Parimal; Pal, Manojit

2013-12-01

A series of novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one (DHPM) derivatives were designed, synthesized and evaluated in vitro as potential inhibitors of chorismate mutase (CM). All these compounds were prepared via a multi-component reaction (MCR) involving sequential I2-mediated Biginelli reaction followed by Cu-free Sonogashira coupling. Some of them showed promising inhibitory activities when tested at 30μM. One compound showed dose dependent inhibition of CM with IC50 value of 14.76±0.54μM indicating o-alkynylphenyl substituted DHPM as a new scaffold for the discovery of promising inhibitors of CM. Copyright © 2013 Elsevier Inc. All rights reserved.

Androgen Receptor Antagonists and Anti-Prostate Cancer Activities of Some Newly Synthesized Substituted Fused Pyrazolo-, Triazolo- and Thiazolo-Pyrimidine Derivatives

PubMed Central

Bahashwan, Saleh A.; Fayed, Ahmed A.; Ramadan, Mohamed A.; Amr, Abd El-Galil E.; Al-Harbi, Naif O.

2014-01-01

A series of substituted pyrazole, triazole and thiazole derivatives (2–13) were synthesized from 1-(naphtho[1,2-d]thiazol-2-yl)hydrazine as starting material and evaluated as androgen receptor antagonists and anti-prostate cancer agents. The newly synthesized compounds showed potent androgen receptor antagonists and anti-prostate cancer activities with low toxicity (lethal dose 50 (LD50)) comparable to Bicalutamide as reference drug. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, and MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, LD50 values and pharmacological activities of the synthesized compounds are reported. PMID:25421248

Breast dose in mammography is about 30% lower when realistic heterogeneous glandular distributions are considered

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

Hernandez, Andrew M., E-mail: amhern@ucdavis.edu; Seibert, J. Anthony; Boone, John M.

2015-11-15

Purpose: Current dosimetry methods in mammography assume that the breast is comprised of a homogeneous mixture of glandular and adipose tissues. Three-dimensional (3D) dedicated breast CT (bCT) data sets were used previously to assess the complex anatomical structure within the breast, characterizing the statistical distribution of glandular tissue in the breast. The purpose of this work was to investigate the effect of bCT-derived heterogeneous glandular distributions on dosimetry in mammography. Methods: bCT-derived breast diameters, volumes, and 3D fibroglandular distributions were used to design realistic compressed breast models comprised of heterogeneous distributions of glandular tissue. The bCT-derived glandular distributions were fitmore » to biGaussian functions and used as probability density maps to assign the density distributions within compressed breast models. The MCNPX 2.6.0 Monte Carlo code was used to estimate monoenergetic normalized mean glandular dose “DgN(E)” values in mammography geometry. The DgN(E) values were then weighted by typical mammography x-ray spectra to determine polyenergetic DgN (pDgN) coefficients for heterogeneous (pDgN{sub hetero}) and homogeneous (pDgN{sub homo}) cases. The dependence of estimated pDgN values on phantom size, volumetric glandular fraction (VGF), x-ray technique factors, and location of the heterogeneous glandular distributions was investigated. Results: The pDgN{sub hetero} coefficients were on average 35.3% (SD, 4.1) and 24.2% (SD, 3.0) lower than the pDgN{sub homo} coefficients for the Mo–Mo and W–Rh x-ray spectra, respectively, across all phantom sizes and VGFs when the glandular distributions were centered within the breast phantom in the coronal plane. At constant breast size, increasing VGF from 7.3% to 19.1% lead to a reduction in pDgN{sub hetero} relative to pDgN{sub homo} of 23.6%–27.4% for a W–Rh spectrum. Displacement of the glandular distribution, at a distance equal to 10% of the compressed breast width in the superior and inferior directions, resulted in a 37.3% and a −26.6% change in the pDgN{sub hetero} coefficient, respectively, relative to the centered distribution for the Mo–Mo spectrum. Lateral displacement of the glandular distribution, at a distance equal to 10% of the compressed breast width, resulted in a 1.5% change in the pDgN{sub hetero} coefficient relative to the centered distribution for the W–Rh spectrum. Conclusions: Introducing bCT-derived heterogeneous glandular distributions into mammography phantom design resulted in decreased glandular dose relative to the widely used homogeneous assumption. A homogeneous distribution overestimates the amount of glandular tissue near the entrant surface of the breast, where dose deposition is exponentially higher. While these findings are based on clinically measured distributions of glandular tissue using a large cohort of women, future work is required to improve the classification of glandular distributions based on breast size and overall glandular fraction.« less

Acute inhalative exposure assessment: derivation of guideline levels with special regard to sensitive subpopulations and time scaling.

PubMed

Mielke, Hans; Gundert, Anna; Abraham, Klaus; Gundert-Remy, Ursula

2005-10-30

Risk assessment for acute airborne exposure to volatile organic compounds (VOCs), including exposure to chemical warfare agents, requires consideration of local and systemic effects at high concentrations. The operating procedure developed by the US Acute Exposure Guideline Level (AEGL) committee has gained special attention, in part because of the international collaboration in the project. The procedure defines three levels (AEGL-1: discomfort; AEGL-2: irreversible or other serious, long-lasting adverse effects; AEGL-3: life-threatening effects or death) for different exposure times (10 and 30 min, and 1, 4 and 8 h). In this article, the methodology for deriving AEGL values is reported. Extending the areas covered by the existing AEGL methodology, sensitive subpopulations are dealt with in more detail. Sensitive persons are expected to suffer from stronger effects when exposed to a given external concentration. Using a kinetic model with the sample substance dichloromethane (DCM), the higher internal exposure of children is quantified and compared to a healthy, young adult. The difference is shown to depend on age, on dose, and on duration of exposure. Furthermore, several ways are presented to derive AEGL values for exposure times which differ from the exposure duration in animal studies ('time scaling'). In comparison to the conventional procedure, the alternative approaches are based on mechanistic models of the toxicodynamic effect. Use of these models results in AEGL values which are biologically justified.

Derivation of mean dose tolerances for new fractionation schemes and treatment modalities

NASA Astrophysics Data System (ADS)

Perkó, Zoltán; Bortfeld, Thomas; Hong, Theodore; Wolfgang, John; Unkelbach, Jan

2018-02-01

Avoiding toxicities in radiotherapy requires the knowledge of tolerable organ doses. For new, experimental fractionation schemes (e.g. hypofractionation) these are typically derived from traditional schedules using the biologically effective dose (BED) model. In this report we investigate the difficulties of establishing mean dose tolerances that arise since the mean BED depends on the entire spatial dose distribution, rather than on the dose level alone. A formula has been derived to establish mean physical dose constraints such that they are mean BED equivalent to a reference treatment scheme. This formula constitutes a modified BED equation where the influence of the spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 24 liver cancer patients for whom both proton and photon IMRT treatment plans were available. The results show that the standard BED equation—neglecting the spatial dose distribution—can overestimate mean dose tolerances for hypofractionated treatments by up to 20%. The shape difference between photon and proton dose distributions can cause 30-40% differences in mean physical dose for plans having identical mean BEDs. Converting hypofractionated, 5/15-fraction proton doses to mean BED equivalent photon doses in traditional 35-fraction regimens resulted in up to 10 Gy higher doses than applying the standard BED formula. The dose shape effect should be accounted for to avoid overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. Additionally, tolerances established for one treatment modality cannot necessarily be applied to other modalities with drastically different dose distributions, such as proton therapy. Last, protons may only allow marginal (5-10%) dose escalation if a fraction-size adjusted organ mean dose is constraining instead of a physical dose.

Direct comparison of radiation dosimetry of six PET tracers using human whole-body imaging and murine biodistribution studies.

PubMed

Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Nariai, Tadashi; Ishiwata, Kiichi

2013-04-01

We investigated the whole-body biodistributions and radiation dosimetry of five (11)C-labeled and one (18)F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies. The radiotracers investigated were (11)C-SA4503, (11)C-MPDX, (11)C-TMSX, (11)C-CHIBA-1001, (11)C-4DST, and (18)F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection. The ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies. Although the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations.

Evaluation of backscatter dose from internal lead shielding in clinical electron beams using EGSnrc Monte Carlo simulations.

PubMed

De Vries, Rowen J; Marsh, Steven

2015-11-08

Internal lead shielding is utilized during superficial electron beam treatments of the head and neck, such as lip carcinoma. Methods for predicting backscattered dose include the use of empirical equations or performing physical measurements. The accuracy of these empirical equations required verification for the local electron beams. In this study, a Monte Carlo model of a Siemens Artiste linac was developed for 6, 9, 12, and 15 MeV electron beams using the EGSnrc MC package. The model was verified against physical measurements to an accuracy of better than 2% and 2mm. Multiple MC simulations of lead interfaces at different depths, corresponding to mean electron energies in the range of 0.2-14 MeV at the interfaces, were performed to calculate electron backscatter values. The simulated electron backscatter was compared with current empirical equations to ascertain their accuracy. The major finding was that the current set of backscatter equations does not accurately predict electron backscatter, particularly in the lower energies region. A new equation was derived which enables estimation of electron backscatter factor at any depth upstream from the interface for the local treatment machines. The derived equation agreed to within 1.5% of the MC simulated electron backscatter at the lead interface and upstream positions. Verification of the equation was performed by comparing to measurements of the electron backscatter factor using Gafchromic EBT2 film. These results show a mean value of 0.997 ± 0.022 to 1σ of the predicted values of electron backscatter. The new empirical equation presented can accurately estimate electron backscatter factor from lead shielding in the range of 0.2 to 14 MeV for the local linacs.

Evaluation of backscatter dose from internal lead shielding in clinical electron beams using EGSnrc Monte Carlo simulations

PubMed Central

Marsh, Steven

2015-01-01

Internal lead shielding is utilized during superficial electron beam treatments of the head and neck, such as lip carcinoma. Methods for predicting backscattered dose include the use of empirical equations or performing physical measurements. The accuracy of these empirical equations required verification for the local electron beams. In this study, a Monte Carlo model of a Siemens Artiste linac was developed for 6, 9, 12, and 15 MeV electron beams using the EGSnrc MC package. The model was verified against physical measurements to an accuracy of better than 2% and 2 mm. Multiple MC simulations of lead interfaces at different depths, corresponding to mean electron energies in the range of 0.2–14 MeV at the interfaces, were performed to calculate electron backscatter values. The simulated electron backscatter was compared with current empirical equations to ascertain their accuracy. The major finding was that the current set of backscatter equations does not accurately predict electron backscatter, particularly in the lower energies region. A new equation was derived which enables estimation of electron backscatter factor at any depth upstream from the interface for the local treatment machines. The derived equation agreed to within 1.5% of the MC simulated electron backscatter at the lead interface and upstream positions. Verification of the equation was performed by comparing to measurements of the electron backscatter factor using Gafchromic EBT2 film. These results show a mean value of 0.997±0.022 to 1σ of the predicted values of electron backscatter. The new empirical equation presented can accurately estimate electron backscatter factor from lead shielding in the range of 0.2 to 14 MeV for the local linacs. PACS numbers: 87.53.Bn, 87.55.K‐, 87.56.bd PMID:26699566

Hit to lead optimization of a series of N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamides as monoacylglycerol lipase inhibitors with potential anticancer activity.

PubMed

Afzal, Obaid; Akhtar, Md Sayeed; Kumar, Suresh; Ali, Md Rahmat; Jaggi, Manu; Bawa, Sandhya

2016-10-04

A total of thirty five new N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamide derivatives were synthesized and structures of all the compounds were confirmed on the basis of elemental analysis and collective use of IR, (1)H NMR, (13)C NMR and mass spectral data. Compounds were tested for their ability to inhibit human monoacylglycerol lipase (hMAGL) enzyme. Eight compounds 4, 19-21, 24-26, and 34 reduced the hMAGL activity less than 50% at 100 nM concentrations. The halogen substituted aniline derivatives 20, 21 and 24-26 were found to be most active among all the synthesized compounds having IC50 value in the range of 6.5-9 nM. Twenty five compounds were selected by NCI, USA for one dose anticancer screening. Compound 21 (NSC: 780167) and 24 (NSC: 780168) fulfilled prearranged doorstep growth inhibition criteria and further selected for NCI full panel five dose assay at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM). Both the compounds 21 and 24 were found to be most active against MCF7 and MDA-MB-468 breast cancer cell lines. The GI50 value of 32.5 nM (MCF7) and 23.8 nM (MDA-MB-468) was observed for compound 21. Compound 24 showed GI50 values of 37.1 nM against MCF7 breast cancer cell line and 25.1 nM against MDA-MB-468 breast cancer cell line. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Pediatric radiation dosimetry for positron-emitting radionuclides using anthropomorphic phantoms

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

Xie, Tianwu; Bolch, Wesley E.; Lee, Choonsik

2013-10-15

Purpose: Positron emission tomography (PET) plays an important role in the diagnosis, staging, treatment, and surveillance of clinically localized diseases. Combined PET/CT imaging exhibits significantly higher sensitivity, specificity, and accuracy than conventional imaging when it comes to detecting malignant tumors in children. However, the radiation dose from positron-emitting radionuclide to the pediatric population is a matter of concern since children are at a particularly high risk when exposed to ionizing radiation.Methods: The authors evaluate the absorbed fractions and specific absorbed fractions (SAFs) of monoenergy photons/electrons as well as S-values of 9 positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Rb-82,more » Y-86, and I-124) in 48 source regions for 10 anthropomorphic pediatric hybrid models, including the reference newborn, 1-, 5-, 10-, and 15-yr-old male and female models, using the Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code.Results: The self-absorbed SAFs and S-values for most organs were inversely related to the age and body weight, whereas the cross-dose terms presented less correlation with body weight. For most source/target organ pairs, Rb-82 and Y-86 produce the highest self-absorbed and cross-absorbed S-values, respectively, while Cu-64 produces the lowest S-values because of the low-energy and high-frequency of electron emissions. Most of the total self-absorbed S-values are contributed from nonpenetrating particles (electrons and positrons), which have a linear relationship with body weight. The dependence of self-absorbed S-values of the two annihilation photons varies to the reciprocal of 0.76 power of the mass, whereas the self-absorbed S-values of positrons vary according to the reciprocal mass.Conclusions: The produced S-values for common positron-emitting radionuclides can be exploited for the assessment of radiation dose delivered to the pediatric population from various PET radiotracers used in clinical and research settings. The mass scaling method for positron-emitters can be used to derive patient-specific S-values from data of reference phantoms.« less

SU-E-CAMPUS-I-05: Internal Dosimetric Calculations for Several Imaging Radiopharmaceuticals in Preclinical Studies and Quantitative Assessment of the Mouse Size Impact On Them. Realistic Monte Carlo Simulations Based On the 4D-MOBY Model

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

Kostou, T; Papadimitroulas, P; Kagadis, GC

2014-06-15

Purpose: Commonly used radiopharmaceuticals were tested to define the most important dosimetric factors in preclinical studies. Dosimetric calculations were applied in two different whole-body mouse models, with varying organ size, so as to determine their impact on absorbed doses and S-values. Organ mass influence was evaluated with computational models and Monte Carlo(MC) simulations. Methods: MC simulations were executed on GATE to determine dose distribution in the 4D digital MOBY mouse phantom. Two mouse models, 28 and 34 g respectively, were constructed based on realistic preclinical exams to calculate the absorbed doses and S-values of five commonly used radionuclides in SPECT/PETmore » studies (18F, 68Ga, 177Lu, 111In and 99mTc).Radionuclide biodistributions were obtained from literature. Realistic statistics (uncertainty lower than 4.5%) were acquired using the standard physical model in Geant4. Comparisons of the dosimetric calculations on the two different phantoms for each radiopharmaceutical are presented. Results: Dose per organ in mGy was calculated for all radiopharmaceuticals. The two models introduced a difference of 0.69% in their brain masses, while the largest differences were observed in the marrow 18.98% and in the thyroid 18.65% masses.Furthermore, S-values of the most important target-organs were calculated for each isotope. Source-organ was selected to be the whole mouse body.Differences on the S-factors were observed in the 6.0–30.0% range. Tables with all the calculations as reference dosimetric data were developed. Conclusion: Accurate dose per organ and the most appropriate S-values are derived for specific preclinical studies. The impact of the mouse model size is rather high (up to 30% for a 17.65% difference in the total mass), and thus accurate definition of the organ mass is a crucial parameter for self-absorbed S values calculation.Our goal is to extent the study for accurate estimations in small animal imaging, whereas it is known that there is a large variety in the anatomy of the organs.« less

The relevance of the urinary concentration of ephedrines in anti-doping analysis: determination of pseudoephedrine, cathine, and ephedrine after administration of over-the-counter medicaments.

PubMed

Strano-Rossi, Sabina; Leone, Daniele; de la Torre, Xavier; Botrè, Francesco

2009-08-01

This article describes a method for the detection and quantitation of cathine, pseudoephedrine, ephedrine, and methylephedrine in urine, using their deuterated analogues as internal standards and derivatization to form the corresponding trimethylsilyl derivatives after a simple liquid-liquid extraction. The study was designed to evaluate whether the urinary cutoff values set by the World Anti-Doping Agency for the banned ephedrines (cathine >5 microg/mL, ephedrine and methylephedrine >10 microg/mL) can be exceeded after the normal self-administration of common over-the-counter medicaments containing nonbanned ephedrines. The present method, after validation, has been applied on real urine samples obtained from 9 healthy volunteers taking different doses of over-the-counter preparations containing ephedrines. Results obtained from excretion studies show high interindividual differences in the urinary concentrations of both pseudoephedrine and cathine, not dependent on body weight or sex nor, in some instances, on the administered dose. The same typical therapeutic dose of pseudoephedrine (60 mg) produced a urinary concentration of more than 5 microg/mL for cathine and of more than 100 microg/mL for pseudoephedrine in 2 of 9 subjects only. When a dose of 120 mg was administered, cathine concentration exceeded 5 microg/mL in 4 of 7 subject, and also concentrations of pseudoephedrine above 100 microg/mL. After administration of 5 x 120 mg of pseudoephedrine (120 mg administered every 7 days for 5 weeks) to one of the subjects exceeding the urinary threshold values, the urinary concentration of cathine and pseudoephedrine exceeded 5 microg/mL (peak concentration 14.8 microg/mL) and 100 microg/mL (peak concentration 275 microg/mL), respectively. When the same subject took 180 mg of pseudoephedrine, the urinary concentration values were below 5 microg/mL for ephedrine and 100 microg/mL for pseudoephedrine. In the case of ephedrine administration in a sustained-release formulation containing 12 mg of ephedrine, 2 of 3 subjects exceeded the urinary cutoff value of 10 microg/mL. The high interindividual variability is still significant even if the urinary concentration values are adjusted by specific gravity and/or creatinine. These results confirm a high interindividual variability in the urinary concentration of ephedrines after the administration of the same therapeutic dose of a preparation.

Blister formation at subcritical doses in tungsten irradiated by MeV protons

NASA Astrophysics Data System (ADS)

Gavish Segev, I.; Yahel, E.; Silverman, I.; Makov, G.

2017-12-01

The material response of tungsten to irradiation by MeV protons has been studied experimentally, in particular with respect to bubble and blister formation. Tungsten samples were irradiated by 2.2 MeV protons at the Soreq Applied Research Accelerator Facility (SARAF) to doses of the order of 1017 protons/cm2 which are below the reported critical threshold for blister formation derived from keV range irradiation studies. Large, well-developed blisters are observed indicating that for MeV range protons the critical threshold is at least an order of magnitude lower than the lowest value reported previously. The effects of fluence, flux, and corresponding temperature on the distribution and characteristics of the obtained blisters were studied. FIB cross sections of several blisters exposed their depth and structure.

Esophageal wall dose-surface maps do not improve the predictive performance of a multivariable NTCP model for acute esophageal toxicity in advanced stage NSCLC patients treated with intensity-modulated (chemo-)radiotherapy.

PubMed

Dankers, Frank; Wijsman, Robin; Troost, Esther G C; Monshouwer, René; Bussink, Johan; Hoffmann, Aswin L

2017-05-07

In our previous work, a multivariable normal-tissue complication probability (NTCP) model for acute esophageal toxicity (AET) Grade  ⩾2 after highly conformal (chemo-)radiotherapy for non-small cell lung cancer (NSCLC) was developed using multivariable logistic regression analysis incorporating clinical parameters and mean esophageal dose (MED). Since the esophagus is a tubular organ, spatial information of the esophageal wall dose distribution may be important in predicting AET. We investigated whether the incorporation of esophageal wall dose-surface data with spatial information improves the predictive power of our established NTCP model. For 149 NSCLC patients treated with highly conformal radiation therapy esophageal wall dose-surface histograms (DSHs) and polar dose-surface maps (DSMs) were generated. DSMs were used to generate new DSHs and dose-length-histograms that incorporate spatial information of the dose-surface distribution. From these histograms dose parameters were derived and univariate logistic regression analysis showed that they correlated significantly with AET. Following our previous work, new multivariable NTCP models were developed using the most significant dose histogram parameters based on univariate analysis (19 in total). However, the 19 new models incorporating esophageal wall dose-surface data with spatial information did not show improved predictive performance (area under the curve, AUC range 0.79-0.84) over the established multivariable NTCP model based on conventional dose-volume data (AUC  =  0.84). For prediction of AET, based on the proposed multivariable statistical approach, spatial information of the esophageal wall dose distribution is of no added value and it is sufficient to only consider MED as a predictive dosimetric parameter.

Esophageal wall dose-surface maps do not improve the predictive performance of a multivariable NTCP model for acute esophageal toxicity in advanced stage NSCLC patients treated with intensity-modulated (chemo-)radiotherapy

NASA Astrophysics Data System (ADS)

Dankers, Frank; Wijsman, Robin; Troost, Esther G. C.; Monshouwer, René; Bussink, Johan; Hoffmann, Aswin L.

2017-05-01

In our previous work, a multivariable normal-tissue complication probability (NTCP) model for acute esophageal toxicity (AET) Grade  ⩾2 after highly conformal (chemo-)radiotherapy for non-small cell lung cancer (NSCLC) was developed using multivariable logistic regression analysis incorporating clinical parameters and mean esophageal dose (MED). Since the esophagus is a tubular organ, spatial information of the esophageal wall dose distribution may be important in predicting AET. We investigated whether the incorporation of esophageal wall dose-surface data with spatial information improves the predictive power of our established NTCP model. For 149 NSCLC patients treated with highly conformal radiation therapy esophageal wall dose-surface histograms (DSHs) and polar dose-surface maps (DSMs) were generated. DSMs were used to generate new DSHs and dose-length-histograms that incorporate spatial information of the dose-surface distribution. From these histograms dose parameters were derived and univariate logistic regression analysis showed that they correlated significantly with AET. Following our previous work, new multivariable NTCP models were developed using the most significant dose histogram parameters based on univariate analysis (19 in total). However, the 19 new models incorporating esophageal wall dose-surface data with spatial information did not show improved predictive performance (area under the curve, AUC range 0.79-0.84) over the established multivariable NTCP model based on conventional dose-volume data (AUC  =  0.84). For prediction of AET, based on the proposed multivariable statistical approach, spatial information of the esophageal wall dose distribution is of no added value and it is sufficient to only consider MED as a predictive dosimetric parameter.

CT image electron density quantification in regions with metal implants: implications for radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

Jechel, Christopher Alexander

In radiotherapy planning, computed tomography (CT) images are used to quantify the electron density of tissues and provide spatial anatomical information. Treatment planning systems use these data to calculate the expected spatial distribution of absorbed dose in a patient. CT imaging is complicated by the presence of metal implants which cause increased image noise, produce artifacts throughout the image and can exceed the available range of CT number values within the implant, perturbing electron density estimates in the image. Furthermore, current dose calculation algorithms do not accurately model radiation transport at metal-tissue interfaces. Combined, these issues adversely affect the accuracy of dose calculations in the vicinity of metal implants. As the number of patients with orthopedic and dental implants grows, so does the need to deliver safe and effective radiotherapy treatments in the presence of implants. The Medical Physics group at the Cancer Centre of Southeastern Ontario and Queen's University has developed a Cobalt-60 CT system that is relatively insensitive to metal artifacts due to the high energy, nearly monoenergetic Cobalt-60 photon beam. Kilovoltage CT (kVCT) images, including images corrected using a commercial metal artifact reduction tool, were compared to Cobalt-60 CT images throughout the treatment planning process, from initial imaging through to dose calculation. An effective metal artifact reduction algorithm was also implemented for the Cobalt-60 CT system. Electron density maps derived from the same kVCT and Cobalt-60 CT images indicated the impact of image artifacts on estimates of photon attenuation for treatment planning applications. Measurements showed that truncation of CT number data in kVCT images produced significant mischaracterization of the electron density of metals. Dose measurements downstream of metal inserts in a water phantom were compared to dose data calculated using CT images from kVCT and Cobalt-60 systems with and without artifact correction. The superior accuracy of electron density data derived from Cobalt-60 images compared to kVCT images produced calculated dose with far better agreement with measured results. These results indicated that dose calculation errors from metal image artifacts are primarily due to misrepresentation of electron density within metals rather than artifacts surrounding the implants.

Comparison of internal dose estimates obtained using organ-level, voxel S value, and Monte Carlo techniques

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

Grimes, Joshua, E-mail: grimes.joshua@mayo.edu; Celler, Anna

2014-09-15

Purpose: The authors’ objective was to compare internal dose estimates obtained using the Organ Level Dose Assessment with Exponential Modeling (OLINDA/EXM) software, the voxel S value technique, and Monte Carlo simulation. Monte Carlo dose estimates were used as the reference standard to assess the impact of patient-specific anatomy on the final dose estimate. Methods: Six patients injected with{sup 99m}Tc-hydrazinonicotinamide-Tyr{sup 3}-octreotide were included in this study. A hybrid planar/SPECT imaging protocol was used to estimate {sup 99m}Tc time-integrated activity coefficients (TIACs) for kidneys, liver, spleen, and tumors. Additionally, TIACs were predicted for {sup 131}I, {sup 177}Lu, and {sup 90}Y assuming themore » same biological half-lives as the {sup 99m}Tc labeled tracer. The TIACs were used as input for OLINDA/EXM for organ-level dose calculation and voxel level dosimetry was performed using the voxel S value method and Monte Carlo simulation. Dose estimates for {sup 99m}Tc, {sup 131}I, {sup 177}Lu, and {sup 90}Y distributions were evaluated by comparing (i) organ-level S values corresponding to each method, (ii) total tumor and organ doses, (iii) differences in right and left kidney doses, and (iv) voxelized dose distributions calculated by Monte Carlo and the voxel S value technique. Results: The S values for all investigated radionuclides used by OLINDA/EXM and the corresponding patient-specific S values calculated by Monte Carlo agreed within 2.3% on average for self-irradiation, and differed by as much as 105% for cross-organ irradiation. Total organ doses calculated by OLINDA/EXM and the voxel S value technique agreed with Monte Carlo results within approximately ±7%. Differences between right and left kidney doses determined by Monte Carlo were as high as 73%. Comparison of the Monte Carlo and voxel S value dose distributions showed that each method produced similar dose volume histograms with a minimum dose covering 90% of the volume (D90) agreeing within ±3%, on average. Conclusions: Several aspects of OLINDA/EXM dose calculation were compared with patient-specific dose estimates obtained using Monte Carlo. Differences in patient anatomy led to large differences in cross-organ doses. However, total organ doses were still in good agreement since most of the deposited dose is due to self-irradiation. Comparison of voxelized doses calculated by Monte Carlo and the voxel S value technique showed that the 3D dose distributions produced by the respective methods are nearly identical.« less

TEMIS UV product validation using NILU-UV ground-based measurements in Thessaloniki, Greece

NASA Astrophysics Data System (ADS)

Zempila, Melina-Maria; van Geffen, Jos H. G. M.; Taylor, Michael; Fountoulakis, Ilias; Koukouli, Maria-Elissavet; van Weele, Michiel; van der A, Ronald J.; Bais, Alkiviadis; Meleti, Charikleia; Balis, Dimitrios

2017-06-01

This study aims to cross-validate ground-based and satellite-based models of three photobiological UV effective dose products: the Commission Internationale de l'Éclairage (CIE) erythemal UV, the production of vitamin D in the skin, and DNA damage, using high-temporal-resolution surface-based measurements of solar UV spectral irradiances from a synergy of instruments and models. The satellite-based Tropospheric Emission Monitoring Internet Service (TEMIS; version 1.4) UV daily dose data products were evaluated over the period 2009 to 2014 with ground-based data from a Norsk Institutt for Luftforskning (NILU)-UV multifilter radiometer located at the northern midlatitude super-site of the Laboratory of Atmospheric Physics, Aristotle University of Thessaloniki (LAP/AUTh), in Greece. For the NILU-UV effective dose rates retrieval algorithm, a neural network (NN) was trained to learn the nonlinear functional relation between NILU-UV irradiances and collocated Brewer-based photobiological effective dose products. Then the algorithm was subjected to sensitivity analysis and validation. The correlation of the NN estimates with target outputs was high (r = 0. 988 to 0.990) and with a very low bias (0.000 to 0.011 in absolute units) proving the robustness of the NN algorithm. For further evaluation of the NILU NN-derived products, retrievals of the vitamin D and DNA-damage effective doses from a collocated Yankee Environmental Systems (YES) UVB-1 pyranometer were used. For cloud-free days, differences in the derived UV doses are better than 2 % for all UV dose products, revealing the reference quality of the ground-based UV doses at Thessaloniki from the NILU-UV NN retrievals. The TEMIS UV doses used in this study are derived from ozone measurements by the SCIAMACHY/Envisat and GOME2/MetOp-A satellite instruments, over the European domain in combination with SEVIRI/Meteosat-based diurnal cycle of the cloud cover fraction per 0. 5° × 0. 5° (lat × long) grid cells. TEMIS UV doses were found to be ˜ 12.5 % higher than the NILU NN estimates but, despite the presence of a visually apparent seasonal pattern, the R2 values were found to be robustly high and equal to 0.92-0.93 for 1588 all-sky coincidences. These results significantly improve when limiting the dataset to cloud-free days with differences of 0.57 % for the erythemal doses, 1.22 % for the vitamin D doses, and 1.18 % for the DNA-damage doses, with standard deviations of the order of 11-13 %. The improvement of the comparative statistics under cloud-free cases further testifies to the importance of the appropriate consideration of the contribution of clouds in the UV radiation reaching the Earth's surface. For the urban area of Thessaloniki, with highly variable aerosol, the weakness of the implicit aerosol information introduced to the TEMIS UV dose algorithm was revealed by comparison of the datasets to aerosol optical depths at 340 nm as reported by a collocated CIMEL sun photometer, operating in Thessaloniki at LAP/AUTh as part of the NASA Aerosol Robotic Network.

Initial experience of ArcCHECK and 3DVH software for RapidArc treatment plan verification

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

Infusino, Erminia; Mameli, Alessandra, E-mail: e.infusino@unicampus.it; Conti, Roberto

2014-10-01

The purpose of this study was to perform delivery quality assurance with ArcCHECK and 3DVH system (Sun Nuclear, FL) and to evaluate the suitability of this system for volumetric-modulated arc therapy (VMAT) (RapidArc [RA]) verification. This software calculates the delivered dose distributions in patients by perturbing the calculated dose using errors detected in fluence or planar dose measurements. The device is tested to correlate the gamma passing rate (%GP) and the composite dose predicted by 3DVH software. A total of 28 patients with prostate cancer who were treated with RA were analyzed. RA treatments were delivered to a diode arraymore » phantom (ArcCHECK), which was used to create a planned dose perturbation (PDP) file. The 3DVH analysis used the dose differences derived from comparing the measured dose with the treatment planning system (TPS)-calculated doses to perturb the initial TPS-calculated dose. The 3DVH then overlays the resultant dose on the patient's structures using the resultant “PDP” beams. Measured dose distributions were compared with the calculated ones using the gamma index (GI) method by applying the global (Van Dyk) normalization and acceptance criteria, i.e., 3%/3 mm. Paired differences tests were used to estimate statistical significance of the differences between the composite dose calculated using 3DVH and %GP. Also, statistical correlation by means of logistic regression analysis has been analyzed. Dose-volume histogram (DVH) analysis for patient plans revealed small differences between treatment plan calculations and 3DVH results for organ at risk (OAR), whereas planning target volume (PTV) of the measured plan was systematically higher than that predicted by the TPS. The t-test results between the planned and the estimated DVH values showed that mean values were incomparable (p < 0.05). The quality assurance (QA) gamma analysis 3%/3 mm showed that in all cases there were only weak-to-moderate correlations (Pearson r: 0.12 to 0.74). Moreover, clinically relevant differences increased with increasing QA passing rate, indicating that some of the largest dose differences occurred in the cases of high QA passing rates, which may be called “false negatives.” The clinical importance of any disagreement between the measured and the calculated dose is often difficult to interpret; however, beam errors (either in delivery or in TPS calculation) can affect the effectiveness of the patient dose. Further research is needed to determinate the role of a PDP-type algorithm to accurately estimate patient dose effect.« less

AREA RADIATION MONITOR

DOEpatents

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

1962-06-12

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

Automated discrimination of dicentric and monocentric chromosomes by machine learning-based image processing.

PubMed

Li, Yanxin; Knoll, Joan H; Wilkins, Ruth C; Flegal, Farrah N; Rogan, Peter K

2016-05-01

Dose from radiation exposure can be estimated from dicentric chromosome (DC) frequencies in metaphase cells of peripheral blood lymphocytes. We automated DC detection by extracting features in Giemsa-stained metaphase chromosome images and classifying objects by machine learning (ML). DC detection involves (i) intensity thresholded segmentation of metaphase objects, (ii) chromosome separation by watershed transformation and elimination of inseparable chromosome clusters, fragments and staining debris using a morphological decision tree filter, (iii) determination of chromosome width and centreline, (iv) derivation of centromere candidates, and (v) distinction of DCs from monocentric chromosomes (MC) by ML. Centromere candidates are inferred from 14 image features input to a Support Vector Machine (SVM). Sixteen features derived from these candidates are then supplied to a Boosting classifier and a second SVM which determines whether a chromosome is either a DC or MC. The SVM was trained with 292 DCs and 3135 MCs, and then tested with cells exposed to either low (1 Gy) or high (2-4 Gy) radiation dose. Results were then compared with those of 3 experts. True positive rates (TPR) and positive predictive values (PPV) were determined for the tuning parameter, σ. At larger σ, PPV decreases and TPR increases. At high dose, for σ = 1.3, TPR = 0.52 and PPV = 0.83, while at σ = 1.6, the TPR = 0.65 and PPV = 0.72. At low dose and σ = 1.3, TPR = 0.67 and PPV = 0.26. The algorithm differentiates DCs from MCs, overlapped chromosomes and other objects with acceptable accuracy over a wide range of radiation exposures. © 2016 Wiley Periodicals, Inc.

One should avoid retro-orbital pharmacokinetic sample collections for intranasal dosing in rats: Illustration of spurious pharmacokinetics generated for anti-migraine drugs zolmitriptan and eletriptan.

PubMed

Patel, Harilal; Patel, Prakash; Modi, Nirav; Shah, Shaival; Ghoghari, Ashok; Variya, Bhavesh; Laddha, Ritu; Baradia, Dipesh; Dobaria, Nitin; Mehta, Pavak; Srinivas, Nuggehally R

2017-08-30

Because of the avoidance of first pass metabolic effects due to direct and rapid absorption with improved permeability, intranasal route represents a good alternative for extravascular drug administration. The aim of the study was to investigate the intranasal pharmacokinetics of two anti-migraine drugs (zolmitriptan and eletriptan), using retro-orbital sinus and jugular vein sites sampling. In a parallel study design, healthy male Sprague-Dawley (SD) rats aged between 8 and 12weeks were divided into groups (n=4 or 5/group). The animals of individual groups were dosed intranasal (~1.0mg/kg) and oral doses of 2.1mg/kg of either zolmitriptan or eletriptan. Serial blood sampling was performed from jugular vein or retro-orbital site and plasma samples were analyzed for drug concentrations using LC-MS/MS assay. Standard pharmacokinetics parameters such as T max , C max , AUC last , AUC 0-inf and T 1/2 were calculated and statistics of derived parameters was performed using unpaired t-test. After intranasal dosing, the mean pharmacokinetic parameters C max and AUC inf of zolmitriptan/eletriptan showed about 17-fold and 3-5-fold higher values for retro-orbital sampling as compared to the jugular vein sampling site. Whereas after oral administration such parameters derived for both drugs were largely comparable between the two sampling sites and statistically non-significant. In conclusion, the assessment of plasma levels after intranasal administration with retro-orbital sampling would result in spurious and misleading pharmacokinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

CURRENT USE AND FUTURE NEEDS OF BIODOSIMETRY IN STUDIES OF LONG-TERM HEALTH RISK FOLLOWING RADIATION EXPOSURE

PubMed Central

Simon, Steven L.; Bouville, André; Kleinerman, Ruth

2009-01-01

Biodosimetry measurements can potentially be an important and integral part of the dosimetric methods used in long-term studies of health risk following radiation exposure. Such studies rely on accurate estimation of doses to the whole body or to specific organs of individuals in order to derive reliable estimates of cancer risk. However, dose estimates based on analytical dose reconstruction (i.e., models) or personnel monitoring measurements, e.g., film-badges, can have substantial uncertainty. Biodosimetry can potentially reduce uncertainty in health risk studies by corroboration of model-based dose estimates or by using them to assess bias in dose models. While biodosimetry has begun to play a more significant role in long-term health risk studies, its use is still generally limited in that context due to one or more factors including, inadequate limits of detection, large inter-individual variability of the signal measured, high per-sample cost, and invasiveness. Presently, the most suitable biodosimetry methods for epidemiologic studies are chromosome aberration frequencies from fluorescence in situ hybridization (FISH) of peripheral blood lymphocytes and electron paramagnetic resonance (EPR) measurements made on tooth enamel. Both types of measurements, however, are usually invasive and require difficult to obtain biological samples. Moreover, doses derived from these methods are not always directly relevant to the tissues of interest. To increase the value of biodosimetry to epidemiologic studies, a number of issues need to be considered including limits of detection, effects of inhomogenous exposure of the body, how to extrapolate from the tissue sampled to the tissues of interest, and how to adjust dosimetry models applied to large populations based on sparse biodosimetry measurements. The requirements of health risk studies suggest a set of characteristics that, if satisfied by new biodosimetry methods, would increase the overall usefulness of biodosimetry to determining radiation health risks. PMID:20065672

Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon

PubMed Central

Verhoef, Talitha I; Redekop, William K; Daly, Ann K; van Schie, Rianne M F; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse

2014-01-01

Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose–response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials. PMID:23919835

Antioxidant Effect of Berberine and its Phenolic Derivatives Against Human Fibrosarcoma Cells.

PubMed

Pongkittiphan, Veerachai; Chavasiri, Warinthorn; Supabphol, Roongtawan

2015-01-01

Berberine (B1), isolated from stems of Coscinium fenestratum (Goetgh.) Colebr, was used as a principle structure to synthesize three phenolic derivatives: berberrubine (B2) with a single phenolic group, berberrubine chloride (B3) as a chloride counter ion derivative, and 2,3,9,10-tetra-hydroxyberberine chloride (B4) with four phenolic groups, to investigate their direct and indirect antioxidant activities. For DPPH assay, compounds B4, B3, and B2 showed good direct antioxidant activity (IC50 values=10.7±1.76, 55.2±2.24, and 87.4±6.65 μM, respectively) whereas the IC50 value of berberine was higher than 500 μM. Moreover, compound B4 exhibited a better DPPH scavenging activity than BHT as a standard antioxidant (IC50=72.7±7.22 μM) due to the ortho position of hydroxyl groups and its capacity to undergo intramolecular hydrogen bonding. For cytotoxicity assay against human fibrosarcoma cells (HT1080) using MTT reagent, the sequence of IC50 value at 7-day treatment stated that B1

Organ doses can be estimated from the computed tomography (CT) dose index for cone-beam CT on radiotherapy equipment.

PubMed

Martin, Colin J; Abuhaimed, Abdullah; Sankaralingam, Marimuthu; Metwaly, Mohamed; Gentle, David J

2016-06-01

Cone beam computed tomography (CBCT) systems are fitted to radiotherapy linear accelerators and used for patient positioning prior to treatment by image guided radiotherapy (IGRT). Radiotherapists' and radiographers' knowledge of doses to organs from CBCT imaging is limited. The weighted CT dose index for a reference beam of width 20 mm (CTDIw,ref) is displayed on Varian CBCT imaging equipment known as an On-Board Imager (OBI) linked to the Truebeam linear accelerator. This has the potential to provide an indication of organ doses. This knowledge would be helpful for guidance of radiotherapy clinicians preparing treatments. Monte Carlo simulations of imaging protocols for head, thorax and pelvic scans have been performed using EGSnrc/BEAMnrc, EGSnrc/DOSXYZnrc, and ICRP reference computational male and female phantoms to derive the mean absorbed doses to organs and tissues, which have been compared with values for the CTDIw,ref displayed on the CBCT scanner console. Substantial variations in dose were observed between male and female phantoms. Nevertheless, the CTDIw,ref gave doses within  ±21% for the stomach and liver in thorax scans and 2  ×  CTDIw,ref can be used as a measure of doses to breast, lung and oesophagus. The CTDIw,ref could provide indications of doses to the brain for head scans, and the colon for pelvic scans. It is proposed that knowledge of the link between CTDIw for CBCT should be promoted and included in the training of radiotherapy staff.

Dosimetry during intramedullary nailing of the tibia

PubMed Central

2009-01-01

Background Intramedullary nailing under fluoroscopic guidance is a common operation. We studied the intraoperative radiation dose received by both the patient and the personnel. Patients and methods 25 intramedullary nailing procedures of the tibia were studied. All patients suffered from tibial fractures and were treated using the Grosse-Kempf intramedullary nail, with free-hand technique for fixation of the distal screws, under fluoroscopic guidance. The exposure, at selected positions, was recorded using an ion chamber, while the dose area product (DAP) was measured with a DAP meter, attached to the tube head. Thermoluminescent dosimeters (TLDs) were used to derive the occupational dose to the personnel, and also to monitor the surface dose on the gonads of some of the patients. Results The mean operation time was 101 (48–240) min, with a mean fluoroscopic time of 72 seconds and a mean DAP value of 75 cGy·cm2. The surface dose to the gonads of the patients was less than 8.8 mGy during any procedure, and thus cannot be considered to be a contraindication for the use of this technique. Occupational dose differed substantially between members of the operating personnel, the maximum dose recorded being to the operator of the fluoroscopic equipment (0.11 mSv). Interpretation Our findings underscore the care required by the primary operator not to exceed the dose constraint of 10 mSv per year. The rest of the operating personnel, although they do not receive very high doses, should focus on the dose optimization of the technique. PMID:19916691

Gamma-dose rates from terrestrial and Chernobyl radionuclides inside and outside settlements in the Bryansk Region, Russia in 1996-2003.

