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Sample records for decreasing fraction doses

  1. A dose-dependent decrease in the fraction of cases harboring M6P/IGF2R mutations in hepatocellular carcinomas from the atomic bomb survivors.

    PubMed

    Iwamoto, Keisuke S; Yano, Shiho; Barber, Chad L; MacPhee, Donald G; Tokuoka, Shoji

    2006-12-01

    The risk for hepatocellular carcinoma (HCC) development is significantly heightened in the atomic bomb survivors, but the mechanism is unclear. We have previously reported finding a radiation dose-dependent increase in HCCs with TP53 mutations from the survivors. We now show that, in the same HCC samples, the frequency of 3'-untranslated region (3'UTR) mutations in M6P/IGF2R, a candidate HCC tumor suppressor gene, decreases with dose (P = 0.0091), implying a radiation dose-dependent negative selection of cells harboring such mutations. The fact that they were in the 3'UTR implicates changes in transcript stability rather than in protein function as the mechanism. Moreover, these M6P/IGF2R 3'UTR mutations and the TP53 mutations detected previously were mutually exclusive in most of the tumors, suggesting two independent pathways to HCC development, with the TP53 pathway being more favored with increasing radiation dose than the M6P/IGF2R pathway. These results suggest that tumors attributable to radiation may be genotypically different from tumors of other etiologies and hence may provide a way of distinguishing radiation-induced cancers from "background" cancers--a shift from the current paradigm.

  2. Adaptive fractionation therapy: II. Biological effective dose

    NASA Astrophysics Data System (ADS)

    Chen, Mingli; Lu, Weiguo; Chen, Quan; Ruchala, Kenneth; Olivera, Gustavo

    2008-10-01

    Radiation therapy is fractionized to differentiate the cell killing between the tumor and organ at risk (OAR). Conventionally, fractionation is done by dividing the total dose into equal fraction sizes. However, as the relative positions (configurations) between OAR and the tumor vary from fractions to fractions, intuitively, we want to use a larger fraction size when OAR and the tumor are far apart and a smaller fraction size when OAR and the tumor are close to each other. Adaptive fractionation accounts for variations of configurations between OAR and the tumor. In part I of this series, the adaptation minimizes the OAR (physical) dose and maintains the total tumor (physical) dose. In this work, instead, the adaptation is based on the biological effective dose (BED). Unlike the linear programming approach in part I, we build a fraction size lookup table using mathematical induction. The lookup table essentially describes the fraction size as a function of the remaining tumor BED, the OAR/tumor dose ratio and the remaining number of fractions. The lookup table is calculated by maximizing the expected survival of OAR and preserving the tumor cell kill. Immediately before the treatment of each fraction, the OAR-tumor configuration and thus the dose ratio can be obtained from the daily setup image, and then the fraction size can be determined by the lookup table. Extensive simulations demonstrate the effectiveness of our method compared with the conventional fractionation method.

  3. Radiotherapy Dose Fractionation under Parameter Uncertainty

    NASA Astrophysics Data System (ADS)

    Davison, Matt; Kim, Daero; Keller, Harald

    2011-11-01

    In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.

  4. Radiotherapy Dose Fractionation under Parameter Uncertainty

    SciTech Connect

    Davison, Matt; Kim, Daero; Keller, Harald

    2011-11-30

    In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.

  5. Effects of Proton Radiation Dose, Dose Rate and Dose Fractionation on Hematopoietic Cells in Mice

    PubMed Central

    Ware, J. H.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X. S.; Rusek, A.; Kennedy, A. R.

    2012-01-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05–0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons. PMID:20726731

  6. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

    SciTech Connect

    Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.

    2010-09-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

  7. Hyperfractionation decreases the deleterious effects of conventional radiation fractionation on vertebral growth in animals

    SciTech Connect

    Hartsell, W.F.; Hanson, W.R.; Conterato, D.J.; Hendrickson, F.R.

    1989-06-15

    Craniospinal axis irradiation in the treatment of pediatric tumors is associated with serious long-term sequelae including decreased bone growth (short sitting stature). In this study, an animal model was used to determine the effects of smaller incremental doses of radiation on bone growth. Sprague-Dawley weanling rats were given 25 Gy to the spine in 8 to 9 days, with fraction sizes ranging from 1.0 to 1.8 Gy. The animals receiving smaller doses per fraction (1.0 or 1.25 Gy) showed significantly more growth of the vertebral bodies in the treated fields than animals given larger incremental doses (1.5 or 1.8 Gy). These findings indicate a protective effect on bone growth for hyperfractionated irradiation of vertebral bodies.

  8. Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

    SciTech Connect

    Ma Lijun; Sahgal, Arjun; Descovich, Martina; Cho, Y.-B.; Chuang, Cynthia; Huang, Kim; Laperriere, Normand J.; Shrieve, Dennis C.; Larson, David A.

    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 (1 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.

  9. Radiation effect in mouse skin: Dose fractionation and wound healing

    SciTech Connect

    Gorodetsky, R.; Mou, X.D.; Fisher, D.R.; Taylor, J.M.; Withers, H.R. )

    1990-05-01

    Radiation induced dermal injury was measured by the gain in the physical strength of healing wounds in mouse skin. A sigmoid dose response for the inhibition of wound healing 14 days after surgery was found for single doses of X rays. The sparing of dermal damage from fractionation of the X-ray dose was quantified in terms of the alpha/beta ratio in the linear-quadratic (LQ) model, at a wide range of doses per fraction reaching as low as about 1 Gy. The fit and the appropriateness of the LQ model for the skin wound healing assay was examined with the use of the Fe-plot in which inverse total dose is plotted versus dose per fraction for wound strength isoeffects. The alpha/beta ratio of the skin was about 2.5 Gy (95% confidence of less than +/- 1 Gy) and was appropriate over a dose range of 1 Gy to about 8 Gy. The low alpha/beta value is typical for a late responding tissue. This assay, therefore, has the advantage of measuring and forecasting late radiation responses of the dermis within a short time after irradiation.

  10. A molecular fraction method for measuring personnel radiation doses

    NASA Astrophysics Data System (ADS)

    Fadel, M. A.; Khalil, W. A.; Krodja, R. P.; Sheta, N.; Abd El-Baset, M. S.

    1987-02-01

    This work represents a development in fast and albedo neutron and gamma ray dosimetry, using cellulose nitrate, as a tissue equivalent material, in which radiation damage was registered. The changes in molecular fractions of the polymer were measured after irradiation with neutron fluences from a 252Cf source in the range 10 5-10 10 n/cm 2 and gamma doses in the range 10 -4-10 -1 Gy through the use of gel filtration chromatography. Effects of irradiation on phantom, phantom to dosimeter distance, phantom thickness and storage at extreme environmental conditions were studied on the detector response and readout. The results showed that main chain scission followed by formation of new molecular configurations is the predominant effect of radiation on the polymer. The method enables measurements of neutron fluences and gamma doses in mixed radiation fields. Empirical formulae for calculating the absorbed dose from the measured changes in molecular fraction intensities are given.

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

    NASA Astrophysics Data System (ADS)

    Zavgorodni, S.

    2004-12-01

    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 ~2 mm wider than the physical dose field. The difference between ECD and the physical dose is greater for normal tissues than for tumours.

  12. Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling

    SciTech Connect

    Edmondson, Elijah F.; Hunter, Nancy R.; Weil, Michael M.; Mason, Kathryn A.

    2015-07-15

    Purpose: To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single-dose or clinically relevant, fractioned-dose γ-ray radiation. Methods and Materials: C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2-Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days after irradiation, and all tumors were characterized histologically. Results: A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed after fractionated irradiation (16.4%) in comparison with single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation tumor observed (n=201), with carcinomas occurring less frequently (n=9). The proportion of mice developing tumors increased significantly with total dose for both single-dose and fractionated schedules, and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice after single-dose irradiation; however, significant differences in tumor susceptibilities after fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common after fractionated irradiation, whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common after single-dose irradiation. Conclusions: This study investigated the tumorigenic effect of acute large doses in comparison with fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiation therapy. Differences in tumor histotype after single-dose or fractionated radiation exposures provide novel in vivo evidence for differences in tumor

  13. Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma

    SciTech Connect

    Zhang, Hualin E-mail: hualinzhang@yahoo.com; Zhong, Hualiang; Barth, Rolf F.; Cao, Minsong; Das, Indra J.

    2014-02-15

    Purpose: To evaluate the impact of dose size in single fraction, spatially fractionated (grid) radiotherapy for selectively killing infiltrated melanoma cancer cells of different tumor sizes, using different radiobiological models. Methods: A Monte Carlo technique was employed to calculate the 3D dose distribution of a commercially available megavoltage grid collimator in a 6 MV beam. The linear-quadratic (LQ) and modified linear quadratic (MLQ) models were used separately to evaluate the therapeutic outcome of a series of single fraction regimens that employed grid therapy to treat both acute and late responding melanomas of varying sizes. The dose prescription point was at the center of the tumor volume. Dose sizes ranging from 1 to 30 Gy at 100% dose line were modeled. Tumors were either touching the skin surface or having their centers at a depth of 3 cm. The equivalent uniform dose (EUD) to the melanoma cells and the therapeutic ratio (TR) were defined by comparing grid therapy with the traditional open debulking field. The clinical outcomes from recent reports were used to verify the authors’ model. Results: Dose profiles at different depths and 3D dose distributions in a series of 3D melanomas treated with grid therapy were obtained. The EUDs and TRs for all sizes of 3D tumors involved at different doses were derived through the LQ and MLQ models, and a practical equation was derived. The EUD was only one fifth of the prescribed dose. The TR was dependent on the prescribed dose and on the LQ parameters of both the interspersed cancer and normal tissue cells. The results from the LQ model were consistent with those of the MLQ model. At 20 Gy, the EUD and TR by the LQ model were 2.8% higher and 1% lower than by the MLQ, while at 10 Gy, the EUD and TR as defined by the LQ model were only 1.4% higher and 0.8% lower, respectively. The dose volume histograms of grid therapy for a 10 cm tumor showed different dosimetric characteristics from those of conventional

  14. Dose fractionation theorem in 3-D reconstruction (tomography)

    SciTech Connect

    Glaeser, R.M.