PubMed

Ramzaev, Valery; Yonehara, Hidenori; Hille, Ralf; Barkovsky, Anatoly; Mishine, Arkady; Sahoo, Sarat Kumar; Kurotaki, Katsumi; Uchiyama, Masafumi

2006-01-01

In order to estimate current external gamma doses to the population of the Russian territories contaminated as a result of the Chernobyl accident, absorbed gamma-dose rates in air (DR) were determined at typical urban and suburban locations. The study was performed in the western districts of the Bryansk Region within the areas of 30 settlements (28 villages and 2 towns) with the initial levels of 137Cs deposition ranging from 13 to 4340 kBqm(-2). In the towns, the living areas considered were private one-story wooden and stone houses. DR values were derived from in situ measurements performed with the help of gamma-dosimeters and gamma-spectrometers as well as from the results of soil samples analysis. In the areas under study, the values of DR from terrestrial radionuclides were 25+/-6, 24+/-5, 50+/-10, 32+/-6, 54+/-11, 24+/-8, 20+/-6, 25+/-8, and 18+/-5 nGyh(-1) at locations of kitchen gardens, dirt surfaces, asphalt surfaces, wooden houses, stone houses, grasslands inside settlement, grasslands outside settlement, ploughed fields, and forests, respectively. In 1996-2001, mean normalized (per MBqm(-2) of 137Cs current inventory in soil) values of DR from (137)Cs were 0.41+/-0.07, 0.26+/-0.13, 0.15+/-0.07, 0.10+/-0.05, 0.05+/-0.04, 0.48+/-0.12, 1.04+/-0.22, 0.37+/-0.07, and 1.15+/-0.19 microGyh(-1) at the locations of kitchen gardens, dirt surfaces, asphalt surfaces, wooden houses, stone houses, grasslands inside settlement, grasslands outside settlement, ploughed fields, and forests, respectively. The radiometric data from this work and the values of occupancy factors determined for the Russian population by others were used for the assessments of annual effective doses to three selected groups of rural population. The normalized (per MBqm(-2) 137Cs current ground deposition) external effective doses to adults from 137Cs ranged from 0.66 to 2.27 mSvy(-1) in the years 1996-2001, in accordance with professional activities and structures of living areas. For the areas under study, the average external effective doses from 137Cs were estimated to be in the range of 0.39-1.34 mSvy(-1) in 2001. The average external effective doses from natural radionuclides appeared to be lower than those from the Chernobyl fallout ranging from 0.15 to 0.27 mSvy(-1).

A phantom study on bladder and rectum dose measurements in brachytherapy of cervix cancer using FBX aqueous chemical dosimeter.

PubMed

Bansal, Anil K; Semwal, Manoj K; Arora, Deepak; Sharma, D N; Julka, P K; Rath, G K

2013-06-01

The ferrous sulphate-benzoic acid-xylenol orange (FBX) chemical dosimeter, due to its aqueous form can measure average volume doses and hence may overcome the limitations of point dosimetry. The present study was undertaken to validate the use of FBX dosimeter for rectum and bladder dose measurement during intracavitary brachytherapy (ICBT) and transperineal interstitial brachytherapy (TIB). We filled cylindrical polypropylene tubes (PT) and Foley balloons (FB) with FBX solution and used them as substitutes for rectum and bladder dose measurements respectively. A water phantom was fabricated with provision to place the Fletcher-type ICBT and MUPIT template applicators, and FBX filled PT and FB within the phantom. The phantom was then CT scanned for treatment planning and subsequent irradiation. Our results show that the average difference between DVH derived dose value and FBX measured dose is 3.5% (PT) and 13.7% (FB) for ICBT, and 9% (PT) and 9.9% (FB) for TIB. We believe that the FBX system should be able to provide accuracy and precision sufficient for routine quality assurance purposes. The advantage of the FBX system is its water equivalent composition, average volume dose measuring capability, and energy and temperature independent response as compared to TLD or semiconductor dosimeters. However, detailed studies will be needed with regards to its safety before actual in-vivo dose measurements are possible with the FBX dosimeter. Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Inhalation dose assessment of indoor radon progeny using biokinetic and dosimetric modeling and its application to Jordanian population.

PubMed

Al-Jundi, J; Li, W B; Abusini, M; Tschiersch, J; Hoeschen, C; Oeh, U

2011-06-01

High indoor radon concentrations in Jordan result in internal exposures of the residents due to the inhalation of radon and its short-lived progeny. It is therefore important to quantify the annual effective dose and further the radiation risk to the radon exposure. This study describes the methodology and the biokinetic and dosimetric models used for calculation of the inhalation doses exposed to radon progeny. The regional depositions of aerosol particles in the human respiratory tract were firstly calculated. For the attached progeny, the activity median aerodynamic diameters of 50 nm, 230 nm and 2500 nm were chosen to represent the nucleation, accumulation and coarse modes of the aerosol particles, respectively. For the unattached progeny, the activity median thermodynamic diameter of 1 nm was chosen to represent the free progeny nuclide in the room air. The biokinetic models developed by the International Commission on Radiological Protection (ICRP) were used to calculate the nuclear transformations of radon progeny in the human body, and then the dosimetric model was applied to estimate the organ equivalent doses and the effective doses with the specific effective energies derived from the mathematical anthropomorphic phantoms. The dose conversion coefficient estimated in this study was 15 mSv WLM(-1) which was in the range of the values of 6-20 mSv WLM(-1) reported by other investigators. Implementing the average indoor radon concentration in Jordan, the annual effective doses were calculated to be 4.1 mSv y(-1) and 0.08 mSv y(-1) due to the inhalation of radon progeny and radon gas, respectively. The total annual effective dose estimated for Jordanian population was 4.2 mSv y(-1). This high annual effective dose calculated by the dosimetric approach using ICRP biokinetic and dosimetric models resulted in an increase of a factor of two in comparison to the value by epidemiological study. This phenomenon was presented by the ICRP in its new published statement on radon. Copyright © 2011 Elsevier Ltd. All rights reserved.

Nano-risk Science: application of toxicogenomics in an adverse outcome pathway framework for risk assessment of multi-walled carbon nanotubes.

PubMed

Labib, Sarah; Williams, Andrew; Yauk, Carole L; Nikota, Jake K; Wallin, Håkan; Vogel, Ulla; Halappanavar, Sabina

2016-03-15

A diverse class of engineered nanomaterials (ENMs) exhibiting a wide array of physical-chemical properties that are associated with toxicological effects in experimental animals is in commercial use. However, an integrated framework for human health risk assessment (HHRA) of ENMs has yet to be established. Rodent 2-year cancer bioassays, clinical chemistry, and histopathological endpoints are still considered the 'gold standard' for detecting substance-induced toxicity in animal models. However, the use of data derived from alternative toxicological tools, such as genome-wide expression profiling and in vitro high-throughput assays, are gaining acceptance by the regulatory community for hazard identification and for understanding the underlying mode-of-action. Here, we conducted a case study to evaluate the application of global gene expression data in deriving pathway-based points of departure (PODs) for multi-walled carbon nanotube (MWCNT)-induced lung fibrosis, a non-cancer endpoint of regulatory importance. Gene expression profiles from the lungs of mice exposed to three individual MWCNTs with different physical-chemical properties were used within the framework of an adverse outcome pathway (AOP) for lung fibrosis to identify key biological events linking MWCNT exposure to lung fibrosis. Significantly perturbed pathways were categorized along the key events described in the AOP. Benchmark doses (BMDs) were calculated for each perturbed pathway and were used to derive transcriptional BMDs for each MWCNT. Similar biological pathways were perturbed by the different MWCNT types across the doses and post-exposure time points studied. The pathway BMD values showed a time-dependent trend, with lower BMDs for pathways perturbed at the earlier post-exposure time points (24 h, 3d). The transcriptional BMDs were compared to the apical BMDs derived by the National Institute for Occupational Safety and Health (NIOSH) using alveolar septal thickness and fibrotic lesions endpoints. We found that regardless of the type of MWCNT, the BMD values for pathways associated with fibrosis were 14.0-30.4 μg/mouse, which are comparable to the BMDs derived by NIOSH for MWCNT-induced lung fibrotic lesions (21.0-27.1 μg/mouse). The results demonstrate that transcriptomic data can be used to as an effective mechanism-based method to derive acceptable levels of exposure to nanomaterials in product development when epidemiological data are unavailable.

Effects of Ionizing Radiation on Human Adipose Derived Mesenchymal Stem Cells and their Differentiation towards the Osteoblastic Lineage

NASA Astrophysics Data System (ADS)

Konda, Bikash; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther; Lau, Patrick

Radiation exposure and musculoskeletal disuse are among the major challenges during space missions. Astronauts face the problem to lose bone calcium due to uncoupling of bone formation and resorption. Bone forming osteoblasts can be derived from the undifferentiated mesenchymal stem cell compartment (MSC). In this study, the ability of human adipose tissue derived stem cells (ATSC) to differentiate into the osteoblastic lineage was examined after radiation exposure in presence of medium supplementation with osteogenic additives (ß-glycerophosphate, ascorbic acid and dexamethasone). The SAOS-2 cell line (human osteosarcoma cell line) was used as control for osteoblastic differentiation. Changes in cellular morphology, cell cycle progression, as well as cellular radiation sensitivity were characterized after ionizing radiation exposure with X-rays and heavy ions (Ti). Rapidly proliferating SAOS-2 cells are less radiation-sensitive than slowly proliferating ATSC cells after X-ray (CFA: dose effect curves show D0 values of 1 Gy and 0.75 Gy for SAOS-2 and ATSC, respectively) exposure. Heavy ion (Ti) exposure resulted in a greater extent of cells accumulating in the G2/M phase of the cell cycle in a dose-dependent manner when compared to X-ray exposure. Differentiation of cells towards the osteoblastic lineage was quantified by hydroxyapatite (HA) deposition using Lonza OsteoImageTM mineralization assay. The deposition of HA after X- and Ti-irradiation for highly proliferating SAOS-2 cells showed a dose-dependent time delay while slowly proliferating ATSC showed no effect from radiation exposure. More detailed investigation is required to reveal the radiation dependent mechanism of bone loss in astronauts.

Polychlorinated biphenyls (PCBs) contamination and aryl hydrocarbon receptor (AhR) agonist activity of Omega-3 polyunsaturated fatty acid supplements: implications for daily intake of dioxins and PCBs.

PubMed

Bourdon, J A; Bazinet, T M; Arnason, T T; Kimpe, L E; Blais, J M; White, P A

2010-11-01

Omega-3 polyunsaturated fatty acid (n-3 PUFA) rich oils derived primarily from fish are frequently consumed as supplements. Due to the tendency of persistent organic pollutants (POPs) to accumulate in exposed organisms, n-3 PUFA supplements can contain sufficient POPs to present a risk to consumers. Here we investigated PCB concentrations and aryl hydrocarbon receptor (AhR) agonist activity in 17 n-3 PUFA supplements available in Canada. PCBs ranged from <0.8 to 793 ng g(-1) oil, with salmon- and seal-derived products yielding the highest values. AhR agonist activity from a reporter gene assay ranged from 1.3 to 72.2 pg TEQ g(-1) oil, with salmon and tuna yielding the highest values. When consumed at the recommended doses and as a supplement to the average Canadian diet, seal-derived oil can contribute to exceedance of the tolerable daily intake of 20 ng PCBs kg-BW(-1)day(-1), and salmon-, tuna-, and sea herring-derived oils can contribute to exceedance of the tolerable daily intake limit of 2.3 pg TEQ kg-BW(-1)day(-1). The beneficial properties of fish and n-3 PUFA supplements, and the results of this study suggest that it is prudent to consume supplements derived from small, cold-water fatty fish. Further research will be necessary to draw firm conclusions. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

β-carboline derivatives and diphenols from soy sauce are in vitro quinone reductase (QR) inducers.

PubMed

Li, Ying; Zhao, Mouming; Parkin, Kirk L

2011-03-23

A murine hepatoma (Hepa 1c1c7) cellular bioassay was used to guide the isolation of phase II enzyme inducers from fermented soy sauce, using quinone reductase (QR) as a biomarker. A crude ethyl acetate extract, accounting for 8.7% of nonsalt soluble solids of soy sauce, was found to double relative QR specific activity at 25 μg/mL (concentration required to double was defined as a "CD value"). Further silica gel column fractionation yielded 17 fractions, 16 of which exhibited CD values for QR induction of <100 μg/mL. The four most potent fractions were subfractionated by column and preparative thin layer chromatography, leading to the isolation and identification of two phenolic compounds (catechol and daidzein) and two β-carbolines (flazin and perlolyrin), with respective CD values of 8, 35, 42, and 2 μM. Western blots confirmed that the increases in QR activity corresponded to dose-dependent increases in cellular levels of NAD[P]H:quinone oxidoreductase 1 protein by these four QR inducers. To the authors' knowledge, this is the first report on the ability of β-carboline-derived alkaloids to induce phase II enzymes.

SU-E-T-252: Developing a Pencil Beam Dose Calculation Algorithm for CyberKnife System

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

Liang, B; Duke University Medical Center, Durham, NC; Liu, B

2015-06-15

Purpose: Currently there are two dose calculation algorithms available in the Cyberknife planning system: ray-tracing and Monte Carlo, which is either not accurate or time-consuming for irregular field shaped by the MLC that was recently introduced. The purpose of this study is to develop a fast and accurate pencil beam dose calculation algorithm which can handle irregular field. Methods: A pencil beam dose calculation algorithm widely used in Linac system is modified. The algorithm models both primary (short range) and scatter (long range) components with a single input parameter: TPR{sub 20}/{sub 10}. The TPR{sub 20}/{sub 20}/{sub 10} value was firstmore » estimated to derive an initial set of pencil beam model parameters (PBMP). The agreement between predicted and measured TPRs for all cones were evaluated using the root mean square of the difference (RMSTPR), which was then minimized by adjusting PBMPs. PBMPs are further tuned to minimize OCR RMS (RMSocr) by focusing at the outfield region. Finally, an arbitrary intensity profile is optimized by minimizing RMSocr difference at infield region. To test model validity, the PBMPs were obtained by fitting to only a subset of cones (4) and applied to all cones (12) for evaluation. Results: With RMS values normalized to the dmax and all cones combined, the average RMSTPR at build-up and descending region is 2.3% and 0.4%, respectively. The RMSocr at infield, penumbra and outfield region is 1.5%, 7.8% and 0.6%, respectively. Average DTA in penumbra region is 0.5mm. There is no trend found in TPR or OCR agreement among cones or depths. Conclusion: We have developed a pencil beam algorithm for Cyberknife system. The prediction agrees well with commissioning data. Only a subset of measurements is needed to derive the model. Further improvements are needed for TPR buildup region and OCR penumbra. Experimental validations on MLC shaped irregular field needs to be performed. This work was partially supported by the National Natural Science Foundation of China (61171005) and the China Scholarship Council (CSC)« less

Benchmark dose and the three Rs. Part I. Getting more information from the same number of animals.

PubMed

Slob, Wout

2014-08-01

Evaluating dose-response data using the Benchmark dose (BMD) approach rather than by the no observed adverse effect (NOAEL) approach implies a considerable step forward from the perspective of the Reduction, Replacement, and Refinement, three Rs, in particular the R of reduction: more information is obtained from the same number of animals, or, vice versa, similar information may be obtained from fewer animals. The first part of this twin paper focusses on the former, the second on the latter aspect. Regarding the former, the BMD approach provides more information from any given dose-response dataset in various ways. First, the BMDL (= BMD lower confidence bound) provides more information by its more explicit definition. Further, as compared to the NOAEL approach the BMD approach results in more statistical precision in the value of the point of departure (PoD), for deriving exposure limits. While part of the animals in the study do not directly contribute to the numerical value of a NOAEL, all animals are effectively used and do contribute to a BMDL. In addition, the BMD approach allows for combining similar datasets for the same chemical (e.g., both sexes) in a single analysis, which further increases precision. By combining a dose-response dataset with similar historical data for other chemicals, the precision can even be substantially increased. Further, the BMD approach results in more precise estimates for relative potency factors (RPFs, or TEFs). And finally, the BMD approach is not only more precise, it also allows for quantification of the precision in the BMD estimate, which is not possible in the NOAEL approach.

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.

PubMed

Mehat, Manjit S; Sundaram, Venki; Ripamonti, Caterina; Robson, Anthony G; Smith, Alexander J; Borooah, Shyamanga; Robinson, Martha; Rosenthal, Adam N; Innes, William; Weleber, Richard G; Lee, Richard W J; Crossland, Michael; Rubin, Gary S; Dhillon, Baljean; Steel, David H W; Anglade, Eddy; Lanza, Robert P; Ali, Robin R; Michaelides, Michel; Bainbridge, James W B

2018-06-05

Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. Subretinal transplantation of up to 200 000 hESC-derived RPE cells with systemic immunosuppressive therapy for 13 weeks. The primary end points were the safety and tolerability of hESC-derived RPE cell administration. We also investigated evidence of the survival of transplanted cells and measured retinal structure and function using microperimetry and spectral-domain OCT. Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. We found no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. Subretinal hyperpigmentation is consistent with the survival of viable transplanted hESC-derived RPE cells, but may reflect released pigment in their absence. The findings demonstrate the value of detailed analysis of spatial correlation of retinal structure and function in determining with appropriate sensitivity the impact of cell transplantation and suggest that intervention in early stage of disease should be approached with caution. Given the slow rate of progressive degeneration at this advanced stage of disease, any protection against further deterioration may be evident only after a more extended period of observation. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

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

A shielding application of perturbation theory to determine changes in neutron and gamma doses due to changes in shield layers

NASA Technical Reports Server (NTRS)

Fieno, D.

1972-01-01

The perturbation theory for fixed sources was applied to radiation shielding problems to determine changes in neutron and gamma ray doses due to changes in various shield layers. For a given source and detector position the perturbation method enables dose derivatives due to all layer changes to be determined from one forward and one inhomogeneous adjoint calculation. The direct approach requires two forward calculations for the derivative due to a single layer change. Hence, the perturbation method for obtaining dose derivatives permits an appreciable savings in computation for a multilayered shield. For an illustrative problem, a comparison was made of the fractional change in the dose per unit change in the thickness of each shield layer as calculated by perturbation theory and by successive direct calculations; excellent agreement was obtained between the two methods.

Model-derived dose rates per unit concentration of radon in air in a generic plant geometry.

PubMed

Vives i Batlle, J; Smith, A; Vives-Lynch, S; Copplestone, D; Pröhl, G; Strand, T

2011-11-01

A model for the derivation of dose rates per unit radon concentration in plants was developed in line with the activities of a Task Group of the International Commission on Radiological Protection (ICRP), aimed at developing more realistic dosimetry for non-human biota. The model considers interception of the unattached and attached fractions of the airborne radon daughters by plant stomata, diffusion of radon gas through stomata, permeation through the plant's epidermis and translocation of deposited activity to plant interior. The endpoint of the model is the derivation of dose conversion coefficients relative to radon gas concentration at ground level. The model predicts that the main contributor to dose is deposition of (214)Po α-activity on the plant surface and that diffusion of radon daughters through the stomata is of relatively minor importance; hence, daily variations have a small effect on total dose.

Redefining relative biological effectiveness in the context of the EQDX formalism: implications for alpha-particle emitter therapy.

PubMed

Hobbs, Robert F; Howell, Roger W; Song, Hong; Baechler, Sébastien; Sgouros, George

2014-01-01

Alpha-particle radiopharmaceutical therapy (αRPT) is currently enjoying increasing attention as a viable alternative to chemotherapy for targeting of disseminated micrometastatic disease. In theory, αRPT can be personalized through pre-therapeutic imaging and dosimetry. However, in practice, given the particularities of α-particle emissions, a dosimetric methodology that accurately predicts the thresholds for organ toxicity has not been reported. This is in part due to the fact that the biological effects caused by α-particle radiation differ markedly from the effects caused by traditional external beam (photon or electron) radiation or β-particle emitting radiopharmaceuticals. The concept of relative biological effectiveness (RBE) is used to quantify the ratio of absorbed doses required to achieve a given biological response with alpha particles versus a reference radiation (typically a beta emitter or external beam radiation). However, as conventionally defined, the RBE varies as a function of absorbed dose and therefore a single RBE value is limited in its utility because it cannot be used to predict response over a wide range of absorbed doses. Therefore, efforts are underway to standardize bioeffect modeling for different fractionation schemes and dose rates for both nuclear medicine and external beam radiotherapy. Given the preponderant use of external beams of radiation compared to nuclear medicine in cancer therapy, the more clinically relevant quantity, the 2 Gy equieffective dose, EQD2(α/β), has recently been proposed by the ICRU. In concert with EQD2(α/β), we introduce a new, redefined RBE quantity, named RBE2(α/β), as the ratio of the two linear coefficients that characterize the α particle absorbed dose-response curve and the low-LET megavoltage photon 2 Gy fraction equieffective dose-response curve. The theoretical framework for the proposed new formalism is presented along with its application to experimental data obtained from irradiation of a breast cancer cell line. Radiobiological parameters are obtained using the linear quadratic model to fit cell survival data for MDA-MB-231 human breast cancer cells that were irradiated with either α particles or a single fraction of low-LET (137)Cs γ rays. From these, the linear coefficient for both the biologically effective dose (BED) and the EQD2(α/β) response lines were derived for fractionated irradiation. The standard RBE calculation, using the traditional single fraction reference radiation, gave RBE values that ranged from 2.4 for a surviving fraction of 0.82-6.0 for a surviving fraction of 0.02, while the dose-independent RBE2(4.6) value was 4.5 for all surviving fraction values. Furthermore, bioeffect modeling with RBE2(α/β) and EQD2(α/β) demonstrated the capacity to predict the surviving fraction of cells irradiated with acute and fractionated low-LET radiation, α particles and chronic exponentially decreasing dose rates of low-LET radiation. RBE2(α/β) is independent of absorbed dose for α-particle emitters and it provides a more logical framework for data reporting and conversion to equieffective dose than the conventional dose-dependent definition of RBE. Moreover, it provides a much needed foundation for the ongoing development of an α-particle dosimetry paradigm and will facilitate the use of tolerance dose data available from external beam radiation therapy, thereby helping to develop αRPT as a single modality as well as for combination therapies.

Redefining Relative Biological Effectiveness in the Context of the EQDX Formalism: Implications for Alpha-Particle Emitter Therapy.

PubMed

Hobbs, Robert F; Howell, Roger W; Song, Hong; Baechler, Sébastien; Sgouros, George

2013-12-30

Alpha-particle radiopharmaceutical therapy (αRPT) is currently enjoying increasing attention as a viable alternative to chemotherapy for targeting of disseminated micrometastatic disease. In theory, αRPT can be personalized through pre-therapeutic imaging and dosimetry. However, in practice, given the particularities of α-particle emissions, a dosimetric methodology that accurately predicts the thresholds for organ toxicity has not been reported. This is in part due to the fact that the biological effects caused by α-particle radiation differ markedly from the effects caused by traditional external beam (photon or electron) radiation or β-particle emitting radiopharmaceuticals. The concept of relative biological effectiveness (RBE) is used to quantify the ratio of absorbed doses required to achieve a given biological response with alpha particles versus a reference radiation (typically a beta emitter or external beam radiation). However, as conventionally defined, the RBE varies as a function of absorbed dose and therefore a single RBE value is limited in its utility because it cannot be used to predict response over a wide range of absorbed doses. Therefore, efforts are underway to standardize bioeffect modeling for different fractionation schemes and dose rates for both nuclear medicine and external beam radiotherapy. Given the preponderant use of external beams of radiation compared to nuclear medicine in cancer therapy, the more clinically relevant quantity, the 2 Gy equieffective dose, EQD2(α/β), has recently been proposed by the ICRU. In concert with EQD2(α/β), we introduce a new, redefined RBE quantity, named RBE2(α/β), as the ratio of the two linear coefficients that characterize the α particle absorbed dose-response curve and the low-LET megavoltage photon 2 Gy fraction equieffective dose-response curve. The theoretical framework for the proposed new formalism is presented along with its application to experimental data obtained from irradiation of a breast cancer cell line. Radiobiological parameters are obtained using the linear quadratic model to fit cell survival data for MDA-MB-231 human breast cancer cells that were irradiated with either α particles or a single fraction of low-LET 137 Cs γ rays. From these, the linear coefficient for both the biologically effective dose (BED) and the EQD2(α/β) response lines were derived for fractionated irradiation. The standard RBE calculation, using the traditional single fraction reference radiation, gave RBE values that ranged from 2.4 for a surviving fraction of 0.82-6.0 for a surviving fraction of 0.02, while the dose-independent RBE2(4.6) value was 4.5 for all surviving fraction values. Furthermore, bioeffect modeling with RBE2(α/β) and EQD2(α/β) demonstrated the capacity to predict the surviving fraction of cells irradiated with acute and fractionated low-LET radiation, α particles and chronic exponentially decreasing dose rates of low-LET radiation. RBE2(α/β) is independent of absorbed dose for α-particle emitters and it provides a more logical framework for data reporting and conversion to equieffective dose than the conventional dose-dependent definition of RBE. Moreover, it provides a much needed foundation for the ongoing development of an α-particle dosimetry paradigm and will facilitate the use of tolerance dose data available from external beam radiation therapy, thereby helping to develop αRPT as a single modality as well as for combination therapies.

Influence of dose calculation algorithms on the predicted dose distribution and NTCP values for NSCLC patients.

PubMed

Nielsen, Tine B; Wieslander, Elinore; Fogliata, Antonella; Nielsen, Morten; Hansen, Olfred; Brink, Carsten

2011-05-01

To investigate differences in calculated doses and normal tissue complication probability (NTCP) values between different dose algorithms. Six dose algorithms from four different treatment planning systems were investigated: Eclipse AAA, Oncentra MasterPlan Collapsed Cone and Pencil Beam, Pinnacle Collapsed Cone and XiO Multigrid Superposition, and Fast Fourier Transform Convolution. Twenty NSCLC patients treated in the period 2001-2006 at the same accelerator were included and the accelerator used for treatments were modeled in the different systems. The treatment plans were recalculated with the same number of monitor units and beam arrangements across the dose algorithms. Dose volume histograms of the GTV, PTV, combined lungs (excluding the GTV), and heart were exported and evaluated. NTCP values for heart and lungs were calculated using the relative seriality model and the LKB model, respectively. Furthermore, NTCP for the lungs were calculated from two different model parameter sets. Calculations and evaluations were performed both including and excluding density corrections. There are found statistical significant differences between the calculated dose to heart, lung, and targets across the algorithms. Mean lung dose and V20 are not very sensitive to change between the investigated dose calculation algorithms. However, the different dose levels for the PTV averaged over the patient population are varying up to 11%. The predicted NTCP values for pneumonitis vary between 0.20 and 0.24 or 0.35 and 0.48 across the investigated dose algorithms depending on the chosen model parameter set. The influence of the use of density correction in the dose calculation on the predicted NTCP values depends on the specific dose calculation algorithm and the model parameter set. For fixed values of these, the changes in NTCP can be up to 45%. Calculated NTCP values for pneumonitis are more sensitive to the choice of algorithm than mean lung dose and V20 which are also commonly used for plan evaluation. The NTCP values for heart complication are, in this study, not very sensitive to the choice of algorithm. Dose calculations based on density corrections result in quite different NTCP values than calculations without density corrections. It is therefore important when working with NTCP planning to use NTCP parameter values based on calculations and treatments similar to those for which the NTCP is of interest.

SU-F-19A-10: Recalculation and Reporting Clinical HDR 192-Ir Head and Neck Dose Distributions Using Model Based Dose Calculation

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

Carlsson Tedgren, A; Persson, M; Nilsson, J

Purpose: To retrospectively re-calculate dose distributions for selected head and neck cancer patients, earlier treated with HDR 192Ir brachytherapy, using Monte Carlo (MC) simulations and compare results to distributions from the planning system derived using TG43 formalism. To study differences between dose to medium (as obtained with the MC code) and dose to water in medium as obtained through (1) ratios of stopping powers and (2) ratios of mass energy absorption coefficients between water and medium. Methods: The MC code Algebra was used to calculate dose distributions according to earlier actual treatment plans using anonymized plan data and CT imagesmore » in DICOM format. Ratios of stopping power and mass energy absorption coefficients for water with various media obtained from 192-Ir spectra were used in toggling between dose to water and dose to media. Results: Differences between initial planned TG43 dose distributions and the doses to media calculated by MC are insignificant in the target volume. Differences are moderate (within 4–5 % at distances of 3–4 cm) but increase with distance and are most notable in bone and at the patient surface. Differences between dose to water and dose to medium are within 1-2% when using mass energy absorption coefficients to toggle between the two quantities but increase to above 10% for bone using stopping power ratios. Conclusion: MC predicts target doses for head and neck cancer patients in close agreement with TG43. MC yields improved dose estimations outside the target where a larger fraction of dose is from scattered photons. It is important with awareness and a clear reporting of absorbed dose values in using model based algorithms. Differences in bone media can exceed 10% depending on how dose to water in medium is defined.« less

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

Brady, S; Shulkin, B

Purpose: To develop ultra-low dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultra-low doses (10–35 mAs). CT quantitation: noise, low-contrast resolution, and CT numbers for eleven tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% CTDIvol (0.39/3.64; mGy) radiation dose from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET images were reconstructed withmore » the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUVbw) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation organ dose, as derived from patient exam size specific dose estimate (SSDE), was converted to effective dose using the standard ICRP report 103 method. Effective dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative patient population dose reduction and noise control. Results: CT numbers were constant to within 10% from the non-dose reduced CTAC image down to 90% dose reduction. No change in SUVbw, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols reconstructed with ASiR and down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62%–86% (3.2/8.3−0.9/6.2; mSv). Noise magnitude in dose-reduced patient images increased but was not statistically different from pre dose-reduced patient images. Conclusion: Using ASiR allowed for aggressive reduction in CTAC dose with no change in PET reconstructed images while maintaining sufficient image quality for co-localization of hybrid CT anatomy and PET radioisotope uptake.« less

Search for the effect of E-beam irradiation on some steroids

NASA Astrophysics Data System (ADS)

Marciniec, B.; Ogrodowczyk, M.; Dettlaff, K.

2005-03-01

Seven steroid derivatives (hydrocortisone, hydrocortisone acetate, prednisolone, prednisolone acetate, methylprednisolone acetate, dexamethasone and fludrocortisone acetate) irradiated in the solid phase 10 MeV electrons, were studied by chromatographic methods (TLC and HPLC). Before the irradiation the derivatives contained different amounts of the following impurities: cortisone, cortisone acetate, prednisolone, prednisolone acetate and prednisone. After irradiation with a dose of upto 200 kGy radiolytic products were identified: cortisone, cortisone acetate, prednisone, prednisolone and methylprednisone acetate. All the identified radiolytic products were formed as a result of oxidation of the substituent at C 11, and in some cases the oxidation was accompanied by cleavage of the ester bond. The content of impurities before irradiation did not exceed 0.8%, while after the irradiation the content of the products of radiolysis depended on the kind of the derivative and the dose, and varied from 0.6% for a dose of 25 kGy to 4.03% for a dose of 200 kGy. For some derivatives, a linear relationship was found between the loss of a given steroid content and the dose. The studied steroid derivatives are characterised by high radiochemical stability and their sterilisation by irradiation does not lead to loss of the active substance below 97%, i.e. the lower limit admissible by the pharmacopoeias.

WE-H-BRA-05: Investigation of LET Spectral Dependence of the Biological Effects of Therapeutic Protons

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

Guan, F; Bronk, L; Kerr, M

Purpose: To investigate the dependence of biologic effect (BE) of therapeutic protons on LET spectra by comparing BEs with equal dose-averaged LET (LETd) derived from different LET spectra using high-throughput in vitro clonogenic survival assays. Methods: We used Geant4 to design the relevant experimental setups and perform the dose, LETd, and LET spectra calculations for spot-scanning protons. The clonogenic assay was performed using the H460 lung cancer cell line cultured in 96-well plates. In the first experimental setup (S1), cells were irradiated using 127.4 MeV protons with a 93.22 mm Lucite buildup resulting in a LETd value of 3.4 keV/µmmore » in the cell layer. In the second experimental setup (S2), cells were irradiated by a combination of 127.4 MeV and 136.4 MeV protons with a 96.61 mm Lucite buildup. The LETd values in the cell layer were 11.4 keV/µm and 1.5 keV/µm respectively, but an average LETd of 3.4 keV/µm was obtained by adjusting the relative fluence of each beam. Ten discrete dose levels with 0.5 Gy increments were delivered. Results: In the two setups, the energies or LET spectra were different but resulted in identical LETd values. We quantified the dose contributions from high-LET (≥10 keV/µm, threshold determined by previous experiments) events in the LET spectra separately for these two setups as 3.2% and 10.5%. The biologic effects at each identical dose level yielded statistically significant different survival curves (extra sum-of-squares F-test, P<0.0001). The second setup with a higher contribution from high-LET events exhibited the higher biologic effect with a dose enhancement factor of 1.17±0.03 at 0.10 surviving fraction. Conclusion: The dose-averaged LET may not be an accurate indicator of the biological effects of protons. Detailed LET spectra may need to be considered explicitly to accurately quantify the biologic effects of protons. Funding Support: U19 CA021239-35, R21 CA187484-01 and MDACC-IRG.« less

Radionuclide concentration ratios in Australian terrestrial wildlife and livestock: data compilation and analysis.

PubMed

Johansen, M P; Twining, J R

2010-11-01

Radionuclide concentrations in Australian terrestrial fauna, including indigenous kangaroos and lizards, as well as introduced sheep and water buffalo, are of interest when considering doses to human receptors and doses to the biota itself. Here, concentration ratio (CR) values for a variety of endemic and introduced Australian animals with a focus on wildlife and livestock inhabiting open rangeland are derived and reported. The CR values are based on U- and Th-series concentration data obtained from previous studies at mining sites and (241)Am and (239/240)Pu data from a former weapons testing site. Soil-to-muscle CR values of key natural-series radionuclides for grazing Australian kangaroo and sheep are one to two orders of magnitude higher than those of grazing cattle in North and South America, and for (210)Po, (230)Th, and (238)U are one to two orders of magnitude higher than the ERICA tool reference values. When comparing paired kangaroo and sheep CR values, results are linearly correlated (r = 0.81) for all tissue types. However, kidney and liver CR values for kangaroo are typically higher than those of sheep, particularly for (210)Pb, and (210)Po, with values in kangaroo liver more than an order of magnitude higher than those in sheep liver. Concentration ratios for organs are typically higher than those for muscle including those for (241)Am and (239/240)Pu in cooked kangaroo and rabbit samples. This study provides CR values for Australian terrestrial wildlife and livestock and suggests higher accumulation rates for select radionuclides in semi-arid Australian conditions compared with those associated with temperate conditions.

Renal dysfunction after total body irradiation: Dose-effect relationship

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

Kal, Henk B.; Kempen-Harteveld, M. Loes van

2006-07-15

Purpose: Late complications related to total body irradiation (TBI) as part of the conditioning regimen for hematopoietic stem cell transplantation have been increasingly noted. We reviewed and compared the results of treatments with various TBI regimens and tried to derive a dose-effect relationship for the endpoint of late renal dysfunction. The aim was to find the tolerance dose for the kidney when TBI is performed. Methods and Materials: A literature search was performed using PubMed for articles reporting late renal dysfunction. For intercomparison, the various TBI regimens were normalized using the linear-quadratic model, and biologically effective doses (BEDs) were calculated.more » Results: Eleven reports were found describing the frequency of renal dysfunction after TBI. The frequency of renal dysfunction as a function of the BED was obtained. For BED >16 Gy an increase in the frequency of dysfunction was observed. Conclusions: The tolerance BED for kidney tissue undergoing TBI is about 16 Gy. This BED can be realized with highly fractionated TBI (e.g., 6 x 1.7 Gy or 9 x 1.2 Gy at dose rates >5 cGy/min). To prevent late renal dysfunction, the TBI regimens with BED values >16 Gy (almost all found in published reports) should be applied with appropriate shielding of the kidneys.« less

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 new method for calculation of the chlorine demand of natural and treated waters.

PubMed

Warton, Ben; Heitz, Anna; Joll, Cynthia; Kagi, Robert

2006-08-01

Conventional methods of calculating chlorine demand are dose dependent, making intercomparison of samples difficult, especially in cases where the samples contain substantially different concentrations of dissolved organic carbon (DOC), or other chlorine-consuming species. Using the method presented here, the values obtained for chlorine demand are normalised, allowing valid comparison of chlorine demand between samples, independent of the chlorine dose. Since the method is not dose dependent, samples with substantially differing water quality characteristics can be reliably compared. In our method, we dosed separate aliquots of a water sample with different chlorine concentrations, and periodically measured the residual chlorine concentrations in these subsamples. The chlorine decay data obtained in this way were then fitted to first-order exponential decay functions, corresponding to short-term demand (0-4h) and long-term demand (4-168 h). From the derived decay functions, the residual concentrations at a given time within the experimental time window were calculated and plotted against the corresponding initial chlorine concentrations, giving a linear relationship. From this linear function, it was then possible to determine the residual chlorine concentration for any initial concentration (i.e. dose). Thus, using this method, the initial chlorine dose required to give any residual chlorine concentration can be calculated for any time within the experimental time window, from a single set of experimental data.

Internal dosimetry with the Monte Carlo code GATE: validation using the ICRP/ICRU female reference computational model

NASA Astrophysics Data System (ADS)

Villoing, Daphnée; Marcatili, Sara; Garcia, Marie-Paule; Bardiès, Manuel

2017-03-01

The purpose of this work was to validate GATE-based clinical scale absorbed dose calculations in nuclear medicine dosimetry. GATE (version 6.2) and MCNPX (version 2.7.a) were used to derive dosimetric parameters (absorbed fractions, specific absorbed fractions and S-values) for the reference female computational model proposed by the International Commission on Radiological Protection in ICRP report 110. Monoenergetic photons and electrons (from 50 keV to 2 MeV) and four isotopes currently used in nuclear medicine (fluorine-18, lutetium-177, iodine-131 and yttrium-90) were investigated. Absorbed fractions, specific absorbed fractions and S-values were generated with GATE and MCNPX for 12 regions of interest in the ICRP 110 female computational model, thereby leading to 144 source/target pair configurations. Relative differences between GATE and MCNPX obtained in specific configurations (self-irradiation or cross-irradiation) are presented. Relative differences in absorbed fractions, specific absorbed fractions or S-values are below 10%, and in most cases less than 5%. Dosimetric results generated with GATE for the 12 volumes of interest are available as supplemental data. GATE can be safely used for radiopharmaceutical dosimetry at the clinical scale. This makes GATE a viable option for Monte Carlo modelling of both imaging and absorbed dose in nuclear medicine.

Data-driven RBE parameterization for helium ion beams

NASA Astrophysics Data System (ADS)

Mairani, A.; Magro, G.; Dokic, I.; Valle, S. M.; Tessonnier, T.; Galm, R.; Ciocca, M.; Parodi, K.; Ferrari, A.; Jäkel, O.; Haberer, T.; Pedroni, P.; Böhlen, T. T.

2016-01-01

Helium ion beams are expected to be available again in the near future for clinical use. A suitable formalism to obtain relative biological effectiveness (RBE) values for treatment planning (TP) studies is needed. In this work we developed a data-driven RBE parameterization based on published in vitro experimental values. The RBE parameterization has been developed within the framework of the linear-quadratic (LQ) model as a function of the helium linear energy transfer (LET), dose and the tissue specific parameter {{(α /β )}\\text{ph}} of the LQ model for the reference radiation. Analytic expressions are provided, derived from the collected database, describing the \\text{RB}{{\\text{E}}α}={α\\text{He}}/{α\\text{ph}} and {{\\text{R}}β}={β\\text{He}}/{β\\text{ph}} ratios as a function of LET. Calculated RBE values at 2 Gy photon dose and at 10% survival (\\text{RB}{{\\text{E}}10} ) are compared with the experimental ones. Pearson’s correlation coefficients were, respectively, 0.85 and 0.84 confirming the soundness of the introduced approach. Moreover, due to the lack of experimental data at low LET, clonogenic experiments have been performed irradiating A549 cell line with {{(α /β )}\\text{ph}}=5.4 Gy at the entrance of a 56.4 MeV u-1He beam at the Heidelberg Ion Beam Therapy Center. The proposed parameterization reproduces the measured cell survival within the experimental uncertainties. A RBE formula, which depends only on dose, LET and {{(α /β )}\\text{ph}} as input parameters is proposed, allowing a straightforward implementation in a TP system.

Investigation of the chamber correction factor (k(ch)) for the UK secondary standard ionization chamber (NE2561/NE2611) using medium-energy x-rays.

PubMed

Rosser, K E

1998-11-01

This paper evaluates the characteristics of ionization chambers for the measurement of absorbed dose to water for medium-energy x-rays. The values of the chamber correction factor, k(ch), used in the IPEMB code of practice for the UK secondary standard (NE2561/NE2611) ionization chamber are derived and their constituent factors examined. The comparison of the chambers' responses in air revealed that of the chambers tested only the NE2561, NE2571 and NE2505 exhibit a flat (within 5%) energy response in air. Under no circumstances should the NACP, Sanders electron chamber, or any chamber that has a wall made of high atomic number material, be used for medium-energy x-ray dosimetry. The measurements in water reveal that a chamber that has a substantial housing, such as the PTW Grenz chamber, should not be used to measure absorbed dose to water in this energy range. The value of k(ch) for an NE2561 chamber was determined by measuring the absorbed dose to water and comparing it with that for an NE2571 chamber, for which k(ch) data have been published. The chamber correction factor varies from 1.023 +/- 0.03 to 1.018 +/- 0.001 for x-ray beams with HVL between 0.15 and 4 mm Cu. The values agree with that for an NE2571 chamber within the experimental uncertainty. The corrections due to the stem, waterproof sleeve and replacement of the phantom material by the chamber for an NE2561 chamber are described.

Lead-induced anemia: Dose-response relationships and evidence for a threshold

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

Schwartz, J.; Landrigan, P.J.; Baker, E.L. Jr.

1990-02-01

We conducted a cross-sectional epidemiologic study to assess the association between blood lead level and hematocrit in 579 one to five year-old children living near a primary lead smelter in 1974. Blood lead levels ranged from 0.53 to 7.91 mumol/L (11 to 164 micrograms/dl). To predict hematocrit as a function of blood lead level and age, we derived non-linear regression models and fit percentile curves. We used logistic regression to predict the probability of hematocrit values less than 35 per cent. We found a strong non-linear, dose-response relationship between blood lead level and hematocrit. This relationship was influenced by age,more » but (in this age group) not by sex; the effect was strongest in youngest children. In one year-olds, the age group most severely affected, the risk of an hematocrit value below 35 percent was 2 percent above background at blood lead levels between 0.97 and 1.88 mumol/L (20 and 39 micrograms/dl), 18 percent above background at lead levels of 1.93 to 2.85 mumol/L (40 to 59 micrograms/dl), and 40 percent above background at lead levels of 2.9 mumol/L (60 micrograms/dl) and greater; background was defined as a blood lead level below 1.88 mumol/L (20 micrograms/dl). This effect appeared independent of iron deficiency. These findings suggest that blood lead levels close to the currently recommended limit value of 1.21 mumol/L (25 micrograms/dl) are associated with dose-related depression of hematocrit in young children.« less

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

Vostrotin, Vadim; Birchall, Alan; Zhdanov, Alexey

The distribution of calculated internal doses was determined for 8043 Mayak Production Associate (Mayak PA) workers according to the epidemiological cohorts and groups of raw data used as well as the type of industrial compounds of inhaled aerosols. Statistical characteristics of point estimates of accumulated doses to 17 different tissues and organs and the uncertainty ranges were calculated. Under the MWDS-2013 dosimetry system, the mean accumulated lung dose was 185585 mGy, with a median value of 31 mGy and a maximum of 8980 mGy maximum. The ranges of relative standard uncertainty were: from 40 to 2200% for accumulated lung dose,more » from 25-90% to 2600-3000% for accumulated dose to different regions of respiratory tract, from 13-18% to 2300-2500% for systemic organs and tissues. The Mayak PA workers accumulated internal plutonium lung dose is shown to be close to lognormal. The accumulated internal plutonium dose to systemic organs was close to a log-triangle. The dependency of uncertainty of accumulated absorbed lung and liver doses on the dose estimates itself is also shown. The accumulated absorbed doses to lung, alveolar-interstitial region, liver, bone surface cells and red bone marrow, calculated both with MWDS-2013 and MWDS-2008 have been compared. In general, the accumulated lung doses increased by a factor of 1.8 in median value, while the accumulated doses to systemic organs decreased by factor of 1.3-1.4 in median value. For the cases with identical initial data, accumulated lung doses increased by a factor of 2.1 in median value, while accumulated doses to systemic organs decreased by 8-13% in median value. For the cases with both identical initial data and all of plutonium activity in urine measurements above the decision threshold, accumulated lung doses increased by a factor of 2.8 in median value, while accumulated doses to systemic organs increased by 6-12% in median value.« less

Probabilistic dose-response modeling: case study using dichloromethane PBPK model results.