    1997-02-01

    It is commonly assumed that the large number of projections for single-axis tomography precludes its application to most beam-labile specimens. However, Hegerl and Hoppe have pointed out that the total dose required to achieve statistical significance for each voxel of a computed 3-D reconstruction is the same as that required to obtain a single 2-D image of that isolated voxel, at the same level of statistical significance. Thus a statistically significant 3-D image can be computed from statistically insignificant projections, as along as the total dosage that is distributed among these projections is high enough that it would have resulted in a statistically significant projection, if applied to only one image. We have tested this critical theorem by simulating the tomographic reconstruction of a realistic 3-D model created from an electron micrograph. The simulations verify the basic conclusions of high absorption, signal-dependent noise, varying specimen contrast and missing angular range. Furthermore, the simulations demonstrate that individual projections in the series of fractionated-dose images can be aligned by cross-correlation because they contain significant information derived from the summation of features from different depths in the structure. This latter information is generally not useful for structural interpretation prior to 3-D reconstruction, owing to the complexity of most specimens investigated by single-axis tomography. These results, in combination with dose estimates for imaging single voxels and measurements of radiation damage in the electron microscope, demonstrate that it is feasible to use single-axis tomography with soft X-ray microscopy of frozen-hydrated specimens.

  15. Fractional model for pharmacokinetics of high dose methotrexate in children with acute lymphoblastic leukaemia

    NASA Astrophysics Data System (ADS)

    Popović, Jovan K.; Spasić, Dragan T.; Tošić, Jela; Kolarović, Jovanka L.; Malti, Rachid; Mitić, Igor M.; Pilipović, Stevan; Atanacković, Teodor M.

    2015-05-01

    The aim of this study is to promote a model based on the fractional differential calculus related to the pharmacokinetic individualization of high dose methotrexate treatment in children with acute lymphoblastic leukaemia, especially in high risk patients. We applied two-compartment fractional model on 8 selected cases with the largest number (4-19) of measured concentrations, among 43 pediatric patients received 24-h methotrexate 2-5 g/m2 infusions. The plasma concentrations were determined by fluorescence polarization immunoassay. Our mathematical procedure, designed by combining Post's and Newton's method, was coded in Mathematica 8.0 and performed on Fujicu Celsius M470-2 PC. Experimental data show that most of the measured values of methotrexate were in decreasing order. However, in certain treatments local maximums were detected. On the other hand, integer order compartmental models do not give values which fit well with the observed data. By the use of our model, we obtained better results, since it gives more accurate behavior of the transmission, as well as the local maximums which were recognized in methotrexate monitoring. It follows from our method that an additional test with a small methotrexate dose can be suggested for the fractional system parameter identification and the prediction of a possible pattern with a full dose in the case of high risk patients. A special feature of the fractional model is that it can also recognize and better fit an observed non-monotonic behavior. A new parameter determination procedure can be successfully used.

  16. Decreasing Methadone Dose Via Anxiety Reduction: A Treatment Manual.

    ERIC Educational Resources Information Center

    Kushner, Marlene; And Others

    This manual describes a Relaxation-Information Presentation program based on the clinical observation that anxiety is a serious barrier to detoxification for many methadone clients, and on experimental evidence indicating that expectations may play a greater role in the discomfort experienced during detoxification than the actual methadone dose.…

  17. Forbush decrease effects on radiation dose received on-board aeroplanes.

    PubMed

    Lantos, P

    2005-01-01

    Doses received on-board aeroplanes during deep Forbush decreases (FDs) have been recently measured and published. Using an operational model of dose calculation, the effects on aviation dose of the FDs observed from 1981 to 2003 using neutron monitors are studied and a simplified method to estimate dose variations from galactic cosmic ray variations during FDs is derived.

  18. Potential Increased Risk of Ischemic Heart Disease Mortality With Significant Dose Fractionation in the Canadian Fluoroscopy Cohort Study

    PubMed Central

    Zablotska, Lydia B.; Little, Mark P.; Cornett, R. Jack

    2014-01-01

    Risks of noncancer causes of death, particularly cardiovascular disease, associated with exposures to high-dose ionizing radiation, are well known. Recent studies have reported excess risk in workers who are occupationally exposed to low doses at a low dose rate, but the risks of moderately fractionated exposures, such as occur during diagnostic radiation procedures, remain unclear. The Canadian Fluoroscopy Cohort Study includes 63,707 tuberculosis patients exposed to multiple fluoroscopic procedures in 1930–1952 and followed-up for death from noncancer causes in 1950–1987. We used a Poisson regression to estimate excess relative risk (ERR) per Gy of cumulative radiation dose to the lung (mean dose = 0.79 Gy; range, 0–11.60). The risk of death from noncancer causes was significantly lower in these subjects compared with the Canadian general population (P < 0.001). We estimated small, nonsignificant increases in the risk of death from noncancer causes with dose. We estimated an ERR/Gy of 0.176 (95% confidence interval: 0.011, 0.393) (n = 5,818 deaths) for ischemic heart disease (IHD) after adjustment for dose fractionation. A significant (P = 0.022) inverse dose fractionation effect in dose trends of IHD was observed, with the highest estimate of ERR/Gy for those with the fewest fluoroscopic procedures per year. Radiation-related risks of IHD decreased significantly with increasing time since first exposure and age at first exposure (both P < 0.05). This is the largest study of patients exposed to moderately fractionated low-to-moderate doses of radiation, and it provides additional evidence of increased radiation-associated risks of death from IHD, in particular, significantly increased radiation risks from doses similar to those from diagnostic radiation procedures. The novel finding of a significant inverse dose-fractionation association in IHD mortality requires further investigation. PMID:24145888

  19. Effect of different doses of un-fractionated green and black tea extracts on thyroid physiology.

    PubMed

    Chandra, Amar K; De, Neela; Choudhury, Shyamosree Roy

    2011-08-01

    Tea is a rich source of polyphenolic flavonoids including catechins, which are thought to contribute to the health benefits of it. Flavonoids have been reported to have antithyroid and goitrogenic effect. The purpose of this study was to evaluate whether high doses of green and black tea have a harmful effect on thyroid physiology. Un-fractionated green and black tea extracts were administered orally to male rats for 30 days at doses of 1.25 g%, 2.5 g% and 5.0 g%. The results showed that green tea extract at 2.5 g% and 5.0 g% doses and black tea extract only at 5.0 g% dose have the potential to alter the thyroid gland physiology and architecture, that is, enlargement of thyroid gland as well as hypertrophy and/or hyperplasia of the thyroid follicles and inhibition of the activity of thyroid peroxidase and 5(')-deiodinase I with elevated thyroidal Na+, K+-ATPase activity along with significant decrease in serum T3 and T4, and a parallel increase in serum thyroid stimulating hormone (TSH). This study concludes that goitrogenic/antithyroidal potential of un-fractionated green tea extract is much more than black tea extract because of the differences in catechin contents in the tea extracts.

  20. Accelerated heavy particles and the lens. III. Cataract enhancement by dose fractionation

    SciTech Connect

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

    1989-04-01

    For a number of biological end points it has been shown that, in contrast to low linear energy transfer (LET) radiation, dose fractionation of high-LET radiation does not result in a reduction in overall effectiveness. Studies were conducted to determine the effect of fractionating the exposures to heavy ion doses on the development of cataracts. Rat eyes were exposed to single doses of 1, 5, and 25 cGy of 570 MeV/amu40Ar ions and to 2, 4, and 10 Gy of 250 kVp X rays. These were compared to unirradiated controls and eyes which were exposed to the same total dose delivered in four fractions over 12 h. While in all cases fractionation of the exposure to X rays produced significant reduction in cataractogenic potential, fractionating doses of 40Ar ions caused a dose- and stage-dependent enhancement in the development of cataracts.

  1. IL-6 Inhibition With MEDI5117 Decreases The Fraction of Head and Neck Cancer Stem Cells and Prevents Tumor Recurrence.

    PubMed

    Finkel, Kelsey A; Warner, Kristy A; Kerk, Samuel; Bradford, Carol R; McLean, Scott A; Prince, Mark E; Zhong, Haihong; Hurt, Elaine M; Hollingsworth, Robert E; Wicha, Max S; Tice, David A; Nör, Jacques E

    2016-05-01

    Head and neck squamous cell carcinomas (HNSCC) exhibit a small population of uniquely tumorigenic cancer stem cells (CSC) endowed with self-renewal and multipotency. We have recently shown that IL-6 enhances the survival and tumorigenic potential of head and neck cancer stem cells (i.e. ALDH(high)CD44(high) cells). Here, we characterized the effect of therapeutic inhibition of IL-6 with a novel humanized anti-IL-6 antibody (MEDI5117) using three low-passage patient-derived xenograft (PDX) models of HNSCC. We observed that single agent MEDI5117 inhibited the growth of PDX-SCC-M1 tumors (P < .05). This PDX model was generated from a previously untreated HNSCC. In contrast, MEDI5117 was not effective at reducing overall tumor volume for PDX models representing resistant disease (PDX-SCC-M0, PDX-SCC-M11). Low dose MEDI5117 (3 mg/kg) consistently decreased the fraction of cancer stem cells in PDX models of HNSCC when compared to IgG-treated controls, as follows: PDX-SCC-M0 (P < .001), PDX-SCC-M1 (P < .001), PDX-SCC-M11 (P = .04). Interestingly, high dose MEDI5117 (30 mg/kg) decreased the CSC fraction in the PDX-SCC-M11 model (P = .002), but not in PDX-SCC-M0 and PDX-SCC-M1. MEDI5117 mediated a dose-dependent decrease in the number of orospheres generated by ALDH(high)CD44(high) cells cultured in ultra-low attachment plates (P < .05), supporting an inhibitory effect on head and neck cancer stem cells. Notably, single agent MEDI5117 reduced the overall recurrence rate of PDX-SCC-M0, a PDX generated from the local recurrence of human HNSCC. Collectively, these data demonstrate that therapeutic inhibition of IL-6 with low-dose MEDI5117 decreases the fraction of cancer stem cells, and that adjuvant MEDI5117 inhibits recurrence in preclinical models of HNSCC.

  2. External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

    NASA Astrophysics Data System (ADS)

    Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

    2009-01-01

    Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

  3. Fractionated dose of 35-MEV fast neutrons and hypoxic tumor cell survival curve.

    PubMed

    U, R; Evans, J C; Cavanaugh, P J; Abramson, N; Thompson, T T; Wheless, D M

    1975-06-01

    The determination of the RBE for the MANTA fast neutrons produced by NRL is inprogress, with the model system using tumor cell population kinetic response patterns assayed in vitro after irradiation in vivo. Ascites tumor cells BW-5147 were irradiated with a clinically usable fast neutron beam from the NRL cyclotron, which is produced by accelrating deuterons to 35 MeV and using htem to bombard a thick berylliumtarget. The comparison of dose-effect relationships was made for doses ranging from30 to 1000 rads. The doses required for an isoeffect on BW-5147 hypoxic tumor cell survival and impairment of its reproductive capacity from fast neutron exposure were not different wheither it was given a single dose or the same dose given in three fractions separated by long recovery periods in situ. No intracellular repair of sublethal injury when the dose was given in three fractions, although the hypoxic BWp5147 tumor cells haveno effective reoxygenation or repopulation in this time interval. The RBE for the fast neutron beam is 4 relative to x rays for fractionated doses at the surviving fractionlevel of 0.6-0.7, while the RBE IS 2.5 FOR SINGLE DOSES. However, at a surviving fraction of 0.1, the RBE is 1.9 for single and 2.8 for fractionated doses. Analysis of thedaily cell population rate or mitotic delay between the two types of radiations at a similiar level of survival.

  4. The effect of fractionated doses of radiation on mouse spinal cord

    SciTech Connect

    Lo, Y.C. Memorial Sloan-Kettering Cancer Center, New York, NY ); Taylor, J.M.G.; McBridge, W.H.; Withers, H.R. )

    1993-09-20

    The purpose was to determine: (a) the dose-response relationship and latent time to paralysis following fractionated doses of radiation in mice, (b) the values of parameters for isoeffect curves, and (c) whether these parameters depend on the size of dose per fraction and the severity of injury. The spinal cords (T[sub 9]-L[sub 5]) of 608 C[sub 3]Hf/Sed/Kam mice were irradiated with fractionated doses of x-radiation. Three levels of neurological damage were used to grade the spinal cord response. Animals which did not develop paralysis were observed for at least 18 months after irradiation. The fractionated schedules consisted of either 2, 3, 4, 6, 10, or 20 fractions in addition to single doses. For the fractionated regimes the daily fraction size ranged from 2 Gy to 24 Gy, and for single doses the range was 12 Gy to 52 Gy. Both the latent time to paralysis and the incidence of paralysis were considered as endpoints. For analysis of the sparing associated with fractionation, the dose points were divided into two groups: a [open quotes]low damage[close quotes] group consisting of doses of near or less than the ED[sub 50] at 450 days and a [open quotes]high damage[close quotes] group consisting of doses much larger than the ED[sub 50] at 450 days in which there was 100% incidence of paralysis. The latent time depended on the radiation dose; for each fixed fraction number the latent period became progressively shorter with higher total doses. Differences in histology in fractionation sensitivity are observed between the two groups. The low damage data in each fractionation treatment are the important data in the analysis of long-term incidence of paralysis. On the other hand, the high damage data were emphasized for the analysis of latency. Three statistical methods (mixture model, Cox model, and Fe-plot) were used to fit the linear-quadratic dose response model and the [open quotes]Nominal Standard Dose[close quotes] (NSD) model. 29 refs., 4 figs., 5 tabs.

  5. Dose-Volume Response Relationship for Brain Metastases Treated with Frameless Single-Fraction Linear Accelerator-Based Stereotactic Radiosurgery

    PubMed Central

    Pan, Jianmin; Yusuf, Mehran B; Dragun, Anthony; Dunlap, Neal; Guan, Timothy; Boling, Warren; Rai, Shesh; Woo, Shiao

    2016-01-01

    Background: Our aim was to identify a dose-volume response relationship for brain metastases treated with frameless stereotactic radiosurgery (SRS). Methods: We reviewed patients who underwent frameless single-fraction linear accelerator SRS for brain metastases between 2007 and 2013 from an institutional database. Proportional hazards modeling was used to identify predictors of outcome. A ratio of maximum lesion dose per mm-diameter (Gy/mm) was constructed to establish a dose-volume relationship. Results: There were 316 metastases evaluated in 121 patients (2 - 33 mm in the largest diameter). The median peripheral dose was 18.0 Gy (range: 10.0 – 24.0 Gy). Local control was 84.8% for all lesions and was affected by location, peripheral dose, maximum dose, and lesion size (p values < 0.050). A dose-volume response relationship was constructed using the maximum dose and lesion size. A unit increase in Gy/mm was associated with decreased local failure (p = 0.005). Local control of 80%, 85%, and 90% corresponded to maximum doses per millimeter of 1.67 Gy/mm, 2.86 Gy/mm, and 4.4 Gy/mm, respectively. Toxicity was uncommon and only 1.0% of lesions developed radionecrosis requiring surgery. Conclusions: For brain metastases less than 3 cm, a dose-volume response relationship exists between maximum radiosurgical dose and lesion size, which is predictive of local control. PMID:27284495

  6. Dose fractionation and single subject studies in PET

    NASA Astrophysics Data System (ADS)

    Balakrishnan, Karthikayan

    Conventional positron emission tomography (PET) for cognitive brain studies typically relies on information collected from the distribution of decays following an injection of 15O-labeled water. The number of injections that can be administered to the subject are constrained by radiation dose to the subject and total length of the PET scan. The standard protocol involves 8--10 injections of H152O separated by approximately 5--7 half-lives of 15O. The number of activation conditions that can be realistically studied in a standard PET session is between 8 and 10. This work investigates the physiological response of a simulated subject to H152O injections that are administered in small doses (1--5 mCi) with short inter-injection intervals (40--180 seconds). A larger number of activation conditions are presented to the subject with a wider variation in the activation paradigm. Repeat conditions are studies. Signal averaging methods are feasible with this method of dose administration. Sinograms from scans with similar activation conditions are summed together before reconstruction. The signal in the primary activation region of the brain is shown to increase while suppressing the contribution of secondary activation regions in the brain. The contrast of the final image is similarly increased which leads to easier identification of the primary activation region. An automated H152O -production unit controlled by a PC running LabView software was developed to produce the dose required for the injection sequence by controlling the flow of H152O -vapor that diffuses across a semi-permeable membrane into saline. The unit is capable of producing H152O rapidly for both the standard and the proposed dose administration methods. The system also detects the bolus arrival time at the subject's lungs using a small external plastic detector. Activation sequence commences with the rise in radioactivity observed by the detector. The simulations indicate that inter-injection intervals

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

    SciTech Connect

    Viani, Gustavo Arruda; De Fendi, Ligia Issa; Fonseca, Ellen Carrara; Stefano, Eduardo Jose

    2012-02-01

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

  8. ANALYSIS OF RESPIRATORY DESPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS

    EPA Science Inventory

    ANALYSIS OF RESPIRATORY DEPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS. Chong S. Kim, SC. Hu**, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711; **IIT Research Institute, Chicago, IL; *S...

  9. Simultaneous optimization of dose distributions and fractionation schemes in particle radiotherapy

    SciTech Connect

    Unkelbach, Jan; Zeng, Chuan; Engelsman, Martijn

    2013-09-15

    Purpose: The paper considers the fractionation problem in intensity modulated proton therapy (IMPT). Conventionally, IMPT fields are optimized independently of the fractionation scheme. In this work, we discuss the simultaneous optimization of fractionation scheme and pencil beam intensities.Methods: This is performed by allowing for distinct pencil beam intensities in each fraction, which are optimized using objective and constraint functions based on biologically equivalent dose (BED). The paper presents a model that mimics an IMPT treatment with a single incident beam direction for which the optimal fractionation scheme can be determined despite the nonconvexity of the BED-based treatment planning problem.Results: For this model, it is shown that a small α/β ratio in the tumor gives rise to a hypofractionated treatment, whereas a large α/β ratio gives rise to hyperfractionation. It is further demonstrated that, for intermediate α/β ratios in the tumor, a nonuniform fractionation scheme emerges, in which it is optimal to deliver different dose distributions in subsequent fractions. The intuitive explanation for this phenomenon is as follows: By varying the dose distribution in the tumor between fractions, the same total BED can be achieved with a lower physical dose. If it is possible to achieve this dose variation in the tumor without varying the dose in the normal tissue (which would have an adverse effect), the reduction in physical dose may lead to a net reduction of the normal tissue BED. For proton therapy, this is indeed possible to some degree because the entrance dose is mostly independent of the range of the proton pencil beam.Conclusions: The paper provides conceptual insight into the interdependence of optimal fractionation schemes and the spatial optimization of dose distributions. It demonstrates the emergence of nonuniform fractionation schemes that arise from the standard BED model when IMPT fields and fractionation scheme are optimized

  10. Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

    SciTech Connect

    Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M. )

    1993-03-20

    The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.

  11. Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

    SciTech Connect

    Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tome, Wolfgang A.

    2012-08-15

    Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

  12. A comparative analysis of radiobiological models for cell surviving fractions at high doses.

    PubMed

    Andisheh, B; Edgren, M; Belkić, Dž; Mavroidis, P; Brahme, A; Lind, B K

    2013-04-01

    For many years the linear-quadratic (LQ) model has been widely used to describe the effects of total dose and dose per fraction at low-to-intermediate doses in conventional fractionated radiotherapy. Recent advances in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have increased the interest in finding a reliable cell survival model, which will be accurate at high doses, as well. Different models have been proposed for improving descriptions of high dose survival responses, such as the Universal Survival Curve (USC), the Kavanagh-Newman (KN) and several generalizations of the LQ model, e.g. the Linear-Quadratic-Linear (LQL) model and the Pade Linear Quadratic (PLQ) model. The purpose of the present study is to compare a number of models in order to find the best option(s) which could successfully be used as a fractionation correction method in SRT. In this work, six independent experimental data sets were used: CHOAA8 (Chinese hamster fibroblast), H460 (non-small cell lung cancer, NSLC), NCI-H841 (small cell lung cancer, SCLC), CP3 and DU145 (human prostate carcinoma cell lines) and U1690 (SCLC). By detailed comparisons with these measurements, the performance of nine different radiobiological models was examined for the entire dose range, including high doses beyond the shoulder of the survival curves. Using the computed and measured cell surviving fractions, comparison of the goodness-of-fit for all the models was performed by means of the reduced χ (2)-test with a 95% confidence interval. The obtained results indicate that models with dose-independent final slopes and extrapolation numbers generally represent better choices for SRT. This is especially important at high doses where the final slope and extrapolation numbers are presently found to play a major role. The PLQ, USC and LQL models have the least number of shortcomings at all doses. The extrapolation numbers and final slopes of these models do not depend on dose. Their asymptotes

  13. Leaf litter decomposition in temperate deciduous forest stands with a decreasing fraction of beech (Fagus sylvatica).