PubMed

Marino, Dale J; Starr, Thomas B

2007-12-01

A revised assessment of dichloromethane (DCM) has recently been reported that examines the influence of human genetic polymorphisms on cancer risks using deterministic PBPK and dose-response modeling in the mouse combined with probabilistic PBPK modeling in humans. This assessment utilized Bayesian techniques to optimize kinetic variables in mice and humans with mean values from posterior distributions used in the deterministic modeling in the mouse. To supplement this research, a case study was undertaken to examine the potential impact of probabilistic rather than deterministic PBPK and dose-response modeling in mice on subsequent unit risk factor (URF) determinations. Four separate PBPK cases were examined based on the exposure regimen of the NTP DCM bioassay. These were (a) Same Mouse (single draw of all PBPK inputs for both treatment groups); (b) Correlated BW-Same Inputs (single draw of all PBPK inputs for both treatment groups except for bodyweights (BWs), which were entered as correlated variables); (c) Correlated BW-Different Inputs (separate draws of all PBPK inputs for both treatment groups except that BWs were entered as correlated variables); and (d) Different Mouse (separate draws of all PBPK inputs for both treatment groups). Monte Carlo PBPK inputs reflect posterior distributions from Bayesian calibration in the mouse that had been previously reported. A minimum of 12,500 PBPK iterations were undertaken, in which dose metrics, i.e., mg DCM metabolized by the GST pathway/L tissue/day for lung and liver were determined. For dose-response modeling, these metrics were combined with NTP tumor incidence data that were randomly selected from binomial distributions. Resultant potency factors (0.1/ED(10)) were coupled with probabilistic PBPK modeling in humans that incorporated genetic polymorphisms to derive URFs. Results show that there was relatively little difference, i.e., <10% in central tendency and upper percentile URFs, regardless of the case evaluated. Independent draws of PBPK inputs resulted in the slightly higher URFs. Results were also comparable to corresponding values from the previously reported deterministic mouse PBPK and dose-response modeling approach that used LED(10)s to derive potency factors. This finding indicated that the adjustment from ED(10) to LED(10) in the deterministic approach for DCM compensated for variability resulting from probabilistic PBPK and dose-response modeling in the mouse. Finally, results show a similar degree of variability in DCM risk estimates from a number of different sources including the current effort even though these estimates were developed using very different techniques. Given the variety of different approaches involved, 95th percentile-to-mean risk estimate ratios of 2.1-4.1 represent reasonable bounds on variability estimates regarding probabilistic assessments of DCM.

Effect of alkaloids derived from jellyfish (Aeginura sp.) on the intestinal histopathology and relative percentage survival (RPS) of tiger grouper (Epinephelus fuscoguttatus) infected by Vibrio harveyi

NASA Astrophysics Data System (ADS)

Andayani, S.; Fajar, M.; Rahman, M. F.

2018-04-01

The purposes of this research were to determine the effect of alkaloid jellyfish compounds on intestinal histopathology of tiger grouper and to determine the best doses to the relative percent survival (RPS) of tiger grouper. The method of this research was descriptive with completely randomized design. The treatment of active alkaloid compound on feed was investigated for 28 days. The fish were then challenged with Vibrio harveyi at 105 CFU/cell for 7 days. Alkaloids were added to the feed with the doses (g alkaloid/kg feed) of 0 (control); A = 0.5; B = 0.75; C = 1.0; and D = 1.25. The intestinal histopathology and RPS were observed. The best RPS was found at a treatment of C with the value of 100 %.

Radioactivity of Drinking-Water in the Vicinity of Nuclear Power Plants in China Based on a Large-Scale Monitoring Study

PubMed Central

Miao, Xiao-Xiang; Ji, Yan-Qin; Shao, Xian-Zhang; Wang, Huan; Sun, Quan-Fu; Su, Xu

2013-01-01

The public concern for radioactivity of drinking-water has been increasing in recent years after the rapid development of nuclear power plants, and especially after the Fukushima nuclear accident. In this study, the radioactivity of water samples collected in the vicinity of nuclear facilities from seven provinces in China was measured and an average annual equivalent effective dose derived from drinking-water ingestion was calculated. The results showed that, in winter and spring, the activities of gross α and β ranged from 0.009 Bq/L to 0.200 Bq/L and from 0.067 Bq/L to 0.320 Bq/L, respectively. While, in summer and autumn, the activities of gross α and β varied from 0.002 Bq/L to 0.175 Bq/L and from 0.060 Bq/L to 0.334 Bq/L. Our results indicated that the gross α and β activities in these measured water samples were below the WHO recommended values (0.5 Bq/L for gross α and 1.0 Bq/L for gross β) and the annual equivalent effective dose derived from drinking-water ingestion was at a safe level. PMID:24322395

Radioactivity of drinking-water in the vicinity of nuclear power plants in China based on a large-scale monitoring study.

PubMed

Miao, Xiao-Xiang; Ji, Yan-Qin; Shao, Xian-Zhang; Wang, Huan; Sun, Quan-Fu; Su, Xu

2013-12-06

The public concern for radioactivity of drinking-water has been increasing in recent years after the rapid development of nuclear power plants, and especially after the Fukushima nuclear accident. In this study, the radioactivity of water samples collected in the vicinity of nuclear facilities from seven provinces in China was measured and an average annual equivalent effective dose derived from drinking-water ingestion was calculated. The results showed that, in winter and spring, the activities of gross α and β ranged from 0.009 Bq/L to 0.200 Bq/L and from 0.067 Bq/L to 0.320 Bq/L, respectively. While, in summer and autumn, the activities of gross a and β varied from 0.002 Bq/L to 0.175 Bq/L and from 0.060 Bq/L to 0.334 Bq/L. Our results indicated that the gross a and β activities in these measured water samples were below the WHO recommended values (0.5 Bq/L for gross α and 1.0 Bq/L for gross β) and the annual equivalent effective dose derived from drinking-water ingestion was at a safe level.

Anti-inflammatory activity of 6-hydroxy-2,7-dimethoxy-1,4-henanthraquinone from tuberous roots of yam (Dioscorea batatas) through inhibition of prostaglandin D₂ and leukotriene C₄ production in mouse bone marrow-derived mast cells.

PubMed

Jin, Meihua; Lu, Yue; Yang, Ju Hye; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil; Park, Sang-Jo; Son, Kun Ho; Chang, Hyeun Wook

2011-09-01

6-Hydroxy-2,7-dimethoxy-1,4-phenanthraquinone (PAQ) isolated from the tuberous roots of Yam (Dioscorea batatas) inhibited cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) dependent prostaglandin D(2) (PGD(2)) generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with IC(50) values of 0.08 μM and 0.27 μM, respectively. In the Western blotting with specific anti-COX-2 antibodies, the decrease of the quantity of PGD(2) was accompanied by a decrease in the COX-2 protein level. But PAQ did not affect COX-1 protein level. In addition, this compound inhibited 5-lipoxygenase (5-LOX) dependent production of leukotriene C(4) in a dose-dependent manner, with an IC(50) of 0.032 μM. These results demonstrate that PAQ has a dual COX-2/5-LOX inhibitory activity. This compound also inhibited the degranulation reaction in a dose-dependent manner with an IC(50) of 2.7 μM. Thus, these results suggest that PAQ may be useful in regulating mast cell-mediated inflammatory diseases.

Pharmacokinetics of vephylline--a new N-substituted theophylline derivative.

PubMed

Staneva, D; Mihailova, D; Astroug, H; Prodanova, K; Micheva, M

1988-01-01

Vephylline (7,2-bis-2-hydroxyethylamino-1, 3-dimethylxanthine tartarate) is a xanthine derivative with high bronchodilating activity, low toxicity, and weak effects on the central nervous system. The aim of this study is to determine the pharmacokinetic parameters of vephylline after intravenous and oral (in solution and in tablets) administration to rabbits. Vephylline (dose 50 mg/kg b.w. intravenousely and orally in solution and dose 53.5 mg/kg b.w. in the form of tablets) is administered to the rabbits in an autocontrol crossover design at 7-days intervals. After the intravenous administration the distribution is relatively fast (t1/2 alpha = 3.28h). High values of the apparent volume of distribution--12.15 1/kg suggest tissue accumulation. Elimination is considerably slower (t1/2 beta = 19,00 h) than distribution. After oral administration of the drug in solution the absorption half-life is short and the bioavailability is relatively high. Peak plasma levels are attained at the first hour. The differences in the distribution and elimination patterns for vephylline and theophyline could determine a longer effect for the new bronchodilating drug. The results are discussed in regard to the future clinical application of vephylline.

Therapeutic use of recombinant human G-CSF (RHG-CSF) in a canine model of sublethal and lethal whole-body irradiation

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

Macvittie, T.J.; Monroy, R.L.; Patchen, M.L.

The short biologic half-life of the peripheral neutrophil (PMN) requires an active granulopoietic response to replenish functional PMSs and to remain a competent host defence in irradiated animals. Recombinant human G-CSF (rhG-CSF) was studied for its ability to modulate hemopoiesis in normal dogs as well as to decrease therapeutically the severity and duration of neutropenia in sublethally and lethally irradiated dogs. For the normal dog, subcutaneous administration of rhG-CSF induced neutrophilia within hours after the first injection; total PMSs continued to increase (with plateau phases) to mean peak values of 1000 per cent of baseline at the end of themore » treatment period (12-14 days). Bone-marrow-derived granulocyte-macrophage colony-forming cells (GM-CFC) increased significantly during treatment. For a sublethal 200 cGy dose, treatment with rhG-CSF for 14 consecutive days decreased the severity and shortened the duration of neutropenia and thrombocytopenia. The radiation-induced lethality of 60 per cent after a dose of 350 cGy was associated with marrow-derived GM-CFC survival of 1 per cent.« less

Dosimetry of cone-defined stereotactic radiosurgery fields with a commercial synthetic diamond detector.

PubMed

Morales, Johnny E; Crowe, Scott B; Hill, Robin; Freeman, Nigel; Trapp, J V

2014-11-01

Small field x-ray beam dosimetry is difficult due to lack of lateral electronic equilibrium, source occlusion, high dose gradients, and detector volume averaging. Currently, there is no single definitive detector recommended for small field dosimetry. The objective of this work was to evaluate the performance of a new commercial synthetic diamond detector, namely, the PTW 60019 microDiamond, for the dosimetry of small x-ray fields as used in stereotactic radiosurgery (SRS). Small field sizes were defined by BrainLAB circular cones (4-30 mm diameter) on a Novalis Trilogy linear accelerator and using the 6 MV SRS x-ray beam mode for all measurements. Percentage depth doses (PDDs) were measured and compared to an IBA SFD and a PTW 60012 E diode. Cross profiles were measured and compared to an IBA SFD diode. Field factors, ΩQclin,Qmsr (fclin,fmsr) , were calculated by Monte Carlo methods using BEAMnrc and correction factors, kQclin,Qmsr (fclin,fmsr) , were derived for the PTW 60019 microDiamond detector. For the small fields of 4-30 mm diameter, there were dose differences in the PDDs of up to 1.5% when compared to an IBA SFD and PTW 60012 E diode detector. For the cross profile measurements the penumbra values varied, depending upon the orientation of the detector. The field factors, ΩQclin,Qmsr (fclin,fmsr) , were calculated for these field diameters at a depth of 1.4 cm in water and they were within 2.7% of published values for a similar linear accelerator. The corrections factors, kQclin,Qmsr (fclin,fmsr) , were derived for the PTW 60019 microDiamond detector. The authors conclude that the new PTW 60019 microDiamond detector is generally suitable for relative dosimetry in small 6 MV SRS beams for a Novalis Trilogy linear equipped with circular cones.

Synthesis, antimicrobial, and antiproliferative activities of substituted phenylfuranylnicotinamidines

PubMed Central

Youssef, Magdy M; Arafa, Reem K; Ismail, Mohamed A

2016-01-01

This research work deals with the design and synthesis of a series of substituted phenylfuranylnicotinamidines 4a–i. Facile preparation of the target compounds was achieved by Suzuki coupling-based synthesis of the nitrile precursors 3a–i, followed by their conversion to the corresponding nicotinamidines 4a–i utilizing LiN(TMS)2. The antimicrobial activities of the newly synthesized nicotinamidine derivatives were evaluated against the Gram-negative bacterial strains Escherichia coli and Pseudomonas aeruginosa as well as the Gram-positive bacterial strains Staphylococcus aureus and Bacillus megaterium. The minimum inhibitory concentration values of nicotinamidines against all tested microorganisms were in the range of 10–20 μM. In specific, compounds 4a and 4b showed excellent minimum inhibitory concentration values of 10 μM against Staphylococcus aureus bacterial strain and were similar to ampicillin as an antibacterial reference. On the other hand, selected nicotinamidine derivatives were biologically screened for their cytotoxic activities against a panel of 60 cell lines representing nine types of human cancer at a single high dose at National Cancer Institute, Bethesda, MD, USA. Nicotinamidines showing promising activities were further assessed in a five-dose screening assay to determine their compound concentration causing 50% growth inhibition of tested cell (GI50), compound concentration causing 100% growth inhibition of tested cell (TGI), and compound concentration causing 50% lethality of tested cell (LC50) values. Structure-activity relationship studies demonstrated that the activity of members of this series can be modulated from cytostatic to cytotoxic based on the substitution pattern/nature on the terminal phenyl ring. The most active compound was found to be 4e displaying a submicromolar GI50 value of 0.83 μM, with TGI and LC50 values of 2.51 and 100 μM, respectively. Finally, the possible underlying mechanism of action of this series of compounds was investigated by determining their nuclease-like DNA degradation ability in addition to their antioxidant power and all monocations proved to be effective in all assays. PMID:27042005

Correlation between CT numbers and tissue parameters needed for Monte Carlo simulations of clinical dose distributions

NASA Astrophysics Data System (ADS)

Schneider, Wilfried; Bortfeld, Thomas; Schlegel, Wolfgang

2000-02-01

We describe a new method to convert CT numbers into mass density and elemental weights of tissues required as input for dose calculations with Monte Carlo codes such as EGS4. As a first step, we calculate the CT numbers for 71 human tissues. To reduce the effort for the necessary fits of the CT numbers to mass density and elemental weights, we establish four sections on the CT number scale, each confined by selected tissues. Within each section, the mass density and elemental weights of the selected tissues are interpolated. For this purpose, functional relationships between the CT number and each of the tissue parameters, valid for media which are composed of only two components in varying proportions, are derived. Compared with conventional data fits, no loss of accuracy is accepted when using the interpolation functions. Assuming plausible values for the deviations of calculated and measured CT numbers, the mass density can be determined with an accuracy better than 0.04 g cm-3 . The weights of phosphorus and calcium can be determined with maximum uncertainties of 1 or 2.3 percentage points (pp) respectively. Similar values can be achieved for hydrogen (0.8 pp) and nitrogen (3 pp). For carbon and oxygen weights, errors up to 14 pp can occur. The influence of the elemental weights on the results of Monte Carlo dose calculations is investigated and discussed.

Validation of GPU-accelerated superposition-convolution dose computations for the Small Animal Radiation Research Platform.

PubMed

Cho, Nathan; Tsiamas, Panagiotis; Velarde, Esteban; Tryggestad, Erik; Jacques, Robert; Berbeco, Ross; McNutt, Todd; Kazanzides, Peter; Wong, John

2018-05-01

The Small Animal Radiation Research Platform (SARRP) has been developed for conformal microirradiation with on-board cone beam CT (CBCT) guidance. The graphics processing unit (GPU)-accelerated Superposition-Convolution (SC) method for dose computation has been integrated into the treatment planning system (TPS) for SARRP. This paper describes the validation of the SC method for the kilovoltage energy by comparing with EBT2 film measurements and Monte Carlo (MC) simulations. MC data were simulated by EGSnrc code with 3 × 10 8 -1.5 × 10 9 histories, while 21 photon energy bins were used to model the 220 kVp x-rays in the SC method. Various types of phantoms including plastic water, cork, graphite, and aluminum were used to encompass the range of densities of mouse organs. For the comparison, percentage depth dose (PDD) of SC, MC, and film measurements were analyzed. Cross beam (x,y) dosimetric profiles of SC and film measurements are also presented. Correction factors (CFz) to convert SC to MC dose-to-medium are derived from the SC and MC simulations in homogeneous phantoms of aluminum and graphite to improve the estimation. The SC method produces dose values that are within 5% of film measurements and MC simulations in the flat regions of the profile. The dose is less accurate at the edges, due to factors such as geometric uncertainties of film placement and difference in dose calculation grids. The GPU-accelerated Superposition-Convolution dose computation method was successfully validated with EBT2 film measurements and MC calculations. The SC method offers much faster computation speed than MC and provides calculations of both dose-to-water in medium and dose-to-medium in medium. © 2018 American Association of Physicists in Medicine.

Accurate dosimetry with GafChromic EBT film of a 6 MV photon beam in water: what level is achievable?

PubMed

van Battum, L J; Hoffmans, D; Piersma, H; Heukelom, S

2008-02-01

This paper focuses on the accuracy, in absolute dose measurements, with GafChromicTM EBT film achievable in water for a 6 MV photon beam up to a dose of 2.3 Gy. Motivation is to get an absolute dose detection system to measure up dose distributions in a (water) phantom, to check dose calculations. An Epson 1680 color (red green blue) transmission flatbed scanner has been used as film scanning system, where the response in the red color channel has been extracted and used for the analyses. The influence of the flatbed film scanner on the film based dose detection process was investigated. The scan procedure has been optimized; i.e. for instance a lateral correction curve was derived to correct the scan value, up to 10%, as a function of optical density and lateral position. Sensitometric curves of different film batches were evaluated in portrait and landscape scan mode. Between various batches important variations in sensitometric curve were observed. Energy dependence of the film is negligible, while a slight variation in dose response is observed for very large angles between film surface and incident photon beam. Improved accuracy in absolute dose detection can be obtained by repetition of a film measurement to tackle at least the inherent presence of film inhomogeneous construction. We state that the overall uncertainty is random in absolute EBT film dose detection and of the order of 1.3% (1 SD) under the condition that the film is scanned in a limited centered area on the scanner and at least two films have been applied. At last we advise to check a new film batch on its characteristics compared to available information, before using that batch for absolute dose measurements.

Cost Effectiveness of Genotype-Guided Warfarin Dosing in Patients with Mechanical Heart Valve Replacement Under the Fee-for-Service System.

PubMed

Kim, Dong-Jin; Kim, Ho-Sook; Oh, Minkyung; Kim, Eun-Young; Shin, Jae-Gook

2017-10-01

Although studies assessing the cost effectiveness of genotype-guided warfarin dosing for the management of atrial fibrillation, deep vein thrombosis, and pulmonary embolism have been reported, no publications have addressed genotype-guided warfarin therapy in mechanical heart valve replacement (MHVR) patients or genotype-guided warfarin therapy under the fee-for-service (FFS) insurance system. The aim of this study was to evaluate the cost effectiveness of genotype-guided warfarin dosing in patients with MHVR under the FFS system from the Korea healthcare sector perspective. A decision-analytic Markov model was developed to evaluate the cost effectiveness of genotype-guided warfarin dosing compared with standard dosing. Estimates of clinical adverse event rates and health state utilities were derived from the published literature. The outcome measure was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed to explore the range of plausible results. In a base-case analysis, genotype-guided warfarin dosing was associated with marginally higher QALYs than standard warfarin dosing (6.088 vs. 6.083, respectively), at a slightly higher cost (US$6.8) (year 2016 values). The ICER was US$1356.2 per QALY gained. In probabilistic sensitivity analysis, there was an 82.7% probability that genotype-guided dosing was dominant compared with standard dosing, and a 99.8% probability that it was cost effective at a willingness-to-pay threshold of US$50,000 per QALY gained. Compared with only standard warfarin therapy, genotype-guided warfarin dosing was cost effective in MHVR patients under the FFS insurance system.

Robust optimization based upon statistical theory.

PubMed

Sobotta, B; Söhn, M; Alber, M

2010-08-01

Organ movement is still the biggest challenge in cancer treatment despite advances in online imaging. Due to the resulting geometric uncertainties, the delivered dose cannot be predicted precisely at treatment planning time. Consequently, all associated dose metrics (e.g., EUD and maxDose) are random variables with a patient-specific probability distribution. The method that the authors propose makes these distributions the basis of the optimization and evaluation process. The authors start from a model of motion derived from patient-specific imaging. On a multitude of geometry instances sampled from this model, a dose metric is evaluated. The resulting pdf of this dose metric is termed outcome distribution. The approach optimizes the shape of the outcome distribution based on its mean and variance. This is in contrast to the conventional optimization of a nominal value (e.g., PTV EUD) computed on a single geometry instance. The mean and variance allow for an estimate of the expected treatment outcome along with the residual uncertainty. Besides being applicable to the target, the proposed method also seamlessly includes the organs at risk (OARs). The likelihood that a given value of a metric is reached in the treatment is predicted quantitatively. This information reveals potential hazards that may occur during the course of the treatment, thus helping the expert to find the right balance between the risk of insufficient normal tissue sparing and the risk of insufficient tumor control. By feeding this information to the optimizer, outcome distributions can be obtained where the probability of exceeding a given OAR maximum and that of falling short of a given target goal can be minimized simultaneously. The method is applicable to any source of residual motion uncertainty in treatment delivery. Any model that quantifies organ movement and deformation in terms of probability distributions can be used as basis for the algorithm. Thus, it can generate dose distributions that are robust against interfraction and intrafraction motion alike, effectively removing the need for indiscriminate safety margins.

The effect of angiotensin-2 receptor blocker valsartan on circulating level of endothelial progenitor cells in diabetic patients with asymptomatic coronary artery disease.

PubMed

Berezin, Alexander E; Kremzer, Alexander A; Martovitskaya, Yulia V; Samura, Tatyana A

2015-01-01

Decreased circulating endothelial progenitor cells (EPCs) are considered as strong and robust biomarkers for the prediction of cardiovascular outcomes in diabetic populations. The perspectives for modulating EPCs levels in T2DM with known coronary artery disease (CAD) with different drugs, affected mechanisms of improving mobilization of EPCs from tissue, are not still understood. To evaluate an effect of angiotensin-2 receptor blocker valsartan on circulating level of EPCs in diabetic patients with asymptomatic CAD. The study population was structured retrospectively after determining the CAD by contrast-enhanced spiral computed tomography angiography in 126 asymptomatic subjects. All subjects were distributed into two cohorts depending on daily doses of valsartan given. Low (80-160 mg daily orally) and high doses (240-320 mg daily orally) of valsartan were used and they were adjusted depending on achieving BP level less than 140/80 mmHg. The change from baseline in CD34(+) subset cells (frequencies and absolute values) was not significantly different between treatment cohorts. We found a significant increase of circulating level of CD14(+)CD309(+) cells in two patient cohorts. But more prominent change of CD14(+)CD309(+) cells was verified in subjects who were given valsartan in high daily doses when compared with persons who were included into cohort with low daily doses of the drug (1.96% versus 2.59%, respectively; P<0.05). Therefore, both frequencies and absolute values in CD14(+)CD309(+)Tie(2+) were increased significantly in patients who were treated with high doses of valsartan only. We found positive influence of angiotensin-2 receptor blocker valsartan in escalation doses on bone marrow-derived EPCs phenotyped as CD14(+)CD309(+) and CD14(+)CD309(+)Tie(2+) in T2DM patients with known asymptomatic CAD. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Ship-borne measurements of erythemal UV irradiance and ozone content in various climate zones.

PubMed

Wuttke, Sigrid; El Naggar, Saad; Bluszcz, Thaddäus; Schrems, Otto

2007-10-01

Ship-borne measurements of spectral as well as biologically effective UV irradiance have been performed on the German research vessel Polarstern during the Atlantic transect from Bremerhaven, Germany (53.5 degrees N, 8.5 degrees E), to Cape Town, South Africa (33.6 degrees S, 18.3 degrees E), from 13 October to 17 November 2005. Such measurements are required to study UV effects on marine organisms. They are also necessary to validate satellite-derived surface UV irradiance. Cloud free radiative transfer calculations support the investigation of this latitudinal dependence. Input parameters, such as total ozone column and aerosol optical depth have been measured on board as well. Using these measured parameters, the modelled cloudless noontime UVA irradiance (320-400 nm) shows the expected dependence on varying minimum solar zenith angles (SZA) at different latitudes. The modelled cloudless noontime UVB irradiance (290-320 nm) does not show this clear dependence on SZA due to the strong influence of ozone absorption in this spectral range. The maximum daily dose of erythemal irradiance of 5420 J m(-1) was observed on 14 November 2005, when the ship was in the tropical Atlantic south of the equator. The expected UV maximum should have been observed with the sun in the zenith during local noon (11 November). Stratiform clouds reduced the dose to 3835 J m(-1). In comparison, the daily erythemal doses in the mid-latitudinal Bay of Biscay only reached values between 410 and 980 J m(-1) depending on cloud conditions. The deviation in daily erythemal dose derived from different instruments is around 5%. The feasibility to perform ship-borne measurements of spectral UV irradiance is demonstrated.

[Decision process of Notification Value by the Dose Index Registry system in X-ray computed tomography].

PubMed

Shinozaki, Masafumi; Muramatsu, Yoshihisa; Sasaki, Toru

2014-01-01

A new technical standard for X-ray computed tomography (CT) has been published by the National Electrical Manufacturers Association (NEMA) that allows the Alert Value and Notification Value for cumulative dose to be configurable by CT systems operators in conjunction with the XR-25 (Dose check) standard. In this study, a decision method of the Notification Values for reducing the radiation dose was examined using the dose index registry (DIR) system, during 122 continuous days from August 1, 2012 to November 30, 2012. CT images were obtained using the Discovery CT 750HD (GE Healthcare) and the dose index was calculated using the DoseWatch DIR system. The CT dose index-volume (CTDIvol) and dose-length product (DLP) were output from the DIR system in comma-separated value (CSV) file format for each examination protocol. All data were shown as a schematic boxplot using statistical processing software. The CTDIvol of a routine chest examination showed the following values (maximum: 23.84 mGy; minimum: 2.55 mGy; median: 7.60 mGy; 75% tile: 10.01 mGy; 25% tile: 6.54 mGy). DLP showed the following values (maximum: 944.56 mGy·cm; minimum: 97.25 mGy·cm; median: 307.35 mGy·cm; 75% tile: 406.87 mGy·cm; 25% tile: 255.75 mGy·cm). These results indicate that the 75% tile of CTDIvol and DLP as an initial value proved to be safe and efficient for CT examination and operation. We have thus established one way of determining the Notification Value from the output of the DIR system. Transfer back to the protocol of the CT and automated processing each numeric value in the DIR system is desired.

[STUDYING SOME PHARMACOLOGICAL EFFECTS OF NEW 3-HYDROXYPYRIDINE DERIVATIVE].

PubMed

Yasnetsov, V V; Tsublova, E G; Yasnetsov, Vic V; Skachilova, S Ya; Karsanova, S K; Ivanov, Yu V

2016-01-01

It was established that a new 3-hydroxypyridine (3-HP) derivative, 2-ethyl-6-methyl-3-hydroxypyridine L-aspartate (3-HP), in small doses (1 and 5 mg/kg) increased physical performance in treadmill and swimming tests on rats. The new substance showed greater or equal effects compared to the reference actoprotector drugs metaprot and ladasten in much higher doses. The gluconeogenesis inhibitor tryptophan significantly (74 ± 5%, p < 0.01) prevented this stimulatory effect of 3-HPA in the treadmill test on rats. 3-HPA at a higher dose (30 mg/kg) had marked antiamnesic effect on various models of amnesia in mice. It was more effective than reference drugs mexidol (another 3-HP derivative) in a dose of 30 mg/kg and nootropic drug piracetam in a dose of 200 mg/kg, but had equal effect with these drugs in doses of 50 and 800 mg/kg, respectively. 3-HPA (30 mg/kg per day) had neuroprotective effect in rats with brain ischemia and decreased the neurologic deficiency more effectively than mexidol (50 mg/kg per day).

Risk assessment of free hydroquinone derived from Arctostaphylos Uva-ursi folium herbal preparations.

PubMed

de Arriba, Susana Garcia; Naser, Belal; Nolte, Klaus-Ulrich

2013-01-01

Uva-ursi folium (bearberry leaf) has been traditionally used to treat symptoms of lower urinary tract infections. The most representative constituent of this herbal drug is arbutin that is rapidly absorbed in the small intestine and undergoes hepatic conjugation to form hydroquinone (HQ) conjugates. As free HQ is crucial for the safety of the herbal preparation, we reviewed published and unpublished experimental and human studies to clarify some outdated assumptions and to support the safety of therapeutic daily doses of Uva-ursi folium extract. Specifically, data on pharmacokinetics and the human exposure of arbutin and HQ were reviewed. A therapeutic recommended human daily dose of bearberry leaf extract (420 mg hydroquinone derivatives calculated as anhydrous arbutin) liberates free HQ in urine at a maximum exposure level of 11 µg/kg body weight (bw)/d. By means of an experimental no observed effect level value, a permitted daily exposure dose below which there is a negligible risk to human health was estimated for free HQ (100 µg/kg bw/d). Dietary sources of arbutin/HQ that are regularly consumed long term by humans generate comparable free HQ exposure levels. There is no direct evidence, regarding human data, supporting the fact that free HQ causes convulsion, hepatotoxicity, nephrotoxicity, or promotion of tumors in humans. Free HQ had no activity promoting pancreatic, bladder, stomach, or liver carcinogenesis. In conclusion, under the recommended use conditions Uva-ursi folium is a safe therapeutic option for treating lower urinary tract infections.

The two-dimensional Monte Carlo: a new methodologic paradigm for dose reconstruction for epidemiological studies.

PubMed

Simon, Steven L; Hoffman, F Owen; Hofer, Eduard

2015-01-01

Retrospective dose estimation, particularly dose reconstruction that supports epidemiological investigations of health risk, relies on various strategies that include models of physical processes and exposure conditions with detail ranging from simple to complex. Quantification of dose uncertainty is an essential component of assessments for health risk studies since, as is well understood, it is impossible to retrospectively determine the true dose for each person. To address uncertainty in dose estimation, numerical simulation tools have become commonplace and there is now an increased understanding about the needs and what is required for models used to estimate cohort doses (in the absence of direct measurement) to evaluate dose response. It now appears that for dose-response algorithms to derive the best, unbiased estimate of health risk, we need to understand the type, magnitude and interrelationships of the uncertainties of model assumptions, parameters and input data used in the associated dose estimation models. Heretofore, uncertainty analysis of dose estimates did not always properly distinguish between categories of errors, e.g., uncertainty that is specific to each subject (i.e., unshared error), and uncertainty of doses from a lack of understanding and knowledge about parameter values that are shared to varying degrees by numbers of subsets of the cohort. While mathematical propagation of errors by Monte Carlo simulation methods has been used for years to estimate the uncertainty of an individual subject's dose, it was almost always conducted without consideration of dependencies between subjects. In retrospect, these types of simple analyses are not suitable for studies with complex dose models, particularly when important input data are missing or otherwise not available. The dose estimation strategy presented here is a simulation method that corrects the previous deficiencies of analytical or simple Monte Carlo error propagation methods and is termed, due to its capability to maintain separation between shared and unshared errors, the two-dimensional Monte Carlo (2DMC) procedure. Simply put, the 2DMC method simulates alternative, possibly true, sets (or vectors) of doses for an entire cohort rather than a single set that emerges when each individual's dose is estimated independently from other subjects. Moreover, estimated doses within each simulated vector maintain proper inter-relationships such that the estimated doses for members of a cohort subgroup that share common lifestyle attributes and sources of uncertainty are properly correlated. The 2DMC procedure simulates inter-individual variability of possibly true doses within each dose vector and captures the influence of uncertainty in the values of dosimetric parameters across multiple realizations of possibly true vectors of cohort doses. The primary characteristic of the 2DMC approach, as well as its strength, are defined by the proper separation between uncertainties shared by members of the entire cohort or members of defined cohort subsets, and uncertainties that are individual-specific and therefore unshared.

Nurse dose: what's in a concept?

PubMed

Manojlovich, Milisa; Sidani, Souraya

2008-08-01

Many researchers have sought to address the relationship between nursing care and patient outcomes, with inconsistent and contradictory findings. We conducted a concept analysis and concept derivation, basing our work on theoretical and empirical literature, to derive nurse dose as a concept that pulls into a coherent whole disparate variables used in staffing studies. We defined nurse dose as the level of nursing reflected in the purity, amount, frequency, and duration of nursing care needed to produce favorable outcomes. All four parameters of nurse dose used together can facilitate our understanding of how nursing contributes to patient outcomes. Ongoing investigation will help to identify the parameters of nurse dose that have the greatest effect on outcomes. 2008 Wiley Periodicals, Inc

A Feasibility Study of Bihormonal Closed-Loop Blood Glucose Control Using Dual Subcutaneous Infusion of Insulin and Glucagon in Ambulatory Diabetic Swine

PubMed Central

El-Khatib, Firas H.; Jiang, John; Damiano, Edward R.

2009-01-01

Background We sought to test the feasibility and efficacy of bihormonal closed-loop blood glucose (BG) control that utilizes subcutaneous (SC) infusion of insulin and glucagon, a model-predictive control algorithm for determining insulin dosing, and a proportional-derivative control algorithm for determining glucagon dosing. Methods Thirteen closed-loop experiments (∼7–27 h in length) were conducted in six ambulatory diabetic pigs weighing 26–50 kg. In all experiments, venous BG was sampled through a central line in the vena cava. Efficacy was evaluated in terms of the controller's ability to regulate BG in response to large meal disturbances (∼5 g of carbohydrate per kilogram of body mass per meal) based only on regular frequent venous BG sampling and requiring only the subject's weight for initialization. Results Closed-loop results demonstrated successful BG regulation to normoglycemic range, with average insulin-to-carbohydrate ratios between ∼1:20 and 1:40 U/g. The total insulin bolus doses averaged ∼6 U for a meal containing ∼6 g per kilogram body mass. Mean BG values in two 24 h experiments were ∼142 and ∼155 mg/dl, with the total daily dose (TDD) of insulin being ∼0.8–1.0 U per kilogram of body mass and the TDD of glucagon being ∼0.02–0.05 mg. Results also affirmed the efficacy of SC doses of glucagon in staving off episodic hypoglycemia. Conclusions We demonstrate the feasibility of bihormonal closed-loop BG regulation using a control system that employs SC infusion of insulin and glucagon as governed by an algorithm that reacts only to BG without any feed-forward information regarding carbohydrate consumption or physical activity. As such, this study can reasonably be regarded as the first practical implementation of an artificial endocrine pancreas that has a hormonally derived counterregulatory capability. PMID:20144330

The effects of temperature and pressure on airborne exposure concentrations when performing compliance evaluations using ACGIH TLVs and OSHA PELs.

PubMed

Stephenson, D J; Lillquist, D R

2001-04-01

Occupational hygienists perform air sampling to characterize airborne contaminant emissions, assess occupational exposures, and establish allowable workplace airborne exposure concentrations. To perform these air sampling applications, occupational hygienists often compare an airborne exposure concentration to a corresponding American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) or an Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL). To perform such comparisons, one must understand the physiological assumptions used to establish these occupational exposure limits, the relationship between a workplace airborne exposure concentration and its associated TLV or PEL, and the effect of temperature and pressure on the performance of an accurate compliance evaluation. This article illustrates the correct procedure for performing compliance evaluations using airborne exposure concentrations expressed in both parts per million and milligrams per cubic meter. In so doing, a brief discussion is given on the physiological assumptions used to establish TLVs and PELs. It is further shown how an accurate compliance evaluation is fundamentally based on comparison of a measured work site exposure dose (derived from the sampling site exposure concentration estimate) to an estimated acceptable exposure dose (derived from the occupational exposure limit concentration). In addition, this article correctly illustrates the effect that atmospheric temperature and pressure have on airborne exposure concentrations and the eventual performance of a compliance evaluation. This article also reveals that under fairly moderate conditions of temperature and pressure, 30 degrees C and 670 torr, a misunderstanding of how varying atmospheric conditions affect concentration values can lead to a 15 percent error in assessing compliance.

Pharmacodynamics of temazepam in primary insomnia: assessment of the value of quantitative electroencephalography and saccadic eye movements in predicting improvement of sleep.

PubMed

Tuk, B; Oberyé, J J; Pieters, M S; Schoemaker, R C; Kemp, B; van Gerven, J; Danhof, M; Kamphuisen, H A; Cohen, A F; Breimer, D D; Peck, C C

1997-10-01

Quantitative electroencephalographic parameters and saccadic eye movements are frequently used as pharmacodynamic measures of benzodiazepine effect. We investigated the relationship between these measures and the hypnotic effect. The correlation between the pharmacodynamic measures and sleep quality was determined in 21 patients with primary insomnia. The pharmacokinetic-pharmacodynamic relationships were characterized after administration of 20 mg oral temazepam. The hypnotic effect was determined on the basis of polysomnographic sleep recordings and a subjective sleep evaluation questionnaire. Correlations between pharmacodynamic measures and the improvement of sleep were investigated. The pharmacokinetic-pharmacodynamic relationships for the parameters derived from electroencephalography and saccadic eye movements showed considerable interindividual variability. Administration of temazepam led to a significant improvement in the objective parameters sleep period efficiency, wake time after sleep onset, and sleep efficiency and in the subjective assessment of sleep quality. No significant correlations were observed between the pharmacokinetic-pharmacodynamic-derived parameters and the improvement in objective or subjective sleep parameters. In subjects with primary insomnia the administration of 20 mg oral temazepam results in changes in both the pharmacodynamic measures and in quality of sleep. No individual correlations between the pharmacodynamic measures and quality of sleep were observed. We concluded that the investigated pharmacodynamic measures are of value in the first assessment of clinical efficacy and for the selection of the dose(s) to be investigated in subsequent trials that aim at showing clinical efficacy. However, the conclusive quantification of clinical efficacy should be performed only on the basis of the clinical end point itself.

Analysis of uncertainties in Monte Carlo simulated organ dose for chest CT

NASA Astrophysics Data System (ADS)

Muryn, John S.; Morgan, Ashraf G.; Segars, W. P.; Liptak, Chris L.; Dong, Frank F.; Primak, Andrew N.; Li, Xiang

2015-03-01

In Monte Carlo simulation of organ dose for a chest CT scan, many input parameters are required (e.g., half-value layer of the x-ray energy spectrum, effective beam width, and anatomical coverage of the scan). The input parameter values are provided by the manufacturer, measured experimentally, or determined based on typical clinical practices. The goal of this study was to assess the uncertainties in Monte Carlo simulated organ dose as a result of using input parameter values that deviate from the truth (clinical reality). Organ dose from a chest CT scan was simulated for a standard-size female phantom using a set of reference input parameter values (treated as the truth). To emulate the situation in which the input parameter values used by the researcher may deviate from the truth, additional simulations were performed in which errors were purposefully introduced into the input parameter values, the effects of which on organ dose per CTDIvol were analyzed. Our study showed that when errors in half value layer were within ± 0.5 mm Al, the errors in organ dose per CTDIvol were less than 6%. Errors in effective beam width of up to 3 mm had negligible effect (< 2.5%) on organ dose. In contrast, when the assumed anatomical center of the patient deviated from the true anatomical center by 5 cm, organ dose errors of up to 20% were introduced. Lastly, when the assumed extra scan length was longer by 4 cm than the true value, dose errors of up to 160% were found. The results answer the important question: to what level of accuracy each input parameter needs to be determined in order to obtain accurate organ dose results.

A CONCEPTUAL FRAMEWORK FOR MANAGING RADIATION DOSE TO PATIENTS IN DIAGNOSTIC RADIOLOGY USING REFERENCE DOSE LEVELS.

PubMed

Almén, Anja; Båth, Magnus

2016-06-01

The overall aim of the present work was to develop a conceptual framework for managing radiation dose in diagnostic radiology with the intention to support optimisation. An optimisation process was first derived. The framework for managing radiation dose, based on the derived optimisation process, was then outlined. The outset of the optimisation process is four stages: providing equipment, establishing methodology, performing examinations and ensuring quality. The optimisation process comprises a series of activities and actions at these stages. The current system of diagnostic reference levels is an activity in the last stage, ensuring quality. The system becomes a reactive activity only to a certain extent engaging the core activity in the radiology department, performing examinations. Three reference dose levels-possible, expected and established-were assigned to the three stages in the optimisation process, excluding ensuring quality. A reasonably achievable dose range is also derived, indicating an acceptable deviation from the established dose level. A reasonable radiation dose for a single patient is within this range. The suggested framework for managing radiation dose should be regarded as one part of the optimisation process. The optimisation process constitutes a variety of complementary activities, where managing radiation dose is only one part. This emphasises the need to take a holistic approach integrating the optimisation process in different clinical activities. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Empirical determination of collimator scatter data for use in Radcalc commercial monitor unit calculation software: Implication for prostate volumetric modulated-arc therapy calculations.

PubMed

Richmond, Neil; Tulip, Rachael; Walker, Chris

2016-01-01

The aim of this work was to determine, by measurement and independent monitor unit (MU) check, the optimum method for determining collimator scatter for an Elekta Synergy linac with an Agility multileaf collimator (MLC) within Radcalc, a commercial MU calculation software package. The collimator scatter factors were measured for 13 field shapes defined by an Elekta Agility MLC on a Synergy linac with 6MV photons. The value of the collimator scatter associated with each field was also calculated according to the equation Sc=Sc(mlc)+Sc(corr)(Sc(open)-Sc(mlc)) with Sc(corr) varied between 0 and 1, where Sc(open) is the value of collimator scatter calculated from the rectangular collimator-defined field and Sc(mlc) the value using only the MLC-defined field shape by applying sector integration. From this the optimum value of the correction was determined as that which gives the minimum difference between measured and calculated Sc. Single (simple fluence modulation) and dual-arc (complex fluence modulation) treatment plans were generated on the Monaco system for prostate volumetric modulated-arc therapy (VMAT) delivery. The planned MUs were verified by absolute dose measurement in phantom and by an independent MU calculation. The MU calculations were repeated with values of Sc(corr) between 0 and 1. The values of the correction yielding the minimum MU difference between treatment planning system (TPS) and check MU were established. The empirically derived value of Sc(corr) giving the best fit to the measured collimator scatter factors was 0.49. This figure however was not found to be optimal for either the single- or dual-arc prostate VMAT plans, which required 0.80 and 0.34, respectively, to minimize the differences between the TPS and independent-check MU. Point dose measurement of the VMAT plans demonstrated that the TPS MUs were appropriate for the delivered dose. Although the value of Sc(corr) may be obtained by direct comparison of calculation with measurement, the efficacy of the value determined for VMAT-MU calculations are very much dependent on the complexity of the MLC delivery. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Improvement of single detector proton radiography by incorporating intensity of time-resolved dose rate functions

NASA Astrophysics Data System (ADS)

Zhang, Rongxiao; Jee, Kyung-Wook; Cascio, Ethan; Sharp, Gregory C.; Flanz, Jacob B.; Lu, Hsiao-Ming

2018-01-01

Proton radiography, which images patients with the same type of particles as those with which they are to be treated, is a promising approach to image guidance and water equivalent path length (WEPL) verification in proton radiation therapy. We have shown recently that proton radiographs could be obtained by measuring time-resolved dose rate functions (DRFs) using an x-ray amorphous silicon flat panel. The WEPL values were derived solely from the root-mean-square (RMS) of DRFs, while the intensity information in the DRFs was filtered out. In this work, we explored the use of such intensity information for potential improvement in WEPL accuracy and imaging quality. Three WEPL derivation methods based on, respectively, the RMS only, the intensity only, and the intensity-weighted RMS were tested and compared in terms of the quality of obtained radiograph images and the accuracy of WEPL values. A Gammex CT calibration phantom containing inserts made of various tissue substitute materials with independently measured relative stopping powers (RSP) was used to assess the imaging performances. Improved image quality with enhanced interfaces was achieved while preserving the accuracy by using intensity information in the calibration. Other objects, including an anthropomorphic head phantom, a proton therapy range compensator, a frozen lamb’s head and an ‘image quality phantom’ were also imaged. Both the RMS only and the intensity-weighted RMS methods derived RSPs within  ±  1% for most of the Gammex phantom inserts, with a mean absolute percentage error of 0.66% for all inserts. In the case of the insert with a titanium rod, the method based on RMS completely failed, whereas that based on the intensity-weighted RMS was qualitatively valid. The use of intensity greatly enhanced the interfaces between different materials in the obtained WEPL images, suggesting the potential for image guidance in areas such as patient positioning and tumor tracking by proton radiography.

Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia

PubMed Central

Fan, Yongjun; Wali, Gautam; Sutharsan, Ratneswary; Bellette, Bernadette; Crane, Denis I.; Sue, Carolyn M.; Mackay-Sim, Alan

2014-01-01

ABSTRACT Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS) cells, spastin mutations lead to lower levels of acetylated α-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 µM noscapine) that rescued acetylated α-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated α-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials. PMID:24857849

Radiobiological modeling of two stereotactic body radiotherapy schedules in patients with stage I peripheral non-small cell lung cancer.

PubMed

Huang, Bao-Tian; Lin, Zhu; Lin, Pei-Xian; Lu, Jia-Yang; Chen, Chuang-Zhen

2016-06-28

This study aims to compare the radiobiological response of two stereotactic body radiotherapy (SBRT) schedules for patients with stage I peripheral non-small cell lung cancer (NSCLC) using radiobiological modeling methods. Volumetric modulated arc therapy (VMAT)-based SBRT plans were designed using two dose schedules of 1 × 34 Gy (34 Gy in 1 fraction) and 4 × 12 Gy (48 Gy in 4 fractions) for 19 patients diagnosed with primary stage I NSCLC. Dose to the gross target volume (GTV), planning target volume (PTV), lung and chest wall (CW) were converted to biologically equivalent dose in 2 Gy fraction (EQD2) for comparison. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three additional models were utilized to estimate the normal tissue complication probability (NTCP) value for the lung and the modified equivalent uniform dose (mEUD) value to the CW. Our result indicates that the 1 × 34 Gy dose schedule provided a higher EQD2 dose to the tumor, lung and CW. Radiobiological modeling revealed that the TCP value for the tumor, NTCP value for the lung and mEUD value for the CW were 7.4% (in absolute value), 7.2% (in absolute value) and 71.8% (in relative value) higher on average, respectively, using the 1 × 34 Gy dose schedule.

Individual dose reconstruction among residents living in the vicinity of the Semipalatinsk nuclear test site using EPR spectroscopy of tooth enamel.

PubMed

Ivannikov, A I; Zhumadilov, Zh; Gusev, B I; Miyazawa, Ch; Jiao, L; Skvortsov, V G; Stepanenko, V F; Takada, J; Hoshi, M

2002-08-01

Individual accumulated doses were determined by EPR spectroscopy of tooth enamel for 26 adult persons residing in territories adjacent to the Semipalatinsk Nuclear Test Site (SNTS). The absorbed dose values due to radiation from nuclear tests were obtained after subtracting the contribution of natural background radiation from the total accumulated dose. The determined dose values ranged up to 250 mGy, except for one person from Semipalatinsk city with a measured dose of 2.8 +/- 0.4 Gy. Increased dose values were determined for the individuals whose teeth were formed before 1962, the end of the atmospheric nuclear tests. These values were found to be significantly larger than those obtained for a group of younger residents of heavily exposed territories and the residents of territories not exposed to radioactive fallout. These increased dose values are consistent with those based on officially registered data for the Northeastern part of Kazakstan adjacent to SNTS, which was exposed to high levels of radioactive fallout from nuclear tests in period 1949-1962.

Betulinic acid derivatives NVX-207 and B10 for treatment of glioblastoma--an in vitro study of cytotoxicity and radiosensitization.

PubMed

Bache, Matthias; Bernhardt, Stephan; Passin, Sarina; Wichmann, Henri; Hein, Anja; Zschornak, Martin; Kappler, Matthias; Taubert, Helge; Paschke, Reinhard; Vordermark, Dirk

2014-10-30

Betulinic acid (BA), a pentacyclic triterpene, represents a new therapeutic substance that has potential benefits for treating glioblastoma. Recently, new strategies for producing BA derivatives with improved properties have evolved. However, few studies have examined the combination of BA or BA derivatives using radiotherapy. The effects of two BA derivatives, NVX-207 and B10, on cellular and radiobiological behavior were analyzed using glioblastoma cell lines (U251MG, U343MG and LN229). Based on IC50 values under normoxic conditions, we detected a 1.3-2.9-fold higher cytotoxicity of the BA derivatives B10 and NVX-207, respectively, compared to BA. Incubation using both BA derivatives led to decreased cell migration, cleavage of PARP and decreased protein expression levels of Survivin. Weak radiation sensitivity enhancement was observed in U251MG cells after treatment with both BA derivatives. The enhancement factors at an irradiation dose of 6 Gy after treatment with 5 µM NVX-207 and 5 µM B10 were 1.32 (p=0.029) and 1.55 (p=0.002), respectively. In contrast to BA, neither NVX-207 nor B10 had additional effects under hypoxic conditions. Our results suggest that the BA derivatives NVX-207 and B10 improve the effects of radiotherapy on human malignant glioma cells, particularly under normoxic conditions.

Betulinic Acid Derivatives NVX-207 and B10 for Treatment of Glioblastoma—An in Vitro Study of Cytotoxicity and Radiosensitization

PubMed Central

Bache, Matthias; Bernhardt, Stephan; Passin, Sarina; Wichmann, Henri; Hein, Anja; Zschornak, Martin; Kappler, Matthias; Taubert, Helge; Paschke, Reinhard; Vordermark, Dirk

2014-01-01

Betulinic acid (BA), a pentacyclic triterpene, represents a new therapeutic substance that has potential benefits for treating glioblastoma. Recently, new strategies for producing BA derivatives with improved properties have evolved. However, few studies have examined the combination of BA or BA derivatives using radiotherapy. The effects of two BA derivatives, NVX-207 and B10, on cellular and radiobiological behavior were analyzed using glioblastoma cell lines (U251MG, U343MG and LN229). Based on IC50 values under normoxic conditions, we detected a 1.3–2.9-fold higher cytotoxicity of the BA derivatives B10 and NVX-207, respectively, compared to BA. Incubation using both BA derivatives led to decreased cell migration, cleavage of PARP and decreased protein expression levels of Survivin. Weak radiation sensitivity enhancement was observed in U251MG cells after treatment with both BA derivatives. The enhancement factors at an irradiation dose of 6 Gy after treatment with 5 µM NVX-207 and 5 µM B10 were 1.32 (p = 0.029) and 1.55 (p = 0.002), respectively. In contrast to BA, neither NVX-207 nor B10 had additional effects under hypoxic conditions. Our results suggest that the BA derivatives NVX-207 and B10 improve the effects of radiotherapy on human malignant glioma cells, particularly under normoxic conditions. PMID:25361208

LET spectra measurements from the STS-35 CPDs

NASA Technical Reports Server (NTRS)

1995-01-01

Linear energy transfer (LET) spectra derived form automated track analysis system (ATAS) track parameter measurements for crew passive dosimeters (CPD's) flown with the astronauts on STS-35 are plotted. The spread between the seven individual spectra is typical of past manual measurements of sets of CPD's. This difference is probably due to the cumulative net shielding variations experienced by the CPD's as the astronauts carrying them went about their activities on the Space Shuttle. The STS-35 mission was launched on Dec. 2, 1990, at 28.5 degrees inclination and 352-km altitude. This is somewhat higher than the nominal 300-km flights and the orbit intersects more of the high intensity trapped proton region in the South Atlantic Anomaly (SAA). However, in comparison with APD spectra measured on earlier lower altitude missions (STS-26, -29, -30, -32), the flux spectra are all roughly comparable. This may be due to the fact that the STS-35 mission took place close to solar maximum (Feb. 1990), or perhaps to shielding differences. The corresponding dose and dose equivalent spectra for this mission are shown. The effect of statistical fluctuations at the higher LET values, where track densities are small, is very noticeable. This results in an increased spread within the dose rate and dose equivalent rate spectra, as compared to the flux spectra. The contribution to dose and dose equivalent per measured track is much greater in the high LET region and the differences, though numerically small, are heavily weighted in the integral spectra. The optimum measurement and characterization of the high LET tails of the spectra represent an important part of the research into plastic nuclear track detector (PNTD) response. The integral flux, dose rate, dose equivalent rate and mission dose equivalent for the seven astronauts are also given.

Evaluation of effective dose for a patient under Ga-67 nuclear examination using TLD, water phantom and a simplified model

PubMed Central

Chu, Kuang Hua; Lin, Yu Ting; Hsu, Chia Chun; Chen, Chien Yi; Pan, Lung Kwang

2012-01-01

This study evaluated the effective dose of Ga-67 for a patient undergoing Ga-67 citrate nuclear examination by applying thermoluminescent dosimeter (TLD) technique and an indigenous water phantom. The Ga-67 radionuclide remaining in the body inevitably generated a measurable internal dose even though gamma camera scanning took only minutes to complete the clinical examination. For effective simulation of the cumulated effective dose for a patient undergoing examination, 150 TLDs were placed inside the water phantom for 6 days to monitor the gamma ray dose from the distributed Ga-67 citrate solution. The inserted TLDs represented internal organs, and the effective dose was calculated according to data in the ICRP-60 report. The water phantom was designed to model the body of a healthy human weighing 70 kg, and the water that was mixed with Ga-67 citrate solution was slowly replaced with fresh feed water to yield the required biological half life of the phantom. After continuously feeding in fresh water throughout the 6 days of TLD exposure, the TLDs were analyzed to determine the effective doses from the various biological half lives of the phantom. The derived effective dose of 185 MBq Ga-67 citrate solution for male/female (M/F) was 10.7/12.2, 10.7/12.0, 8.7/9.9 and 6.0/6.8 mSv, of biological half lives of 6.0, 4.5, 3.0 and 1.5 days, respectively. Although these experimental results correlated well with earlier empirical studies, they were lower than most calculated values. The cumulated uncertainty in the effective dose was 12.5–19.4%, which was acceptable in terms of both TLD counting statistic and reproducibility. PMID:22915780

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

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

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

Development of a method to estimate organ doses for pediatric CT examinations

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

Papadakis, Antonios E., E-mail: apapadak@pagni.gr; Perisinakis, Kostas; Damilakis, John

Purpose: To develop a method for estimating doses to primarily exposed organs in pediatric CT by taking into account patient size and automatic tube current modulation (ATCM). Methods: A Monte Carlo CT dosimetry software package, which creates patient-specific voxelized phantoms, accurately simulates CT exposures, and generates dose images depicting the energy imparted on the exposed volume, was used. Routine head, thorax, and abdomen/pelvis CT examinations in 92 pediatric patients, ranging from 1-month to 14-yr-old (49 boys and 43 girls), were simulated on a 64-slice CT scanner. Two sets of simulations were performed in each patient using (i) a fixed tubemore » current (FTC) value over the entire examination length and (ii) the ATCM profile extracted from the DICOM header of the reconstructed images. Normalized to CTDI{sub vol} organ dose was derived for all primary irradiated radiosensitive organs. Normalized dose data were correlated to patient’s water equivalent diameter using log-transformed linear regression analysis. Results: The maximum percent difference in normalized organ dose between FTC and ATCM acquisitions was 10% for eyes in head, 26% for thymus in thorax, and 76% for kidneys in abdomen/pelvis. In most of the organs, the correlation between dose and water equivalent diameter was significantly improved in ATCM compared to FTC acquisitions (P < 0.001). Conclusions: The proposed method employs size specific CTDI{sub vol}-normalized organ dose coefficients for ATCM-activated and FTC acquisitions in pediatric CT. These coefficients are substantially different between ATCM and FTC modes of operation and enable a more accurate assessment of patient-specific organ dose in the clinical setting.« less

The frequency of U-shaped dose responses in the toxicological literature.

PubMed

Calabrese, E J; Baldwin, L A

2001-08-01

Hormesis has been defined as a dose-response relationship in which there is a stimulatory response at low doses, but an inhibitory response at high doses, resulting in a U- or inverted U-shaped dose response. To assess the proportion of studies satisfying criteria for evidence of hormesis, a database was created from published toxicological literature using rigorous a priori entry and evaluative criteria. One percent (195 out of 20,285) of the published articles contained 668 dose-response relationships that met the entry criteria. Subsequent application of evaluative criteria revealed that 245 (37% of 668) dose-response relationships from 86 articles (0.4% of 20,285) satisfied requirements for evidence of hormesis. Quantitative evaluation of false-positive and false-negative responses indicated that the data were not very susceptible to such influences. A complementary analysis of all dose responses assessed by hypothesis testing or distributional analyses, where the units of comparison were treatment doses below the NOAEL, revealed that of 1089 doses below the NOAEL, 213 (19.5%) satisfied statistical significance or distributional data evaluative criteria for hormesis, 869 (80%) did not differ from the control, and 7 (0.6%) displayed evidence of false-positive values. The 32.5-fold (19.5% vs 0.6%) greater occurrence of hormetic responses than a response of similar magnitude in the opposite (negative) direction strongly supports the nonrandom nature of hormetic responses. This study, which provides the first documentation of a data-derived frequency of hormetic responses in the toxicologically oriented literature, indicates that when the study design satisfies a priori criteria (i.e., a well-defined NOAEL, > or = 2 doses below the NOAEL, and the end point measured has the capacity to display either stimulatory or inhibitory responses), hormesis is frequently encountered and is broadly represented according to agent, model, and end point. These findings have broad-based implications for study design, risk assessment methods, and the establishment of optimal drug doses and suggest important evolutionarily adaptive strategies for dose-response relationships.

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.

Pharmacokinetics, safety and tolerability of rotigotine transdermal patch in healthy Japanese and Caucasian subjects.

PubMed

Cawello, Willi; Kim, Seong R; Braun, Marina; Elshoff, Jan-Peer; Ikeda, Junji; Funaki, Tomoo

2014-02-01

Rotigotine is a dopamine receptor agonist with activity across the D1 through to D5 receptors as well as select serotonergic and adrenergic sites; continuous transdermal delivery of rotigotine with replacement of the patch once daily maintains stable plasma concentrations over 24 h. Rotigotine is indicated for the treatment of early and advanced-stage Parkinson's disease and moderate-to-severe idiopathic restless legs syndrome. The pharmacokinetics and pharmacodynamics of a drug may vary between subjects of different ethnic origin. This study evaluated the pharmacokinetics, safety, and tolerability of single-dose treatment with rotigotine transdermal patch in Japanese and Caucasian subjects. In this open-label, parallel-group study, healthy male and female subjects of Japanese or Caucasian ethnic origin were matched by sex, body mass index, and age. A single transdermal patch delivering 2 mg/24 h rotigotine (patch content 4.5 mg) was applied to the ventral/lateral abdomen for 24 h. The main outcome measures were the plasma concentrations of unconjugated and total rotigotine and its desalkyl metabolites and derived pharmacokinetic parameters (area under the concentration-time curve from time zero to last quantifiable concentration [AUClast], maximum plasma concentration [Cmax], and body weight- and dose-normalized values). The pharmacokinetic analysis included 48 subjects (24 Japanese, 24 Caucasian). The mean apparent dose of rotigotine was 2.0±0.5 mg for Japanese subjects and 2.08±0.58 mg for Caucasians. Plasma concentration-time profiles of unconjugated rotigotine and of the main metabolites were similar for both ethnic groups. Parameters of model-independent pharmacokinetics, Cmax, time to Cmax (tmax), and AUClast, for unconjugated rotigotine showed no statistically significant differences between Japanese and Caucasian subjects. Values of concentration-dependent pharmacokinetic parameters were higher in female subjects; this difference was minimized after correction for body weight. A statistically significant difference between ethnic groups was observed for total rotigotine concentrations (total rotigotine=unconjugated rotigotine+conjugated rotigotine), with slightly lower values in Caucasians after correction for body weight and apparent dose. No relevant differences were observed between males and females. Inter-individual variability was high. The terminal half-life for unconjugated rotigotine was 5.3 h in Japanese subjects and 5.7 h in Caucasians; corresponding values for total rotigotine were 8.6 h and 9.6 h. Less than 0.1% of the apparent dose was renally excreted as the parent compound. Renal elimination of total rotigotine covers 11.7% of absorbed dose in Japanese subjects and 10.8% of the absorbed dose in Caucasians, whereas the renal elimination via total despropyl rotigotine was 8.2 and 7.1%, respectively. The corresponding values for total desthienylethyl rotigotine were 3.5% in Japanese subjects and 4.2% Caucasians. Most adverse events were mild in intensity and typical for dopamine agonists or for transdermal therapeutics. Administration of a single patch delivering 2 mg/24 h rotigotine resulted in comparable pharmacokinetic profiles in Japanese and Caucasian subjects. The rotigotine transdermal patch was generally well-tolerated. Our findings suggest similar dose requirements for Japanese and Caucasian populations.

SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

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

Ma, L; Braunstein, S; Chiu, J

2016-06-15

Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

Long-term immunogenicity of an initial booster dose of an inactivated, Vero cell culture-derived Japanese encephalitis vaccine (JE-VC) and the safety and immunogenicity of a second JE-VC booster dose in children previously vaccinated with an inactivated, mouse brain-derived Japanese encephalitis vaccine.

PubMed

Yun, Ki Wook; Lee, Hoan Jong; Park, Ji Young; Cho, Hye-Kyung; Kim, Yae-Jean; Kim, Kyung-Hyo; Kim, Nam Hee; Hong, Young Jin; Kim, Dong Ho; Kim, Hwang Min; Cha, Sung-Ho

2018-03-07

This study was performed with the aim of determining the long-term immunogenicity of an inactivated, Vero cell culture-derived Japanese encephalitis (JE) vaccine (JE-VC) and an inactivated, mouse brain-derived JE vaccine (JE-MB) after the 1st booster dose at 2 years of age, as well as the safety and immunogenicity of the 2nd booster dose of JE-VC at 6 years of age, in children primed and given a 1st booster dose of either JE-VC or JE-MB. In this multicenter, open-label clinical trial, the study population consisted of healthy Korean children (aged 6 years) who participated in the previous JE vaccine trial. All subjects were subcutaneously vaccinated once for the booster immunization with Boryung Cell Culture Japanese Encephalitis Vaccine® (JE-VC). Approximately 4 years after the 1st booster dose of JE-VC, the seroprotection rate (SPR) and geometric mean titer (GMT) of the neutralizing antibody were 100% and 1113.8, respectively. In children primed and given a 1st booster dose of JE-MB, the SPR and GMT were 88.5% and 56.3, respectively. After the 2nd booster dose of JE-VC, all participants primed and given a 1st booster dose of either JE-MB or JE-VC were seroprotective against JE virus. The GMT of the neutralizing antibody was higher in children primed and given a 1st booster dose of JE-VC (8144.1) than in those primed and given a 1st booster dose of JE-MB (942.5) after the vaccination (p < 0.001). In addition, the 2nd booster dose of JE-VC showed a good safety profile with no serious vaccine-related adverse events. The 1st booster dose of JE-VC and JE-MB showed long-term immunogenicity of at least 4 years, and the 2nd booster dose of JE-VC showed a good safety and immunogenicity profile in children primed and given a 1st booster dose of either JE-VC or JE-MB. ClinicalTtrials.gov Identifier: NCT02532569. Copyright © 2018 Elsevier Ltd. All rights reserved.

OCCUPATIONAL DOSE DURING ADULT INTERVENTIONAL CARDIOLOGY: FIRST VALUES WITH PERSONAL ACTIVE DOSIMETERS IN CHILE.

PubMed

Ubeda, Carlos; Morales, Claudio; Gutiérrez, Diego; Oliveira, Marcus; Manterola, Carlos

2018-05-11

The objective of this article is to present initial occupational dose values using digital active personal dosimeters for medical staff during adult interventional cardiology procedures in a public hospital in Chile. Personal dose equivalent Hp(10) over the lead apron of physician, nurse and radiographer were measured during 59 procedures. Mean values of occupational dose Hp(10) per procedure were 47.6, 6.2 and 4.3 μSv for physician, nurse and radiographer, respectively. If no protective tools are used, physician dose can exceed the new eye lens dose limit.

Pharmacokinetic profiles of repaglinide in elderly subjects with type 2 diabetes.

PubMed

Hatorp, V; Huang, W C; Strange, P

1999-04-01

Pharmacokinetic profiles of single- and multiple-dose regimens of repaglinide were evaluated in 12 elderly subjects with type 2 diabetes. On day 1, following a 10-hour fast, subjects received a single 2-mg dose of repaglinide. Starting on day 2 and continuing for 7 days, each subject received a 2-mg dose of repaglinide 15 minutes before each of the three main meals. On day 9, subjects received a single 2-mg dose of repaglinide. Pharmacokinetic profiles, including area under the curve (AUC), log(AUC), maximal concentration (Cmax), log(Cmax), time to maximal concentration (Tmax), and half-life (T(1/2)), were determined at completion of the single- and multiple-dose regimens (days 1 and 9, respectively). Trough repaglinide values were collected on days 2 through 7. The mean log(AUC) values after multiple dosing were significantly higher than the values obtained after a single dose. The mean values for log(Cmax), and Tmax were comparable after each dosing regimen. The T(1/2) of repaglinide after multiple dosing was 1.7 hours. The trough values for repaglinide were low. No hypoglycemic events were reported. The pharmacokinetic profiles of repaglinide after single- and multiple-dose regimens were similar, and repaglinide was well tolerated by elderly subjects with type 2 diabetes.

Determination of absorbed dose to water around a clinical HDR {sup 192}Ir source using LiF:Mg,Ti TLDs demonstrates an LET dependence of detector response

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

Carlsson Tedgren, Aasa; Elia, Rouba; Hedtjaern, Haakan

2012-02-15

Purpose: Experimental radiation dosimetry with thermoluminescent dosimeters (TLDs), calibrated in a {sup 60}Co or megavoltage (MV) photon beam, is recommended by AAPM TG-43U1for verification of Monte Carlo calculated absorbed doses around brachytherapy sources. However, it has been shown by Carlsson Tedgren et al.[Med. Phys. 38, 5539-5550 (2011)] that for TLDs of LiF:Mg,Ti, detector response was 4% higher in a {sup 137}Cs beam than in a {sup 60}Co one. The aim of this work was to investigate if similar over-response exists when measuring absorbed dose to water around {sup 192}Ir sources, using LiF:Mg,Ti dosimeters calibrated in a 6 MV photon beam.more » Methods: LiF dosimeters were calibrated to measure absorbed dose to water in a 6 MV photon beam and used to measure absorbed dose to water at distances of 3, 5, and 7 cm from a clinical high dose rate (HDR) {sup 192}Ir source in a polymethylmethacrylate (PMMA) phantom. Measured values were compared to values of absorbed dose to water calculated using a treatment planning system (TPS) including corrections for the difference in energy absorption properties between calibration quality and the quality in the users'{sup 192}Ir beam and for the use of a PMMA phantom instead of the water phantom underlying dose calculations in the TPS. Results: Measured absorbed doses to water around the {sup 192}Ir source were overestimated by 5% compared to those calculated by the TPS. Corresponding absorbed doses to water measured in a previous work with lithium formate electron paramagnetic resonance (EPR) dosimeters by Antonovic et al. [Med. Phys. 36, 2236-2247 (2009)], using the same irradiation setup and calibration procedure as in this work, were 2% lower than those calculated by the TPS. The results obtained in the measurements in this work and those obtained using the EPR lithium formate dosimeters were, within the expanded (k = 2) uncertainty, in agreement with the values derived by the TPS. The discrepancy between the results using LiF:Mg,Ti TLDs and the EPR lithium formate dosimeters was, however, statistically significant and in agreement with the difference in relative detector responses found for the two detector systems by Carlsson Tedgren et al. [Med. Phys. 38, 5539-5550 (2011)] and by Adolfsson et al.[Med. Phys. 37, 4946-4959 (2010)]. Conclusions: When calibrated in {sup 60}Co or MV photon beams, correction for the linear energy transfer (LET) dependence of LiF:Mg,Ti detector response will be needed as to measure absorbed doses to water in a {sup 192}Ir beam with highest accuracy. Such corrections will depend on the manufacturing process (MTS-N Poland or Harshaw TLD-100) and details of the annealing and read-out schemes used.« less

Determination of absorbed dose to water around a clinical HDR (192)Ir source using LiF:Mg,Ti TLDs demonstrates an LET dependence of detector response.

PubMed

Carlsson Tedgren, Asa; Elia, Rouba; Hedtjarn, Hakan; Olsson, Sara; Alm Carlsson, Gudrun

2012-02-01

Experimental radiation dosimetry with thermoluminescent dosimeters (TLDs), calibrated in a (60)Co or megavoltage (MV) photon beam, is recommended by AAPM TG-43U1for verification of Monte Carlo calculated absorbed doses around brachytherapy sources. However, it has been shown by Carlsson Tedgren et al. [Med. Phys. 38, 5539-5550 (2011)] that for TLDs of LiF:Mg,Ti, detector response was 4% higher in a (137)Cs beam than in a (60)Co one. The aim of this work was to investigate if similar over-response exists when measuring absorbed dose to water around (192)Ir sources, using LiF:Mg,Ti dosimeters calibrated in a 6 MV photon beam. LiF dosimeters were calibrated to measure absorbed dose to water in a 6 MV photon beam and used to measure absorbed dose to water at distances of 3, 5, and 7 cm from a clinical high dose rate (HDR) (192)Ir source in a polymethylmethacrylate (PMMA) phantom. Measured values were compared to values of absorbed dose to water calculated using a treatment planning system (TPS) including corrections for the difference in energy absorption properties between calibration quality and the quality in the users' (192)Ir beam and for the use of a PMMA phantom instead of the water phantom underlying dose calculations in the TPS. Measured absorbed doses to water around the (192)Ir source were overestimated by 5% compared to those calculated by the TPS. Corresponding absorbed doses to water measured in a previous work with lithium formate electron paramagnetic resonance (EPR) dosimeters by Antonovic et al. [Med. Phys. 36, 2236-2247 (2009)], using the same irradiation setup and calibration procedure as in this work, were 2% lower than those calculated by the TPS. The results obtained in the measurements in this work and those obtained using the EPR lithium formate dosimeters were, within the expanded (k = 2) uncertainty, in agreement with the values derived by the TPS. The discrepancy between the results using LiF:Mg,Ti TLDs and the EPR lithium formate dosimeters was, however, statistically significant and in agreement with the difference in relative detector responses found for the two detector systems by Carlsson Tedgren et al. [Med. Phys. 38, 5539-5550 (2011)] and by Adolfsson et al. [Med. Phys. 37, 4946-4959 (2010)]. When calibrated in (60)Co or MV photon beams, correction for the linear energy transfer (LET) dependence of LiF:Mg,Ti detector response will be needed as to measure absorbed doses to water in a (192)Ir beam with highest accuracy. Such corrections will depend on the manufacturing process (MTS-N Poland or Harshaw TLD-100) and details of the annealing and read-out schemes used.

Development and validation of a GEANT4 radiation transport code for CT dosimetry

PubMed Central

Carver, DE; Kost, SD; Fernald, MJ; Lewis, KG; Fraser, ND; Pickens, DR; Price, RR; Stabin, MG

2014-01-01

We have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate our simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air, a standard 16-cm acrylic head phantom, and a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of our Monte Carlo simulations. We found that simulated and measured CTDI values were within an overall average of 6% of each other. PMID:25706135

Development and validation of a GEANT4 radiation transport code for CT dosimetry.

PubMed

Carver, D E; Kost, S D; Fernald, M J; Lewis, K G; Fraser, N D; Pickens, D R; Price, R R; Stabin, M G

2015-04-01

The authors have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate their simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air with a standard 16-cm acrylic head phantom and with a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of the Monte Carlo simulations. It was found that simulated and measured CTDI values were within an overall average of 6% of each other.

Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

USGS Publications Warehouse

Vyas, Nimish B.; Rattner, Barnett A.

2012-01-01

Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

SU-F-T-274: Modified Dose Calibration Methods for IMRT QA

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

Luo, W; Westlund, S

2016-06-15

Purpose: To investigate IMRT QA uncertainties caused by dose calibration and modify widely used dose calibration procedures to improve IMRT QA accuracy and passing rate. Methods: IMRT QA dose measurement is calibrated using a calibration factor (CF) that is the ratio between measured value and expected value corresponding to the reference fields delivered on a phantom. Two IMRT QA phantoms were used for this study: a 30×30×30 cm3 solid water cube phantom (Cube), and the PTW Octavius phantom. CF was obtained by delivering 100 MUs to the phantoms with different reference fields ranging from 3×3 cm2 to 20×20 cm{sup 2}.more » For Cube, CFs were obtained using the following beam arrangements: 2-AP Field - chamber at dmax, 2-AP Field - chamber at isocenter, 4-beam box - chamber at isocenter, and 8 equally spaced fields and chamber at isocenter. The same plans were delivered on Octavius and CFs were derived for the dose at the isocenter using the above beam arrangements. The Octavius plans were evaluated with PTW-VeriSoft (Gamma criteria of 3%/3mm). Results: Four head and neck IMRT plans were included in this study. For point dose measurement with Cube, the CFs with 4-Field gave the best agreement between measurement and calculation within 4% for large field plans. All the measurement results agreed within 2% for a small field plan. Compared with calibration field sizes, 5×5 to 15×15 were more accurate than other field sizes. For Octavius, 4-Field calibration increased passing rate by up to 10% compared to AP calibration. Passing rate also increased by up to 4% with the increase of field size from 3×3 to 20×20. Conclusion: IMRT QA results are correlated with calibration methods used. The dose calibration using 4-beam box with field sizes from 5×5 to 20×20 can improve IMRT QA accuracy and passing rate.« less

RBE, reference RBE and clinical RBE: applications of these concepts in hadron therapy.

PubMed

Wambersie, A

1999-06-01

Introduction of heavy particles (hadrons) into radiation therapy aims at improving the physical selectivity of the irradiation (e.g. proton beams), or the radiobiological differential effect (e.g. fast neutrons), or both (e.g. heavy-ion beams). Each of these new therapy modalities requires several types of information before prescribing safely the doses to patients, as well as for recording and reporting the treatments: (i) absorbed dose measured in a homogeneous phantom in reference conditions; (ii) dose distribution computed at the level of the target volume(s) and the normal tissues at risk; (iii) radiation quality from which a RBE evaluation could be predicted and (iv) RBE measured on biological systems or derived from clinical observation. In hadron therapy, the RBE of the different beams raises specific problems. For fast neutrons, the RBE varies within wide limits (about 2 to 5) depending on the neutron energy spectrum, dose, and biological system. For protons, the RBE values range between smaller limits (about 1.0 to 1.2). A clinical benefit can thus not be expected from RBE differences. However, the proton RBE problem cannot be ignored since dose differences of about 5% can be detected clinically in some cases. The situation is most complex with heavy ions since RBE variations are at least as large as for fast neutrons, as a function of particle type and energy, dose and biological system. In addition, RBE varies with depth. Radiation quality thus has to be taken into account when prescribing and reporting a treatment. This can be done in different ways: (a) description of the method of beam production; (b) computed LET spectra and/or measured microdosimetric spectra at the points clinically relevant; (c) RBE determination. The most relevant RBE data are those obtained for late tolerance of normal tissues at 2 Gy per fraction ("reference RBE"). The "clinical RBE" selected by the radiation oncologist when prescribing the treatment will be close to the reference RBE, but other factors (such as heterogeneity in dose distribution) may influence the selection of the clinical RBE. Combination of microdosimetric data and experimental RBE values improves the confidence in both sets of data.

Mechanistic link between uptake of sulfonamides and bacteriostatic effect: model development and application to experimental data from two soil microorganisms.

PubMed

Focks, Andreas; Klasmeier, Jörg; Matthies, Michael

2010-07-01

Sulfonamides (SA) are antibiotic compounds that are widely used as human and veterinary pharmaceuticals. They are not rapidly biodegradable and have been detected in various environmental compartments. Effects of sulfonamides on microbial endpoints in soil have been reported from laboratory incubation studies. Sulfonamides inhibit the growth of sensitive microorganisms by competitive binding to the dihydropteroate-synthase (DHPS) enzyme of folic acid production. A mathematical model was developed that relates the extracellular SA concentration to the inhibition of the relative bacterial growth rate. Two factors--the anionic accumulation factor (AAF) and the cellular affinity factor (CAF)--determine the effective concentration of an SA. The AAF describes the SA uptake into bacterial cells and varies with both the extra- and intracellular pH values and with the acidic pKa value of an SA. The CAF subsumes relevant cellular and enzyme properties, and is directly proportional to the DHPS affinity constant for an SA. Based on the model, a mechanistic dose-response relationship is developed and evaluated against previously published data, where differences in the responses of Pseudomonas aeruginosa and Panthoea agglomerans toward changing medium pH values were found, most likely as a result of their diverse pH regulation. The derived dose-response relationship explains the pH and pKa dependency of mean effective concentration values (EC50) of eight SA and two soil bacteria based on AAF and CAF values. The mathematical model can be used to extrapolate sulfonamide effects to other pH values and to calculate the CAF as a pH-independent measure for the SA effects on microbial growth. Copyright (c) 2010 SETAC.

SU-E-T-504: Intensity-Modulated Radiosurgery Treatments Derived by Optimizing Delivery of Sphere Packing Treatment Plans

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

Hermansen, M; Bova, F; John, T St.

2015-06-15

Purpose To minimize the number of monitor units required to deliver a sphere packing stereotactic radiosurgery (SRS) plan by eliminating overlaps of individual beam projections. Methods An algorithm was written in C{sup ++} to calculate SRS treatment doses using sphere packing. Three fixed beams were used to approximate each arc in a typical SRS treatment plan. For cases involving multiple isocenters, at each gantry and table angle position beams directed to individual spheres overlap to produce regions of high dose, resulting in intensity modulated beams. These high dose regions were dampened by post-processing of the combined beam profile. The post-processmore » dampening involves removing the excess overlapping fluence from all but the highest contributing beam. The dampened beam profiles at each table and gantry angle position were then summed to produce the new total dose distribution. Results Delivery times for even the most complex multiple sphere plans can be reduced to consistent times of about 20 to 30 minutes. The total MUs required to deliver the plan can also be reduced by as much as 85% of the original plan’s MUs. Conclusion Regions of high dose are removed. Dampening overlapping radiation fluence can produce the new beam profiles that have more uniform dose distributions using less MUs. This results in a treatment that requires significantly fewer intensity values than traditional IMRT or VAMT planning.« less

Variability and Reproducibility of 3rd-generation dual-source dynamic volume perfusion CT Parameters in Comparison to MR-perfusion Parameters in Rectal Cancer.

PubMed

Sudarski, Sonja; Henzler, Thomas; Floss, Teresa; Gaa, Tanja; Meyer, Mathias; Haubenreisser, Holger; Schoenberg, Stefan O; Attenberger, Ulrike I

2018-05-02

To compare in patients with untreated rectal cancer quantitative perfusion parameters calculated from 3 rd -generation dual-source dynamic volume perfusion CT (dVPCT) with 3-Tesla-MR-perfusion with regard to data variability and tumour differentiation. In MR-perfusion, plasma flow (PF), plasma volume (PV) and mean transit time (MTT) were assessed in two measurements (M1 and M2) by the same reader. In dVPCT, blood flow (BF), blood volume (BV), MTT and permeability (PERM) were assessed respectively. CT dose values were calculated. 20 patients (60 ± 13 years) were analysed. Intra-individual and intra-reader variability of duplicate MR-perfusion measurements was higher compared to duplicate dVPCT measurements. dVPCT-derived BF, BV and PERM could differentiate between tumour and normal rectal wall (significance level for M1 and M2, respectively, regarding BF: p < 0.0001*/0.0001*; BV: p < 0.0001*/0.0001*; MTT: p = 0.93/0.39; PERM: p < 0.0001*/0.0001*), with MR-perfusion this was true for PF and PV (p-values M1/M2 for PF: p = 0.04*/0.01*; PV: p = 0.002*/0.003*; MTT: p = 0.70/0.27*). Mean effective dose of CT-staging incl. dVPCT was 29 ± 6 mSv (20 ± 5 mSv for dVPCT alone). In conclusion, dVPCT has a lower data variability than MR-perfusion while both dVPCT and MR-perfusion could differentiate tumour tissue from normal rectal wall. With 3 rd -generation dual-source CT dVPCT could be included in a standard CT-staging without exceeding national dose reference values.

Regulating the risk of tuberculosis transmission among health care workers.

PubMed

Nicas, M

2000-01-01

The 1994 Centers for Disease Control and Prevention guidelines on preventing tuberculosis (TB) transmission among health care workers (HCWs), and the 1997 Occupational Safety and Health Administration (OSHA) proposed TB standard, do not address the issue of acceptable risk. Further, many infection control personnel oppose OSHA's promulgating a standard because they believe most TB infections among HCWs are nonoccupational in origin. This article examines the relationship between TB infection and disease rates, and introduces a probability framework to apportion infection risk between occupational and nonoccupational exposure. It is argued that most TB infections among HCWs are work-related. A 0.2% overall annual risk of TB infection (accounting for both workplace and community exposure) is proposed as acceptable, because in the context of an infection surveillance program it limits an HCW's cumulative disease risk close to the value for the general United States population. Based on the probability framework, an estimate of the background community infection rate, and the traditional Wells-Riley risk model, it is shown that a target workplace infection risk value can be derived and expressed in terms of an expected pulmonary dose. The latter target dose informs risk management decision-making.

Modeling intersubject variability of bronchial doses for inhaled radon progeny.

PubMed

Hofmann, Werner; Winkler-Heil, Renate; Hussain, Majid

2010-10-01

The main sources of intersubject variations considered in the present study were: (1) size and structure of nasal and oral passages, affecting extrathoracic deposition and, in further consequence, the fraction of the inhaled activity reaching the bronchial region; (2) size and asymmetric branching of the human bronchial airway system, leading to variations of diameters, lengths, branching angles, etc.; (3) respiratory parameters, such as tidal volume, and breathing frequency; (4) mucociliary clearance rates; and (5) thickness of the bronchial epithelium and depth of target cells, related to airway diameters. For the calculation of deposition fractions, retained surface activities, and bronchial doses, parameter values were randomly selected from their corresponding probability density functions, derived from experimental data, by applying Monte Carlo methods. Bronchial doses, expressed in mGy WLM-1, were computed for specific mining conditions, i.e., for defined size distributions, unattached fractions, and physical activities. Resulting bronchial dose distributions could be approximated by lognormal distributions. Geometric standard deviations illustrating intersubject variations ranged from about 2 in the trachea to about 7 in peripheral bronchiolar airways. The major sources of the intersubject variability of bronchial doses for inhaled radon progeny are the asymmetry and variability of the linear airway dimensions, the filtering efficiency of the nasal passages, and the thickness of the bronchial epithelium, while fluctuations of the respiratory parameters and mucociliary clearance rates seem to compensate each other.

SU-C-207-02: A Method to Estimate the Average Planar Dose From a C-Arm CBCT Acquisition

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

Supanich, MP

2015-06-15

Purpose: The planar average dose in a C-arm Cone Beam CT (CBCT) acquisition had been estimated in the past by averaging the four peripheral dose measurements in a CTDI phantom and then using the standard 2/3rds peripheral and 1/3 central CTDIw method (hereafter referred to as Dw). The accuracy of this assumption has not been investigated and the purpose of this work is to test the presumed relationship. Methods: Dose measurements were made in the central plane of two consecutively placed 16cm CTDI phantoms using a 0.6cc ionization chamber at each of the 4 peripheral dose bores and in themore » central dose bore for a C-arm CBCT protocol. The same setup was scanned with a circular cut-out of radiosensitive gafchromic film positioned between the two phantoms to capture the planar dose distribution. Calibration curves for color pixel value after scanning were generated from film strips irradiated at different known dose levels. The planar average dose for red and green pixel values was calculated by summing the dose values in the irradiated circular film cut out. Dw was calculated using the ionization chamber measurements and film dose values at the location of each of the dose bores. Results: The planar average dose using both the red and green pixel color calibration curves were within 10% agreement of the planar average dose estimated using the Dw method of film dose values at the bore locations. Additionally, an average of the planar average doses calculated using the red and green calibration curves differed from the ionization chamber Dw estimate by only 5%. Conclusion: The method of calculating the planar average dose at the central plane of a C-arm CBCT non-360 rotation by calculating Dw from peripheral and central dose bore measurements is a reasonable approach to estimating the planar average dose. Research Grant, Siemens AG.« less

Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS

PubMed Central

Madigan, Nicolas N.; Morris, Jonathan; Jentoft, Mark; Sorenson, Eric J.; Butler, Greg; Gastineau, Dennis; Dietz, Allan; Windebank, Anthony J.

2016-01-01

Objective: To determine the safety of intrathecal autologous adipose-derived mesenchymal stromal cell treatment for amyotrophic lateral sclerosis (ALS). Methods: Participants with ALS were enrolled and treated in this phase I dose-escalation safety trial, ranging from 1 × 107 (single dose) to 1 × 108 cells (2 monthly doses). After intrathecal treatments, participants underwent standardized follow-up, which included clinical examinations, revised ALS Functional Rating Scale (ALSFRS-R) questionnaire, blood and CSF sampling, and MRI of the neuroaxis. Results: Twenty-seven patients with ALS were enrolled and treated in this study. The safety profile was positive, with the most common side effects reported being temporary low back and radicular leg pain at the highest dose level. These clinical findings were associated with elevated CSF protein and nucleated cells with MRI of thickened lumbosacral nerve roots. Autopsies from 4 treated patients did not show evidence of tumor formation. Longitudinal ALSFRS-R questionnaires confirmed continued progression of disease in all treated patients. Conclusions: Intrathecal treatment of autologous adipose-derived mesenchymal stromal cells appears safe at the tested doses in ALS. These results warrant further exploration of efficacy in phase II trials. Classification of evidence: This phase I study provides Class IV evidence that in patient with ALS, intrathecal autologous adipose-derived mesenchymal stromal cell therapy is safe. PMID:27784774

Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

NASA Astrophysics Data System (ADS)

Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

2009-02-01

This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p < 3.323E-08) and 200 μL dose (p < 0.0007396). Discussion: In this preliminary study, the 150 μL Gd-DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

Ultraviolet radiation exposure of children and adolescents in Durban, South Africa.