    PubMed

    Jacob, Mascha; Viedenz, Karin; Polle, Andrea; Thomas, Frank M

    2010-12-01

    We hypothesised that the decomposition rates of leaf litter will increase along a gradient of decreasing fraction of the European beech (Fagus sylvatica) and increasing tree species diversity in the generally beech-dominated Central European temperate deciduous forests due to an increase in litter quality. We studied the decomposition of leaf litter including its lignin fraction in monospecific (pure beech) stands and in stands with up to five tree genera (Acer spp., Carpinus betulus, Fagus sylvatica, Fraxinus excelsior, Tilia spp.) using a litterbag approach. Litter and lignin decomposition was more rapid in stand-representative litter from multispecific stands than in litter from pure beech stands. Except for beech litter, the decomposition rates of species-specific tree litter did not differ significantly among the stand types, but were most rapid in Fraxinus excelsior and slowest in beech in an interspecific comparison. Pairwise comparisons of the decomposition of beech litter with litter of the other tree species (except for Acer platanoides) revealed a "home field advantage" of up to 20% (more rapid litter decomposition in stands with a high fraction of its own species than in stands with a different tree species composition). Decomposition of stand-representative litter mixtures displayed additive characteristics, not significantly more rapid than predicted by the decomposition of litter from the individual tree species. Leaf litter decomposition rates were positively correlated with the initial N and Ca concentrations of the litter, and negatively with the initial C:N, C:P and lignin:N ratios. The results support our hypothesis that the overall decomposition rates are mainly influenced by the chemical composition of the individual litter species. Thus, the fraction of individual tree species in the species composition seems to be more important for the litter decomposition rates than tree species diversity itself.

  14. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women.

    PubMed

    Moretti, Diego; Goede, Jeroen S; Zeder, Christophe; Jiskra, Markus; Chatzinakou, Vaiya; Tjalsma, Harold; Melse-Boonstra, Alida; Brittenham, Gary; Swinkels, Dorine W; Zimmermann, Michael B

    2015-10-22

    Iron supplements acutely increase hepcidin, but the duration and magnitude of the increase, its dose dependence, and its effects on subsequent iron absorption have not been characterized in humans. Better understanding of these phenomena might improve oral iron dosing schedules. We investigated whether the acute iron-induced increase in hepcidin influences iron absorption of successive daily iron doses and twice-daily iron doses. We recruited 54 nonanemic young women with plasma ferritin ≤20 µg/L and conducted: (1) a dose-finding investigation with 40-, 60-, 80-, 160-, and 240-mg labeled Fe as [(57)Fe]-, [(58)Fe]-, or [(54)Fe]-FeSO4 given at 8:00 am fasting on 1 or on 2 consecutive days (study 1, n = 25; study 2, n = 16); and (2) a study giving three 60-mg Fe doses (twice-daily dosing) within 24 hours (study 3, n = 13). In studies 1 and 2, 24 hours after doses ≥60 mg, serum hepcidin was increased (P < .01) and fractional iron absorption was decreased by 35% to 45% (P < .01). With increasing dose, fractional absorption decreased (P < .001), whereas absolute absorption increased (P < .001). A sixfold increase in iron dose (40-240 mg) resulted in only a threefold increase in iron absorbed (6.7-18.1 mg). In study 3, total iron absorbed from 3 doses (2 mornings and an afternoon) was not significantly greater than that from 2 morning doses. Providing lower dosages (40-80 mg Fe) and avoiding twice-daily dosing maximize fractional absorption. The duration of the hepcidin response supports alternate day supplementation, but longer-term effects of these schedules require further investigation. These clinical trials were registered at www.ClinicalTrials.gov as #NCT01785407 and #NCT02050932.

  15. SU-E-T-511: Do Presage 3D Dosimeters Show Dose Fractionation Sensitivity?

    SciTech Connect

    Klawikowski, S; Alqathami, M; Ibbott, G; Adamovics, J; Benning, R

    2014-06-01

    Purpose: To determine whether Presage 3D polymer dosimeter dose response is sensitive to dose delivery fractionation. Bang gels have demonstrated a dose fractionation related dependence in which a single 400 cGy irradiation would produce a different detector response than four 100 cGy irradiations even if delivered closely in time to one another. Such a fractional dependent response in Presage would be detrimental for measuring multi-beam irradiations. Methods: Two separate batches of Presage were poured into cuvettes, and a third batch was molded into cuvette shaped blocks. A total of 37 cuvettes/blocks were irradiated in a Cobalt-60 irradiator to 400 cGy within solid water phantoms in either one, eight, or sixteen fractions. Another group of 15 cuvettes were also kept unirradiated and used for background subtraction between the pre-scan and post-scan results. The times between fractional deliveries were held constant at 30 seconds and the Cobalt irradiator dose rate was 49 cGy/min. Each Presage batch has a separate dose sensitivity and therefore fractionation response comparisons were only performed within the same batch. The cuvettes were first pre-scanned the day prior to irradiation and post-scanned the day after irradiation. Other than approximately 3 hours warming time prior to each irradiation and optical density measurement the cuvettes were stored in a refrigerator. All cuvettes were stored in a lightless environment throughout manufacturing and testing. The cuvettes’ optical densities were optically measured at 632 nm with a spectrophotometer. Results: No noticeable dose fractionation dependence was detected for any of the three independent batches of Presage for either the eight or sixteen fraction irradiation schemes. Conclusion: These results indicate using Presage 3D dosimeters to measure multi-beam photon irradiations common in IMRT, Gamma Knife, and Cyberknife treatment delivery schemes. Presage dosimeters are made by and trademarked by Heuris

  16. The dependence of optimal fractionation schemes on the spatial dose distribution

    NASA Astrophysics Data System (ADS)

    Unkelbach, Jan; Craft, David; Salari, Ehsan; Ramakrishnan, Jagdish; Bortfeld, Thomas

    2013-01-01

    We consider the fractionation problem in radiation therapy. Tumor sites in which the dose-limiting organ at risk (OAR) receives a substantially lower dose than the tumor, bear potential for hypofractionation even if the α/β-ratio of the tumor is larger than the α/β-ratio of the OAR. In this work, we analyze the interdependence of the optimal fractionation scheme and the spatial dose distribution in the OAR. In particular, we derive a criterion under which a hypofractionation regimen is indicated for both a parallel and a serial OAR. The approach is based on the concept of the biologically effective dose (BED). For a hypothetical homogeneously irradiated OAR, it has been shown that hypofractionation is suggested by the BED model if the α/β-ratio of the OAR is larger than α/β-ratio of the tumor times the sparing factor, i.e. the ratio of the dose received by the tumor and the OAR. In this work, we generalize this result to inhomogeneous dose distributions in the OAR. For a parallel OAR, we determine the optimal fractionation scheme by minimizing the integral BED in the OAR for a fixed BED in the tumor. For a serial structure, we minimize the maximum BED in the OAR. This leads to analytical expressions for an effective sparing factor for the OAR, which provides a criterion for hypofractionation. The implications of the model are discussed for lung tumor treatments. It is shown that the model supports hypofractionation for small tumors treated with rotation therapy, i.e. highly conformal techniques where a large volume of lung tissue is exposed to low but nonzero dose. For larger tumors, the model suggests hyperfractionation. We further discuss several non-intuitive interdependencies between optimal fractionation and the spatial dose distribution. For instance, lowering the dose in the lung via proton therapy does not necessarily provide a biological rationale for hypofractionation.

  17. Recalculation of dose for each fraction of treatment on TomoTherapy

    PubMed Central

    Romanchikova, Marina; Harrison, Karl; Parker, Michael A; Bates, Amy M; Scaife, Jessica E; Sutcliffe, Michael PF; Burnet, Neil G

    2016-01-01

    Objective: The VoxTox study, linking delivered dose to toxicity requires recalculation of typically 20–37 fractions per patient, for nearly 2000 patients. This requires a non-interactive interface permitting batch calculation with multiple computers. Methods: Data are extracted from the TomoTherapy® archive and processed using the computational task-management system GANGA. Doses are calculated for each fraction of radiotherapy using the daily megavoltage (MV) CT images. The calculated dose cube is saved as a digital imaging and communications in medicine RTDOSE object, which can then be read by utilities that calculate dose–volume histograms or dose surface maps. The rectum is delineated on daily MV images using an implementation of the Chan–Vese algorithm. Results: On a cluster of up to 117 central processing units, dose cubes for all fractions of 151 patients took 12 days to calculate. Outlining the rectum on all slices and fractions on 151 patients took 7 h. We also present results of the Hounsfield unit (HU) calibration of TomoTherapy MV images, measured over an 8-year period, showing that the HU calibration has become less variable over time, with no large changes observed after 2011. Conclusion: We have developed a system for automatic dose recalculation of TomoTherapy dose distributions. This does not tie up the clinically needed planning system but can be run on a cluster of independent machines, enabling recalculation of delivered dose without user intervention. Advances in knowledge: The use of a task management system for automation of dose calculation and outlining enables work to be scaled up to the level required for large studies. PMID:26728661

  18. Intradermal fractional booster dose of inactivated poliomyelitis vaccine with a jet injector in healthy adults.

    PubMed

    Soonawala, Darius; Verdijk, Pauline; Wijmenga-Monsuur, Alienke J; Boog, Claire J; Koedam, Patrick; Visser, Leo G; Rots, Nynke Y

    2013-08-12

    For global eradication of poliomyelitis, inactivated poliovirus vaccine (IPV) needs to become available in all countries. Using fractional-doses (reduced-doses) may impact affordability and optimize the utilization of the production capacity. Intradermal administration has the potential to lower the dose without reducing immunogenicity. A needle-free jet injector may be a reliable way to administer vaccines intradermally. The primary objective of this randomized controlled trial was to compare the immunogenicity and tolerability of fractional-dose intradermal IPV (Netherlands Vaccine Institute, NVI) booster vaccination administered with a jet injector (PharmaJet) to full-dose and fractional-dose intramuscular vaccination with a needle and syringe. Immunogenicity was assessed by comparing the differences in the post-vaccination log2 geometric mean concentrations of neutralizing antibodies (GMC) between the study groups. A total of 125 Dutch adult volunteers with a well-documented vaccination history were randomized to one of four groups: full-dose intramuscular needle (IM-NS-0.5), full-dose intramuscular jet injector (IM-JI-0.5), 1/5th dose intramuscular needle (IM-NS-0.1), 1/5th dose intradermal jet injector (ID-JI-0.1). Vaccination with the JI was less painful (87% no pain) than vaccination with a NS (60% no pain), but caused more transient erythema (JI 85%, NS 24%) and swelling (JI 50%, NS 5%). Intradermal vaccination caused less vaccination site soreness (ID 16%, IM 52%). At baseline all subjects had seroprotective antibody concentrations. After 28 days, GMC were slightly lower in the ID-JI-0.1 group than in the reference group (IM-NS-0.5). The differences were not statistically significant, but the stringent non-inferiority criterion (i.e. a difference of 1 serum dilution in the microneutralization assay) was not met. After one year, differences in GMC were no longer apparent. In contrast, intramuscular vaccination with a fractional dose administered with a

  19. Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul

    2016-01-01

    Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer. PMID:27306773

  20. Comparison of particle lung doses from the fine and coarse fractions of urban PM-10 aerosols.

    PubMed

    Venkataraman, C; Kao, A S

    1999-02-01

    The U.S. Environmental Protection Agency (EPA) recently revised the national ambient air quality standards to include a new PM-2.5 particulate standard. We examine the contributions of fine (PM-2.5) and coarse (PM-2.5 to -10) fraction of typical urban aerosols to particle doses in different lung airways resulting from 24-h exposure to the standard concentration of 150 microg m-3. The aerosol is assumed to have a bimodal lognormal mass distribution with mass median diameters of 0.2 and 5 microm, and geometric standard deviation of 1.7 and 57% of the mass in the fine (PM-2.5) mode. The daily mass dose from exposure to 150 microg m-3 of PM-10 in the nasopharyngeal (NPL) region is 20-51 microg day-1 (1.5% of inhaled fines) and 377-687 microg day-1 (30% of inhaled coarse), respectively, of fine and coarse mass filtered in the nose. Similar daily mass doses from fine and coarse fractions, respectively, to the tracheobronchial (TBL) region are 28-38 (1.5%) and 40-52 (4%) microg day-1 and to the pulmonary (PUL) region are 18-194 (6%) and 32-55 microg day-1 (2%). The daily number dose in the NPL region is 5-15 x 10(8) (0.06% of inhaled fines) and 5-10 x 10(6) day-1 (13% of inhaled coarse) respectively, of fine and coarse particles. Similar number doses to the TBL region are 2.2-3.1 x 10(10) (2%) and 7.1-11. 1 x 10(5) (2%) day-1 and to the PUL region are 1.6-16.7 x 10(10) (9%) and 2.9-17.0 x 10(5) (3%) day-1. The daily surface mass dose (microg cm-2 day-1) from coarse fraction particles is large in generations 3-5. The daily number dose (particles day-1) and surface number dose (particles cm-2 day-1) are higher from the fine than the coarse fraction, by about 10(3) to 10(5) times in all lung airways. Fine fraction particles result in 10,000 times greater particle number dose per macrophage than coarse fraction particles. Particle number doses do not follow trends in mass doses, are much larger from fine than coarse fraction, and must be considered in assessing PM health

  1. Acute tolerance to rate-decreasing effects of single doses of ethanol.

    PubMed

    Ginsburg, Brett C; Martinez, Gerardo; Friesenhahn, Gregory; Javors, Martin; Lamb, R J

    2008-06-01

    Acute tolerance occurs when behavioral impairment is greater at a given blood ethanol concentration (BAC) on the ascending versus descending limb of the BAC-time curve following administration of a single dose of ethanol, however studies utilizing learned behaviors have not been widely reported. We assessed acute tolerance to single doses of ethanol in five Lewis rats responding under a fixed-ratio (FR8) schedule of food presentation. Response rates for food during 1-min components (ending 2, 4, 11, 18, 33, and 57 min after ethanol administration) were determined, and BAC was measured immediately after each component using a rat breathalyzer. Ethanol (0.4, 0.6, 0.8, and 1.2 g/kg, i.p.) produced dose-related decreases in responding for food that tended to recover over time for all but the highest dose tested. Similarly, dose-related increases in BAC were also observed. Using either an analysis that expressed impairment per unit BAC on the ascending limb versus the descending limb (by assessing the area under the curve (AUC) for behavior and BAC on each limb), the slope of the function that relates the behavioral effect to BAC (each expressed as percent maximum effect), or a variant of the Mellanby method (hysteresis), acute tolerance was observed following a dose of 0.4 g/kg ethanol. Though behavior appeared to recover on the descending limb following higher doses (especially 0.6 and 0.8 g/kg), acute tolerance to these doses was not present. PMID:18328511

  2. PROPRANOLOL DECREASES CARDIAC WORK IN A DOSE-DEPENDENT MANNER IN SEVERELY BURNED CHILDREN

    PubMed Central

    Williams, Felicia N; Herndon, David N; Kulp, Gabriela A; Jeschke, Marc G

    2010-01-01

    Background Severe burn is followed by profound cardiac stress. Propranolol, a non selective β1, β2-receptor antagonist, decreases cardiac stress, but little is known about the dose necessary to cause optimal effect. Thus, the aim of this study was to determine in a large prospective randomized controlled trial the dose of propranolol that would decrease heart rate at least 15% of admission heart rate and improve cardiac function. Four-hundred six patients with burns >30% total body surface area (TBSA) were enrolled and randomized to receive standard care (controls, n=235) or standard care plus propranolol (n=171). Methods Dose-response and drug kinetics of propranolol were performed. Heart rate and mean arterial pressure were measured continuously. Cardiac output (CO), cardiac index (CI), stroke volume (SV), rate pressure product, and cardiac work (CW) were determined at regular intervals. Statistical analysis was performed using ANOVA with Tukey and Bonferroni corrections and Student’s t-test when applicable. Significance was accepted at p<0.05. Results Propranolol given initially at 1 mg/kg/day decreased heart rate by 15% compared to control patients but was increased to 4 mg/kg/day within the first 10 days to sustain treatment benefits (p<0.05). Propranolol decreased CO, rate pressure product, and CW without deleterious effects on mean arterial pressure. The effective plasma drug concentrations were achieved in 30 minutes, and the half-life was 4 hours. Conclusions The data suggest that propranolol is an efficacious modulator of the post-burn cardiac response when given at a dose of 4 mg/kg/day, which decreases and sustains heart rate 15% below admission heart rate. PMID:20598332

  3. Heavy metal pollution decreases microbial abundance, diversity and activity within particle-size fractions of a paddy soil.

    PubMed

    Chen, Junhui; He, Feng; Zhang, Xuhui; Sun, Xuan; Zheng, Jufeng; Zheng, Jinwei

    2014-01-01

    Chemical and microbial characterisations of particle-size fractions (PSFs) from a rice paddy soil subjected to long-term heavy metal pollution (P) and nonpolluted (NP) soil were performed to investigate whether the distribution of heavy metals (Cd, Cu, Pb and Zn) regulates microbial community activity, abundance and diversity at the microenvironment scale. The soils were physically fractionated into coarse sand, fine sand, silt and clay fractions. Long-term heavy metal pollution notably decreased soil basal respiration (a measurement of the total activity of the soil microbial community) and microbial biomass carbon (MBC) across the fractions by 3-45% and 21-53%, respectively. The coarse sand fraction was more affected by pollution than the clay fraction and displayed a significantly lower MBC content and respiration and dehydrogenase activity compared with the nonpolluted soils. The abundances and diversities of bacteria were less affected within the PSFs under pollution. However, significant decreases in the abundances and diversities of fungi were noted, which may have strongly contributed to the decrease in MBC. Sequencing of denaturing gradient gel electrophoresis bands revealed that the groups Acidobacteria, Ascomycota and Chytridiomycota were clearly inhibited under pollution. Our findings suggest that long-term heavy metal pollution decreased the microbial biomass, activity and diversity in PSFs, particularly in the large-size fractions.

  4. Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy

    PubMed Central

    Roch-Lefèvre, S; Pouzoulet, F; Giraudet, A L; Voisin, Pa; Vaurijoux, A; Gruel, G; Grégoire, E; Buard, V; Delbos, M; Voisin, Ph; Bourhis, J; Roy, L

    2010-01-01

    The purpose of this study was to evaluate the in vivo dose–response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35±0.2 Gy) than the calculated equivalent whole-body dose (0.07±0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2±0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1±0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p = 0.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p = 0.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate. PMID:20739344

  5. Decreasing effects of glycerol-fractions extracted from ox diaphragm muscles on acetylcholine-induced contractions of smooth muscles.

    PubMed

    Kimura, M; Kimura, I

    1979-04-01

    Extracts of 5% glycerol obtained from ox diaphragm muscles were fractionated into four (A, B, C and D) with (NH4)2SO4. The activity as acetylcholine (ACh) receptor-like substance containing fraction was evidenced as follows; the ACh-induced contraction of tracheal muscles decreased with addition of the fraction, and such could not be attributed to the reaction with ACh receptors of tracheal smooth muscles. Fraction D had the most potent activity in the presence of neostigmine. This reaction induced by fraction D was reversed by addition of d-tubocurarine (d-TC). Fraction D was fractionated into three (I, II and III) by gel filtration on Sephadex G-75 with 50 mM phosphate buffer (pH 7.5). The purified fraction III was identified by electrophoresis, UV and visible absorption spectrum, and ion-exchange chromatography to be myoglobin. Pure myoglobin also proved to have a decreasing effect on ACh-induced contraction. PMID:537248

  6. Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway

    PubMed Central

    Franchin, Marcelo; da Cunha, Marcos Guilherme; Denny, Carina; Napimoga, Marcelo Henrique; Cunha, Thiago Mattar; Bueno-Silva, Bruno; Matias de Alencar, Severino; Ikegaki, Masaharu; Luiz Rosalen, Pedro

    2013-01-01

    The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1) was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity. PMID:23737853

  7. High-Dose-Rate Brachytherapy Boost for Prostate Cancer: Comparison of Two Different Fractionation Schemes

    SciTech Connect

    Kaprealian, Tania; Weinberg, Vivian; Speight, Joycelyn L.; Gottschalk, Alexander R.; Roach, Mack; Shinohara, Katsuto; Hsu, I.-Chow

    2012-01-01

    Purpose: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy Multiplication-Sign 3 fractions (patient group 1) and 950 cGy Multiplication-Sign 2 fractions (patient group 2). Methods and Materials: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy Multiplication-Sign 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy Multiplication-Sign 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score {>=}7, and/or clinical stage T3 disease. Results: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Conclusions: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

  8. Effects of single-dose and fractionated cranial irradiation on rat brain accumulation of methotrexate

    SciTech Connect

    Kamen, B.A.; Moulder, J.E.; Kun, L.E.; Ring, B.J.; Adams, S.M.; Fish, B.L.; Holcenberg, J.S.