PubMed

Guy, Caradee; Diab, Roseanne; Martincigh, Bice

2003-03-01

The solar ultraviolet radiation (UVR) exposure of 30 children and adolescents in three age groups (4-6 years, 7-9 years and 13-14 years) was measured for 1 week in late summer (February-March) in Durban, South Africa, using UVR-sensitive polysulfone film badges (PSFB) attached to the lapel region of the body. The mean and median values for all ages over the study period were 2.0 and 1.2 standard erythemal dose (SED) units, respectively, where 1 SED = 100 J x m(-2). Individual PSFB doses were analyzed as a function of age, gender and behavior. No significant statistical differences were found between different age groups; however, there was a statistical difference between males and females, with males generally receiving higher PSFB doses. Subjects completed UVR exposure journals documenting their time outdoors, shade versus sun conditions, nature of their activities, clothing worn and their use of sunscreen for each day of the study. Activity patterns were noted as the most important factor influencing individual UVR dose. Ambient erythemal UVR was measured by a Yankee Environmental Systems UVB pyranometer, and a relationship between ambient UVR and individual UVR dose was derived. On average, subjects received a dose of 4.6% of the total daily erythemal UVR. Based on this factor, the potential dose of an individual over a full annual cycle was estimated. Accordingly, there were 139 days during the year when an individual with skin type I (light skin) would be likely to experience minimal erythema and 97 and 32 days for individuals with skin types II and III, respectively.

Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis: in silico evaluation of currently recommended doses.

PubMed

Zvada, Simbarashe P; Denti, Paolo; Donald, Peter R; Schaaf, H Simon; Thee, Stephanie; Seddon, James A; Seifart, Heiner I; Smith, Peter J; McIlleron, Helen M; Simonsson, Ulrika S H

2014-05-01

To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators. Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing.

Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

PubMed Central

Kuempel, Eileen D.; Sweeney, Lisa M.; Morris, John B.; Jarabek, Annie M.

2015-01-01

The purpose of this article is to provide an overview and practical guide to occupational health professionals concerning the derivation and use of dose estimates in risk assessment for development of occupational exposure limits (OELs) for inhaled substances. Dosimetry is the study and practice of measuring or estimating the internal dose of a substance in individuals or a population. Dosimetry thus provides an essential link to understanding the relationship between an external exposure and a biological response. Use of dosimetry principles and tools can improve the accuracy of risk assessment, and reduce the uncertainty, by providing reliable estimates of the internal dose at the target tissue. This is accomplished through specific measurement data or predictive models, when available, or the use of basic dosimetry principles for broad classes of materials. Accurate dose estimation is essential not only for dose-response assessment, but also for interspecies extrapolation and for risk characterization at given exposures. Inhalation dosimetry is the focus of this paper since it is a major route of exposure in the workplace. Practical examples of dose estimation and OEL derivation are provided for inhaled gases and particulates. PMID:26551218

Mollolide A, a diterpenoid with a new 1,10:2,3-disecograyanane skeleton from the roots of Rhododendron molle.

PubMed

Li, Yong; Liu, Yun-Bao; Zhang, Jian-Jun; Li, Yu-Huan; Jiang, Jian-Dong; Yu, Shi-Shan; Ma, Shuang-Gang; Qu, Jing; Lv, Hai-Ning

2013-06-21

Mollolide A (1), a diterpenoid featuring a new 1,10:2,3-disecograyanane skeleton, was isolated from the roots of Rhododendron molle. Its structure was elucidated through extensive MS, IR, and NMR spectroscopy analyses. The absolute configuration was determined by single-crystal X-ray diffraction of its p-bromobenzoate derivative (1b). Compound 1 exhibits a significant analgesic effect at a dose of 20 mg/kg and antiviral activity against the Coxsackie B3 virus with an IC50 value of 27.7 μM.

Helical Tomotherapy for Whole-Brain Irradiation With Integrated Boost to Multiple Brain Metastases: Evaluation of Dose Distribution Characteristics and Comparison With Alternative Techniques

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

Levegrün, Sabine, E-mail: sabine.levegruen@uni-due.de; Pöttgen, Christoph; Wittig, Andrea

2013-07-15

Purpose: To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques. Methods and Materials: Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (N{sub mets}) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTV{sub mets}) and of the individual metastasis planning target volume (PTV{sub ind} {sub met}) were 8.7 ± 8.9 cm{sup 3} (range, 1.3-35.5more » cm{sup 3}) and 2.5 ± 4.5 cm{sup 3} (range, 0.19-24.7 cm{sup 3}), respectively. Dose distributions in PTV{sub mets} and PTV{sub ind} {sub met} were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and N{sub mets} was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review. Results: Mean ± standard deviation of dose distribution characteristics derived for PTV{sub mets} amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTV{sub ind} {sub met} were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTV{sub mets} (CN = 0.737 for PTV{sub mets} ≤4.32 cm{sup 3} vs CN = 0.848 for PTV{sub mets} >4.32 cm{sup 3}, P=.006), in contrast to N{sub mets}. The achieved dose conformity to PTV{sub mets}, assessed by both CN and PITV, was in all investigated volume strata well within the best quartile of the values reported for alternative irradiation techniques. Conclusions: HT is a well-suited technique to deliver WBRT with IB to multiple brain metastases, yielding high-quality dose distributions. A multi-institutional prospective randomized phase 2 clinical trial to exploit efficacy and safety of the treatment concept is currently under way.« less

Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study.

PubMed

Ehmann, Lisa; Zoller, Michael; Minichmayr, Iris K; Scharf, Christina; Maier, Barbara; Schmitt, Maximilian V; Hartung, Niklas; Huisinga, Wilhelm; Vogeser, Michael; Frey, Lorenz; Zander, Johannes; Kloft, Charlotte

2017-10-21

Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCR CG ). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T >MIC , 50%T >4×MIC ) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCR CG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T >MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T >4×MIC . A hyperbolic relationship between CLCR CG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C 8h ) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment). The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy- and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed. Clinicaltrials.gov, NCT01793012 . Registered on 24 January 2013.

Improved in silico prediction of carcinogenic potency (TD50) and the risk specific dose (RSD) adjusted Threshold of Toxicological Concern (TTC) for genotoxic chemicals and pharmaceutical impurities.

PubMed

Contrera, Joseph F

2011-02-01

The Threshold of Toxicological Concern (TTC) is a level of exposure to a genotoxic impurity that is considered to represent a negligible risk to humans. The TTC was derived from the results of rodent carcinogenicity TD50 values that are a measure of carcinogenic potency. The TTC currently sets a default limit of 1.5 μg/day in food contact substances and pharmaceuticals for all genotoxic impurities without carcinogenicity data. Bercu et al. (2010) used the QSAR predicted TD50 to calculate a risk specific dose (RSD) which is a carcinogenic potency adjusted TTC for genotoxic impurities. This promising approach is currently limited by the software used, a combination of MC4PC (www.multicase.com) and a Lilly Inc. in-house software (VISDOM) that is not available to the public. In this report the TD50 and RSD were predicted using a commercially available software, SciQSAR (formally MDL-QSAR, www.scimatics.com) employing the same TD50 training data set and external validation test set that was used by Bercu et al. (2010). The results demonstrate the general applicability of QSAR predicted TD50 values to determine the RSDs for genotoxic impurities and the improved performance of SciQSAR for predicting TD50 values. Copyright © 2010 Elsevier Inc. All rights reserved.

The protective effect of autophagy on mouse spermatocyte derived cells exposure to 1800MHz radiofrequency electromagnetic radiation.

PubMed

Liu, Kaijun; Zhang, Guowei; Wang, Zhi; Liu, Yong; Dong, Jianyun; Dong, Xiaomei; Liu, Jinyi; Cao, Jia; Ao, Lin; Zhang, Shaoxiang

2014-08-04

The increasing exposure to radiofrequency (RF) radiation emitted from mobile phone use has raised public concern regarding the biological effects of RF exposure on the male reproductive system. Autophagy contributes to maintaining intracellular homeostasis under environmental stress. To clarify whether RF exposure could induce autophagy in the spermatocyte, mouse spermatocyte-derived cells (GC-2) were exposed to 1800MHz Global System for Mobile Communication (GSM) signals in GSM-Talk mode at specific absorption rate (SAR) values of 1w/kg, 2w/kg or 4w/kg for 24h, respectively. The results indicated that the expression of LC3-II increased in a dose- and time-dependent manner with RF exposure, and showed a significant change at the SAR value of 4w/kg. The autophagosome formation and the occurrence of autophagy were further confirmed by GFP-LC3 transient transfection assay and transmission electron microscopy (TEM) analysis. Furthermore, the conversion of LC3-I to LC3-II was enhanced by co-treatment with Chloroquine (CQ), indicating autophagic flux could be enhanced by RF exposure. Intracellular ROS levels significantly increased in a dose- and time-dependent manner after cells were exposed to RF. Pretreatment with anti-oxidative NAC obviously decreased the conversion of LC3-I to LC3-II and attenuated the degradation of p62 induced by RF exposure. Meanwhile, phosphorylated extracellular-signal-regulated kinase (ERK) significantly increased after RF exposure at the SAR value of 2w/kg and 4w/kg. Moreover, we observed that RF exposure did not increase the percentage of apoptotic cells, but inhibition of autophagy could increase the percentage of apoptotic cells. These findings suggested that autophagy flux could be enhanced by 1800MHz GSM exposure (4w/kg), which is mediated by ROS generation. Autophagy may play an important role in preventing cells from apoptotic cell death under RF exposure stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Stopping-power ratios for clinical electron beams from a scatter-foil linear accelerator.

PubMed

Kapur, A; Ma, C M

1999-09-01

Restricted mass collision stopping-power ratios for electron beams from a scatter-foil medical linear accelerator (Varian Clinac 2100C) were calculated for various combinations of beams, phantoms and detector materials using the Monte Carlo method. The beams were of nominal energy 6, 12 or 20 MeV, with square dimensions 1 x 1 cm2 to 10 x 10 cm2. They were incident at nominal SSDs of 100 or 120 cm and inclined at 90 degrees or 30 degrees to the surface of homogeneous water phantoms or water phantoms interspersed with layered lung or bone-like materials. The broad beam water-to-air stopping-power ratios were within 1.3% of the AAPM TG21 protocol values and consistent with the results of Ding et al to within 0.2%. On the central axis the stopping-power ratio variations for narrow beams compared with normally incident broad beams were 0.1% or less for water-to-LiF-100, graphite, ferrous sulfate dosimeter solution, polystyrene and PMMA, 0.5% for water-to-silicon and 1% for water-to-air and water-to-photographic-film materials. The transverse variations of the stopping-power ratios were up to 4% for water-to-silicon, 7% for water-to-photographic-film materials and 10% for water-to-air in the penumbral regions (where the dose was 10% of the global dose maximum) at shallow depths compared with the values at the same depths on the central axis. In the inhomogeneous phantoms studied, the stopping-power ratio correction factors varied more significantly for air, followed by photographic materials and silicon, at various depths on the central axis in the heterogeneous regions. For the simple layered phantoms studied, the estimation of the stopping-power ratio correction factors based on the relative electron-density derived effective depth approach yielded results that were within 0.5% of the Monte Carlo derived values for all the detector materials studied.

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

Sanchez-Nieto, Beatriz, E-mail: bsanchez@fis.puc.cl; Goset, Karen C.; Caviedes, Ivan

Purpose: To propose multivariate predictive models for changes in pulmonary function tests ({Delta}PFTs) with respect to preradiotherapy (pre-RT) values in patients undergoing RT for breast cancer and lymphoma. Methods and Materials: A prospective study was designed to measure {Delta}PFTs of patients undergoing RT. Sixty-six patients were included. Spirometry, lung capacity (measured by helium dilution), and diffusing capacity of carbon monoxide tests were used to measure lung function. Two lung definitions were considered: paired lung vs. irradiated lung (IL). Correlation analysis of dosimetric parameters (mean lung dose and the percentage of lung volume receiving more than a threshold dose) and {Delta}PFTsmore » was carried out to find the best dosimetric predictor. Chemotherapy, age, smoking, and the selected dose-volume parameter were considered as single and interaction terms in a multivariate analysis. Stability of results was checked by bootstrapping. Results: Both lung definitions proved to be similar. Modeling was carried out for IL. Acute and late damage showed the highest correlations with volumes irradiated above {approx}20 Gy (maximum R{sup 2} = 0.28) and {approx}40 Gy (maximum R{sup 2} = 0.21), respectively. RT alone induced a minor and transitory restrictive defect (p = 0.013). Doxorubicin-cyclophosphamide-paclitaxel (Taxol), when administered pre-RT, induced a late, large restrictive effect, independent of RT (p = 0.031). Bootstrap values confirmed the results. Conclusions: None of the dose-volume parameters was a perfect predictor of outcome. Thus, different predictor models for {Delta}PFTs were derived for the IL, which incorporated other nondosimetric parameters mainly through interaction terms. Late {Delta}PFTs seem to behave more serially than early ones. Large restrictive defects were demonstrated in patients pretreated with doxorubicin-cyclophosphamide-paclitaxel.« less

In vivo labeling of phencyclidine (PCP) receptors with sup 3 H-TCP in the mouse brain

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

Maurice, T.; Vignon, J.

1990-07-01

The phencyclidine (PCP) derivative N-(1-(2-thienyl)cyclohexyl)-piperidine (3H-TCP) was used to label in vivo the N-methyl-D-aspartate (NMDA) receptor-associated ionic channel in the mouse brain. After the injection of a tracer dose of 3H-TCP, a spread labeling throughout the brain was observed, but was the highest in the cerebellum. Preadministration of unlabeled TCP (30 mg/kg) resulted in a 90% reduction of 3H-TCP binding. PCP, TCP, MK-801, dexoxadrol, ketamine, and SKF 10,047 isomers dose-dependently prevented the in vivo 3H-TCP binding. ID50 determined in the cerebrum and the cerebellum were respectively correlated with K0.5 for 3H TCP high (rat cortex) and low affinity (rat cerebellum)more » sites in vitro. The pharmacological specificity of the 3H-TCP binding site in the cerebellum was significantly different from that in the cerebrum. ID50 values were generally higher than in the cerebrum and, particularly, MK-801, the most potent drug in the cerebrum, was without significant effect in the cerebellum, at any time and at doses as high as 30 mg/kg. N-(1-(2-benzo(b) thiophenyl)cyclohexyl)piperidine (BTCP), desipramine, and atropine showed a more efficient prevention of 3H-TCP binding in the cerebellum than in the cerebrum. The prevention of the binding by TCP or PCP, at doses close to their ID50 values, was rapid and then decreased slowly. The effect of MK-801 was long-lasting. This study confirm previous in vitro studies: 3H-TCP is an efficient tool for the labeling of the NMDA receptor-associated ionic channel.« less

Single-dose toxicokinetics of permethrin in broiler chickens.

PubMed

Gögebakan, T; Eraslan, G

2015-01-01

Single-dose toxicokinetics of permethrin was investigated in broiler chickens. A total of 20 male broiler chickens were assigned at random to two groups of 10 at 30 days of age. A single dose of 10 mg/kg body weight of permethrin was administered intravenously to the first group; in the second group, the same dose was administered into the crop. Serum permethrin was measured using an electron capture detector and gas chromatography equipment. The derived serum permethrin concentration/time curve demonstrated that the distribution kinetics of permethrin was well described by a two-compartment open model. For intravenous permethrin administration, the half-life at λ phase (t1/2λ), mean residence time (MRT) and area under the concentration-time curve in 0→∞ (AUC0→∞) values respectively were 4.73 ± 1.00 h, 5.06 ± 1.05 h and 16.45 ± 3.28 mg/h/l. In contrast, the Cmax, tmax, t1/2λ, MRT and AUC0→∞ values respectively of the group given intra-crop permethrin were 0.60 ± 0.42 μg/ml, 0.55 ± 0.19 h, 5.54 ± 0.78 h, 7.06 ± 0.63 h and 1.95 ± 0.97 mg/h/l. The bioavailability of permethrin was 0.11. For both administration routes, the residence time of permethrin in the body was short and the bioavailability of permethrin was low. These results are relevant for assessing the use and safety of permethrin.

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.

Evaluation of radiation doses and associated risk from the Fukushima nuclear accident to marine biota and human consumers of seafood

PubMed Central

Fisher, Nicholas S.; Beaugelin-Seiller, Karine; Hinton, Thomas G.; Baumann, Zofia; Madigan, Daniel J.; Garnier-Laplace, Jacqueline

2013-01-01

Radioactive isotopes originating from the damaged Fukushima nuclear reactor in Japan following the earthquake and tsunami in March 2011 were found in resident marine animals and in migratory Pacific bluefin tuna (PBFT). Publication of this information resulted in a worldwide response that caused public anxiety and concern, although PBFT captured off California in August 2011 contained activity concentrations below those from naturally occurring radionuclides. To link the radioactivity to possible health impairments, we calculated doses, attributable to the Fukushima-derived and the naturally occurring radionuclides, to both the marine biota and human fish consumers. We showed that doses in all cases were dominated by the naturally occurring alpha-emitter 210Po and that Fukushima-derived doses were three to four orders of magnitude below 210Po-derived doses. Doses to marine biota were about two orders of magnitude below the lowest benchmark protection level proposed for ecosystems (10 µGy⋅h−1). The additional dose from Fukushima radionuclides to humans consuming tainted PBFT in the United States was calculated to be 0.9 and 4.7 µSv for average consumers and subsistence fishermen, respectively. Such doses are comparable to, or less than, the dose all humans routinely obtain from naturally occurring radionuclides in many food items, medical treatments, air travel, or other background sources. Although uncertainties remain regarding the assessment of cancer risk at low doses of ionizing radiation to humans, the dose received from PBFT consumption by subsistence fishermen can be estimated to result in two additional fatal cancer cases per 10,000,000 similarly exposed people. PMID:23733934

Electroencephalographic, behavioral and receptor binding correlates of phencyclinoids in the rat

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

Mattia, A.; Marquis, K.L.; Leccese, A.P.

1988-08-01

The pharmacology and structure-activity relationship of phencyclidine (PCP)-like drugs (phencyclinoids) were studied using electroencephalographic (EEG), behavioral and receptor binding techniques. The effects of PCP, 1-phenylcyclohexylamine HCl, N-methyl-1-phenycyclohexylamine HCl, N-ethyl-1-phenylcyclohexylamine HCl, N-(s-butyl)-1-phenylcyclohexylamine HCL, 1-(1-phenylcyclo-hexyl)-pyrrolidine HCl, 1-(1-(2-thienyl)cyclohexyl) piperidine HCl, 1-(1-(2-thienyl)cyclohexyl)-pyrrolidine HCl, ketamine and (+/-)-SKF 10047 were evaluated on the direct EEG and EEG spectra after acute i.v. injections (0.1-17.8 mg/kg). Similarities and differences were noted in the EEG dose-response curves. At lower doses of PCP and its analogs, low-amplitude theta waves predominated; however, at higher doses, high-amplitude, lower-frequency waves predominated. Qualitatively, the N-piperidine derivatives were similar to PCP and differed primarily inmore » potency. The benzomorphan (+/-)-SKF 10047 produced only theta activity at doses up to 12.8 mg/kg. These EEG effects occurred in conjunction with overt behaviors including locomotion, stereotypy and ataxia, concurrently assessed via observer-based rating scales. A strong correlation (r = 0.98) was obtained between the EEG and behavioral effects and the IC50 values from (/sup 3/H)PCP displacement experiments using crude rat brain homogenates.« less

Comparative risk assessment of tobacco smoke constituents using the margin of exposure approach: the neglected contribution of nicotine

PubMed Central

Baumung, Claudia; Rehm, Jürgen; Franke, Heike; Lachenmeier, Dirk W.

2016-01-01

Nicotine was not included in previous efforts to identify the most important toxicants of tobacco smoke. A health risk assessment of nicotine for smokers of cigarettes was conducted using the margin of exposure (MOE) approach and results were compared to literature MOEs of various other tobacco toxicants. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Dose-response modelling of human and animal data was used to derive the benchmark dose. The MOE was calculated using probabilistic Monte Carlo simulations for daily cigarette smokers. Benchmark dose values ranged from 0.004 mg/kg bodyweight for symptoms of intoxication in children to 3 mg/kg bodyweight for mortality in animals; MOEs ranged from below 1 up to 7.6 indicating a considerable consumer risk. The dimension of the MOEs is similar to those of other tobacco toxicants with high concerns relating to adverse health effects such as acrolein or formaldehyde. Owing to the lack of toxicological data in particular relating to cancer, long term animal testing studies for nicotine are urgently necessary. There is immediate need of action concerning the risk of nicotine also with regard to electronic cigarettes and smokeless tobacco. PMID:27759090

External radiation in Dolon village due to local fallout from the first USSR atomic bomb test in 1949.

PubMed

Imanaka, Tetsuji; Fukutani, Satoshi; Yamamoto, Masayoshi; Sakaguchi, Aya; Hoshi, Masaharu

2006-02-01

Dolon village, located about 60 km from the border of the Semipalatinsk Nuclear Test Site, is known to be heavily contaminated by local fallout from the first USSR atomic bomb test in 1949. External radiation in Dolon was evaluated based on recent 137Cs data in soil and calculation of temporal change in the fission product composition. After fitting a log-normal distribution to the soil data, a 137Cs deposition of 32 kBq m-2, which corresponds to the 90th-percentile of the distribution, was tentatively chosen as a value to evaluate the radiation situation in 1949. Our calculation indicated that more than 95% of the cumulative dose for 50 y had been delivered within 1 y after the deposition. The resulting cumulative dose for 1 y after the deposition, normalized to the initial contamination containing 1 kBq m-2 of 137Cs, was 15.6 mGy, assuming a fallout arrival time of 3 h and a medium level of fractionation. Finally, 0.50 Gy of absorbed dose in air was derived as our tentative estimate for 1-year cumulative external dose in Dolon due to local fallout from the first USSR test in 1949.

Low-dose intradermal and intramuscular vaccination against hepatitis B.

PubMed

Bryan, J P; Sjogren, M H; Perine, P L; Legters, L J

1992-03-01

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Computational lymphatic node models in pediatric and adult hybrid phantoms for radiation dosimetry

NASA Astrophysics Data System (ADS)

Lee, Choonsik; Lamart, Stephanie; Moroz, Brian E.

2013-03-01

We developed models of lymphatic nodes for six pediatric and two adult hybrid computational phantoms to calculate the lymphatic node dose estimates from external and internal radiation exposures. We derived the number of lymphatic nodes from the recommendations in International Commission on Radiological Protection (ICRP) Publications 23 and 89 at 16 cluster locations for the lymphatic nodes: extrathoracic, cervical, thoracic (upper and lower), breast (left and right), mesentery (left and right), axillary (left and right), cubital (left and right), inguinal (left and right) and popliteal (left and right), for different ages (newborn, 1-, 5-, 10-, 15-year-old and adult). We modeled each lymphatic node within the voxel format of the hybrid phantoms by assuming that all nodes have identical size derived from published data except narrow cluster sites. The lymph nodes were generated by the following algorithm: (1) selection of the lymph node site among the 16 cluster sites; (2) random sampling of the location of the lymph node within a spherical space centered at the chosen cluster site; (3) creation of the sphere or ovoid of tissue representing the node based on lymphatic node characteristics defined in ICRP Publications 23 and 89. We created lymph nodes until the pre-defined number of lymphatic nodes at the selected cluster site was reached. This algorithm was applied to pediatric (newborn, 1-, 5-and 10-year-old male, and 15-year-old males) and adult male and female ICRP-compliant hybrid phantoms after voxelization. To assess the performance of our models for internal dosimetry, we calculated dose conversion coefficients, called S values, for selected organs and tissues with Iodine-131 distributed in six lymphatic node cluster sites using MCNPX2.6, a well validated Monte Carlo radiation transport code. Our analysis of the calculations indicates that the S values were significantly affected by the location of the lymph node clusters and that the values increased for smaller phantoms due to the shorter inter-organ distances compared to the bigger phantoms. By testing sensitivity of S values to random sampling and voxel resolution, we confirmed that the lymph node model is reasonably stable and consistent for different random samplings and voxel resolutions.

Task-based image quality evaluation of iterative reconstruction methods for low dose CT using computer simulations

NASA Astrophysics Data System (ADS)

Xu, Jingyan; Fuld, Matthew K.; Fung, George S. K.; Tsui, Benjamin M. W.

2015-04-01

Iterative reconstruction (IR) methods for x-ray CT is a promising approach to improve image quality or reduce radiation dose to patients. The goal of this work was to use task based image quality measures and the channelized Hotelling observer (CHO) to evaluate both analytic and IR methods for clinical x-ray CT applications. We performed realistic computer simulations at five radiation dose levels, from a clinical reference low dose D0 to 25% D0. A fixed size and contrast lesion was inserted at different locations into the liver of the XCAT phantom to simulate a weak signal. The simulated data were reconstructed on a commercial CT scanner (SOMATOM Definition Flash; Siemens, Forchheim, Germany) using the vendor-provided analytic (WFBP) and IR (SAFIRE) methods. The reconstructed images were analyzed by CHOs with both rotationally symmetric (RS) and rotationally oriented (RO) channels, and with different numbers of lesion locations (5, 10, and 20) in a signal known exactly (SKE), background known exactly but variable (BKEV) detection task. The area under the receiver operating characteristic curve (AUC) was used as a summary measure to compare the IR and analytic methods; the AUC was also used as the equal performance criterion to derive the potential dose reduction factor of IR. In general, there was a good agreement in the relative AUC values of different reconstruction methods using CHOs with RS and RO channels, although the CHO with RO channels achieved higher AUCs than RS channels. The improvement of IR over analytic methods depends on the dose level. The reference dose level D0 was based on a clinical low dose protocol, lower than the standard dose due to the use of IR methods. At 75% D0, the performance improvement was statistically significant (p < 0.05). The potential dose reduction factor also depended on the detection task. For the SKE/BKEV task involving 10 lesion locations, a dose reduction of at least 25% from D0 was achieved.

Quantitative imaging of peripheral trabecular bone microarchitecture using MDCT.

PubMed

Chen, Cheng; Zhang, Xiaoliu; Guo, Junfeng; Jin, Dakai; Letuchy, Elena M; Burns, Trudy L; Levy, Steven M; Hoffman, Eric A; Saha, Punam K

2018-01-01

Osteoporosis associated with reduced bone mineral density (BMD) and microarchitectural changes puts patients at an elevated risk of fracture. Modern multidetector row CT (MDCT) technology, producing high spatial resolution at increasingly lower dose radiation, is emerging as a viable modality for trabecular bone (Tb) imaging. Wide variation in CT scanners raises concerns of data uniformity in multisite and longitudinal studies. A comprehensive cadaveric study was performed to evaluate MDCT-derived Tb microarchitectural measures. A human pilot study was performed comparing continuity of Tb measures estimated from two MDCT scanners with significantly different image resolution features. Micro-CT imaging of cadaveric ankle specimens (n=25) was used to examine the validity of MDCT-derived Tb microarchitectural measures. Repeat scan reproducibility of MDCT-based Tb measures and their ability to predict mechanical properties were examined. To assess multiscanner data continuity of Tb measures, the distal tibias of 20 volunteers (age:26.2±4.5Y,10F) were scanned using the Siemens SOMATOM Definition Flash and the higher resolution Siemens SOMATOM Force scanners with an average 45-day time gap between scans. The correlation of Tb measures derived from the two scanners over 30% and 60% peel regions at the 4% to 8% of distal tibia was analyzed. MDCT-based Tb measures characterizing bone network area density, plate-rod microarchitecture, and transverse trabeculae showed good correlations (r∈0.85,0.92) with the gold standard micro-CT-derived values of matching Tb measures. However, other MDCT-derived Tb measures characterizing trabecular thickness and separation, erosion index, and structure model index produced weak correlation (r<0.8) with their micro-CT-derived values. Most MDCT Tb measures were found repeatable (ICC∈0.94,0.98). The Tb plate-width measure showed a strong correlation (r = 0.89) with experimental yield stress, while the transverse trabecular measure produced the highest correlation (r = 0.81) with Young's modulus. The data continuity experiment showed that, despite significant differences in image resolution between two scanners (10% MTF along xy-plane and z-direction - Flash: 16.2 and 17.9 lp/cm; Force: 24.8 and 21.0 lp/cm), most Tb measures had high Pearson correlations (r > 0.95) between values estimated from the two scanners. Relatively lower correlation coefficients were observed for the bone network area density (r = 0.91) and Tb separation (r = 0.93) measures. Most MDCT-derived Tb microarchitectural measures are reproducible and their values derived from two scanners strongly correlate with each other as well as with bone strength. This study has highlighted those MDCT-derived measures which show the greatest promise for characterization of bone network area density, plate-rod and transverse trabecular distributions with a good correlation (r ≥ 0.85) compared with their micro-CT-derived values. At the same time, other measures representing trabecular thickness and separation, erosion index, and structure model index produced weak correlations (r < 0.8) with their micro-CT-derived values, failing to accurately portray the projected trabecular microarchitectural features. Strong correlations of Tb measures estimated from two scanners suggest that image data from different scanners can be used successfully in multisite and longitudinal studies with linear calibration required for some measures. In summary, modern MDCT scanners are suitable for effective quantitative imaging of peripheral Tb microarchitecture if care is taken to focus on appropriate quantitative metrics. © 2017 American Association of Physicists in Medicine.

The leaching of inorganic species from activated carbons produced from waste tyre rubber.

PubMed

San Miguel, G; Fowler, G D; Sollars, C J

2002-04-01

Waste tyre rubber can be used as a precursor for the production of high quality activated carbons. However, there is concern that inorganic impurities present in the rubber feed may restrict their use in liquid phase applications with high purity requirements. This paper presents an investigation of the presence and the leaching of inorganic species from activated carbons derived from waste tyre rubber. For the purpose of this work, a number of carbons were produced, characterised for their BET surface area and analysed for their inorganic composition. Subsequently, a number of tests were performed to evaluate the leaching of different inorganic species into solution at various pH values and carbon doses. Results showed that rubber-derived carbons contained elevated concentrations of sulphur and zinc, as well as traces of other metals such as lead, cadmium, chromium and molybdenum. Inorganic levels were significantly affected by production conditions, particularly degree of carbon activation and the nature of the gasification agent. However, leaching tests showed that the availability of these species in neutral pH conditions was very limited. Results demonstrated that, when using carbons doses comparable to those employed in water treatment works, only sulphur levels exceeded, in some occasions, health based quality standards proposed for drinking water.

New stomatal flux-based critical levels for ozone effects on vegetation

NASA Astrophysics Data System (ADS)

Mills, Gina; Pleijel, Håkan; Braun, Sabine; Büker, Patrick; Bermejo, Victoria; Calvo, Esperanza; Danielsson, Helena; Emberson, Lisa; Fernández, Ignacio González; Grünhage, Ludger; Harmens, Harry; Hayes, Felicity; Karlsson, Per-Erik; Simpson, David

2011-09-01

The critical levels for ozone effects on vegetation have been reviewed and revised by the LRTAP Convention. Eight new or revised critical levels based on the accumulated stomatal flux of ozone (POD Y, the Phytotoxic Ozone Dose above a threshold flux of Y nmol m -2 PLA s -1, where PLA is the projected leaf area) have been agreed. For each receptor, data were combined from experiments conducted under naturally fluctuating environmental conditions in 2-4 countries, resulting in linear dose-response relationships with response variables specific to each receptor ( r2 = 0.49-0.87, p < 0.001 for all). For crops, critical levels were derived for effects on wheat (grain yield, grain mass, and protein yield), potato (tuber yield) and tomato (fruit yield). For forest trees, critical levels were derived for effects on changes in annual increment in whole tree biomass for beech and birch, and Norway spruce. For (semi-)natural vegetation, the critical level for effects on productive and high conservation value perennial grasslands was based on effects on important component species of the genus Trifolium (clover species). These critical levels can be used to assess protection against the damaging effects of ozone on food security, important ecosystem services provided by forest trees (roundwood production, C sequestration, soil stability and flood prevention) and the vitality of pasture.

The impact on CT dose of the variability in tube current modulation technology: a theoretical investigation

NASA Astrophysics Data System (ADS)

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

2014-08-01

Body CT scans are routinely performed using tube-current-modulation (TCM) technology. There is notable variability across CT manufacturers in terms of how TCM technology is implemented. Some manufacturers aim to provide uniform image noise across body regions and patient sizes, whereas others aim to provide lower noise for smaller patients. The purpose of this study was to conduct a theoretical investigation to understand how manufacturer-dependent TCM scheme affects organ dose, and to develop a generic approach for assessing organ dose across TCM schemes. The adult reference female extended cardiac-torso (XCAT) phantom was used for this study. A ray-tracing method was developed to calculate the attenuation of the phantom for a given projection angle based on phantom anatomy, CT system geometry, x-ray energy spectrum, and bowtie filter filtration. The tube current (mA) for a given projection angle was then calculated as a log-linear function of the attenuation along that projection. The slope of this function, termed modulation control strength, α, was varied from 0 to 1 to emulate the variability in TCM technology. Using a validated Monte Carlo program, organ dose was simulated for five α values (α = 0, 0.25, 0.5, 0.75, and 1) in the absence and presence of a realistic system mA limit. Organ dose was further normalized by volume-weighted CT dose index (CTDIvol) to obtain conversion factors (h factors) that are relatively independent of system specifics and scan parameters. For both chest and abdomen-pelvis scans and for 24 radiosensitive organs, organ dose conversion factors varied with α, following second-order polynomial equations. This result suggested the need for α-specific organ dose conversion factors (i.e., conversion factors specific to the modulation scheme used). On the other hand, across the full range of α values, organ dose in a TCM scan could be derived from the conversion factors established for a fixed-mA scan (hFIXED). This was possible by multiplying hFIXED by a revised definition of CTDIvol that accounts for two factors: (a) the tube currents at the location of an organ and (b) the variation in organ volume along the longitudinal direction. This α-generic approach represents an approximation. The error associated with this approximation was evaluated using the α-specific organ dose (i.e., the organ dose obtained by using α-specific mA profiles as inputs into the Monte Carlo simulation) as the reference standard. When the mA profiles were constrained by a realistic system limit, this α-generic approach had errors of less than ~20% for the full range of α values. This was the case for 24 radiosensitive organs in both chest and abdomen-pelvis CT scans with the exception of thyroid in the chest scan and bladder in the abdomen-pelvis scan. For these two organs, the errors were less than ~40%. The results of this theoretical study suggested that knowing the mA modulation profile and the fixed-mA conversion factors, organ dose may be estimated for a TCM scan independent of the specific modulation scheme applied.

Dosimetric comparison between 10MV-FFF and 6MV-FFF for lung SBRT

NASA Astrophysics Data System (ADS)

Durmus, I. F.; Atalay, E. D.

2017-02-01

Plans were prepared by using same non-coplanar fields and physical parameters in 6MV-FFF and 10MV-FFF energies for fourteen lung Stereotactic Body Radio Therapy (SBRT) patients. In two plans which have different energies, critic organ doses, PTV doses, quality of plans (Gradient Index (GI), Homogeneity Index (HI), Conformity Index (CI)) and Monitor Unit (MU) values were compared. Quality controls were performed with 2D-Array Iba MatriXX Evolution® dosimetry system for each plans. As a results, plan with 6MV-FFF energy give better results in terms of CI and GI values. In this way, when more conformal dose distributions were provided, there was a rapid dose decrease at out of target volume. Lower MU values were obtained in plans which was prepared with 10MV-FFF energy. In plan with 10MV-FFF energy lower MU values are obtained. Lower values in heart and spinal cord doses are founded and better results are obtained in Body and Ipsa-Lung V5, V10, V20 values with 6MV-FFF energies. When differences were very small in volume which were taken low dose (V5), these differences increased in volume which were taken high dose (V20). High dose rates can be reached by both two unfiltered energies and can be used in lung SBRT.

Analgesic, antioedematous and antioxidant activity of γ-butyrolactone derivatives in rodents.

PubMed

Salat, Kinga; Librowski, Tadeusz; Moniczewski, Andrzej; Stanisz-Wallis, Krystyna; Wieckowski, Krzysztof; Malawska, Barbara

2012-08-01

In this paper, the analgesic, antioedematous, motor-impairing and antioxidant properties of four γ-butyrolactone derivatives (BM113, BM113A, BM138 and BM138A) are described. Pain was induced by thermal (hot-plate test), chemical (writhing test) or mechanical (Randall-Selitto model) stimulation. All in-vivo assays were carried out in mice pretreated intraperitoneally with the test compounds, except for the evaluation of anti-inflammatory and analgesic activities in the carrageenan-induced paw oedema model, in which rats were pretreated orally with these compounds. In the hot-plate assay, BM113A and BM138A dose dependently prolonged the latency of the nociceptive reaction. Their analgesic activity, measured as a median effective dose (ED(50)=4.7 mg/kg), was similar to that of morphine (2.4 mg/kg). In the writhing test, all four compounds, in particular BM113A and BM138A, showed higher potency than the reference drug acetylsalicylic acid (the ED(50) values were 3.7, 2.3 and 46.1 mg/kg, respectively). BM138 caused a dose-dependent diminution of paw oedema (up to 49%) in the carrageenan model and BM138A at 200 mg/kg reduced mechanical hyperalgesia in the Randall-Selitto test (∼30% when compared with the control). None of the γ-butyrolactone derivatives tested at the ED(50) obtained in the hot-plate test influenced the locomotor activity of mice, although in the rotarod test at 24 rpm, BM113A and BM138 at 100 mg/kg showed some motor-impairing properties. In vitro, a concentration-dependent ABTS radical cation-scavenging activity of BM138 and BM138A (up to 80% inhibition of the radical absorbance) was observed. The results of the present study suggest that BM138 and BM138A could be of interest for future investigations as antinociceptive and antioedematous agents with potential free radical-scavenging properties.

SU-F-I-41: Calibration-Free Material Decomposition for Dual-Energy CT

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

Zhao, W; Xing, L; Zhang, Q

2016-06-15

Purpose: To eliminate tedious phantom calibration or manually region of interest (ROI) selection as required in dual-energy CT material decomposition, we establish a new projection-domain material decomposition framework with incorporation of energy spectrum. Methods: Similar to the case of dual-energy CT, the integral of the basis material image in our model is expressed as a linear combination of basis functions, which are the polynomials of high- and low-energy raw projection data. To yield the unknown coefficients of the linear combination, the proposed algorithm minimizes the quadratic error between the high- and low-energy raw projection data and the projection calculated usingmore » material images. We evaluate the algorithm with an iodine concentration numerical phantom at different dose and iodine concentration levels. The x-ray energy spectra of the high and low energy are estimated using an indirect transmission method. The derived monochromatic images are compared with the high- and low-energy CT images to demonstrate beam hardening artifacts reduction. Quantitative results were measured and compared to the true values. Results: The differences between the true density value used for simulation and that were obtained from the monochromatic images, are 1.8%, 1.3%, 2.3%, and 2.9% for the dose levels from standard dose to 1/8 dose, and are 0.4%, 0.7%, 1.5%, and 1.8% for the four iodine concentration levels from 6 mg/mL to 24 mg/mL. For all of the cases, beam hardening artifacts, especially streaks shown between dense inserts, are almost completely removed in the monochromatic images. Conclusion: The proposed algorithm provides an effective way to yield material images and artifacts-free monochromatic images at different dose levels without the need for phantom calibration or ROI selection. Furthermore, the approach also yields accurate results when the concentration of the iodine concentrate insert is very low, suggesting the algorithm is robust with respect to the low-contrast scenario.« less

Monte Carlo evaluation of glandular dose in cone-beam X-ray computed tomography dedicated to the breast: Homogeneous and heterogeneous breast models.

PubMed

Sarno, Antonio; Mettivier, Giovanni; Tucciariello, Raffaele M; Bliznakova, Kristina; Boone, John M; Sechopoulos, Ioannis; Di Lillo, Francesca; Russo, Paolo

2018-06-07

In cone-beam computed tomography dedicated to the breast (BCT), the mean glandular dose (MGD) is the dose metric of reference, evaluated from the measured air kerma by means of normalized glandular dose coefficients (DgN CT ). This work aimed at computing, for a simple breast model, a set of DgN CT values for monoenergetic and polyenergetic X-ray beams, and at validating the results vs. those for patient specific digital phantoms from BCT scans. We developed a Monte Carlo code for calculation of monoenergetic DgN CT coefficients (energy range 4.25-82.25 keV). The pendant breast was modelled as a cylinder of a homogeneous mixture of adipose and glandular tissue with glandular fractions by mass of 0.1%, 14.3%, 25%, 50% or 100%, enveloped by a 1.45 mm-thick skin layer. The breast diameter ranged between 8 cm and 18 cm. Then, polyenergetic DgN CT coefficients were analytically derived for 49-kVp W-anode spectra (half value layer 1.25-1.50 mm Al), as in a commercial BCT scanner. We compared the homogeneous models to 20 digital phantoms produced from classified 3D breast images. Polyenergetic DgN CT resulted 13% lower than most recent published data. The comparison vs. patient specific breast phantoms showed that the homogeneous cylindrical model leads to a DgN CT percentage difference between -15% and +27%, with an average overestimation of 8%. A dataset of monoenergetic and polyenergetic DgN CT coefficients for BCT was provided. Patient specific breast models showed a different volume distribution of glandular dose and determined a DgN CT 8% lower, on average, than homogeneous breast model. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Environmental monitoring through use of silica-based TLD.

PubMed

Rozaila, Z Siti; Khandaker, M U; Abdul Sani, S F; Sabtu, Siti Norbaini; Amin, Y M; Maah, M J; Bradley, D A

2017-09-25

The sensitivity of a novel silica-based fibre-form thermoluminescence dosimeter was tested off-site of a rare-earths processing plant, investigating the potential for obtaining baseline measurements of naturally occurring radioactive materials. The dosimeter, a Ge-doped collapsed photonic crystal fibre (PCFc) co-doped with B, was calibrated against commercially available thermoluminescent dosimetry (TLD) (TLD-200 and TLD-100) using a bremsstrahlung (tube-based) x-ray source. Eight sampling sites within 1 to 20 km of the perimeter of the rare-earth facility were identified, the TLDs (silica- as well as TLD-200 and TLD-100) in each case being buried within the soil at fixed depth, allowing measurements to be obtained, in this case for protracted periods of exposure of between two to eight months. The values of the dose were then compared against values projected on the basis of radioactivity measurements of the associated soils, obtained via high-purity germanium gamma-ray spectrometry. Accord was found in relative terms between the TL evaluations at each site and the associated spectroscopic results. Thus said, in absolute terms, the TL evaluated doses were typically less than those derived from gamma-ray spectroscopy, by ∼50% in the case of PCFc-Ge. Gamma spectrometry analysis typically provided an upper limit to the projected dose, and the Marinelli beaker contents were formed from sieving to provide a homogenous well-packed medium. However, with the radioactivity per unit mass typically greater for smaller particles, with preferential adsorption on the surface and the surface area per unit volume increasing with decrease in radius, this made for an elevated dose estimate. Prevailing concentrations of key naturally occurring radionuclides in soil, 226 Ra, 232 Th and 40 K, were also determined, together with radiological dose evaluation. To date, the area under investigation, although including a rare-earth processing facility, gives no cause for concern from radiological impact. The current study reveals the suitability of the optical fibre based micro-dosimeter for all-weather monitoring of low-level environmental radioactivity.

Testing equality and interval estimation in binary responses when high dose cannot be used first under a three-period crossover design.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao

2015-01-01

When comparing two doses of a new drug with a placebo, we may consider using a crossover design subject to the condition that the high dose cannot be administered before the low dose. Under a random-effects logistic regression model, we focus our attention on dichotomous responses when the high dose cannot be used first under a three-period crossover trial. We derive asymptotic test procedures for testing equality between treatments. We further derive interval estimators to assess the magnitude of the relative treatment effects. We employ Monte Carlo simulation to evaluate the performance of these test procedures and interval estimators in a variety of situations. We use the data taken as a part of trial comparing two different doses of an analgesic with a placebo for the relief of primary dysmenorrhea to illustrate the use of the proposed test procedures and estimators.