    1984-11-01

    The effects of single-dose and fractionated whole-brain irradiation on brain methotrexate (MTX) has been studied in a rat model. The amount of MTX present in the brain 24 hr after a single i.p. dose (100 mg/kg) was the same whether animals were sham irradiated or given a single dose of 2000 rads 6 or 48 hr prior to the drug (6.9, 8.3, and 6.8 pmol MTX/g, wet weight, respectively). Animals sham irradiated or given 2000 rads in 10 fractions over 11 days and treated with an average dose of 1.2 mg MTX/kg i.p. twice a week for 24 weeks did not differ significantly in their brain MTX concentration (7.9 and 8.3 pmol MTX/g, wet weight, respectively). Chronically MTX-treated animals became folate deficient whether they were irradiated or not (450 and 670 pmol folate/g, wet weight, brain in MTX-treated and control animals). Thus, MTX accumulates in the brain with acute or chronic administration, and this accumulation is not altered by this amount of brain irradiation.

  9. Elective Lymph Node Irradiation With Intensity-Modulated Radiotherapy: Is Conventional Dose Fractionation Necessary?

    SciTech Connect

    Bedi, Meena; Firat, Selim; Semenenko, Vladimir A.; Schultz, Christopher; Tripp, Patrick; Byhardt, Roger; Wang, Dian

    2012-05-01

    Purpose: Intensity-modulated radiation therapy (IMRT) is the standard of care for head-and-neck cancer (HNC). We treated patients with HNC by delivering either a moderate hypofractionation (MHF) schedule (66 Gy at 2.2 Gy per fraction to the gross tumor [primary and nodal]) with standard dose fractionation (54-60 Gy at 1.8-2.0 Gy per fraction) to the elective neck lymphatics or a conventional dose and fractionation (CDF) schedule (70 Gy at 2.0 Gy per fraction) to the gross tumor (primary and nodal) with reduced dose to the elective neck lymphatics. We analyzed these two cohorts for treatment outcomes. Methods and Materials: Between November 2001 and February 2009, 89 patients with primary carcinomas of the oral cavity, larynx, oropharynx, hypopharynx, and nasopharynx received definitive IMRT with or without concurrent chemotherapy. Twenty patients were treated using the MHF schedule, while 69 patients were treated with the CDF schedule. Patient characteristics and dosimetry plans were reviewed. Patterns of failure including local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), overall survival (OS), and toxicities, including rate of feeding tube placement and percentage of weight loss, were reviewed and analyzed. Results: Median follow-up was 31.2 months. Thirty-five percent of patients in the MHF cohort and 77% of patients in the CDF cohort received chemotherapy. No RR was observed in either cohort. OS, DFS, LR, and DM rates for the entire group at 2 years were 89.3%, 81.4%, 7.1%, and 9.4%, respectively. Subgroup analysis showed no significant differences in OS (p = 0.595), DFS (p = 0.863), LR (p = 0.833), or DM (p = 0.917) between these two cohorts. Similarly, no significant differences were observed in rates of feeding tube placement and percentages of weight loss. Conclusions: Similar treatment outcomes were observed for MHF and CDF cohorts. A dose of 50 Gy at 1.43 Gy per fraction may be sufficient to electively

  10. Phase I Dose Escalation Trial of Vandetanib With Fractionated Radiosurgery in Patients With Recurrent Malignant Gliomas

    SciTech Connect

    Fields, Emma C.; Damek, Denise; Gaspar, Laurie E.; Liu, Arthur K.; Kavanagh, Brian D.; Waziri, Allen; Lillehei, Kevin; Chen, Changhu

    2012-01-01

    Purpose: To determine the maximum tolerated dose (MTD) of vandetanib with fractionated stereotactic radiosurgery (SRS) in patients with recurrent malignant gliomas. Methods and Materials: Patients with a recurrent malignant glioma and T1-enhancing recurrent tumor {<=}6 cm were eligible. Vandetanib was given orally, once per day, 7 days a week, starting at least 7 days before SRS and continued until a dose-limiting toxicity (DLT) or disease progression. The planned vandetanib daily dose was 100 mg, 200 mg, and 300 mg for the cohorts 1, 2, and 3, respectively, and was escalated using a standard 3+3 design. A total SRS dose of 36 Gy, 12 Gy per fraction, was delivered over 3 consecutive days. The MTD was defined as the dose of vandetanib at which less than 33% of patients developed DLTs, defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3 as any Grade 3 or greater nonhematologic toxicity and Grade 4 or greater hematologic toxicity. Results: Ten patients were treated, 6 on cohort 1 and 4 on cohort 2. Treatment characteristics were: 7 men, 3 women; median age, 40 years (range, 22-72); 7 GBM, 3 anaplastic astrocytoma (AA); median initial radiation (RT) dose, 60 Gy (range, 59.4-70); median interval since initial RT, 14.5 months (range, 7-123); All patients received SRS per protocol. The median follow-up time was 4 months (range, 1-10 months). Median time on vandetanib was 3 months (range 1-11). One of 6 patients in the first cohort developed a DLT of Grade 3 hemothorax while on anticoagulation. The MTD was reached when 2 of the 4 patients enrolled in the second cohort developed DLTs. Six patients had radiographic response, 2 with stable disease. Conclusion: The MTD of vandetanib, with SRS in recurrent malignant glioma, is 100 mg daily. Further evaluation of safety and efficacy is warranted.

  11. Uncertainties in electron-absorbed fractions and lung doses from inhaled beta-emitters.

    PubMed

    Farfán, Eduardo B; Bolch, Wesley E; Huston, Thomas E; Rajon, Didier A; Huh, Chulhaeng; Bolch, W Emmett

    2005-01-01

    The computer code LUDUC (Lung Dose Uncertainty Code), developed at the University of Florida, was originally used to investigate the range of potential doses from the inhalation of either plutonium or uranium oxides. The code employs the ICRP Publication 66 Human Respiratory Tract model; however, rather than using simple point estimates for each of the model parameters associated with particle deposition, clearance, and lung-tissue dosimetry, probability density functions are ascribed to these parameters based upon detailed literature review. These distributions are subsequently sampled within LUDUC using Latin hypercube sampling techniques to generate multiple (e.g., approximately 1,000) sets of input vectors (i.e., trials), each yielding a unique estimate of lung dose. In the present study, the dosimetry component of the ICRP-66 model within LUDUC has been extended to explicitly consider variations in the beta particle absorbed fraction due to corresponding uncertainties and biological variabilities in both source and target tissue depths and thicknesses within the bronchi and bronchioles of the thoracic airways. Example dose distributions are given for the inhalation of absorption Type S compounds of 90Sr (Tmax = 546 keV) and 90Y (Tmax = 2,284 keV) as a function of particle size. Over the particle size range of 0.001 to 1 microm, estimates of total lung dose vary by a factor of 10 for 90Sr particles and by a factor of 4 to 10 for 90Y particles. As the particle size increases to 10 microm, dose uncertainties reach a factor of 100 for both radionuclides. In comparisons to identical exposures scenarios run by the LUDEP 2.0 code, Reference Man doses for inhaled beta-emitters were shown to provide slightly conservative estimates of lung dose compared to those in this study where uncertainties in lung airway histology are considered.

  12. Uncertainties in electron-absorbed fractions and lung doses from inhaled beta-emitters.

    PubMed

    Farfán, Eduardo B; Bolch, Wesley E; Huston, Thomas E; Rajon, Didier A; Huh, Chulhaeng; Bolch, W Emmett

    2005-01-01

    The computer code LUDUC (Lung Dose Uncertainty Code), developed at the University of Florida, was originally used to investigate the range of potential doses from the inhalation of either plutonium or uranium oxides. The code employs the ICRP Publication 66 Human Respiratory Tract model; however, rather than using simple point estimates for each of the model parameters associated with particle deposition, clearance, and lung-tissue dosimetry, probability density functions are ascribed to these parameters based upon detailed literature review. These distributions are subsequently sampled within LUDUC using Latin hypercube sampling techniques to generate multiple (e.g., approximately 1,000) sets of input vectors (i.e., trials), each yielding a unique estimate of lung dose. In the present study, the dosimetry component of the ICRP-66 model within LUDUC has been extended to explicitly consider variations in the beta particle absorbed fraction due to corresponding uncertainties and biological variabilities in both source and target tissue depths and thicknesses within the bronchi and bronchioles of the thoracic airways. Example dose distributions are given for the inhalation of absorption Type S compounds of 90Sr (Tmax = 546 keV) and 90Y (Tmax = 2,284 keV) as a function of particle size. Over the particle size range of 0.001 to 1 microm, estimates of total lung dose vary by a factor of 10 for 90Sr particles and by a factor of 4 to 10 for 90Y particles. As the particle size increases to 10 microm, dose uncertainties reach a factor of 100 for both radionuclides. In comparisons to identical exposures scenarios run by the LUDEP 2.0 code, Reference Man doses for inhaled beta-emitters were shown to provide slightly conservative estimates of lung dose compared to those in this study where uncertainties in lung airway histology are considered. PMID:15596988

  13. Evaluation of an abbreviated impactor for fine particle fraction (FPF) determination of metered dose inhalers (MDI).

    PubMed

    Guo, Changning; Ngo, Diem; Ahadi, Shafiq; Doub, William H

    2013-09-01

    Abbreviated impactors have been developed recently to allow more rapid evaluation of inhalation products as alternates to the eight-stage Andersen Cascade Impactor (ACI) which has been widely used in the pharmaceutical industry for assessing aerodynamic particle size distribution. In this paper, a two-stage abbreviated impactor, Westech Fine Particle Dose Impactor (WFPD), was used to characterize the aerodynamic particle size of metered dose inhaler (MDI) products, and the results were compared with those obtained using the standard eight-stage ACI. Seven commercial MDI products, with different propellants (chlorofluorocarbon/hydrofluoroalkane) and formulation types (suspension/solution, dry/normal/wet), were tested in this study by both WFPD and ACI. Substantially equivalent measures of fine particle fraction were obtained for most of the tested MDI products, but larger coarse particle fraction and extra-fine particle fraction values were measured from WFPD relative to those measured using the ACI. Use of the WFPD also produced more wall loss than the ACI. Therefore, it is recommended that the system suitability be evaluated on a product-by-product basis to establish substantial equivalency before implementing an abbreviated impactor measurement methodology for routine use in inhaler product characterization. PMID:23780781

  14. A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images

    SciTech Connect

    Liu, Yixun; Summers, Ronald M.; Yao, Jianhua; Liu, Songtao; Sibley, Christopher T.; Bluemke, David A.; Nacif, Marcelo S.

    2013-10-15

    Purpose: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image. Methods: To deal with this difficulty, the authors present a complete ECVF measurement framework including a point-guided myocardial modeling, a deformable model-based myocardium segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation. Results: The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR. Conclusions: The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use.

  15. Evaluation of an abbreviated impactor for fine particle fraction (FPF) determination of metered dose inhalers (MDI).

    PubMed

    Guo, Changning; Ngo, Diem; Ahadi, Shafiq; Doub, William H

    2013-09-01

    Abbreviated impactors have been developed recently to allow more rapid evaluation of inhalation products as alternates to the eight-stage Andersen Cascade Impactor (ACI) which has been widely used in the pharmaceutical industry for assessing aerodynamic particle size distribution. In this paper, a two-stage abbreviated impactor, Westech Fine Particle Dose Impactor (WFPD), was used to characterize the aerodynamic particle size of metered dose inhaler (MDI) products, and the results were compared with those obtained using the standard eight-stage ACI. Seven commercial MDI products, with different propellants (chlorofluorocarbon/hydrofluoroalkane) and formulation types (suspension/solution, dry/normal/wet), were tested in this study by both WFPD and ACI. Substantially equivalent measures of fine particle fraction were obtained for most of the tested MDI products, but larger coarse particle fraction and extra-fine particle fraction values were measured from WFPD relative to those measured using the ACI. Use of the WFPD also produced more wall loss than the ACI. Therefore, it is recommended that the system suitability be evaluated on a product-by-product basis to establish substantial equivalency before implementing an abbreviated impactor measurement methodology for routine use in inhaler product characterization.

  16. Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

    SciTech Connect

    Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

    2012-08-01

    Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher's exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade {>=}3 acute or late toxicity was 6.8% (14 patients). Fisher's exact test resulted in significant median splits for grade {>=}3 toxicity at V12 = 3.78 cm{sup 3} (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm{sup 3} (RR 13, P=.0013), V20 = 0.11 cm{sup 3} (RR 6, P=0.01), and V22 = 0.0 cm{sup 3} (RR 13, P=.0013). The median split for D2.5 cm{sup 3} (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm{sup 3}. One hundred percent (n = 7) of grade {>=}4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade {>=}3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation

  17. Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy

    PubMed Central

    Yang, Ying-Chieh; Chiang, Chi-Shiun

    2016-01-01

    Radiotherapy is crucial and substantially contributes to multimodal cancer treatment. The combination of conventional fractionation radiotherapy (CFRT) and systemic therapy has been established as the standard treatment for many cancer types. With advances in linear accelerators and image-guided techniques, high-dose fractionation radiotherapy (HFRT) is increasingly introduced in cancer centers. Clinicians are currently integrating HFRT into multimodality treatment. The shift from CFRT to HFRT reveals different effects on the tumor microenvironment and responses, particularly the immune response. Furthermore, the combination of HFRT and drugs yields different results in different types of tumors or using different treatment schemes. We have reviewed clinical trials and preclinical evidence on the combination of HFRT with drugs, such as chemotherapy, targeted therapy, and immune therapy. Notably, HFRT apparently enhances tumor cell killing and antigen presentation, thus providing opportunities and challenges in treating cancer. PMID:27446811

  18. Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy.

    PubMed

    Yang, Ying-Chieh; Chiang, Chi-Shiun

    2016-01-01

    Radiotherapy is crucial and substantially contributes to multimodal cancer treatment. The combination of conventional fractionation radiotherapy (CFRT) and systemic therapy has been established as the standard treatment for many cancer types. With advances in linear accelerators and image-guided techniques, high-dose fractionation radiotherapy (HFRT) is increasingly introduced in cancer centers. Clinicians are currently integrating HFRT into multimodality treatment. The shift from CFRT to HFRT reveals different effects on the tumor microenvironment and responses, particularly the immune response. Furthermore, the combination of HFRT and drugs yields different results in different types of tumors or using different treatment schemes. We have reviewed clinical trials and preclinical evidence on the combination of HFRT with drugs, such as chemotherapy, targeted therapy, and immune therapy. Notably, HFRT apparently enhances tumor cell killing and antigen presentation, thus providing opportunities and challenges in treating cancer. PMID:27446811

  19. Spatial fractionation of the dose using neon and heavier ions: A Monte Carlo study

    SciTech Connect

    Peucelle, C.; Martínez-Rovira, I.; Prezado, Y.

    2015-10-15

    Purpose: This work explores a new radiation therapy approach which might trigger a renewed use of neon and heavier ions to treat cancers. These ions were shown to be extremely efficient in radioresistant tumor killing. Unfortunately, the efficient region also extends into the normal tissue in front of the tumor. The strategy the authors propose is to profit from the well-established sparing effect of thin spatially fractionated beams, so that the impact on normal tissues might be minimized while a high tumor control is achieved. The main goal of this work is to provide a proof of concept of this new approach. With that aim, a dosimetric study was carried out as a first step to evaluate the interest of further explorations of this avenue. Methods: The GATE/GEANT4 v.6.1 Monte Carlo simulation platform was employed to simulate arrays of rectangular minibeams (700 μm × 2 cm) of four ions (Ne, Si, Ar, and Fe). The irradiations were performed with a 2 cm-long spread-out Bragg peak centered at 7 cm-depth. Dose distributions in a water phantom were scored considering two minibeams center-to-center distances: 1400 and 3500 μm. Peak and valley doses, peak-to-valley dose ratios (PVDRs), beam penumbras, and relative contribution of nuclear fragments and electromagnetic processes were assessed as figures of merit. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions. Results: Extremely high PVDR values (>100) and low valley doses were obtained. The higher the atomic number (Z) of the primary ion is, the lower the valleys and the narrower the penumbras. Although the yield of secondary nuclear products increases with Z, the actual dose being deposited by the secondary nuclear fragments in the valleys starts to be the dominant contribution at deeper points, helping in the sparing of proximal normal tissues. Additionally, a wider center-to-center distance leads to a minimized contribution of heavier secondary

  20. Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in non–small cell lung cancer

    SciTech Connect

    Pedicini, Piernicola; Strigari, Lidia; Benassi, Marcello; Caivano, Rocchina; Fiorentino, Alba; Nappi, Antonio; Salvatore, Marco; Storto, Giovanni

    2014-04-01

    To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.

  1. A plausible radiobiological model of cardiovascular disease at low or fractionated doses

    NASA Astrophysics Data System (ADS)

    Little, Mark; Vandoolaeghe, Wendy; Gola, Anna; Tzoulaki, Ioanna

    Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally-exposed groups receiving small daily radia-tion doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis, and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1) concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and can-cer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapo-lation would be appropriate for this endpoint.

  2. Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

    SciTech Connect

    Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya

    2015-10-01

    Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

  3. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    SciTech Connect

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  4. Fraction of a dose absorbed estimation for structurally diverse low solubility compounds.

    PubMed

    Sugano, Kiyohiko

    2011-02-28

    The purpose of the present study was to investigate the prediction accuracy of the fully mechanistic gastrointestinal unified theoretical (GUT) framework for in vivo oral absorption of low solubility drugs. Solubility in biorelevant media, molecular weight, logP(oct), pK(a), Caco-2 permeability, dose and particle size were used as the input parameters. To neglect the effect of the low stomach pH on dissolution of a drug, the fraction of a dose absorbed (Fa%) of undissociable and free acids were used. In addition, Fa% of free base drugs with the high pH stomach was also included to increase the number of model drugs. In total twenty nine structurally diverse compounds were used as the model drugs. Fa% data at several doses and particle sizes in humans and dogs were collated from the literature (total 110 Fa% data). In approximately 80% cases, the prediction error was within 2 fold, suggesting that the GUT framework has practical predictability for drug discovery, but not for drug development. The GUT framework appropriately captured the dose and particle size dependency of Fa% as the particle drifting effect was taken into account. It should be noted that the present validation results cannot be applied for salt form cases and other special formulations such as solid dispersions and emulsion formulations.

  5. Radiosensitivity of human clonogenic myeloma cells and normal bone marrow precursors: Effect of different dose rates and fractionation

    SciTech Connect

    Glueck, S.; Van Dyk, J.; Messner, H.A. )

    1994-03-01

    Evaluation of radiation dose rate and fractionation effects on clonogenic myeloma cells was carried out. The radiosensitivity of clonogenic myeloma cells was evaluated for seven human myeloma cell lines. The lines were maintained in liquid suspension culture. Following radiation, cells were plated in semisolid medium using methylcellulose as viscous support. Radiation doses up to 12 Gy were delivered at dose rates of 0.05 and 0.5 Gy/min by a [sup 60]Co source. Each total dose was administered either as a single dose or in multiple fractions of 2 Gy. The data were analyzed according to the linear quadratic and multi target model of irradiation. Clonogenic progenitors of the seven myeloma cell lines differed in their radiosensitivity as measured by multiple parameters. The differences were mainly observed at low dose. The most effective cytoreduction was seen when radiation was administered in a single fraction at high dose rate. The cytoreductive effect on clonogenic myeloma cells was compared for clinically practiced total body irradiation (TBI) schedules delivered either in a single or in multiple fractions without causing significant pulmonary toxicity. The administration of 12 Gy delivered in six fractions of 2 Gy resulted in a superior reduction of clonogenic cells compared to a single fraction of 5 Gy. The preparation of bone marrow transplant recipients with multiple myeloma using fractionated radiation with a total dose of 12 Gy appears to afford better ablation than a single dose of 5 Gy while maintaining a low incidence of pulmonary toxicity. 20 refs., 4 figs., 4 tabs.

  6. Chronic Low Dose Fructose infusion Does Not Reverse Glucagon-Mediated Decrease in Hepatic Glucose Utilization

    PubMed Central

    Johnson, Paulette M.; Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E; Lacy, D. Brooks; McGuinness, Owen P.

    2013-01-01

    Objective An adaptation to chronic total parenteral nutrition (TPN; 75% of non protein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if chronic fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Material/methods Studies were performed in conscious insulin-treated chronically catheterized pancreatectomized dogs that adapted to TPN for 33 h. They were then assigned to one of 4 groups: TPN (C), TPN + fructose (4.4 μmol·kg−1·min−1, F), TPN+ glucagon (0.2 pmol·kg−1·min−1, GGN), or a TPN + fructose and glucagon (F+GGN) for an additional 63h (33–96h). Insulin, fructose and glucagon were infused into the portal vein. During that period all animals received a fixed insulin infusion 0.4mU· kg−1·min−1 (33–96h) and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mM). Results Chronic fructose infusion was unable to further enhance net hepatic glucose uptake (NHGU; μmol·kg−1·min−1) (31.1±2.8 vs. 36.1±5.0; C vs. F) nor was it able to overcome glucagon-mediated decrease in NHGU (10.0±4.4 vs. 12.2±3.9; GGN vs. F+GGN). Conclusion In summary, chronic fructose infusion cannot augment liver glucose uptake during TPN nor can it overcome the inhibitory effects of glucagon. PMID:20940071

  7. Rice bran extract containing acylated steryl glucoside fraction decreases elevated blood LDL cholesterol level in obese Japanese men.