Use of DAC-Hours for Radiation Work Permit Suspension Guides and Validation of Respiratory Equipment Selection at the Savannah River Site

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

Hadlock, D.J.

Historically, the Savannah River Site, like many Department of Energy sites, has used some multiple of the expected Derived Air Concentration (DAC) of a radionuclide as a suspension guide for Radiological Work Permits (RWP) or validation of selected respiratory protection equipment. The term DAC expresses the concentration of a radionuclide in air, typically in mCi/cc. Even though the term DAC is derived from an intake of radioactivity (Annual Limit on Intake) that would result in defined estimated dose to a worker, knowing only the DAC value does not allow a worker's potential dose to be determined. Recently, the Savannah Rivemore » Site has converted to the use of DAC-hours for RWP suspension guides and respiratory equipment validation. The term DAC-hr takes into account not only the concentration of the radionuclide in air (DAC) but also the time the individual was exposed allowing an estimate of a worker's dose to be determined. The conversion to DAC-hrs resulted in four benefits to the radiation protection program without increasing the risk to workers; (1) consistency with the constant air monitor (CAM) alarm setpoint protocol; (2) consistency with Internal Dosimetry terminology; (3) an a priori determination of the potential risk to a worker; and (4) reduced complexity/error in field calculations. This paper outlines the justification for the conversion to DAC-hrs, the protocols used for field and count room calculations, and the implementation process utilized at the Savannah River Site« less

In vitro anticancer property of a novel thalidomide analogue through inhibition of NF-kappaB activation in HL-60 cells.

PubMed

Li, Min; Sun, Wan; Yang, Ya-ping; Xu, Bo; Yi, Wen-yuan; Ma, Yan-xia; Li, Zhong-jun; Cui, Jing-rong

2009-01-01

To investigate the anticancer property and possible mechanism of action of a novel sugar-substituted thalidomide derivative (STA-35) on HL-60 cells in vitro. TNF-alpha-induced NF-kappaB activation was determined using a reporter gene assay. The MTT assay was used to measure cytotoxicity of the compound. The appearance of apoptotic Sub-G1 cells was detected by flow cytometry analysis. PARP cleavage and protein expression of NF-kappaB p65 and its inhibitor IkappaB were viewed by Western blotting. TA-35 (1-20 micromol/L) suppressed TNF-alpha-induced NF-kappaB activation in transfected cells (HEK293/pNiFty-SEAP) in a dose- (1-20 micromol/L) and time-dependent (0-48 h) manner. It was also shown that STA-35 exerted a dose-dependent inhibitory effect on HL-60 cell proliferation with an IC(50) value of 9.05 micromol/L. In addition, STA-35 induced apoptosis in HL-60 cells, as indicated by the appearance of a Sub-G1 peak in the cell cycle distribution, as well as poly ADP-ribose polymerase (PARP) cleavage. Subsequently, both NF-kappaB p65 and its inhibitor IkappaB gradually accumulated in cytoplasmic extracts in a dose- and time-dependent manner, indicating the blockage of NF-kappaB translocation induced by TNF-alpha from the cytoplasm to the nucleus. A novel sugar-substituted thalidomide derivative, STA-35, is potent toward HL-60 cells in vitro and induces apoptosis by the suppression of NF-kappaB activation.

Variability of serial same-day left ventricular ejection fraction using quantitative gated SPECT.

PubMed

Vallejo, Enrique; Chaya, Hugo; Plancarte, Gerardo; Victoria, Diana; Bialostozky, David

2002-01-01

The accuracy of quantitative gated single photon emission computed tomography (SPECT) (QGS) and the potential limitations for estimation of left ventricular ejection fraction (LVEF) have been extensively evaluated. However, few studies have focused on the serial variability of QGS. This study was conducted to assess the serial variability of QGS for determination of LVEF between 2 sequential technetium 99m sestamibi-gated SPECT acquisitions at rest in both healthy and unhealthy subjects. The study population consisted of 2 groups: group I included 21 volunteers with a low likelihood of CAD, and group II included 22 consecutive patients with documented CAD. Both groups underwent serial SPECT imaging. The overall correlation between sequential images was high (r = 0.94, SEE = 5.3%), and the mean serial variability of LVEF was 5.15% +/- 3.51%. Serial variability was lower for images with high counts (3.45% +/- 3.23%) than for images with low counts (6.85% +/- 3.77%). The mean serial variability was not different between normal and abnormal high-dose images (3.0% +/- 1.56% vs 3.9% +/- 2.77%). However, mean serial variability for images derived from abnormal low-dose images was significantly greater than that derived from normal low-dose images (9.6% +/- 2.22% vs 3.1% +/- 2.12%, P <.05). Although QGS is an efficacious method to approximate LVEF values and is extremely valuable for incremental risk stratification of patients with coronary artery disease, it has significant variability in the estimation of LVEF on serial images. This should be taken into account when used for serial evaluation of LVEF.

Safe bunker designing for the 18 MV Varian 2100 Clinac: a comparison between Monte Carlo simulation based upon data and new protocol recommendations.

PubMed

Beigi, Manije; Afarande, Fatemeh; Ghiasi, Hosein

2016-01-01

The aim of this study was to compare two bunkers designed by only protocols recommendations and Monte Carlo (MC) based upon data derived for an 18 MV Varian 2100Clinac accelerator. High energy radiation therapy is associated with fast and thermal photoneutrons. Adequate shielding against the contaminant neutron has been recommended by IAEA and NCRP new protocols. The latest protocols released by the IAEA (safety report No. 47) and NCRP report No. 151 were used for the bunker designing calculations. MC method based upon data was also derived. Two bunkers using protocols and MC upon data were designed and discussed. From designed door's thickness, the door designed by the MC simulation and Wu-McGinley analytical method was closer in both BPE and lead thickness. In the case of the primary and secondary barriers, MC simulation resulted in 440.11 mm for the ordinary concrete, total concrete thickness of 1709 mm was required. Calculating the same parameters value with the recommended analytical methods resulted in 1762 mm for the required thickness using 445 mm as recommended by TVL for the concrete. Additionally, for the secondary barrier the thickness of 752.05 mm was obtained. Our results showed MC simulation and the followed protocols recommendations in dose calculation are in good agreement in the radiation contamination dose calculation. Difference between the two analytical and MC simulation methods revealed that the application of only one method for the bunker design may lead to underestimation or overestimation in dose and shielding calculations.

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

PubMed

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

2002-10-01

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

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

Hobbs, R; Le, Y; Armour, E

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

Grid removal and impact on population dose in full-field digital mammography.

PubMed

Gennaro, Gisella; Katz, Luc; Souchay, Henri; Klausz, Remy; Alberelli, Claudio; di Maggio, Cosimo

2007-02-01

The study purpose was to determine the impact of anti-scatter grid removal on patient dose, in full field digital mammography. Dose saving, phantom based, was evaluated with the constraint that images acquired with and without grid would provide the same contrast-to-noise ratio (CNR). The digital equipment employed a flat panel detector with cesium iodide for x-ray to light conversion, 100 microm pixel size; the x-ray source was a dual-track tube with selectable filtration. Poly(methyl-emathocrylate) (PMMA) layers in the range 20-70 mm were used to simulate the absorption of different breast thickness, while two Al foils, 0.1 and 0.2 mm thick were used to provide a certain CNR. Images with grid were acquired with the same beam quality as selected in full automatic exposure mode and the mAs levels as close as possible, and the CNR measured for each thickness between 20 and 70 mm. Phantom images without grid were acquired in manual exposure mode, by selecting the same anode/filter combination and kVp as the image with grid at the same thickness, but varying mAs from 10 to 200. For each thickness, an image without aluminum was acquired for each mAs value, in order to obtain a flat image to be used to subtract the scatter nonuniformity from the phantom images. After scatter subtraction, the CNR was measured on images without grid. The mAs value that should be set to acquire a phantom image without grid so that it has the same CNR as the corresponding grid image was calculated. Therefore, mAs reduction percentage was determined versus phantom thickness. Results showed that dose saving was lower than 30% for PMMA equivalent breast thinner than 40 mm, decreased below 10% for intermediate thickness (45-50 mm), but there was no dose gain for thickness beyond 60 mm. By applying the mAs reduction factors to a clinical population derived from a data base of 4622 breasts, dose benefit was quantified in terms of population dose. On the average, the overall dose reduction was about 8%. It was considered small, not sufficient to justify a clinical implementation, and the anti-scatter grid was maintained.

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

Yasumatsu, S; Iwase, K; Shimizu, Y

Purpose: The exposure index (EI) proposed by the International Electrotechnical Commission (IEC) 62494-1 is expected to be utilized as a standard dose index by every manufacturer. The IEC recommended the usage of RQA5 for the EI. However, X-ray beam qualities, particularly in clinical practices, vary depending on the examination objects and exposure conditions, including usage of anti-scatter grids. We investigated the effects of the X-ray beam qualities other than RQA5 on the EI. Methods: The Xray beam qualities of RQA3, 5, 7, and 9 in IEC 61267 Ed. 1.0 were adopted in a computed radiography system. A uniform exposure withoutmore » objects was performed to measure the exposure indicators (S values) and air kerma (K). The relational equations between the S values and K were derived for the determination of the EI values. The EI values for RQA3, 7, and 9 were compared to those for RQA5 at the fixed S values of 100, 200, 400, and 600. Finally, the half-value layers (HVLs) using four grids (ratio 6:1, 8:1, 10:1, and 12:1) for the RQA5 X-ray were compared to those with RQA3–9. Results: The EI values for RQA3, 7, and 9 were up to 35.3%, 11.8%, and 38.7% higher, respectively, than that for RQA5 at the S value of 600. The HVLs without grids and with various grids for RQA5 were 6.85 mm Al. and in the range of 6.94–7.29 mm Al. (ΔHVL: up to 0.44 mm Al.), respectively. This variation in the HVLs with grids was smaller than that observed for RQA3–9 (ΔHVL: 2.0–7.5 mm Al.). Conclusion: Although the usage of grids may not greatly affect the EI, the X-ray beam quality for the determination of the EI cannot be ignored in the clinical evaluation of the dose index.« less

Equivalence of Gyn GEC-ESTRO guidelines for image guided cervical brachytherapy with EUD-based dose prescription

PubMed Central

2013-01-01

Background To establish a generalized equivalent uniform dose (gEUD) -based prescription method for Image Guided Brachytherapy (IGBT) that reproduces the Gyn GEC-ESTRO WG (GGE) prescription for cervix carcinoma patients on CT images with limited soft tissue resolution. Methods The equivalence of two IGBT planning approaches was investigated in 20 patients who received external beam radiotherapy (EBT) and 5 concomitant high dose rate IGBT treatments. The GGE planning strategy based on dose to the most exposed 2 cm3 (D2cc) was used to derive criteria for the gEUD-based planning of the bladder and rectum. The safety of gEUD constraints in terms of GGE criteria was tested by maximizing dose to the gEUD constraints for individual fractions. Results The gEUD constraints of 3.55 Gy for the rectum and 5.19 Gy for the bladder were derived. Rectum and bladder gEUD-maximized plans resulted in D2cc averages very similar to the initial GGE criteria. Average D2ccs and EUDs from the full treatment course were comparable for the two techniques within both sets of normal tissue constraints. The same was found for the tumor doses. Conclusions The derived gEUD criteria for normal organs result in GGE-equivalent IGBT treatment plans. The gEUD-based planning considers the entire dose distribution of organs in contrast to a single dose-volume-histogram point. PMID:24225184

SU-F-T-336: A Quick Auto-Planning (QAP) Method for Patient Intensity Modulated Radiotherapy (IMRT)

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

Peng, J; Zhang, Z; Wang, J

2016-06-15

Purpose: The aim of this study is to develop a quick auto-planning system that permits fast patient IMRT planning with conformal dose to the target without manual field alignment and time-consuming dose distribution optimization. Methods: The planning target volume (PTV) of the source and the target patient were projected to the iso-center plane in certain beameye- view directions to derive the 2D projected shapes. Assuming the target interior was isotropic for each beam direction boundary analysis under polar coordinate was performed to map the source shape boundary to the target shape boundary to derive the source-to-target shape mapping function. Themore » derived shape mapping function was used to morph the source beam aperture to the target beam aperture over all segments in each beam direction. The target beam weights were re-calculated to deliver the same dose to the reference point (iso-center) as the source beam did in the source plan. The approach was tested on two rectum patients (one source patient and one target patient). Results: The IMRT planning time by QAP was 5 seconds on a laptop computer. The dose volume histograms and the dose distribution showed the target patient had the similar PTV dose coverage and OAR dose sparing with the source patient. Conclusion: The QAP system can instantly and automatically finish the IMRT planning without dose optimization.« less

In vivo dosimetry using a linear Mosfet-array dosimeter to determine the urethra dose in 125I permanent prostate implants.

PubMed

Bloemen-van Gurp, Esther J; Murrer, Lars H P; Haanstra, Björk K C; van Gils, Francis C J M; Dekker, Andre L A J; Mijnheer, Ben J; Lambin, Philippe

2009-01-01

In vivo dosimetry during brachytherapy of the prostate with (125)I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the low-dose region outside the prostate (< 100 Gy), larger deviations occurred. MOSFET detectors are suitable for in vivo dosimetry during (125)I brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions.

4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites.

PubMed

Singh, Shailja; Agarwal, Drishti; Sharma, Kumkum; Sharma, Manish; Nielsen, Morten A; Alifrangis, Michael; Singh, Ashok K; Gupta, Rinkoo D; Awasthi, Satish K

2016-10-21

Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Studies on the physicochemical characteristics of oil extracted from gamma irradiated pistachio (Pistacia vera L.).

PubMed

Al-Bachir, Mahfouz

2015-01-15

The present study evaluated the quality of pistachio oil, as a function of irradiation, to determine the dose level causing undesirable changes to pistachio oil. Physicochemical fatty acid composition, acidity value, peroxide value, iodine value specification number, thiobarbituric acid (TBA) value and colour of pistachio oil extracted from samples treated with 0, 1, 2 and 3 kGy doses of gamma irradiation were determined. Gamma irradiation caused the alteration of fatty acids of pistachio oil which showed a decrease in oleic acid (C18:1) and an increase in linoleic acid (C18:2). All other fatty acids remained unaffected after irradiation. The higher used doses (2 and 3 kGy) decreased acidity value, peroxide value and iodine value, and increased specification number, with no effect on TBA value. Irradiation had a significant effect on colour values of pistachio oil. Parameters L, a and b increased at doses of 1 and 2 kGy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Value of public health and safety actions and radiation dose avoided

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

Baum, J.W.

1994-05-01

The values judged best to reflect the willingness of society to pay for the avoidance or reduction of risk were deduced from studies of costs of health care, transportation safety, consumer product safety, government agency actions, wage-risk compensation, consumer behavior (market) studies, and willingness-to-pay surveys. The results ranged from $1,400,000 to $2,700,000 per life saved. Applying the mean of these values ($2,100,000) and the latest risk per unit dose coefficients used by the ICRP (1991), which take into account risks to the general public, including genetic effects and nonfatal cancers, yields a value of dose avoided of $750 to $1,500more » per person-cSv for public exposures. The lower value applies if adjustments are made for years of life lost per fatality. A nominal value of $1,000 per person-cSv seems appropriate in light of the many uncertainties involved in deducing these values. These values are consistent with values recommended by several European countries for individual doses in the region of 1 mSv/y (100 mrem/y). Below this dose rate, most countries have values a factor of 7 to 10 lower, based on the assumption that society is less concerned with fatality risks below about 10{sup {minus}4}/y.« less

Air kerma calibration factors and chamber correction values for PTW soft x-ray, NACP and Roos ionization chambers at very low x-ray energies.

PubMed

Ipe, N E; Rosser, K E; Moretti, C J; Manning, J W; Palmer, M J

2001-08-01

This paper evaluates the characteristics of ionization chambers for the measurement of absorbed dose to water using very low-energy x-rays. The values of the chamber correction factor, k(ch), used in the IPEMB 1996 code of practice for the UK secondary standard ionization chambers (PTW type M23342 and PTW type M23344), the Roos (PTW type 34001) and NACP electron chambers are derived. The responses in air of the small and large soft x-ray chambers (PTW type M23342 and PTW type M23344) and the NACP and Roos electron ionization chambers were compared. Besides the soft x-ray chambers, the NACP and Roos chambers can be used for very low-energy x-ray dosimetry provided that they are used in the restricted energy range for which their response does not change by more than 5%. The chamber correction factor was found by comparing the absorbed dose to water determined using the dosimetry protocol recommended for low-energy x-rays with that for very low-energy x-rays. The overlap energy range was extended using data from Grosswendt and Knight. Chamber correction factors given in this paper are chamber dependent, varying from 1.037 to 1.066 for a PTW type M23344 chamber, which is very different from a value of unity given in the IPEMB code. However, the values of k(ch) determined in this paper agree with those given in the DIN standard within experimental uncertainty. The authors recommend that the very low-energy section of the IPEMB code is amended to include the most up-to-date values of k(ch).

Quantifying annual internal effective 137Cesium dose utilizing direct body-burden measurement and ecological dose modeling.

PubMed

Jelin, Benjamin A; Sun, Wenjie; Kravets, Alexandra; Naboka, Maryna; Stepanova, Eugenia I; Vdovenko, Vitaliy Y; Karmaus, Wilfried J; Lichosherstov, Alex; Svendsen, Erik R

2016-11-01

The Chernobyl Nuclear Power Plant (CNPP) accident represents one of the most significant civilian releases of 137 Cesium ( 137 Cs, radiocesium) in human history. In the Chernobyl-affected region, radiocesium is considered to be the greatest on-going environmental hazard to human health by radiobiologists and public health scientists. The goal of this study was to characterize dosimetric patterns and predictive factors for whole-body count (WBC)-derived radiocesium internal dose estimations in a CNPP-affected children's cohort, and cross-validate these estimations with a soil-based ecological dose estimation model. WBC data were used to estimate the internal effective dose using the International Commission on Radiological Protection (ICRP) 67 dose conversion coefficient for 137 Cs and MONDAL Version 3.01 software. Geometric mean dose estimates from each model were compared utilizing paired t-tests and intra-class correlation coefficients. Additionally, we developed predictive models for WBC-derived dose estimation in order to determine the appropriateness of EMARC to estimate dose for this population. The two WBC-derived dose predictive models identified 137 Cs soil concentration (P<0.0001) as the strongest predictor of annual internal effective dose from radiocesium validating the use of the soil-based EMARC model. The geometric mean internal effective dose estimate of the EMARC model (0.183 mSv/y) was the highest followed by the ICRP 67 dose estimates (0.165 mSv/y) and the MONDAL model estimates (0.149 mSv/y). All three models yielded significantly different geometric mean dose (P<0.05) estimates for this cohort when stratified by sex, age at time of exam and season of exam, except for the mean MONDAL and EMARC estimates for 15- and 16-year olds and mean ICRP and MONDAL estimates for children examined in Winter. Further prospective and retrospective radio-epidemiological studies utilizing refined WBC measurements and ecological model dose estimations, in conjunction with findings from animal toxicological studies, should help elucidate possible deterministic radiogenic health effects associated with chronic low-dose internal exposure to 137 Cs.

2,4-Dihydroxychalcone derivatives as novel potent cell division cycle 25B phosphatase inhibitors and protein tyrosine phosphatase 1B inhibitors.

PubMed

Xie, Chao; Sun, Yuan; Pan, Cheng-Yan; Tang, Li-Ming; Guan, Li-Ping

2014-04-01

Eleven 2,4-dihydroxychalcone compounds were synthesized and identified as reversible and competitive cell division cycle 25 (CDC25) B and protein tyrosine phosphatase (PTP) 1B inhibitors with inhibition values in the micromolar range. The results showed that nine compounds significantly inhibited CDC25B phosphatase, whereas seven compounds inhibited the activity against PTP1B in vitro. Compound 8 had the greatest inhibition activity against CDC25B and PTP1B in vitro, with percentage inhibition values of 97.5% and 96.3% at a dose of 20 microg/mL, respectively. Cytotoxic activity assays revealed that compound 8 was the most potent against HCT116, HeLa, and A549 cells. Furthermore, compound 8 exhibited potent antitumor activity in a colo205 xenograft model.

Dose reduction and image quality optimizations in CT of pediatric and adult patients: phantom studies

NASA Astrophysics Data System (ADS)

Jeon, P.-H.; Lee, C.-L.; Kim, D.-H.; Lee, Y.-J.; Jeon, S.-S.; Kim, H.-J.

2014-03-01

Multi-detector computed tomography (MDCT) can be used to easily and rapidly perform numerous acquisitions, possibly leading to a marked increase in the radiation dose to individual patients. Technical options dedicated to automatically adjusting the acquisition parameters according to the patient's size are of specific interest in pediatric radiology. A constant tube potential reduction can be achieved for adults and children, while maintaining a constant detector energy fluence. To evaluate radiation dose, the weighted CT dose index (CTDIw) was calculated based on the CT dose index (CTDI) measured using an ion chamber, and image noise and image contrast were measured from a scanned image to evaluate image quality. The dose-weighted contrast-to-noise ratio (CNRD) was calculated from the radiation dose, image noise, and image contrast measured from a scanned image. The noise derivative (ND) is a quality index for dose efficiency. X-ray spectra with tube voltages ranging from 80 to 140 kVp were used to compute the average photon energy. Image contrast and the corresponding contrast-to-noise ratio (CNR) were determined for lesions of soft tissue, muscle, bone, and iodine relative to a uniform water background, as the iodine contrast increases at lower energy (i.e., k-edge of iodine is 33 keV closer to the beam energy) using mixed water-iodine contrast normalization (water 0, iodine 25, 100, 200, and 1000 HU, respectively). The proposed values correspond to high quality images and can be reduced if only high-contrast organs are assessed. The potential benefit of lowering the tube voltage is an improved CNRD, resulting in a lower radiation dose and optimization of image quality. Adjusting the tube potential in abdominal CT would be useful in current pediatric radiography, where the choice of X-ray techniques generally takes into account the size of the patient as well as the need to balance the conflicting requirements of diagnostic image quality and radiation dose optimization.

Derivation of the expressions for γ50 and D50 for different individual TCP and NTCP models

NASA Astrophysics Data System (ADS)

Stavreva, N.; Stavrev, P.; Warkentin, B.; Fallone, B. G.

2002-10-01

This paper presents a complete set of formulae for the position (D50) and the normalized slope (γ50) of the dose-response relationship based on the most commonly used radiobiological models for tumours as well as for normal tissues. The functional subunit response models (critical element and critical volume) are used in the derivation of the formulae for the normal tissue. Binomial statistics are used to describe the tumour control probability, the functional subunit response as well as the normal tissue complication probability. The formulae are derived for the single hit and linear quadratic models of cell kill in terms of the number of fractions and dose per fraction. It is shown that the functional subunit models predict very steep, almost step-like, normal tissue individual dose-response relationships. Furthermore, the formulae for the normalized gradient depend on the cellular parameters α and β when written in terms of number of fractions, but not when written in terms of dose per fraction.

Biomonitoring Data for 2,4-Dichlorophenoxyacetic Acid in the United States and Canada: Interpretation in a Public Health Risk Assessment Context Using Biomonitoring Equivalents

PubMed Central

Aylward, Lesa L.; Morgan, Marsha K.; Arbuckle, Tye E.; Barr, Dana B.; Burns, Carol J.; Alexander, Bruce H.; Hays, Sean M.

2010-01-01

Background Several extensive studies of exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) using urinary concentrations in samples from the general population, farm applicators, and farm family members are now available. Reference doses (RfDs) exist for 2,4-D, and Biomonitoring Equivalents (BEs; concentrations in urine or plasma that are consistent with those RfDs) for 2,4-D have recently been derived and published. Objective We reviewed the available biomonitoring data for 2,4-D from the United States and Canada and compared them with BE values to draw conclusions regarding the margin of safety for 2,4-D exposures within each population group. Data sources Data on urinary 2,4-D excretion in general and target populations from recent published studies are tabulated and the derivation of BE values for 2,4-D summarized. Data synthesis The biomonitoring data indicate margins of safety (ratio of BE value to biomarker concentration) of approximately 200 at the central tendency and 50 at the extremes in the general population. Median exposures for applicators and their family members during periods of use appear to be well within acute exposure guidance values. Conclusions Biomonitoring data from these studies indicate that current exposures to 2,4-D are below applicable exposure guidance values. This review demonstrates the value of biomonitoring data in assessing population exposures in the context of existing risk assessments using the BE approach. Risk managers can use this approach to integrate the available biomonitoring data into an overall assessment of current risk management practices for 2,4-D. PMID:20123603

Toxicity and motor changes in Africanized honey bees (Apis mellifera L.) exposed to fipronil and imidacloprid.

PubMed

Bovi, Thaís S; Zaluski, Rodrigo; Orsi, Ricardo O

2018-01-01

This study evaluated the in vitro toxicity and motor activity changes in African-derived adult honey bees (Apis mellifera L.) exposed to lethal or sublethal doses of the insecticides fipronil and imidacloprid. Mortality of bees was assessed to determine the ingestion and contact lethal dose for 24 h using probit analysis. Motor activities in bees exposed to lethal (LD50) and sublethal doses (1/500th of the lethal dose) of both insecticides were evaluated in a behavioral observation box at 1 and 4 h. Ingestion and contact lethal doses of fipronil were 0.2316 ? 0.0626 and 0.0080 ? 0.0021 μg/bee, respectively. Ingestion and contact lethal doses of imidacloprid were 0.1079 ? 0.0375 and 0.0308 ? 0.0218 μg/bee, respectively. Motor function of bees exposed to lethal doses of fipronil and imidacloprid was impaired; exposure to sublethal doses of fipronil but not imidacloprid impaired motor function. The insecticides evaluated in this study were highly toxic to African-derived A. mellifera and caused impaired motor function in these pollinators.

TH-CD-202-08: Feasibility Study of Planning Phase Optimization Using Patient Geometry-Driven Information for Better Dose Sparing of Organ at Risks

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

Kang, S; Kim, D; Kim, T

2016-06-15

Purpose: To propose a simple and effective cost value function to search optimal planning phase (gating window) and demonstrated its feasibility for respiratory correlated radiation therapy. Methods: We acquired 4DCT of 10 phases for 10 lung patients who have tumor located near OARs such as esophagus, heart, and spinal cord (i.e., central lung cancer patients). A simplified mathematical optimization function was established by using overlap volume histogram (OVH) between the target and organ at risk (OAR) at each phase and the tolerance dose of selected OARs to achieve surrounding OARs dose-sparing. For all patients and all phases, delineation of themore » target volume and selected OARs (esophagus, heart, and spinal cord) was performed (by one observer to avoid inter-observer variation), then cost values were calculated for all phases. After the breathing phases were ranked according to cost value function, the relationship between score and dose distribution at highest and lowest cost value phases were evaluated by comparing the mean/max dose. Results: A simplified mathematical cost value function showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. The lowest cost value which may result in lower mean/max dose to OARs was distributed at various phases for all patients. The mean doses of the OARs significantly decreased about 10% with statistical significance for all 3 OARs at the phase with the lowest cost value. Also, the max doses of the OARs were decreased about 2∼5% at the phase with the lowest cost value compared to the phase with the highest cost value. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist differently through each patient and the proposed cost value function can be a useful tool for determining such phases without performing dose optimization calculations. This research was supported by the Mid-career Researcher Program through NRF funded by the Ministry of Science, ICT & Future Planning of Korea (NRF-2014R1A2A1A10050270) and by the Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2013M2A2A7038291)« less

Derivation of new diagnostic reference levels for neuro-paediatric computed tomography examinations in Switzerland.

PubMed

Wagner, Franca; Bize, Julie; Racine, Damien; Le Coultre, Regis; Francis, Verdun; Trueb, Philipp; Treier, Reto

2018-05-22

Definition of new national diagnostic reference levels (DRLs) for volume computed tomography dose index (CTDIvol) and dose length product (DLP) for neuro-paediatric CT examinations depending on the medical indication. Methods: Paediatric cranial CT data sets acquired between January 2013 and December 2016 were retrospectively collected between July 2016 and March 2017 from the eight largest university and cantonal hospitals that perform most of the neuro-paediatric CTs in Switzerland. A consensus review of CTDIvol and DLP was undertaken for the three defined anatomical regions: brain, facial bone and petrous bone; each with and without contrast medium application. All indications for cranial CT imaging in paediatrics were assigned to one of these three regions. Descriptive statistical analysis of the distribution of the median values for CTDIvol and DLP yielded minimum, maximum, 25th percentile (1st quartile), median (2nd quartile) and 75th percentile (3rd quartile). New DRLs for neuro-paediatric CT examinations in Switzerland were based on the 75th percentiles of the distributions of the median values of all eight centres. Where appropriate, values were rounded such that the DRLs increase or at least remain constant as the age of the patient increases. Results: Our results revealed DRLs for CTDIvol and DLP up to 20% lower than the DRLs used so far in Switzerland and elsewhere in Europe. Conclusions: This study provides Swiss neuro-paediatric CT DRL values to establish optimum conditions for paediatric cranial CT examinations. Periodic national updates of DRLs, following international comparisons, are essential. . Creative Commons Attribution license.

Derivation of soil screening thresholds to protect chisel-toothed kangaroo rat from uranium mine waste in northern Arizona

USGS Publications Warehouse

Hinck, Jo E.; Linder, Greg L.; Otton, James K.; Finger, Susan E.; Little, Edward E.; Tillitt, Donald E.

2013-01-01

Chemical data from soil and weathered waste material samples collected from five uranium mines north of the Grand Canyon (three reclaimed, one mined but not reclaimed, and one never mined) were used in a screening-level risk analysis for the Arizona chisel-toothed kangaroo rat (Dipodomys microps leucotis); risks from radiation exposure were not evaluated. Dietary toxicity reference values were used to estimate soil-screening thresholds presenting risk to kangaroo rats. Sensitivity analyses indicated that body weight critically affected outcomes of exposed-dose calculations; juvenile kangaroo rats were more sensitive to the inorganic constituent toxicities than adult kangaroo rats. Species-specific soil-screening thresholds were derived for arsenic (137 mg/kg), cadmium (16 mg/kg), copper (1,461 mg/kg), lead (1,143 mg/kg), nickel (771 mg/kg), thallium (1.3 mg/kg), uranium (1,513 mg/kg), and zinc (731 mg/kg) using toxicity reference values that incorporate expected chronic field exposures. Inorganic contaminants in soils within and near the mine areas generally posed minimal risk to kangaroo rats. Most exceedances of soil thresholds were for arsenic and thallium and were associated with weathered mine wastes.

Multi-photon microscopy of tobacco-exposed organotypic skin models

NASA Astrophysics Data System (ADS)

Dao, Belinda; Yamazaki, Alissa; Sun, Chung Ho; Wang, Zifu; Pham, Nguyen; Oldham, Michael; Wong, Brian J. F.

2006-02-01

Cigarette smoking is the most preventable cause of death in the United States. Researchers have extensively studied smoking in regards to its association with cancer, cardiovascular, and pulmonary disease. In contrast, the impact of cigarette smoking on skin has received much less attention. To provide a better understanding of the effect of cigarette smoking on the human dermal layer, this study used multi-photon microscopy (MPM) to examine collagen in organotypic skin models exposed to cigarette smoke condensate (CSC). Adult and neonatal organotypic tissue-engineered artificial skin models (RAFTs) were constructed and exposed to varying concentrations of CSC. Imaging of the RAFTs was performed using MPM and second-harmonic generation signals (SHG), which allowed for collagen structure to be viewed and analyzed as well as for collagen density to be assessed from derived depth-dependent decay (DDD) values. RAFT contraction as related to exposure concentration was monitored as well. Results indicated a dose dependent between contraction rates and CSC concentration. Collagen structure showed more preservation of its original structure at a greater depth in RAFTs with higher concentrations of CSC. No clear trends could be drawn from analysis of derived DDD values.

Derivatives of Dictyostelium differentiation-inducing factors inhibit lysophosphatidic acid-stimulated migration of murine osteosarcoma LM8 cells.

PubMed

Kubohara, Yuzuru; Komachi, Mayumi; Homma, Yoshimi; Kikuchi, Haruhisa; Oshima, Yoshiteru

2015-08-07

Osteosarcoma is a common metastatic bone cancer that predominantly develops in children and adolescents. Metastatic osteosarcoma remains associated with a poor prognosis; therefore, more effective anti-metastatic drugs are needed. Differentiation-inducing factor-1 (DIF-1), -2, and -3 are novel lead anti-tumor agents that were originally isolated from the cellular slime mold Dictyostelium discoideum. Here we investigated the effects of a panel of DIF derivatives on lysophosphatidic acid (LPA)-induced migration of mouse osteosarcoma LM8 cells by using a Boyden chamber assay. Some DIF derivatives such as Br-DIF-1, DIF-3(+2), and Bu-DIF-3 (5-20 μM) dose-dependently suppressed LPA-induced cell migration with associated IC50 values of 5.5, 4.6, and 4.2 μM, respectively. On the other hand, the IC50 values of Br-DIF-1, DIF-3(+2), and Bu-DIF-3 versus cell proliferation were 18.5, 7.2, and 2.0 μM, respectively, in LM8 cells, and >20, 14.8, and 4.3 μM, respectively, in mouse 3T3-L1 fibroblasts (non-transformed). Together, our results demonstrate that Br-DIF-1 in particular may be a valuable tool for the analysis of cancer cell migration, and that DIF derivatives such as DIF-3(+2) and Bu-DIF-3 are promising lead anti-tumor agents for the development of therapies that suppress osteosarcoma cell proliferation, migration, and metastasis. Copyright © 2015 Elsevier Inc. All rights reserved.

Estimating pediatric entrance skin dose from digital radiography examination using DICOM metadata: A quality assurance tool.

PubMed

Brady, S L; Kaufman, R A

2015-05-01

To develop an automated methodology to estimate patient examination dose in digital radiography (DR) imaging using DICOM metadata as a quality assurance (QA) tool. Patient examination and demographical information were gathered from metadata analysis of DICOM header data. The x-ray system radiation output (i.e., air KERMA) was characterized for all filter combinations used for patient examinations. Average patient thicknesses were measured for head, chest, abdomen, knees, and hands using volumetric images from CT. Backscatter factors (BSFs) were calculated from examination kVp. Patient entrance skin air KERMA (ESAK) was calculated by (1) looking up examination technique factors taken from DICOM header metadata (i.e., kVp and mA s) to derive an air KERMA (k air) value based on an x-ray characteristic radiation output curve; (2) scaling k air with a BSF value; and (3) correcting k air for patient thickness. Finally, patient entrance skin dose (ESD) was calculated by multiplying a mass-energy attenuation coefficient ratio by ESAK. Patient ESD calculations were computed for common DR examinations at our institution: dual view chest, anteroposterior (AP) abdomen, lateral (LAT) skull, dual view knee, and bone age (left hand only) examinations. ESD was calculated for a total of 3794 patients; mean age was 11 ± 8 yr (range: 2 months to 55 yr). The mean ESD range was 0.19-0.42 mGy for dual view chest, 0.28-1.2 mGy for AP abdomen, 0.18-0.65 mGy for LAT view skull, 0.15-0.63 mGy for dual view knee, and 0.10-0.12 mGy for bone age (left hand) examinations. A methodology combining DICOM header metadata and basic x-ray tube characterization curves was demonstrated. In a regulatory era where patient dose reporting has become increasingly in demand, this methodology will allow a knowledgeable user the means to establish an automatable dose reporting program for DR and perform patient dose related QA testing for digital x-ray imaging.

Estimating pediatric entrance skin dose from digital radiography examination using DICOM metadata: A quality assurance tool

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

Brady, S. L., E-mail: samuel.brady@stjude.org; Kaufman, R. A., E-mail: robert.kaufman@stjude.org

Purpose: To develop an automated methodology to estimate patient examination dose in digital radiography (DR) imaging using DICOM metadata as a quality assurance (QA) tool. Methods: Patient examination and demographical information were gathered from metadata analysis of DICOM header data. The x-ray system radiation output (i.e., air KERMA) was characterized for all filter combinations used for patient examinations. Average patient thicknesses were measured for head, chest, abdomen, knees, and hands using volumetric images from CT. Backscatter factors (BSFs) were calculated from examination kVp. Patient entrance skin air KERMA (ESAK) was calculated by (1) looking up examination technique factors taken frommore » DICOM header metadata (i.e., kVp and mA s) to derive an air KERMA (k{sub air}) value based on an x-ray characteristic radiation output curve; (2) scaling k{sub air} with a BSF value; and (3) correcting k{sub air} for patient thickness. Finally, patient entrance skin dose (ESD) was calculated by multiplying a mass–energy attenuation coefficient ratio by ESAK. Patient ESD calculations were computed for common DR examinations at our institution: dual view chest, anteroposterior (AP) abdomen, lateral (LAT) skull, dual view knee, and bone age (left hand only) examinations. Results: ESD was calculated for a total of 3794 patients; mean age was 11 ± 8 yr (range: 2 months to 55 yr). The mean ESD range was 0.19–0.42 mGy for dual view chest, 0.28–1.2 mGy for AP abdomen, 0.18–0.65 mGy for LAT view skull, 0.15–0.63 mGy for dual view knee, and 0.10–0.12 mGy for bone age (left hand) examinations. Conclusions: A methodology combining DICOM header metadata and basic x-ray tube characterization curves was demonstrated. In a regulatory era where patient dose reporting has become increasingly in demand, this methodology will allow a knowledgeable user the means to establish an automatable dose reporting program for DR and perform patient dose related QA testing for digital x-ray imaging.« less

SU-E-J-85: Leave-One-Out Perturbation (LOOP) Fitting Algorithm for Absolute Dose Film Calibration

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

Chu, A; Ahmad, M; Chen, Z

2014-06-01

Purpose: To introduce an outliers-recognition fitting routine for film dosimetry. It cannot only be flexible with any linear and non-linear regression but also can provide information for the minimal number of sampling points, critical sampling distributions and evaluating analytical functions for absolute film-dose calibration. Methods: The technique, leave-one-out (LOO) cross validation, is often used for statistical analyses on model performance. We used LOO analyses with perturbed bootstrap fitting called leave-one-out perturbation (LOOP) for film-dose calibration . Given a threshold, the LOO process detects unfit points (“outliers”) compared to other cohorts, and a bootstrap fitting process follows to seek any possibilitiesmore » of using perturbations for further improvement. After that outliers were reconfirmed by a traditional t-test statistics and eliminated, then another LOOP feedback resulted in the final. An over-sampled film-dose- calibration dataset was collected as a reference (dose range: 0-800cGy), and various simulated conditions for outliers and sampling distributions were derived from the reference. Comparisons over the various conditions were made, and the performance of fitting functions, polynomial and rational functions, were evaluated. Results: (1) LOOP can prove its sensitive outlier-recognition by its statistical correlation to an exceptional better goodness-of-fit as outliers being left-out. (2) With sufficient statistical information, the LOOP can correct outliers under some low-sampling conditions that other “robust fits”, e.g. Least Absolute Residuals, cannot. (3) Complete cross-validated analyses of LOOP indicate that the function of rational type demonstrates a much superior performance compared to the polynomial. Even with 5 data points including one outlier, using LOOP with rational function can restore more than a 95% value back to its reference values, while the polynomial fitting completely failed under the same conditions. Conclusion: LOOP can cooperate with any fitting routine functioning as a “robust fit”. In addition, it can be set as a benchmark for film-dose calibration fitting performance.« less

A dramatic response to a single dose of infliximab in a patient with prolonged pustular psoriasis derived from inverse psoriasis.

PubMed

Li, Mengmeng; Dai, Weiwei; Yan, Wei; Liu, Yuanzhen; Wang, Lian; Li, Wei

2017-07-01

We report a case of a 25-year-old Chinese man with an exceptionally prolonged history of pustular psoriasis derived from inverse psoriasis who was unsatisfied with conventional treatment and was successfully treated with a single dose of infliximab without noticeable adverse effects. No recurrence or flaring was observed after 3 months of follow-up. This case illustrates that infliximab may be an effective and safe therapeutic option for patients with refractory pustular psoriasis derived from inverse psoriasis. © 2017 Wiley Periodicals, Inc.

The cyclophosphamide equivalent dose as an approach for quantifying alkylating agent exposure: a report from the Childhood Cancer Survivor Study.

PubMed

Green, Daniel M; Nolan, Vikki G; Goodman, Pamela J; Whitton, John A; Srivastava, DeoKumar; Leisenring, Wendy M; Neglia, Joseph P; Sklar, Charles A; Kaste, Sue C; Hudson, Melissa M; Diller, Lisa R; Stovall, Marilyn; Donaldson, Sarah S; Robison, Leslie L

2014-01-01

Estimation of the risk of adverse long-term outcomes such as second malignant neoplasms and infertility often requires reproducible quantification of exposures. The method for quantification should be easily utilized and valid across different study populations. The widely used Alkylating Agent Dose (AAD) score is derived from the drug dose distribution of the study population and thus cannot be used for comparisons across populations as each will have a unique distribution of drug doses. We compared the performance of the Cyclophosphamide Equivalent Dose (CED), a unit for quantifying alkylating agent exposure independent of study population, to the AAD. Comparisons included associations from three Childhood Cancer Survivor Study (CCSS) outcome analyses, receiver operator characteristic (ROC) curves and goodness of fit based on the Akaike's Information Criterion (AIC). The CED and AAD performed essentially identically in analyses of risk for pregnancy among the partners of male CCSS participants, risk for adverse dental outcomes among all CCSS participants and risk for premature menopause among female CCSS participants, based on similar associations, lack of statistically significant differences between the areas under the ROC curves and similar model fit values for the AIC between models including the two measures of exposure. The CED is easily calculated, facilitating its use for patient counseling. It is independent of the drug dose distribution of a particular patient population, a characteristic that will allow direct comparisons of outcomes among epidemiological cohorts. We recommend the use of the CED in future research assessing cumulative alkylating agent exposure. © 2013 Wiley Periodicals, Inc.

A case control study of multiple myeloma at four nuclear facilities.

PubMed

Wing, S; Richardson, D; Wolf, S; Mihlan, G; Crawford-Brown, D; Wood, J

2000-04-01

Reported elevations of multiple myeloma among nuclear workers exposed to external penetrating ionizing radiation, based on small numbers of cases, prompted this multi-facility study of workers at US Department of Energy facilities. Ninety-eight multiple myeloma deaths and 391 age-matched controls were selected from the combined roster of 115,143 workers hired before 1979 at Hanford, Los Alamos National Laboratory, Oak Ridge National Laboratory, and the Savannah River site. These workers were followed for vital status through 1990 (1986 for Hanford). Demographic, work history, and occupational exposure data were derived from personnel, occupational medicine, industrial hygiene, and health physics records. Exposure-disease associations were evaluated using conditional logistic regression. Cases were disproportionately African American, male, and hired prior to 1948. Lifetime cumulative whole body ionizing radiation dose was not associated with multiple myeloma, however, there was a significant effect of age at exposure, with positive associations between multiple myeloma and doses received at older ages. Dose response associations increased in magnitude with exposure age (from 40 to 50) and lag assumption (from 5 to 15 years), while a likelihood ratio goodness of fit test reached the highest value for cumulative doses received at ages above 45 with a 5-year lag (X2=5.43,1 df; relative risk = 6.9% per 10 mSv). Dose response associations persisted with adjustment for potential confounders. Multiple myeloma was associated with low level whole body penetrating ionizing radiation doses at older ages. The exposure age effect is at odds with interpretations of A-bomb survivor studies but in agreement with several studies of cancer among nuclear workers.

Absorbed dose in AgBr in direct film for photon energies ( < 150 keV): relation to optical density. Theoretical calculation and experimental evaluation.

PubMed

Helmrot, E; Alm Carlsson, G

1996-01-01

In the radiological process it is necessary to develop tools so as to explore how X-rays can be used in the most effective way. Evaluation of models to derive measures of image quality and risk-related parameters is one possibility of getting such a tool. Modelling the image receptor, an important part of the imaging chain, is then required. The aim of this work was to find convenient and accurate ways of describing the blackening of direct dental films by X-rays. Since the beginning of the 20th century, the relation between optical density and photon interactions in the silver bromide in X-ray films has been investigated by many authors. The first attempts used simple quantum theories with no consideration of underlying physical interaction processes. The theories were gradually made more realistic by the introduction of dosimetric concepts and cavity theory. A review of cavity theories for calculating the mean absorbed dose in the AgBr grains of the film emulsion is given in this work. The cavity theories of GREENING (15) and SPIERS-CHARLTON (37) were selected for calculating the mean absorbed dose in the AgBr grains relative to the air collision kerma (Kc,air) of the incident photons of Ultra-speed and Ektaspeed (intraoral) films using up-to-date values of interaction coefficients. GREENING'S theory is a multi-grain theory and the results depend on the relative amounts of silver bromide and gelatine in the emulsion layer. In the single grain theory of SPIERS-CHARLTON, the shape and size of the silver bromide grain are important. Calculations of absorbed dose in the silver bromide were compared with measurements of optical densities in Ultra-speed and Ektaspeed films for a broad range (25-145 kV) of X-ray energy. The calculated absorbed dose values were appropriately averaged over the complete photon energy spectrum, which was determined experimentally using a Compton spectrometer. For the whole range of tube potentials used, the measured optical densities of the films were found to be proportional to the mean absorbed dose in the AgBr grains calculated according to GREENING'S theory. They were also found to be proportional to the collision kerma in silver bromide (Kc,AgBr) indicating proportionality between Kc,AgBr and the mean absorbed dose in silver bromide. While GREENING'S theory shows that the quotient of the mean absorbed dose in silver bromide and Kc,AgBr varies with photon energy, this is not apparent when averaged over the broad (diagnostic) X-ray energy spectra used here. Alternatively, proportionality between Kc,AgBr and the mean absorbed dose in silver bromide can be interpreted as resulting from a combination of the SPIERS-CHARLTON theory, valid at low photon energies ( < 30 keV) and GREENING'S theory, which is strictly valid at energies above 50 keV. This study shows that the blackening of non-screen films can be related directly to the energy absorbed in the AgBr grains of the emulsion layer and that, for the purpose of modelling the imaging chain in intraoral radiography, film response can be represented by Kc,AgBr (at the position of the film) independent of photon energy. The importance of taking the complete X-ray energy spectrum into full account in deriving Kc,AgBr is clearly demonstrated, showing that the concept of effective energy must be used with care.

Total body irradiation, toward optimal individual delivery: dose evaluation with metal oxide field effect transistors, thermoluminescence detectors, and a treatment planning system.

PubMed

Bloemen-van Gurp, Esther J; Mijnheer, Ben J; Verschueren, Tom A M; Lambin, Philippe

2007-11-15

To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

Prospective Evaluation of a Model-Based Dosing Regimen for Amikacin in Preterm and Term Neonates in Clinical Practice

PubMed Central

De Cock, R. F. W.; Allegaert, K.; Vanhaesebrouck, S.; Danhof, M.; Knibbe, C. A. J.

2015-01-01

Based on a previously derived population pharmacokinetic model, a novel neonatal amikacin dosing regimen was developed. The aim of the current study was to prospectively evaluate this dosing regimen. First, early (before and after second dose) therapeutic drug monitoring (TDM) observations were evaluated for achieving target trough (<3 mg/liter) and peak (>24 mg/liter) levels. Second, all observed TDM concentrations were compared with model-predicted concentrations, whereby the results of a normalized prediction distribution error (NPDE) were considered. Subsequently, Monte Carlo simulations were performed. Finally, remaining causes limiting amikacin predictability (i.e., prescription errors and disease characteristics of outliers) were explored. In 579 neonates (median birth body weight, 2,285 [range, 420 to 4,850] g; postnatal age 2 days [range, 1 to 30 days]; gestational age, 34 weeks [range, 24 to 41 weeks]), 90.5% of the observed early peak levels reached 24 mg/liter, and 60.2% of the trough levels were <3 mg/liter (93.4% ≤5 mg/liter). Observations were accurately predicted by the model without bias, which was confirmed by the NPDE. Monte Carlo simulations showed that peak concentrations of >24 mg/liter were reached at steady state in almost all patients. Trough values of <3 mg/liter at steady state were documented in 78% to 100% and 45% to 96% of simulated cases with and without ibuprofen coadministration, respectively; suboptimal trough levels were found in patients with postnatal age <14 days and current weight of >2,000 g. Prospective evaluation of a model-based neonatal amikacin dosing regimen resulted in optimized peak and trough concentrations in almost all patients. Slightly adapted dosing for patient subgroups with suboptimal trough levels was proposed. This model-based approach improves neonatal dosing individualization. PMID:26248375

An international dosimetry exchange for BNCT part II: computational dosimetry normalizations.

PubMed

Riley, K J; Binns, P J; Harling, O K; Albritton, J R; Kiger, W S; Rezaei, A; Sköld, K; Seppälä, T; Savolainen, S; Auterinen, I; Marek, M; Viererbl, L; Nievaart, V A; Moss, R L

2008-12-01

The meaningful sharing and combining of clinical results from different centers in the world performing boron neutron capture therapy (BNCT) requires improved precision in dose specification between programs. To this end absorbed dose normalizations were performed for the European clinical centers at the Joint Research Centre of the European Commission, Petten (The Netherlands), Nuclear Research Institute, Rez (Czech Republic), VTT, Espoo (Finland), and Studsvik, Nyköping (Sweden). Each European group prepared a treatment plan calculation that was bench-marked against Massachusetts Institute of Technology (MIT) dosimetry performed in a large, water-filled phantom to uniformly evaluate dose specifications with an estimated precision of +/-2%-3%. These normalizations were compared with those derived from an earlier exchange between Brookhaven National Laboratory (BNL) and MIT in the USA. Neglecting the uncertainties related to biological weighting factors, large variations between calculated and measured dose are apparent that depend upon the 10B uptake in tissue. Assuming a boron concentration of 15 microg g(-1) in normal tissue, differences in the evaluated maximum dose to brain for the same nominal specification of 10 Gy(w) at the different facilities range between 7.6 and 13.2 Gy(w) in the trials using boronophenylalanine (BPA) as the boron delivery compound and between 8.9 and 11.1 Gy(w) in the two boron sulfhydryl (BSH) studies. Most notably, the value for the same specified dose of 10 Gy(w) determined at the different participating centers using BPA is significantly higher than at BNL by 32% (MIT), 43% (VTT), 49% (JRC), and 74% (Studsvik). Conversion of dose specification is now possible between all active participants and should be incorporated into future multi-center patient analyses.

Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis: in silico evaluation of currently recommended doses

PubMed Central

Zvada, Simbarashe P.; Denti, Paolo; Donald, Peter R.; Schaaf, H. Simon; Thee, Stephanie; Seddon, James A.; Seifart, Heiner I.; Smith, Peter J.; McIlleron, Helen M.; Simonsson, Ulrika S. H.

2014-01-01

Objectives To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. Patients and methods We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. Results The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators. Conclusions Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing. PMID:24486870

Protective effect of skin-derived precursors on photoaging in nude mice.

PubMed

Wang, Siyu; Zhong, Jianqiao; Li, Li

2018-06-25

Currently, innovative methods to prevent photoaging are needed. Skin-derived precursors (SKP) have been shown to play a crucial role in resisting UVB-induced apoptosis in vitro. The objective of this study was to explore the effect of SKP on preventing skin photoaging in vivo. Skin-derived precursors from neonatal BALB/c mice were isolated, identified and intradermally transplanted with a PKH26 label to track their survival. These were then injected at different concentrations into the buttock dermis of nude mice at 2-weekly intervals before UV irradiation. Photographs, assessment of live skin surface, histology with quantitative real-time polymerase chain reaction and immunohistochemistry were used to evaluate the impact of SKP on wrinkles and other relevant indicators of skin photoaging. SKP exhibited a sphere-like structure and could survive for at least 2 weeks after intradermal transplantation. A large dose of SKP transplantation (10 5 SKP +UV) at 2-weekly intervals were able to ameliorate coarse UV-induced wrinkles. Moreover, the skin smoothness value, dermal thickness and collagen percentage were significantly increased in mice that received a large dose of SKP (10 5 SKP +UV). UV radiation induced the mRNA expression of MMP-13 and decreased the mRNA and protein expression of TβRII, but these effects were diminished by SKP transplantation. The transplantation of SKP could increase the mRNA of TIMP-1. We found that transplanted SKP exert a beneficial impact on preventing UV-induced wrinkles in vivo, suggesting that SKP transplantation is a promising candidate for preventing photoaging. © 2018 The Australasian College of Dermatologists.

Pharmacokinetics in Wistar Rats of 5-[(4-Carboxybutanoyl)Amino]-2-Hydroxybenzoic Acid: A Novel Synthetic Derivative of 5-Aminosalicylic Acid (5-ASA) with Possible Anti-Inflammatory Activity

PubMed Central

Correa-Basurto, José; Rosales Hernández, Martha Cecilia; Padilla Martínez, Itzia Irene; Mendieta-Wejebe, Jessica Elena

2016-01-01

5-[(4-carboxybutanoyl)amino]-2-hydroxybenzoic acid (C2) is a novel synthetic derivative of 5-aminosalicylic acid (5-ASA), which is currently being evaluated ex vivo as an anti-inflammatory agent and has shown satisfactory results. This study aimed to obtain the pharmacokinetic profiles, tissue distribution and plasma protein binding of C2 in Wistar Rats. Additionally, an HPLC method was developed and validated to quantify C2 in rat plasma. The pharmacokinetic profiles of intragastric, intravenous and intraperitoneal administration routes at singles doses of 100, 50, and 100 mg/kg, respectively, were studied in Wistar rats. The elimination half-life of intravenously administered C2 was approximately 33 min. The maximum plasma level of C2 was reached approximately 24 min after intragastric administration, with a Cmax value of 2.5 g/mL and an AUCtot value of 157 μg min-1/mL; the oral bioavailability was approximately 13%. Following a single intragastric or oral dose (100 mg/kg), C2 was distributed and detected in all examined tissues (including the brain and colon). The results showed that C2 accumulates over time. The plasma protein binding results indicated that the unbound fraction of C2 at concentrations of 1 to 20 μg/mL ranged from 89.8% to 92.5%, meaning that this fraction of C2 is available to cross tissues. Finally, the blood-plasma partitioning (BP ratio) of C2 in rat plasma was 0.71 and 0.6 at concentrations of 5 and 10 μg/mL, respectively, which indicates that C2 is free in the plasmatic phase and not inside blood cells. The results of this study suggest that a fraction of the administered C2 dose is absorbed in the stomach, and the fraction that is not absorbed reaches the small intestine and colon. This distribution constitutes the main advantage of C2 compared with 5-ASA for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). PMID:27454774

Heavy metals in soils along unpaved roads in south west Cameroon: Contamination levels and health risks.

PubMed

Ngole-Jeme, Veronica M

2016-04-01

Soils enriched with heavy metals from vehicular emission present a significant exposure route of heavy metals to individuals using unpaved roads. This study assessed the extent of Cd, Cr, Co, Cu, Ni, Pb and Zn contamination of soils along unpaved roads in Cameroon, and the health risks presented by incidental ingestion and dermal contact with the soils using metal contamination factor (CF) pollution load index, hazard quotients (HQ) and chronic hazard index (CHI). CF values obtained (0.9-12.2) indicate moderate to high contamination levels. HQ values for Cr, Cd and Pb exceeded the reference doses. Moderate health hazard exists for road users in the areas with intense anthropogenic activities and high average daily traffic (ADT) volume according to CHI values (1-4) obtained. The economy and quality of life in cities with unpaved roads could be threatened by health challenges resulting from long-term exposure to heavy metal derived from high ADT volumes.

Use of Threshold of Toxicological Concern (TTC) with High ...

EPA Pesticide Factsheets

Although progress has been made with HTS (high throughput screening) in profiling biological activity (e.g., EPA’s ToxCast™), challenges arise interpreting HTS results in the context of adversity & converting HTS assay concentrations to equivalent human doses for the broad domain of commodity chemicals. Here, we propose using TTC as a risk screening method to evaluate exposure ranges derived from NHANES for 7968 chemicals. Because the well-established TTC approach uses hazard values derived from in vivo toxicity data, relevance to adverse effects is robust. We compared the conservative TTC (non-cancer) value of 90 μg/day (1.5 μg/kg/day) (Kroes et al., Fd Chem Toxicol, 2004) to quantitative exposure predictions of the upper 95% credible interval (UCI) of median daily exposures for 7968 chemicals in 10 different demographic groups (Wambaugh et al., Environ Sci Technol. 48:12760-7, 2014). Results indicate: (1) none of the median values of credible interval of exposure for any chemical in any demographic group was above the TTC; & (2) fewer than 5% of chemicals had an UCI that exceeded the TTC for any group. However, these median exposure predictions do not cover highly exposed (e.g., occupational) populations. Additionally, we propose an expanded risk-based screening workflow that comprises a TTC decision tree that includes screening compounds for structural alerts for DNA reactivity, OPs & carbamates as well as a comparison with bioactivity-based margins of

Optimization of dose and image quality in adult and pediatric computed tomography scans

NASA Astrophysics Data System (ADS)

Chang, Kwo-Ping; Hsu, Tzu-Kun; Lin, Wei-Ting; Hsu, Wen-Lin

2017-11-01

Exploration to maximize CT image and reduce radiation dose was conducted while controlling for multiple factors. The kVp, mAs, and iteration reconstruction (IR), affect the CT image quality and radiation dose absorbed. The optimal protocols (kVp, mAs, IR) are derived by figure of merit (FOM) based on CT image quality (CNR) and CT dose index (CTDIvol). CT image quality metrics such as CT number accuracy, SNR, low contrast materials' CNR and line pair resolution were also analyzed as auxiliary assessments. CT protocols were carried out with an ACR accreditation phantom and a five-year-old pediatric head phantom. The threshold values of the adult CT scan parameters, 100 kVp and 150 mAs, were determined from the CT number test and line pairs in ACR phantom module 1and module 4 respectively. The findings of this study suggest that the optimal scanning parameters for adults be set at 100 kVp and 150-250 mAs. However, for improved low- contrast resolution, 120 kVp and 150-250 mAs are optimal. Optimal settings for pediatric head CT scan were 80 kVp/50 mAs, for maxillary sinus and brain stem, while 80 kVp /300 mAs for temporal bone. SNR is not reliable as the independent image parameter nor the metric for determining optimal CT scan parameters. The iteration reconstruction (IR) approach is strongly recommended for both adult and pediatric CT scanning as it markedly improves image quality without affecting radiation dose.

Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors.

PubMed

de Oliveira Lopes, Raquel; Romeiro, Nelilma Correia; de Lima, Cleverton Kleiton F; Louback da Silva, Leandro; de Miranda, Ana Luisa Palhares; Nascimento, Paulo Gustavo B D; Cunha, Fernando Q; Barreiro, Eliezer J; Lima, Lídia Moreira

2012-08-01

p38 mitogen-activated protein kinase (p38 MAPK) is an important signal transducing enzyme involved in many cellular regulations, including signaling pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed as drug candidates to treatment of autoimmune disorders, such as rheumatoid arthritis. In this paper we reported the docking, synthesis and pharmacological activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These derivatives presented good theoretical affinity to the target p38 MAPK, standing out compound 4e (LASSBio-998), which showed a better score value compared to the prototype GK-00687. This compound was able to reduce in vitro TNF-α production and was orally active in a hypernociceptive murine model sensible to p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory profile in carrageenan induced paw edema, indicating its potential as a new antiarthritis prototype. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Apoptotic effect of chalcone derivatives of 2-acetylthiophene in human breast cancer cells.

PubMed

Fogaça, Tatiana B; Martins, Rosiane M; Begnini, Karine R; Carapina, Caroline; Ritter, Marina; de Pereira, Claudio M P; Seixas, Fabiana K; Collares, Tiago

2017-02-01

A variety of chalcones have demonstrated cytotoxic activity toward several cancer cell lines. This study aimed to investigate the cytotoxicity of four chalcones derivatives of 2-acetylthiophene in human breast cancer cell lines. MCF-7 and MDA-MB-231 cells were treated with synthesized chalcones and the cytotoxicity was evaluated by tetrazolium dye (MTT), live/dead, and DAPI assays. Chalcones significantly decreased MCF-7 and MDA-MB-231 cells viability in vitro in a dose dependent manner. After 48h treatment, the IC 50 values ranging from 5.52 to 34.23μM. Chalcone 3c displayed the highest cytotoxic activity from all the tested compounds. Cytotoxic effects of compounds were confirmed in the live/dead assay. In addition, DAPI staining revealed that these compounds induce death by apoptosis. The data speculate that chalcone derivatives of 2-acetylthiophene may represent a source of therapeutic agents for human breast cancer. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Inhibition of gamma-radiation induced DNA damage in plasmid pBR322 by TMG, a water-soluble derivative of vitamin E.

PubMed

Rajagopalan, Rema; Wani, Khalida; Huilgol, Nagaraj G; Kagiya, Tsutomu V; Nair, Cherupally K Krishnan

2002-06-01

Alpha-tocopherol monoglucoside (TMG), a water-soluble derivative of alpha-tocopherol, has been examined for its ability to protect DNA against radiation-induced strand breaks. Gamma radiation, up to a dose of 6 Gy (dose rate, 0.7 Gy/minute), induced a dose-dependent increase in single strand breaks (SSBs) in plasmid pBR322 DNA. TMG inhibited the formation of gamma-radiation induced DNA single strand breaks (SSBs) in a concentration-dependent manner; 500 microM of TMG protected the single strand breaks completely. It also protected thymine glycol formation induced by gamma-radiation in a dose-dependent manner, based on an estimation of thymine glycol by HPLC.

Patient-based estimation of organ dose for a population of 58 adult patients across 13 protocol categories

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

Sahbaee, Pooyan, E-mail: psahbae@ncsu.edu; Segars, W. Paul; Samei, Ehsan

2014-07-15

Purpose: This study aimed to provide a comprehensive patient-specific organ dose estimation across a multiplicity of computed tomography (CT) examination protocols. Methods: A validated Monte Carlo program was employed to model a common CT system (LightSpeed VCT, GE Healthcare). The organ and effective doses were estimated from 13 commonly used body and neurological CT examination. The dose estimation was performed on 58 adult computational extended cardiac-torso phantoms (35 male, 23 female, mean age 51.5 years, mean weight 80.2 kg). The organ dose normalized by CTDI{sub vol} (h factor) and effective dose normalized by the dose length product (DLP) (k factor)more » were calculated from the results. A mathematical model was derived for the correlation between the h and k factors with the patient size across the protocols. Based on this mathematical model, a dose estimation iPhone operating system application was designed and developed to be used as a tool to estimate dose to the patients for a variety of routinely used CT examinations. Results: The organ dose results across all the protocols showed an exponential decrease with patient body size. The correlation was generally strong for the organs which were fully or partially located inside the scan coverage (Pearson sample correlation coefficient (r) of 0.49). The correlation was weaker for organs outside the scan coverage for which distance between the organ and the irradiation area was a stronger predictor of dose to the organ. For body protocols, the effective dose before and after normalization by DLP decreased exponentially with increasing patient's body diameter (r > 0.85). The exponential relationship between effective dose and patient's body diameter was significantly weaker for neurological protocols (r < 0.41), where the trunk length was a slightly stronger predictor of effective dose (0.15 < r < 0.46). Conclusions: While the most accurate estimation of a patient dose requires specific modeling of the patient anatomy, a first order approximation of organ and effective doses from routine CT scan protocols can be reasonably estimated using size specific factors. Estimation accuracy is generally poor for organ outside the scan range and for neurological protocols. The dose calculator designed in this study can be used to conveniently estimate and report the dose values for a patient across a multiplicity of CT scan protocols.« less

Comparison of different approaches of estimating effective dose from reported exposure data in 3D imaging with interventional fluoroscopy systems

NASA Astrophysics Data System (ADS)

Svalkvist, Angelica; Hansson, Jonny; Bâth, Magnus

2014-03-01

Three-dimensional (3D) imaging with interventional fluoroscopy systems is today a common examination. The examination includes acquisition of two-dimensional projection images, used to reconstruct section images of the patient. The aim of the present study was to investigate the difference in resulting effective dose obtained using different levels of complexity in calculations of effective doses from these examinations. In the study the Siemens Artis Zeego interventional fluoroscopy system (Siemens Medical Solutions, Erlangen, Germany) was used. Images of anthropomorphic chest and pelvis phantoms were acquired. The exposure values obtained were used to calculate the resulting effective doses from the examinations, using the computer software PCXMC (STUK, Helsinki, Finland). The dose calculations were performed using three different methods: 1. using individual exposure values for each projection image, 2. using the mean tube voltage and the total DAP value, evenly distributed over the projection images, and 3. using the mean kV and the total DAP value, evenly distributed over smaller selection of projection images. The results revealed that the difference in resulting effective dose between the first two methods was smaller than 5%. When only a selection of projection images were used in the dose calculations the difference increased to over 10%. Given the uncertainties associated with the effective dose concept, the results indicate that dose calculations based on average exposure values distributed over a smaller selection of projection angles can provide reasonably accurate estimations of the radiation doses from 3D imaging using interventional fluoroscopy systems.

Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

NASA Technical Reports Server (NTRS)

Ahmed, S.; Sileno, A. P.; deMeireles, J. C.; Dua, R.; Pimplaskar, H. K.; Xia, W. J.; Marinaro, J.; Langenback, E.; Matos, F. J.; Putcha, L.;

Evaluating the Potential of Q-Band ESR Spectroscopy for Dose Reconstruction of Fossil Tooth Enamel

PubMed Central

Guilarte, Verónica; Trompier, François; Duval, Mathieu

2016-01-01

The potential of Q-band Electron Spin Resonance (ESR) for quantitative measurements has been scarcely evaluated in the literature and its application for dose reconstruction of fossil tooth enamel with dating purposes remains still quite unknown. Hence, we have performed a comparative study based on several Early to Middle Pleistocene fossil tooth samples using both X- and Q-band spectroscopies. Our results show that Q-band offers a significant improvement in terms of sensitivity and signal resolution: it allows not only to work with reduced amounts of valuable samples (< 4 mg), but also to identify different components of the main composite ESR signal. However, inherent precision of the ESR intensity measurements at Q-band is clearly lower than that achieved at X-band, highlighting the necessity to carry out repeated measurements. All dose values derived from X- and Q-band are nevertheless systematically consistent at either 1 or 2 sigma. In summary, our results indicate that Q-band could now be considered as a reliable tool for ESR dosimetry/dating of fossil teeth although further work is required to improve the repeatability of the measurements. PMID:26930398

Mechanism-based risk assessment strategy for drug-induced cholestasis using the transcriptional benchmark dose derived by toxicogenomics.

PubMed

Kawamoto, Taisuke; Ito, Yuichi; Morita, Osamu; Honda, Hiroshi

2017-01-01

Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis. The transcriptional benchmark dose (tBMD) and tBMD 95% lower limit (tBMDL) were used for quantitative analyses, which revealed three compound sub-groups that produced different types of differential gene expression; these groups of genes were mainly involved in inflammation, cholesterol biosynthesis, and oxidative stress. Furthermore, the tBMDL values for each test compound were in good agreement with the relevant no observed adverse effect level. These results indicate that our novel strategy for drug safety evaluation using mechanism-based classification and tBMDL would facilitate the application of toxicogenomics for risk assessment of cholestatic DILI.

Effects of ionizing radiation on properties of monolayer and multilayer flexible food packaging materials

NASA Astrophysics Data System (ADS)

Riganakos, K. A.; Koller, W. D.; Ehlermann, D. A. E.; Bauer, B.; Kontominas, M. G.

1999-05-01

Volatile compounds produced in flexible food packaging materials (LDPE, EVAc, PET/PE/EVOH/PE) during electron beam irradiation were isolated by purge and trap technique and identified by combined gas chromatography-mass spectrometry (GC/MS), after thermal desorption and concentration. For comparison purposes non-irradiated films were also studied. Film samples were irradiated at low (5 kGy, corresponding to cold pasteurization), intermediate (20 kGy, corresponding to cold sterilization) and high (100 kGy) doses. It was observed that a number of volatile compounds are produced after irradiation in all cases. Furthermore the amounts of all volatile compounds increase with increasing irradiation dose. Both primary (methyl-derivatives etc.) as well as secondary i.e. oxidation products (ketones, aldehydes, alcohols, carboxylic acids etc.) are produced upon irradiation. These products may affect organoleptic properties and thus shelf-life of prepackaged irradiated foods. No significant changes were observed in the structure of polymer matrices as exhibited by IR spectra after irradiation of the materials at doses tested. Likewise, no significant changes were observed in O 2, H 2O and CO 2 permeability values of plastic packaging materials after irradiation.

Dose Modeling Evaluations and Technical Support Document For the Authorized Limits Request for the DOE-Owned Property Outside the Limited Area, Paducah Gaseous Diffusion Plant Paducah, Kentucky

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

Boerner, A. J.; Maldonado, D. G.; Hansen, Tom

2012-09-01

Environmental assessments and remediation activities are being conducted by the U.S. Department of Energy (DOE) at the Paducah Gaseous Diffusion Plant (PGDP), Paducah, Kentucky. The Oak Ridge Institute for Science and Education (ORISE), a DOE prime contractor, was contracted by the DOE Portsmouth/Paducah Project Office (DOE-PPPO) to conduct radiation dose modeling analyses and derive single radionuclide soil guidelines (soil guidelines) in support of the derivation of Authorized Limits (ALs) for 'DOE-Owned Property Outside the Limited Area' ('Property') at the PGDP. The ORISE evaluation specifically included the area identified by DOE restricted area postings (public use access restrictions) and areas licensedmore » by DOE to the West Kentucky Wildlife Management Area (WKWMA). The licensed areas are available without restriction to the general public for a variety of (primarily) recreational uses. Relevant receptors impacting current and reasonably anticipated future use activities were evaluated. In support of soil guideline derivation, a Conceptual Site Model (CSM) was developed. The CSM listed radiation and contamination sources, release mechanisms, transport media, representative exposure pathways from residual radioactivity, and a total of three receptors (under present and future use scenarios). Plausible receptors included a Resident Farmer, Recreational User, and Wildlife Worker. single radionuclide soil guidelines (outputs specified by the software modeling code) were generated for three receptors and thirteen targeted radionuclides. These soil guidelines were based on satisfying the project dose constraints. For comparison, soil guidelines applicable to the basic radiation public dose limit of 100 mrem/yr were generated. Single radionuclide soil guidelines from the most limiting (restrictive) receptor based on a target dose constraint of 25 mrem/yr were then rounded and identified as the derived soil guidelines. An additional evaluation using the derived soil guidelines as inputs into the code was also performed to determine the maximum (peak) dose for all receptors. This report contains the technical basis in support of the DOE?s derivation of ALs for the 'Property.' A complete description of the methodology, including an assessment of the input parameters, model inputs, and results is provided in this report. This report also provides initial recommendations on applying the derived soil guidelines.« less

Accuracy of two simple methods for estimation of thyroidal {sup 131}I kinetics for dosimetry-based treatment of Graves' disease

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

Traino, A. C.; Xhafa, B.; Sezione di Fisica Medica, U.O. Fisica Sanitaria, Azienda Ospedaliero-Universitaria Pisana, via Roma n. 67, Pisa 56125

2009-04-15

One of the major challenges to the more widespread use of individualized, dosimetry-based radioiodine treatment of Graves' disease is the development of a reasonably fast, simple, and cost-effective method to measure thyroidal {sup 131}I kinetics in patients. Even though the fixed activity administration method does not optimize the therapy, giving often too high or too low a dose to the gland, it provides effective treatment for almost 80% of patients without consuming excessive time and resources. In this article two simple methods for the evaluation of the kinetics of {sup 131}I in the thyroid gland are presented and discussed. Themore » first is based on two measurements 4 and 24 h after a diagnostic {sup 131}I administration and the second on one measurement 4 h after such an administration and a linear correlation between this measurement and the maximum uptake in the thyroid. The thyroid absorbed dose calculated by each of the two methods is compared to that calculated by a more complete {sup 131}I kinetics evaluation, based on seven thyroid uptake measurements for 35 patients at various times after the therapy administration. There are differences in the thyroid absorbed doses between those derived by each of the two simpler methods and the ''reference'' value (derived by more complete uptake measurements following the therapeutic {sup 131}I administration), with 20% median and 40% 90-percentile differences for the first method (i.e., based on two thyroid uptake measurements at 4 and 24 h after {sup 131}I administration) and 25% median and 45% 90-percentile differences for the second method (i.e., based on one measurement at 4 h post-administration). Predictably, although relatively fast and convenient, neither of these simpler methods appears to be as accurate as thyroid dose estimates based on more complete kinetic data.« less

Time-driven activity-based costing of low-dose-rate and high-dose-rate brachytherapy for low-risk prostate cancer.

PubMed

Ilg, Annette M; Laviana, Aaron A; Kamrava, Mitchell; Veruttipong, Darlene; Steinberg, Michael; Park, Sang-June; Burke, Michael A; Niedzwiecki, Douglas; Kupelian, Patrick A; Saigal, Christopher

Cost estimates through traditional hospital accounting systems are often arbitrary and ambiguous. We used time-driven activity-based costing (TDABC) to determine the true cost of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy for prostate cancer and demonstrate opportunities for cost containment at an academic referral center. We implemented TDABC for patients treated with I-125, preplanned LDR and computed tomography based HDR brachytherapy with two implants from initial consultation through 12-month followup. We constructed detailed process maps for provision of both HDR and LDR. Personnel, space, equipment, and material costs of each step were identified and used to derive capacity cost rates, defined as price per minute. Each capacity cost rate was then multiplied by the relevant process time and products were summed to determine total cost of care. The calculated cost to deliver HDR was greater than LDR by $2,668.86 ($9,538 vs. $6,869). The first and second HDR treatment day cost $3,999.67 and $3,955.67, whereas LDR was delivered on one treatment day and cost $3,887.55. The greatest overall cost driver for both LDR and HDR was personnel at 65.6% ($4,506.82) and 67.0% ($6,387.27) of the total cost. After personnel costs, disposable materials contributed the second most for LDR ($1,920.66, 28.0%) and for HDR ($2,295.94, 24.0%). With TDABC, the true costs to deliver LDR and HDR from the health system perspective were derived. Analysis by physicians and hospital administrators regarding the cost of care afforded redesign opportunities including delivering HDR as one implant. Our work underscores the need to assess clinical outcomes to understand the true difference in value between these modalities. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Discovery of novel and potent small-molecule inhibitors of NO and cytokine production as antisepsis agents: synthesis and biological activity of alkyl 6-(N-substituted sulfamoyl)cyclohex-1-ene-1-carboxylate.

PubMed

Yamada, Masami; Ichikawa, Takashi; Ii, Masayuki; Sunamoto, Mie; Itoh, Katsumi; Tamura, Norikazu; Kitazaki, Tomoyuki

2005-11-17

To develop a new therapeutic agent for sepsis, screening of the Takeda chemical library was carried out using mouse macrophages stimulated with lipopolysaccharide (LPS) to identify a new class of small-molecule inhibitors of inflammatory mediator production. The lead compound 5a was discovered, from which a series of novel cyclohexene derivatives I bearing a sulfamoyl and ester group were designed, synthesized and tested for their inhibitory activity against nitric oxide (NO) production. Derivatives I were synthesized by the coupling of sulfonyl chlorides and anilines with concomitant double bond migration in the presence of triethylamine, and phenyl ring substitution and modification of the ester and cyclohexene moieties were carried out. Among the compounds synthesized, ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate [(R)-(+)-5n, TAK-242] was found to exhibit the most potent suppressive activity for the production of not only NO but also inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) induced by LPS-stimulated mouse macrophages with IC50 values of 1.8, 1.9 and 1.3 nM, respectively. It shows marked beneficial effects in vivo also. Intravenous administration of (R)-(+)-5n at doses of 0.1 mg/kg or more suppressed the production of NO and various cytokines [TNF-alpha, IL-6 and IL-1beta] in the mouse endotoxin shock model. Furthermore, it protected mice from death dose-dependently and all mice survived at a dose of 3 mg/kg. The minimum effective dose to protect mice from lethality in this model was 0.3 mg/kg, which was consistent with those for inhibitory effects on the production of NO and cytokines. Compound (R)-(+)-5n is currently undergoing clinical trials for the treatment of sepsis.

A Monte Carlo study of the impact of the choice of rectum volume definition on estimates of equivalent uniform doses and the volume parameter

NASA Astrophysics Data System (ADS)

Kvinnsland, Yngve; Muren, Ludvig Paul; Dahl, Olav

2004-08-01

Calculations of normal tissue complication probability (NTCP) values for the rectum are difficult because it is a hollow, non-rigid, organ. Finding the true cumulative dose distribution for a number of treatment fractions requires a CT scan before each treatment fraction. This is labour intensive, and several surrogate distributions have therefore been suggested, such as dose wall histograms, dose surface histograms and histograms for the solid rectum, with and without margins. In this study, a Monte Carlo method is used to investigate the relationships between the cumulative dose distributions based on all treatment fractions and the above-mentioned histograms that are based on one CT scan only, in terms of equivalent uniform dose. Furthermore, the effect of a specific choice of histogram on estimates of the volume parameter of the probit NTCP model was investigated. It was found that the solid rectum and the rectum wall histograms (without margins) gave equivalent uniform doses with an expected value close to the values calculated from the cumulative dose distributions in the rectum wall. With the number of patients available in this study the standard deviations of the estimates of the volume parameter were large, and it was not possible to decide which volume gave the best estimates of the volume parameter, but there were distinct differences in the mean values of the values obtained.

An imidazopyridine anxiolytic alters glucose tolerance in patients: a pilot investigation.

PubMed

Bottaï, T; Cartault, F; Pouget, R; Blayac, J P; Petit, P

1995-02-01

We have recently shown that compounds with high affinity for peripheral-type benzodiazepine receptors inhibited glucose-induced insulin secretion in vitro. We therefore performed an oral glucose tolerance test in anxious inpatients treated with the imidazopyridine derivative alpidem, which has been shown to display high affinity for these binding sites. The test was performed before and after 1 week of daily administration of the drug. As compared with pretreatment values, a significant alteration of the insulin response to glucose was observed. It is suggested that daily administration of alpidem, at therapeutically effective doses for the treatment of anxiety, may alter glucose tolerance.

Organ dose assessment in pediatric fluoroscopy and CT via a tomographic computational phantom of the newborn patient

NASA Astrophysics Data System (ADS)

Staton, Robert J.

Of the various types of imaging modalities used in pediatric radiology, fluoroscopy and computed tomography (CT) have the highest associated radiation dose. While these examinations are commonly used for pediatric patients, little data exists on the magnitude of the organ and effective dose values for these procedures. Calculation of these dose values is necessary because of children's increased sensitivity to radiation and their long life expectancy for which to express radiation's latent effects. In this study, a newborn tomographic phantom has been implemented in a radiation transport code to evaluate organ and effective doses for newborn patients in commonly performed fluoroscopy and CT examinations. Organ doses were evaluated for voiding cystourethrogram (VCUG) fluoroscopy studies of infant patients. Time-sequence analysis was performed for videotaped VCUG studies of five different patients. Organ dose values were then estimated for each patient through Monte Carlo (MC) simulations. The effective dose values of the VCUG examination for five patients ranged from 0.6 mSv to 3.2 mSv, with a mean of 1.8 +/- 0.9 mSv. Organ doses were also assessed for infant upper gastrointestinal (UGI) fluoroscopy exams. The effective dose values of the UGI examinations for five patients ranged from 1.05 mSv to 5.92 mSv, with a mean of 2.90 +/- 1.97 mSv. MC simulations of helical multislice CT (MSCT) exams were also completed using, the newborn tomographic phantom and a stylized newborn phantom. The helical path of the source, beam shaping filter, beam profile, patient table, were all included in the MC simulations of the helical MSCT scanner. Organ doses and effective doses and their dependence on scan parameters were evaluated for newborn patients. For all CT scans, the effective dose was found to range approximately 1-13 mSv, with the largest values occurring for CAP scans. Tube current modulation strategies to reduce patient dose were also evaluated for newborn patients. Overall, utilization of the newborn tomographic phantom in MC simulations has shown the need for and usefulness of pediatric tomographic phantoms. The newborn tomographic model has shown more versatility and realistic anatomical modeling when compared to the existing stylized newborn phantom. This work has provided important organ dose data for infant patients in common examinations in pediatric radiology.

Long-term effectiveness of plasma-derived hepatitis B vaccine 22-28 years after immunization in a hepatitis B virus endemic rural area: is an adult booster dose needed?

PubMed

Li, H; Li, G J; Chen, Q Y; Fang, Z L; Wang, X Y; Tan, C; Yang, Q L; Wang, F Z; Wang, F; Zhang, S; Bi, S L; Shen, L P

2017-04-01

Longan County is considered a highly endemic area for hepatitis B virus (HBV). The plasma-derived vaccine has been used in newborns in this area since 1987. A cross-sectional survey was conducted to evaluate the long-term effectiveness of this vaccine. In total, 1634 participants born during 1987-1993 and who had received a series of plasma-derived HB vaccinations at ages 0, 1, and 6 months were enrolled. Serological HBV markers were detected and compared with previous survey data. Overall the prevalence of hepatitis B surface antigen (HBsAg) in all participants was 3·79%; 3·47% of subjects who had received the first dose within 24 h were HBsAg positive, and 8·41% of subjects who had received a delayed first dose were also HBsAg positive. There were 1527 subjects identified who had received the first dose within 24 h and whose HBsAg and anti-HBc prevalence increased yearly after immunization, while the anti-HBs-positive rate and vaccine effectiveness declined. The geometric mean concentration of antibody in the anti-HB-positive participants was 55·13 mIU/ml and this declined after immunization. Fewer than 2·0% of participants had anti-HB levels ⩾1000 mIU/ml. The data show that the protective efficacy of the plasma-derived vaccinations declined and administration of HB vaccine within 24 h of birth was very important. To reduce the risk of HBV infection in this highly endemic area, a booster dose might be necessary if anti-HBs levels fall below 10 mIU/ml after age 18 years. Furthermore, studies on the immune memory induced by plasma-derived HB vaccine are needed.

A revised burial dose estimation procedure for optical dating of youngand modern-age sediments

USGS Publications Warehouse

Arnold, L.J.; Roberts, R.G.; Galbraith, R.F.; DeLong, S.B.

2009-01-01

The presence of genuinely zero-age or near-zero-age grains in modern-age and very young samples poses a problem for many existing burial dose estimation procedures used in optical (optically stimulated luminescence, OSL) dating. This difficulty currently necessitates consideration of relatively simplistic and statistically inferior age models. In this study, we investigate the potential for using modified versions of the statistical age models of Galbraith et??al. [Galbraith, R.F., Roberts, R.G., Laslett, G.M., Yoshida, H., Olley, J.M., 1999. Optical dating of single and multiple grains of quartz from Jinmium rock shelter, northern Australia: Part I, experimental design and statistical models. Archaeometry 41, 339-364.] to provide reliable equivalent dose (De) estimates for young and modern-age samples that display negative, zero or near-zero De estimates. For this purpose, we have revised the original versions of the central and minimum age models, which are based on log-transformed De values, so that they can be applied to un-logged De estimates and their associated absolute standard errors. The suitability of these 'un-logged' age models is tested using a series of known-age fluvial samples deposited within two arroyo systems from the American Southwest. The un-logged age models provide accurate burial doses and final OSL ages for roughly three-quarters of the total number of samples considered in this study. Sensitivity tests reveal that the un-logged versions of the central and minimum age models are capable of producing accurate burial dose estimates for modern-age and very young (<350??yr) fluvial samples that contain (i) more than 20% of well-bleached grains in their De distributions, or (ii) smaller sub-populations of well-bleached grains for which the De values are known with high precision. Our results indicate that the original (log-transformed) versions of the central and minimum age models are still preferable for most routine dating applications, since these age models are better suited to the statistical properties of typical single-grain and multi-grain single-aliquot De datasets. However, the unique error properties of modern-age samples, combined with the problems of calculating natural logarithms of negative or zero-Gy De values, mean that the un-logged versions of the central and minimum age models currently offer the most suitable means of deriving accurate burial dose estimates for very young and modern-age samples. ?? 2009 Elsevier Ltd. All rights reserved.

Pharmacokinetics, pharmacodynamics, and dose-response relationship of repaglinide in type 2 diabetes.

PubMed

Strange, P; Schwartz, S L; Graf, R J; Polvino, W; Weston, I; Marbury, T C; Huang, W C; Goldberg, R B

1999-01-01

The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes. Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean). Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events. These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.

A single institution study of radiation dose received from CT imaging: A comparison to Malaysian NDRL

NASA Astrophysics Data System (ADS)

Osman, N. D.; Shamsuri, S. B. M.; Tan, Y. W.; Razali, M. A. S. M.; Isa, S. M.

2017-05-01

Advancement of CT technology has led to an increase in CT scanning as it improves the diagnosis. However, it is important to assess health risk of patients associated with ionising radiation received from CT. This study evaluated current dose distributions at Advanced Medical and Dental Institute (AMDI), Malaysia and was used to establish Local Diagnostic Reference Level (LDRL). Dose indicators such as CT Dose Index (CTDIvol and CTDIw) and Dose-Length Product (DLP) were gathered for all routine CT examinations performed at the Imaging Unit, AMDI from January 2015 to June 2016. The first and third quartile values for each dose indicator were determined. A total of 364 CT studies were performed during that period with the highest number of cases being Thorax-Abdomen-Pelvis (TAP) study (57% of total study). The CTDIw ranged between 2.0 mGy to 23.4 mGy per procedure. DLP values were ranged between 94 mGy.cm to 1687 mGy.cm. The local dose data was compared with the national DRL to monitor the current CT practice at AMDI and LDRL will be established from the calculated third quartile values of dose distribution. From the results, some of the local dose values exceeded the Malaysian and further evaluation is important to ensure the dose optimisation for patients.

Use of computer code for dose distribution studies in A 60CO industrial irradiator

NASA Astrophysics Data System (ADS)

Piña-Villalpando, G.; Sloan, D. P.

1995-09-01

This paper presents a benchmark comparison between calculated and experimental absorbed dose values tor a typical product, in a 60Co industrial irradiator, located at ININ, México. The irradiator is a two levels, two layers system with overlapping product configuration with activity around 300kCi. Experimental values were obtanied from routine dosimetry, using red acrylic pellets. Typical product was Petri dishes packages, apparent density 0.13 g/cm3; that product was chosen because uniform size, large quantity and low density. Minimum dose was fixed in 15 kGy. Calculated values were obtained from QAD-CGGP code. This code uses a point kernel technique, build-up factors fitting was done by geometrical progression and combinatorial geometry is used for system description. Main modifications for the code were related with source sumilation, using punctual sources instead of pencils and an energy and anisotropic emission spectrums were included. Results were, for maximum dose, calculated value (18.2 kGy) was 8% higher than experimental average value (16.8 kGy); for minimum dose, calculated value (13.8 kGy) was 3% higher than experimental average value (14.3 kGy).

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.

Historical Doses from Tritiated Water and Tritiated Hydrogen Gas Released to the Atmosphere from Lawrence Livermore National Laboratory (LLNL). Part 5. Accidental Releases

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

Peterson, S

2007-08-15

Over the course of fifty-three years, LLNL had six acute releases of tritiated hydrogen gas (HT) and one acute release of tritiated water vapor (HTO) that were too large relative to the annual releases to be included as part of the annual releases from normal operations detailed in Parts 3 and 4 of the Tritium Dose Reconstruction (TDR). Sandia National Laboratories/California (SNL/CA) had one such release of HT and one of HTO. Doses to the maximally exposed individual (MEI) for these accidents have been modeled using an equation derived from the time-dependent tritium model, UFOTRI, and parameter values based onmore » expert judgment. All of these acute releases are described in this report. Doses that could not have been exceeded from the large HT releases of 1965 and 1970 were calculated to be 43 {micro}Sv (4.3 mrem) and 120 {micro}Sv (12 mrem) to an adult, respectively. Two published sets of dose predictions for the accidental HT release in 1970 are compared with the dose predictions of this TDR. The highest predicted dose was for an acute release of HTO in 1954. For this release, the dose that could not have been exceeded was estimated to have been 2 mSv (200 mrem), although, because of the high uncertainty about the predictions, the likely dose may have been as low as 360 {micro}Sv (36 mrem) or less. The estimated maximum exposures from the accidental releases were such that no adverse health effects would be expected. Appendix A lists all accidents and large routine puff releases that have occurred at LLNL and SNL/CA between 1953 and 2005. Appendix B describes the processes unique to tritium that must be modeled after an acute release, some of the time-dependent tritium models being used today, and the results of tests of these models.« less

Experimental design and statistical analysis for three-drug combination studies.

PubMed

Fang, Hong-Bin; Chen, Xuerong; Pei, Xin-Yan; Grant, Steven; Tan, Ming

2017-06-01

Drug combination is a critically important therapeutic approach for complex diseases such as cancer and HIV due to its potential for efficacy at lower, less toxic doses and the need to move new therapies rapidly into clinical trials. One of the key issues is to identify which combinations are additive, synergistic, or antagonistic. While the value of multidrug combinations has been well recognized in the cancer research community, to our best knowledge, all existing experimental studies rely on fixing the dose of one drug to reduce the dimensionality, e.g. looking at pairwise two-drug combinations, a suboptimal design. Hence, there is an urgent need to develop experimental design and analysis methods for studying multidrug combinations directly. Because the complexity of the problem increases exponentially with the number of constituent drugs, there has been little progress in the development of methods for the design and analysis of high-dimensional drug combinations. In fact, contrary to common mathematical reasoning, the case of three-drug combinations is fundamentally more difficult than two-drug combinations. Apparently, finding doses of the combination, number of combinations, and replicates needed to detect departures from additivity depends on dose-response shapes of individual constituent drugs. Thus, different classes of drugs of different dose-response shapes need to be treated as a separate case. Our application and case studies develop dose finding and sample size method for detecting departures from additivity with several common (linear and log-linear) classes of single dose-response curves. Furthermore, utilizing the geometric features of the interaction index, we propose a nonparametric model to estimate the interaction index surface by B-spine approximation and derive its asymptotic properties. Utilizing the method, we designed and analyzed a combination study of three anticancer drugs, PD184, HA14-1, and CEP3891 inhibiting myeloma H929 cell line. To our best knowledge, this is the first ever three drug combinations study performed based on the original 4D dose-response surface formed by dose ranges of three drugs.

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

Kauweloa, K; Gutierrez, A; Bergamo, A

Purpose: There is growing interest about biological effective dose (BED) and its application in treatment plan evaluation due to its stronger correlation with treatment outcome. An approximate biological effective dose (BEDA) equation was introduced to simplify BED calculations by treatment planning systems in multi-phase treatments. The purpose of this work is to reveal its mathematical properties relative to the true, multi-phase BED (BEDT) equation. Methods: The BEDT equation was derived and used to reveal the mathematical properties of BEDA. MATLAB (MathWorks, Natick, MA) was used to simulate and analyze common and extreme clinical multi-phase cases. In those cases, percent errormore » (Perror) and Bland-Altman analysis were used to study the significance of the inaccuracies of BEDA for different combinations of total doses, numbers of fractions, doses per fractions and α over β values. All the calculations were performed on a voxel-basis in order to study how dose distributions would affect the accuracy of BEDA. Results: When the voxel dose-per-fractions (DPF) delivered by both phases are equal, BEDA and BEDT are equal. In heterogeneous dose distributions, which significantly vary between the phases, there are fewer occurrences of equal DPFs and hence the imprecision of BEDA is greater. It was shown that as the α over β ratio increased the accuracy of BEDA would improve. Examining twenty-four cases, it was shown that the range of DPF ratios for a 3 Perror varied from 0.32 to 7.50Gy, whereas for Perror of 1 the range varied from 0.50 to 2.96Gy. Conclusion: The DPF between the different phases should be equal in order to render BEDA accurate. OARs typically receive heterogeneous dose distributions hence the probability of equal DPFs is low. Consequently, the BEDA equation should only be used for targets or OARs that receive uniform or very similar dose distributions by the different treatment phases.« less

[The determination of the discrepancy between the mathematically ascertained and experimentally provable efficiency of UV facilities for water disinfection].

PubMed

Leuker, G; Hingst, V

1992-10-01

Using three UV-plants of different technical designs for water disinfection, we studied the conformity between experimental germ reduction using standard test organisms and calculated UV-doses under various water flow conditions. Taking into consideration the style of construction of the UV-plants, the irradiation area and the layer thickness were used as constant parameters for dose calculations. This was also employed for the irradiation intensity, since the experiments were performed for a relatively short period compared of the life span of the UV-irradiators. Both exposure time and water transmission were employed as variable parameters in the dose calculations and experimental procedures respectively. The calculated UV-dose and experimentally obtained germ reduction values were comparatively the same for two of the three UV-plants studied. However, no correlation was observed between the reduction of E. coli and the corresponding calculated UV-dose values. Therefore, the calculated UV-dose values for any given UV-plant should be considered to be relative and by no means absolute values. We are of the opinion that within a certain range of water flow rate and transmission, antimicrobial effectiveness of different UV-plants should be demonstrated independent of dose values, technical and other construction characteristics. The applicability of the UV-plants studied is discussed.

Effective dose rate coefficients for exposure to contaminated soil

DOE PAGES

Veinot, Kenneth G.; Eckerman, Keith F.; Bellamy, Michael B.; ...

2017-05-10

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose ratemore » calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. As a result, the coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.« less

Effective dose rate coefficients for exposure to contaminated soil

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

Veinot, Kenneth G.; Eckerman, Keith F.; Bellamy, Michael B.

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose ratemore » calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. As a result, the coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.« less

Systematic Review of Observational Studies with Dose-Response Meta-Analysis between Folate Intake and Status Biomarkers in Adults and the Elderly.

PubMed

Novaković, Romana; Geelen, Anouk; Ristić-Medić, Danijela; Nikolić, Marina; Souverein, Olga W; McNulty, Helene; Duffy, Maresa; Hoey, Leane; Dullemeijer, Carla; Renkema, Jacoba M S; Gurinović, Mirjana; Glibetić, Marija; de Groot, Lisette C P G M; Van't Veer, Pieter

2018-06-07

Dietary reference values for folate intake vary widely across Europe. MEDLINE and Embase through November 2016 were searched for data on the association between folate intake and biomarkers (serum/plasma folate, red blood cell [RBC] folate, plasma homocysteine) from observational studies in healthy adults and elderly. The regression coefficient of biomarkers on intake (β) was extracted from each study, and the overall and stratified pooled β and SE (β) were obtained by random effects meta-analysis on a double log scale. These dose-response estimates may be used to derive folate intake reference values. For every doubling in folate intake, the changes in serum/plasma folate, RBC folate and plasma homocysteine were +22, +21, and -16% respectively. The overall pooled regression coefficients were β = 0.29 (95% CI 0.21-0.37) for serum/plasma folate (26 estimates from 17 studies), β = 0.28 (95% CI 0.21-0.36) for RBC (13 estimates from 11 studies), and β = -0.21 (95% CI -0.31 to -0.11) for plasma homocysteine (10 estimates from 6 studies). These estimates along with those from randomized controlled trials can be used for underpinning dietary recommendations for folate in adults and elderly. © 2018 S. Karger AG, Basel.

Derivatives of Dictyostelium differentiation-inducing factors inhibit lysophosphatidic acid–stimulated migration of murine osteosarcoma LM8 cells

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

Kubohara, Yuzuru, E-mail: ykuboha@juntendo.ac.jp; Department of Health Science, Juntendo University Graduate School of Health and Sports Science, Inzai 270-1695; Komachi, Mayumi

Osteosarcoma is a common metastatic bone cancer that predominantly develops in children and adolescents. Metastatic osteosarcoma remains associated with a poor prognosis; therefore, more effective anti-metastatic drugs are needed. Differentiation-inducing factor-1 (DIF-1), −2, and −3 are novel lead anti-tumor agents that were originally isolated from the cellular slime mold Dictyostelium discoideum. Here we investigated the effects of a panel of DIF derivatives on lysophosphatidic acid (LPA)-induced migration of mouse osteosarcoma LM8 cells by using a Boyden chamber assay. Some DIF derivatives such as Br-DIF-1, DIF-3(+2), and Bu-DIF-3 (5–20 μM) dose-dependently suppressed LPA-induced cell migration with associated IC{sub 50} values of 5.5, 4.6, andmore » 4.2 μM, respectively. On the other hand, the IC{sub 50} values of Br-DIF-1, DIF-3(+2), and Bu-DIF-3 versus cell proliferation were 18.5, 7.2, and 2.0 μM, respectively, in LM8 cells, and >20, 14.8, and 4.3 μM, respectively, in mouse 3T3-L1 fibroblasts (non-transformed). Together, our results demonstrate that Br-DIF-1 in particular may be a valuable tool for the analysis of cancer cell migration, and that DIF derivatives such as DIF-3(+2) and Bu-DIF-3 are promising lead anti-tumor agents for the development of therapies that suppress osteosarcoma cell proliferation, migration, and metastasis. - Highlights: • LPA induces cell migration (invasion) in murine osteosarcoma LM8 cells. • DIFs are novel lead anti-tumor agents found in Dictyostelium discoideum. • We examined the effects of DIF derivatives on LPA-induced LM8 cell migration in vitro. • Some of the DIF derivatives inhibited LPA-induced LM8 cell migration.« less

Double-blind evaluation of the safety and pharmacokinetics of multiple oral once-daily 750-milligram and 1-gram doses of levofloxacin in healthy volunteers.

PubMed

Chien, S C; Wong, F A; Fowler, C L; Callery-D'Amico, S V; Williams, R R; Nayak, R; Chow, A T

1998-04-01

The safety and pharmacokinetics of once-daily oral levofloxacin in 16 healthy male volunteers were investigated in a randomized, double-blind, placebo-controlled study. Subjects were randomly assigned to the treatment (n = 10) or placebo group (n = 6). In study period 1, 750 mg of levofloxacin or a placebo was administered orally as a single dose on day 1, followed by a washout period on days 2 and 3; dosing resumed for days 4 to 10. Following a 3-day washout period, 1 g of levofloxacin or a placebo was administered in a similar fashion in period 2. Plasma and urine levofloxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. Levofloxacin was rapidly absorbed after single and multiple once-daily 750-mg and 1-g doses with an apparently large volume of distribution. Peak plasma levofloxacin concentration (Cmax) values were generally attained within 2 h postdose. The mean values of Cmax and area under the concentration-time curve from 0 to 24 h (AUC0-24) following a single 750-mg dose were 7.1 microg/ml and 71.3 microg x h/ml, respectively, compared to 8.6 microg/ml and 90.7 microg x h/ml, respectively, at steady state. Following the single 1-g dose, mean Cmax and AUC0-24 values were 8.9 microg/ml and 95.4 microg x h/ml, respectively; corresponding values at steady state were 11.8 microg/ml and 118 microg x h/ml. These Cmax and AUC0-24 values indicate modest and similar degrees of accumulation upon multiple dosing at the two dose levels. Values of apparent total body clearance (CL/F), apparent volume of distribution (Vss/F), half-life (t1/2), and renal clearance (CL[R]) were similar for the two dose levels and did not vary from single to multiple dosing. Mean steady-state values for CL/F, Vss/F, t1/2, and CL(R) following 750 mg of levofloxacin were 143 ml/min, 100 liters, 8.8 h, and 116 ml/min, respectively; corresponding values for the 1-g dose were 146 ml/min, 105 liters, 8.9 h, and 105 ml/min. In general, the pharmacokinetics of levofloxacin in healthy subjects following 750-mg and 1-g single and multiple once-daily oral doses appear to be consistent with those found in previous studies of healthy volunteers given 500-mg doses. Levofloxacin was well tolerated at either high dose level. The most frequently reported drug-related adverse events were nausea and headache.

Double-Blind Evaluation of the Safety and Pharmacokinetics of Multiple Oral Once-Daily 750-Milligram and 1-Gram Doses of Levofloxacin in Healthy Volunteers

PubMed Central

Chien, Shu-Chean; Wong, Frank A.; Fowler, Cynthia L.; Callery-D’Amico, Susan V.; Williams, R. Rex; Nayak, Ramchandra; Chow, Andrew T.

1998-01-01

The safety and pharmacokinetics of once-daily oral levofloxacin in 16 healthy male volunteers were investigated in a randomized, double-blind, placebo-controlled study. Subjects were randomly assigned to the treatment (n = 10) or placebo group (n = 6). In study period 1, 750 mg of levofloxacin or a placebo was administered orally as a single dose on day 1, followed by a washout period on days 2 and 3; dosing resumed for days 4 to 10. Following a 3-day washout period, 1 g of levofloxacin or a placebo was administered in a similar fashion in period 2. Plasma and urine levofloxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. Levofloxacin was rapidly absorbed after single and multiple once-daily 750-mg and 1-g doses with an apparently large volume of distribution. Peak plasma levofloxacin concentration (Cmax) values were generally attained within 2 h postdose. The mean values of Cmax and area under the concentration-time curve from 0 to 24 h (AUC0–24) following a single 750-mg dose were 7.1 μg/ml and 71.3 μg · h/ml, respectively, compared to 8.6 μg/ml and 90.7 μg · h/ml, respectively, at steady state. Following the single 1-g dose, mean Cmax and AUC0–24 values were 8.9 μg/ml and 95.4 μg · h/ml, respectively; corresponding values at steady state were 11.8 μg/ml and 118 μg · h/ml. These Cmax and AUC0–24 values indicate modest and similar degrees of accumulation upon multiple dosing at the two dose levels. Values of apparent total body clearance (CL/F), apparent volume of distribution (Vss/F), half-life (t1/2), and renal clearance (CLR) were similar for the two dose levels and did not vary from single to multiple dosing. Mean steady-state values for CL/F, Vss/F, t1/2, and CLR following 750 mg of levofloxacin were 143 ml/min, 100 liters, 8.8 h, and 116 ml/min, respectively; corresponding values for the 1-g dose were 146 ml/min, 105 liters, 8.9 h, and 105 ml/min. In general, the pharmacokinetics of levofloxacin in healthy subjects following 750-mg and 1-g single and multiple once-daily oral doses appear to be consistent with those found in previous studies of healthy volunteers given 500-mg doses. Levofloxacin was well tolerated at either high dose level. The most frequently reported drug-related adverse events were nausea and headache. PMID:9559801

Comparison of vitamins K1, K2 and K3 effects on growth of rat glioma and human glioblastoma multiforme cells in vitro.

PubMed

Oztopçu, Pinar; Kabadere, Selda; Mercangoz, Ayşe; Uyar, Ruhi

2004-09-01

Glioblastoma multiforme is characterized as highly invasive and rapidly growing astrocytomas, and scientists have sought for efficient treatment against malignant gliomas for a long time. Therefore, we compared the respond of rat glioma (C6) and glioblastoma multiforme cells derived from two patients to vitamins K1, K2 and K3. The cells were exposed to 100, 250, 500, 750 and 1000 microM of vitamins K1 and K2, and 1, 10, 25, 50, 75 and 100 microM of vitamin K3 for 24 hours in an incubator atmosphere of 5% CO2, 37 degrees C and 100% humidity. Cell viability was estimated by MTT assay. Vitamin K1 showed no growth effect on all the glioma cells examined. Vitamin K2 did not cause any change in number of C6, however induced growth inhibition in a dose-dependent manner on glioblastoma multiforme. The IC50 values of vitamin K2 were 960 microM and 970 microM for glioblastoma multiforme, respectively. Vitamin K3 had also growth inhibitory effect in a dose-dependent manner on both C6 and glioblastoma multiforme. The IC50 values were 41 microM, 24 microM and 23 microM for vitamin K3, respectively. We concluded that vitamin K3 is more effective than vitamin K2 for inhibition of cancer cell growth, and might have an alternative value as an anticancer drug against glioblastoma multiforme.

Application of the "threshold of toxicological concern" to derive tolerable concentrations of "non-relevant metabolites" formed from plant protection products in ground and drinking water.

PubMed

Melching-Kollmuss, Stephanie; Dekant, Wolfgang; Kalberlah, Fritz

2010-03-01

Limits for tolerable concentrations of ground water metabolites ("non-relevant metabolites" without targeted toxicities and specific classification and labeling) derived from active ingredients (AI) of plant protection products (PPPs) are discussed in the European Union. Risk assessments for "non-relevant metabolites" need to be performed when concentrations are above 0.75 microg/L. Since oral uptake is the only relevant exposure pathway for "non-relevant metabolites", risk assessment approaches as used for other chemicals with predominantly oral exposure in humans are applicable. The concept of "thresholds of toxicological concern" (TTC) defines tolerable dietary intakes for chemicals without toxicity data and is widely applied to chemicals present in food in low concentrations such as flavorings. Based on a statistical evaluation of the results of many toxicity studies and considerations of chemical structures, the TTC concept derives a maximum daily oral intake without concern of 90 microg/person/day for non-genotoxic chemicals, even for those with appreciable toxicity. When using the typical exposure assessment for drinking water contaminants (consumption of 2L of drinking water/person/day, allocation of 10% of the tolerable daily intake to drinking water), a TTC-based upper concentration limit of 4.5 microg/L for "non-relevant metabolites" in ground/drinking water is delineated. In the present publication it has been evaluated, whether this value would cover all relevant toxicities (repeated dose, reproductive and developmental, and immune effects). Taking into account, that after evaluation of specific reproduction toxicity data from chemicals and pharmaceuticals, a value of 1 microg/kgbw/day has been assessed as to cover developmental and reproduction toxicity, a TTC value of 60 microg/person/day was assessed as to represent a safe value. Based on these reasonable worst case assumptions, a TTC-derived threshold of 3 microg/L in drinking water is derived. When a non-relevant metabolite is present in concentration below 3 microg/L, animal testing for toxicity is not considered necessary for a compound-specific risk assessment since the application of the TTC covers all relevant toxicities to be considered in such assessment and any health risk resulting from these exposures is very low. (c) 2009 Elsevier Inc. All rights reserved.

Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun

2001-11-01

A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

Analysis of EPR and FISH studies of radiation doses in persons who lived in the upper reaches of the Techa River.

PubMed

Degteva, M O; Shagina, N B; Shishkina, E A; Vozilova, A V; Volchkova, A Y; Vorobiova, M I; Wieser, A; Fattibene, P; Della Monaca, S; Ainsbury, E; Moquet, J; Anspaugh, L R; Napier, B A

2015-11-01

Waterborne radioactive releases into the Techa River from the Mayak Production Association in Russia during 1949-1956 resulted in significant doses to about 30,000 persons who lived in downstream settlements. The residents were exposed to internal and external radiation. Two methods for reconstruction of the external dose are considered in this paper, electron paramagnetic resonance (EPR) measurements of teeth, and fluorescence in situ hybridization (FISH) measurements of chromosome translocations in circulating lymphocytes. The main issue in the application of the EPR and FISH methods for reconstruction of the external dose for the Techa Riverside residents was strontium radioisotopes incorporated in teeth and bones that act as a source of confounding local exposures. In order to estimate and subtract doses from incorporated (89,90)Sr, the EPR and FISH assays were supported by measurements of (90)Sr-body burdens and estimates of (90)Sr concentrations in dental tissues by the luminescence method. The resulting dose estimates derived from EPR to FISH measurements for residents of the upper Techa River were found to be consistent: The mean values vary from 510 to 550 mGy for the villages located close to the site of radioactive release to 130-160 mGy for the more distant villages. The upper bound of individual estimates for both methods is equal to 2.2-2.3 Gy. The EPR- and FISH-based dose estimates were compared with the doses calculated for the donors using the most recent Techa River Dosimetry System (TRDS). The TRDS external dose assessments are based on the data on contamination of the Techa River floodplain, simulation of air kerma above the contaminated soil, age-dependent lifestyles and individual residence histories. For correct comparison, TRDS-based doses were calculated from two sources: external exposure from the contaminated environment and internal exposure from (137)Cs incorporated in donors' soft tissues. It is shown here that the TRDS-based absorbed doses in tooth enamel and muscle are in agreement with EPR- and FISH-based estimates within uncertainty bounds. Basically, this agreement between the estimates has confirmed the validity of external doses calculated with the TRDS.

TH-CD-201-03: A Real-Time Method to Simultaneously Measure Linear Energy Transfer and Dose for Proton Therapy Using Organic Scintillators

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

Alsanea, F; Therriault-Proulx, F; Sawakuchi, G

Purpose: The light generated in organic scintillators depends on both the radiation dose and the linear energy transfer (LET). The LET dependence leads to an under-response of the detector in the Bragg peak of proton beams. This phenomenon, called ionization quenching, must be corrected to obtain accurate dose measurements of proton beams. This work exploits the ionization quenching phenomenon to provide a method of measuring LET and auto correcting quenching. Methods: We exposed simultaneously four different organic scintillators (BCF-12, PMMA, PVT, and LSD; 1mm in diameter) and a plane parallel ionization chamber in passively scattered proton beams to doses betweenmore » 32 and 43 cGy and fluence averaged LET values from 0.47 to 1.26 keV/µm. The LET values for each irradiation condition were determined using a validated Monte Carlo model of the beam line. We determined the quenching parameter in the Birk’s equation for scintillation in BCF-12 for dose measurements. One set of irradiation conditions was used to correlate the scintillation response ratio to the LET values and plot a scintillation response ratio versus LET calibration curve. Irradiation conditions independent from the calibration ones were used to validate this method. Comparisons to the expected values were made on both the basis of dose and LET. Results: Among all the scintillators investigated, the ratio of PMMA to BCF-12 provided the best correlation to LET values and was used as the LET calibration curve. The expected LET values in the validation set were within 2%±6%, which resulted in dose accuracy of 1.5%±5.8% for the range of LET values investigated in this work. Conclusion: We have demonstrated the feasibility of using the ratio between the light output of two organic scintillators to simultaneously measure LET and dose of therapeutic proton beams. Further studies are needed to verify the response in higher LET values.« less

Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

PubMed

Deng, Yun-xia; Cao, Mei; Shi, Dong-xia; Yin, Zhong-qiong; Jia, Ren-yong; Xu, Jiao; Wang, Chuan; Lv, Cheng; Liang, Xiao-xia; He, Chang-liang; Yang, Zhi-rong; Zhao, Jian

2013-03-01

Neem (Azadirachta indica), popularly known as traditional medicine is a native plant in India. Neem oil is a vegetable oil derived from seeds or fruits of the neem tree through pressing or solvent extraction, and largely used in popular medicine to have antifungal, antibacterial, antimalarial, antiparasitic, anti-inflammatory, as well as immunemodulatory properties in different animal species. In the present study, acute and 28-day subacute toxicity tests were carried out. In the acute toxicity test, the LD50 values of neem oil were found to be 31.95g/kg. The subacute treatment with neem oil failed to change body weight gain, food and water consumption. Serum biochemistry analysis showed no significant differences in any of the parameters examined under the dose of 1600mg/kg/day. Histopathological exams showed that the target organs of neem oil were testicle, liver and kidneys up to the dose of 1600mg/kg/day. Copyright © 2013 Elsevier B.V. All rights reserved.

Three further triterpenoid saponins from Gleditsia caspica fruits and protective effect of the total saponin fraction on cyclophosphamide-induced genotoxicity in mice.

PubMed

Melek, Farouk R; Aly, Fawzia A; Kassem, Iman A A; Abo-Zeid, Mona A M; Farghaly, Ayman A; Hassan, Zeinab M

2015-01-01

Three triterpenoidal saponins were isolated from the saponin fraction derived from a Gleditsia caspica Desf. methanolic fruit extract. The isolated saponins were identified as gleditsiosides B, C, and Q based on spectral data. The saponin-containing fraction was evaluated in vivo for genotoxic and antigenotoxic activities. The fraction caused no DNA damage in Swiss albino male mice treated with a dose of 45 mg/kg body weight for 24 h, although it significantly inhibited the number of chromosomal aberrations induced by cyclophosphamide (CP) in bone marrow and germ cells when applied before or after CP administration. The inhibitory indices in chromosomal aberrations were 59% and 41% for bone marrow and 48% and 43% for germ cells, respectively. In addition, the saponin fraction was found to reduce the viability of the human tumor cell line MCF-7 in a dose-dependent manner with an extrapolated IC50 value in the range of 220 μg/mL.

Confidence limit calculation for antidotal potency ratio derived from lethal dose 50

PubMed Central

Manage, Ananda; Petrikovics, Ilona

2013-01-01

AIM: To describe confidence interval calculation for antidotal potency ratios using bootstrap method. METHODS: We can easily adapt the nonparametric bootstrap method which was invented by Efron to construct confidence intervals in such situations like this. The bootstrap method is a resampling method in which the bootstrap samples are obtained by resampling from the original sample. RESULTS: The described confidence interval calculation using bootstrap method does not require the sampling distribution antidotal potency ratio. This can serve as a substantial help for toxicologists, who are directed to employ the Dixon up-and-down method with the application of lower number of animals to determine lethal dose 50 values for characterizing the investigated toxic molecules and eventually for characterizing the antidotal protections by the test antidotal systems. CONCLUSION: The described method can serve as a useful tool in various other applications. Simplicity of the method makes it easier to do the calculation using most of the programming software packages. PMID:25237618

Estimating Toxicity Pathway Activating Doses for High Throughput Chemical Risk Assessments

EPA Science Inventory

Estimating a Toxicity Pathway Activating Dose (TPAD) from in vitro assays as an analog to a reference dose (RfD) derived from in vivo toxicity tests would facilitate high throughput risk assessments of thousands of data-poor environmental chemicals. Estimating a TPAD requires def...

Reconstruction of erythemal UV irradiance at Hohenpeissenberg (1968-2001) considering trends of total ozone, cloudiness, and turbidity

NASA Astrophysics Data System (ADS)

Trepte, S.; Winkler, P.

2003-04-01

The global mean total column ozone amount for the period 1997-2001 was approximately 3% below the 1964-1980 average. The largest ozone decreases in the northern hemisphere midlatitudes are observed during winter-spring (˜4%), with summer-autumn decreases approximately half as large. Total ozone measured at Hohenpeissenberg, Germany (48^oN, 11^oE) shows a strong decrease by about 10% since 1968, representing the long-term downward trend over Central Europe. The main consequence of this phenomenon is the expected increase of solar ultraviolet irradiation (UV-B) reaching the Earth's surface with the known harmful effects on the biosphere. Global data records of reliable routine observations of UV irradiance are still too short for accurate estimation of long-term UV variations and trends. While direct UV mesaurements at Hohenpeissenberg are available only since 1990, the long-term development of UV-B have to be reconstructed. Besides on the amount of total ozone the UV irradiation at the ground depends also on atmospheric turbidity and cloudiness. The reconstruction method is based on statistical correlations of measured UV-B data with the influencing parameters total ozone, turbidity and cloud modification factors derived from eye-observations in connection with total solar irradiance data. These observed data allow a realistic reconstruction of the UV-B time series, since no assumption on these influencing data have to be made. A model is presented, using hourly observed spectral UV-B irradiance (1990-1998), total solar irradiance, total ozone amount (daily mean) and clouds to derive erythemal UV irradiance and daily doses at Hohenpeissenberg in the period 1968-2001. A comparison with recorded UV data shows good agreement. Due to long-term total ozone loss, peak values of erythemal UV irradiance in spring and summer at clear-sky conditions have strongly increased (+4.2%/decade in June). Mean daily doses have also increased in this season (+5.4%/decade in May) but meteorological changes like reduced sunshine duration and increased cloudiness lead to a partly compensation of the ozone-loss effect in spring and to an overcompensation in autumn, where we found a long-term decrease of the daily dose (-3.0%/decade in September). Model calculations also demonstrate large year-to-year fluctuations of UV doses induced by meteorological variability, which exceed the long-term trend of the various months significantly. Nevertheless, this investigation has shown that on a long-term time scale the daily doses develop in a different way as compared to the peak values because the reasons for ozone decline (anthropogenic CFC's) and the cloud cover (hydrological cycle changes due to greenhouse effect) are caused by different phenomena.

Sensitivity of NTCP parameter values against a change of dose calculation algorithm.

PubMed

Brink, Carsten; Berg, Martin; Nielsen, Morten

2007-09-01

Optimization of radiation treatment planning requires estimations of the normal tissue complication probability (NTCP). A number of models exist that estimate NTCP from a calculated dose distribution. Since different dose calculation algorithms use different approximations the dose distributions predicted for a given treatment will in general depend on the algorithm. The purpose of this work is to test whether the optimal NTCP parameter values change significantly when the dose calculation algorithm is changed. The treatment plans for 17 breast cancer patients have retrospectively been recalculated with a collapsed cone algorithm (CC) to compare the NTCP estimates for radiation pneumonitis with those obtained from the clinically used pencil beam algorithm (PB). For the PB calculations the NTCP parameters were taken from previously published values for three different models. For the CC calculations the parameters were fitted to give the same NTCP as for the PB calculations. This paper demonstrates that significant shifts of the NTCP parameter values are observed for three models, comparable in magnitude to the uncertainties of the published parameter values. Thus, it is important to quote the applied dose calculation algorithm when reporting estimates of NTCP parameters in order to ensure correct use of the models.

Sensitivity of NTCP parameter values against a change of dose calculation algorithm

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

Brink, Carsten; Berg, Martin; Nielsen, Morten

2007-09-15

Optimization of radiation treatment planning requires estimations of the normal tissue complication probability (NTCP). A number of models exist that estimate NTCP from a calculated dose distribution. Since different dose calculation algorithms use different approximations the dose distributions predicted for a given treatment will in general depend on the algorithm. The purpose of this work is to test whether the optimal NTCP parameter values change significantly when the dose calculation algorithm is changed. The treatment plans for 17 breast cancer patients have retrospectively been recalculated with a collapsed cone algorithm (CC) to compare the NTCP estimates for radiation pneumonitis withmore » those obtained from the clinically used pencil beam algorithm (PB). For the PB calculations the NTCP parameters were taken from previously published values for three different models. For the CC calculations the parameters were fitted to give the same NTCP as for the PB calculations. This paper demonstrates that significant shifts of the NTCP parameter values are observed for three models, comparable in magnitude to the uncertainties of the published parameter values. Thus, it is important to quote the applied dose calculation algorithm when reporting estimates of NTCP parameters in order to ensure correct use of the models.« less

A procedure to determine the planar integral spot dose values of proton pencil beam spots

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

Anand, Aman; Sahoo, Narayan; Zhu, X. Ronald

2012-02-15

Purpose: Planar integral spot dose (PISD) of proton pencil beam spots (PPBSs) is a required input parameter for beam modeling in some treatment planning systems used in proton therapy clinics. The measurement of PISD by using commercially available large area ionization chambers, like the PTW Bragg peak chamber (BPC), can have large uncertainties due to the size limitation of these chambers. This paper reports the results of our study of a novel method to determine PISD values from the measured lateral dose profiles and peak dose of the PPBS. Methods: The PISDs of 72.5, 89.6, 146.9, 181.1, and 221.8 MeVmore » energy PPBSs were determined by area integration of their planar dose distributions at different depths in water. The lateral relative dose profiles of the PPBSs at selected depths were measured by using small volume ion chambers and were investigated for their angular anisotropies using Kodak XV films. The peak spot dose along the beam's central axis (D{sub 0}) was determined by placing a small volume ion chamber at the center of a broad field created by the superposition of spots at different locations. This method allows eliminating positioning uncertainties and the detector size effect that could occur when measuring it in single PPBS. The PISD was then calculated by integrating the measured lateral relative dose profiles for two different upper limits of integration and then multiplying it with corresponding D{sub 0}. The first limit of integration was set to radius of the BPC, namely 4.08 cm, giving PISD{sub RBPC}. The second limit was set to a value of the radial distance where the profile dose falls below 0.1% of the peak giving the PISD{sub full}. The calculated values of PISD{sub RBPC} obtained from area integration method were compared with the BPC measured values. Long tail dose correction factors (LTDCFs) were determined from the ratio of PISD{sub full}/PISD{sub RBPC} at different depths for PPBSs of different energies. Results: The spot profiles were found to have angular anisotropy. This anisotropy in PPBS dose distribution could be accounted in a reasonable approximate manner by taking the average of PISD values obtained using the in-line and cross-line profiles. The PISD{sub RBPC} values fall within 3.5% of those measured by BPC. Due to inherent dosimetry challenges associated with PPBS dosimetry, which can lead to large experimental uncertainties, such an agreement is considered to be satisfactory for validation purposes. The PISD{sub full} values show differences ranging from 1 to 11% from BPC measured values, which are mainly due to the size limitation of the BPC to account for the dose in the long tail regions of the spots extending beyond its 4.08 cm radius. The dose in long tail regions occur both for high energy beams such as 221.8 MeV PPBS due to the contributions of nuclear interactions products in the medium, and for low energy PPBS because of their larger spot sizes. The calculated LTDCF values agree within 1% with those determined by the Monte Carlo (MC) simulations. Conclusions: The area integration method to compute the PISD from PPBS lateral dose profiles is found to be useful both to determine the correction factors for the values measured by the BPC and to validate the results from MC simulations.« less

Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas.

PubMed

Silveira, Edna Aparecida; Siman, Fabiana Dayse Magalhães; de Oliveira Faria, Thaís; Vescovi, Marcos Vinícius Altoé; Furieri, Lorena Barros; Lizardo, Juliana Hott Fúcio; Stefanon, Ivanita; Padilha, Alessandra Simão; Vassallo, Dalton Valentim

2014-02-01

Chronic lead exposure induces hypertension affecting endothelial function. We investigated whether low-concentration lead exposure alters blood pressure and vascular reactivity, focusing on the roles of NO, oxidative stress, cyclooxygenase-derived vasoconstrictor prostanoids, and the local angiotensin-renin system. Aortic rings from 3-month-old Wistar rats were treated daily with lead acetate (first dose 4mg/100g, subsequent doses 0.05mg/100g, im) or vehicle for 30 days. Treatment increased lead blood levels (12μg/dl), blood pressure, and aortic ring contractile response to phenylephrine (1nM-100mM). Contractile response after L-NAME administration increased in both groups but was higher after lead treatment. Lead effects on Rmax decreased more after apocynin and superoxide dismutase administration compared to control. Indomethacin reduced phenylephrine response more after lead treatment than in controls. The selective COX-2 inhibitor NS398, thromboxane A2/prostaglandin H2 receptor antagonist SQ 29,548, TXA2 synthase inhibitor furegrelate, EP1 receptor antagonist SC 19220, and ACE inhibitor and AT1 receptor antagonist losartan reduced phenylephrine responses only in vessels from lead-treated rats. Basal and stimulated NO release was reduced and local O2(-) liberation increased in the lead-treated group compared to controls. eNOS, iNOS, and AT1 receptor protein expression increased with lead exposure, but COX-2 protein expression decreased. This is the first demonstration that blood Pb(2+) (12µg/dl) concentrations below the WHO-established values increased systolic blood pressure and vascular phenylephrine reactivity. This effect was associated with reduced NO bioavailability, increased reactive oxygen species production, increased participation of COX-derived contractile prostanoids, and increased renin-angiotensin system activity. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Safe bunker designing for the 18 MV Varian 2100 Clinac: a comparison between Monte Carlo simulation based upon data and new protocol recommendations

PubMed Central

Beigi, Manije; Afarande, Fatemeh; Ghiasi, Hosein

2016-01-01

Aim The aim of this study was to compare two bunkers designed by only protocols recommendations and Monte Carlo (MC) based upon data derived for an 18 MV Varian 2100Clinac accelerator. Background High energy radiation therapy is associated with fast and thermal photoneutrons. Adequate shielding against the contaminant neutron has been recommended by IAEA and NCRP new protocols. Materials and methods The latest protocols released by the IAEA (safety report No. 47) and NCRP report No. 151 were used for the bunker designing calculations. MC method based upon data was also derived. Two bunkers using protocols and MC upon data were designed and discussed. Results From designed door's thickness, the door designed by the MC simulation and Wu–McGinley analytical method was closer in both BPE and lead thickness. In the case of the primary and secondary barriers, MC simulation resulted in 440.11 mm for the ordinary concrete, total concrete thickness of 1709 mm was required. Calculating the same parameters value with the recommended analytical methods resulted in 1762 mm for the required thickness using 445 mm as recommended by TVL for the concrete. Additionally, for the secondary barrier the thickness of 752.05 mm was obtained. Conclusion Our results showed MC simulation and the followed protocols recommendations in dose calculation are in good agreement in the radiation contamination dose calculation. Difference between the two analytical and MC simulation methods revealed that the application of only one method for the bunker design may lead to underestimation or overestimation in dose and shielding calculations. PMID:26900357

Georgia fishery study: implications for dose calculations. Revision 1

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

Turcotte, M.D.S.

Fish consumption will contribute a major portion of the estimated individual and population doses from L-Reactor liquid releases and Cs-137 remobilization in Steel Creek. It is therefore important that the values for fish consumption used in dose calculations be as realistic as possible. Since publication of the L-Reactor Environmental Information Document (EID), data have become available on sport fishing in the Savannah River. These data provide SRP with a site-specific sport fish harvest and consumption values for use in dose calculations. The Georgia fishery data support the total population fish consumption and calculated dose reported in the EID. The datamore » indicate, however, that both the EID average and maximum individual fish consumption have been underestimated, although each to a different degree. The average fish consumption value used in the EID is approximately 3% below the lower limit of the fish consumption range calculated using the Georgia data. Maximum fish consumption in the EID has been underestimated by approximately 60%, and doses to the maximum individual should also be recalculated. Future dose calculations should utilize an average adult fish consumption value of 11.3 kg/yr, and a maximum adult fish consumption value of 34 kg/yr. Consumption values for the teen and child age groups should be increased proportionally: (1) teen average = 8.5; maximum = 25.9 kg/yr; and (2) child average = 3.6; maximum = 11.2 kg/yr. 8 refs.« less

Medical and occupational dose reduction in pediatric barium meal procedures

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Direct evaluation of radiobiological parameters from clinical data in the case of ion beam therapy: an alternative approach to the relative biological effectiveness.

PubMed

Cometto, A; Russo, G; Bourhaleb, F; Milian, F M; Giordanengo, S; Marchetto, F; Cirio, R; Attili, A

2014-12-07

The relative biological effectiveness (RBE) concept is commonly used in treatment planning for ion beam therapy. Whether models based on in vitro/in vivo RBE data can be used to predict human response to treatments is an open issue. In this work an alternative method, based on an effective radiobiological parameterization directly derived from clinical data, is presented. The method has been applied to the analysis of prostate cancer trials with protons and carbon ions.Prostate cancer trials with proton and carbon ion beams reporting 5 year-local control (LC5) and grade 2 (G2) or higher genitourinary toxicity rates (TOX) were selected from literature to test the method. Treatment simulations were performed on a representative subset of patients to produce dose and linear energy transfer distribution, which were used as explicative physical variables for the radiobiological modelling. Two models were taken into consideration: the microdosimetric kinetic model (MKM) and a linear model (LM). The radiobiological parameters of the LM and MKM were obtained by coupling them with the tumor control probability and normal tissue complication probability models to fit the LC5 and TOX data through likelihood maximization. The model ranking was based on the Akaike information criterion.Results showed large confidence intervals due to the limited variety of available treatment schedules. RBE values, such as RBE = 1.1 for protons in the treated volume, were derived as a by-product of the method, showing a consistency with current approaches. Carbon ion RBE values were also derived, showing lower values than those assumed for the original treatment planning in the target region, whereas higher values were found in the bladder. Most importantly, this work shows the possibility to infer the radiobiological parametrization for proton and carbon ion treatment directly from clinical data.

Dosimetry and image quality assessment in a direct radiography system

PubMed Central

Oliveira, Bruno Beraldo; de Oliveira, Marcio Alves; Paixão, Lucas; Teixeira, Maria Helena Araújo; Nogueira, Maria do Socorro

2014-01-01

Objective To evaluate the mean glandular dose with a solid state detector and the image quality in a direct radiography system, utilizing phantoms. Materials and Methods Irradiations were performed with automatic exposure control and polymethyl methacrylate slabs with different thicknesses to calculate glandular dose values. The image quality was evaluated by means of the structures visualized on the images of the phantoms. Results Considering the uncertainty of the measurements, the mean glandular dose results are in agreement with the values provided by the equipment and with internationally adopted reference levels. Results obtained from images of the phantoms were in agreement with the reference values. Conclusion The present study contributes to verify the equipment conformity as regards dose values and image quality. PMID:25741119

Towards quantitative imaging: stability of fully automated nodule segmentation across varied dose levels and reconstruction parameters in a low-dose CT screening patient cohort

NASA Astrophysics Data System (ADS)

Wahi-Anwar, M. Wasil; Emaminejad, Nastaran; Hoffman, John; Kim, Grace H.; Brown, Matthew S.; McNitt-Gray, Michael F.

2018-02-01

Quantitative imaging in lung cancer CT seeks to characterize nodules through quantitative features, usually from a region of interest delineating the nodule. The segmentation, however, can vary depending on segmentation approach and image quality, which can affect the extracted feature values. In this study, we utilize a fully-automated nodule segmentation method - to avoid reader-influenced inconsistencies - to explore the effects of varied dose levels and reconstruction parameters on segmentation. Raw projection CT images from a low-dose screening patient cohort (N=59) were reconstructed at multiple dose levels (100%, 50%, 25%, 10%), two slice thicknesses (1.0mm, 0.6mm), and a medium kernel. Fully-automated nodule detection and segmentation was then applied, from which 12 nodules were selected. Dice similarity coefficient (DSC) was used to assess the similarity of the segmentation ROIs of the same nodule across different reconstruction and dose conditions. Nodules at 1.0mm slice thickness and dose levels of 25% and 50% resulted in DSC values greater than 0.85 when compared to 100% dose, with lower dose leading to a lower average and wider spread of DSC values. At 0.6mm, the increased bias and wider spread of DSC values from lowering dose were more pronounced. The effects of dose reduction on DSC for CAD-segmented nodules were similar in magnitude to reducing the slice thickness from 1.0mm to 0.6mm. In conclusion, variation of dose and slice thickness can result in very different segmentations because of noise and image quality. However, there exists some stability in segmentation overlap, as even at 1mm, an image with 25% of the lowdose scan still results in segmentations similar to that seen in a full-dose scan.