    PubMed

    Ito, Yukihiko; Nakashima, Yuri; Matsuoka, Sayuri

    2015-01-01

    People who frequently consume whole grains show a lower incidence of arteriosclerotic disease than people who consume primarily refined grains. We examined whether or not rice bran extract containing the acylated steryl glucosides (ASG) fraction decreases blood LDL cholesterol levels in obese Japanese men with high blood levels of LDL cholesterol. The study utilized a randomized, double-blind design. A total of 51 subjects were randomly allocated to either a rice bran extract containing ASG fraction (RB-ASG) group or a placebo group. Subjects in the RB-ASG group received 30-50 mg/day of RB-ASG, and the placebo group took 9 capsules/day for 12 weeks. Before and after intake, height, weight, body fat percentage, systolic and diastolic blood pressure were measured, blood was collected, and visceral fat area, subcutaneous fat area, and abdominal circumference were determined based on umbilical computed tomography. Percentage decreases in blood LDL cholesterol, non-HDL cholesterol, LDL/HDL ratio, abdominal circumference and subcutaneous fat area were significantly better in the RB-ASG group than in the placebo group. These findings suggest that RB-ASG fraction may reduce blood LDL cholesterol levels and the risk of arteriosclerosis in obese Japanese men with high LDL cholesterol levels.

  8. High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

    SciTech Connect

    Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

    1981-11-01

    Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.

  9. Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with 131I-mIBG

    NASA Astrophysics Data System (ADS)

    Mínguez, Pablo; Gustafsson, Johan; Flux, Glenn; Sjögreen Gleisner, Katarina

    2016-03-01

    In this work, the biologically effective dose (BED) is investigated for fractionated molecular radiotherapy (MRT). A formula for the Lea-Catcheside G-factor is derived which takes the possibility of combinations of sub-lethal damage due to radiation from different administrations of activity into account. In contrast to the previous formula, the new G-factor has an explicit dependence on the time interval between administrations. The BED of tumour and liver is analysed in MRT of neuroblastoma with 131I-mIBG, following a common two-administration protocol with a mass-based activity prescription. A BED analysis is also made for modified schedules, when due to local regulations there is a maximum permitted activity for each administration. Modifications include both the simplistic approach of delivering this maximum permitted activity in each of the two administrations, and also the introduction of additional administrations while maintaining the protocol-prescribed total activity. For the cases studied with additional (i.e. more than two) administrations, BED of tumour and liver decreases at most 12% and 29%, respectively. The decrease in BED of the tumour is however modest compared to the two-administration schedule using the maximum permitted activity, where the decrease compared to the original schedule is 47%.

  10. Impact of conventional fractionated RT to pelvic lymph nodes and dose-escalated hypofractionated RT to prostate gland using IMRT treatment delivery in high-risk prostate cancer

    NASA Astrophysics Data System (ADS)

    Pervez, Nadeem

    Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.

  11. The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible.

    PubMed

    Monson, Laura A; Cavaliere, Christi M; Deshpande, Sagar S; Ayzengart, Alexander L; Buchman, Steven R

    2012-09-07

    The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague-Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.

  12. Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

    PubMed

    Hoffmann, Aswin L; Nahum, Alan E

    2013-10-01

    The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes. PMID:24029492

  13. [Technical parameters to decrease the radiation dose from conventional and digital radiographs].

    PubMed

    Foulquier, J N

    2010-11-01

    Reducing radiation dose while maintaining adequate image quality on conventional and digital radiographs requires optimal use of the unit. Additional filtration avoids unnecessary tissue exposure and improves photon transmission. Automatic exposure control may reduce exposure and dose. The volume of tissue imaged must be limited by the use of diaphragms and shutters or compression. Sensitive detectors with increased photon detection also contribute to reduce dose. Radiographic films combined to rare-earth screens also afford a good photon-conversion efficiency. Large area flat panel amorphous silicon x-ray sensors may also reduce dose up to 50% compared to films. Finally, calculation of the Kerma-area product independent of the source distance constitutes an important indicator of radiation dose.

  14. A framework of whole heart extracellular volume fraction estimation for low dose cardiac CT images

    NASA Astrophysics Data System (ADS)

    Chen, Xinjian; Summers, Ronald M.; Nacif, Marcelo Souto; Liu, Songtao; Bluemke, David A.; Yao, Jianhua

    2012-02-01

    Cardiac magnetic resonance imaging (CMRI) has been well validated and allows quantification of myocardial fibrosis in comparison to overall mass of the myocardium. Unfortunately, CMRI is relatively expensive and is contraindicated in patients with intracardiac devices. Cardiac CT (CCT) is widely available and has been validated for detection of scar and myocardial stress/rest perfusion. In this paper, we sought to evaluate the potential of low dose CCT for the measurement of myocardial whole heart extracellular volume (ECV) fraction. A novel framework was proposed for CCT whole heart ECV estimation, which consists of three main steps. First, a shape constrained graph cut (GC) method was proposed for myocardium and blood pool segmentation for post-contrast image. Second, the symmetric Demons deformable registrations method was applied to register pre-contrast to post-contrast images. Finally, the whole heart ECV value was computed. The proposed method was tested on 7 clinical low dose CCT datasets with pre-contrast and post-contrast images. The preliminary results demonstrated the feasibility and efficiency of the proposed method.

  15. Impact of Fractionation and Dose in a Multivariate Model for Radiation-Induced Chest Wall Pain

    SciTech Connect

    Din, Shaun U.; Williams, Eric L.; Jackson, Andrew; Rosenzweig, Kenneth E.; Wu, Abraham J.; Foster, Amanda; Yorke, Ellen D.; Rimner, Andreas

    2015-10-01

    Purpose: To determine the role of patient/tumor characteristics, radiation dose, and fractionation using the linear-quadratic (LQ) model to predict stereotactic body radiation therapy–induced grade ≥2 chest wall pain (CWP2) in a larger series and develop clinically useful constraints for patients treated with different fraction numbers. Methods and Materials: A total of 316 lung tumors in 295 patients were treated with stereotactic body radiation therapy in 3 to 5 fractions to 39 to 60 Gy. Absolute dose–absolute volume chest wall (CW) histograms were acquired. The raw dose-volume histograms (α/β = ∞ Gy) were converted via the LQ model to equivalent doses in 2-Gy fractions (normalized total dose, NTD) with α/β from 0 to 25 Gy in 0.1-Gy steps. The Cox proportional hazards (CPH) model was used in univariate and multivariate models to identify and assess CWP2 exposed to a given physical and NTD. Results: The median follow-up was 15.4 months, and the median time to development of CWP2 was 7.4 months. On a univariate CPH model, prescription dose, prescription dose per fraction, number of fractions, D83cc, distance of tumor to CW, and body mass index were all statistically significant for the development of CWP2. Linear-quadratic correction improved the CPH model significance over the physical dose. The best-fit α/β was 2.1 Gy, and the physical dose (α/β = ∞ Gy) was outside the upper 95% confidence limit. With α/β = 2.1 Gy, V{sub NTD99Gy} was most significant, with median V{sub NTD99Gy} = 31.5 cm{sup 3} (hazard ratio 3.87, P<.001). Conclusion: There were several predictive factors for the development of CWP2. The LQ-adjusted doses using the best-fit α/β = 2.1 Gy is a better predictor of CWP2 than the physical dose. To aid dosimetrists, we have calculated the physical dose equivalent corresponding to V{sub NTD99Gy} = 31.5 cm{sup 3} for the 3- to 5-fraction groups.

  16. Low-Dose Steroid Therapy Is Associated with Decreased IL-12 Production in PBMCs of Severe Septic Patients.

    PubMed

    Wu, Huang-Pin; Shih, Chi-Chung; Chuang, Duen-Yau; Chen, Tien-Hsing

    2016-01-01

    Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients. PMID:27555669

  17. Low-Dose Steroid Therapy Is Associated with Decreased IL-12 Production in PBMCs of Severe Septic Patients

    PubMed Central

    Shih, Chi-Chung; Chuang, Duen-Yau; Chen, Tien-Hsing

    2016-01-01

    Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients. PMID:27555669

  18. Predicting Rectal and Bladder Overdose During the Course of Prostate Radiotherapy Using Dose-Volume Data From Initial Treatment Fractions

    SciTech Connect

    Murthy, Vedang; Shukla, Pragya; Adurkar, Pranjal; Master, Zubin; Mahantshetty, Umesh; Shrivastava, Shyamkishore

    2012-09-01

    Purpose: To evaluate whether information from the initial fractions can determine which patients are likely to consistently exceed their planning dose-volume constraints during the course of radiotherapy for prostate cancer. Methods and Materials: Ten patients with high-risk prostate cancer were treated with helical tomotherapy to a dose of 60 Gy in 20 fractions. The prostate, rectum, and bladder were recontoured on their daily megavoltage computed tomography scans and the dose was recalculated. The bladder and rectal volumes (in mL) receiving {>=}100% and {>=}70% of the prescribed dose in each fraction and in the original plans were recorded. A fraction for which the difference between planned and delivered was more than 2 mL was considered a volume failure. Similarly if the difference in the planned and delivered maximum dose (D{sub max}) was {>=}1% for the rectum and bladder, the fraction was considered a dose failure. Each patient's first 3 to 5 fractions were analyzed to determine if they correctly identified those patients who would consistently fail (i.e., {>=}20% of fractions) during the course of their radiotherapy. Results: Six parameters were studied; the rectal volume (RV) and bladder volumes (BV) (in mL) received {>=}100% and {>=}70% of the prescribed dose and maximum dose to 2 mL of the rectum and bladder. This was given by RV{sub 100}, RV{sub 70}, BV{sub 100}, BV{sub 70}, RD{sub max}, and BD{sub max}, respectively. When more than 1 of the first 3 fractions exceed the planning constraint as defined, it accurately predicts consistent failures through the course of the treatment. This method is able to correctly identify the consistent failures about 80% (RV{sub 70}, BV{sub 100}, and RV{sub 100}), 90% (BV{sub 70}), and 100% (RD{sub max} and BD{sub max}) of the times. Conclusions: This study demonstrates the feasibility of a method accurately identifying patients who are likely to consistently exceed the planning constraints during the course of their

  19. Pressor doses of angiotensin II increase hepatic glucose output and decrease insulin sensitivity in rats.

    PubMed

    Rao, R H

    1996-02-01

    The metabolic effects of angiotensin II (AII) were studied under steady-state conditions of euglycaemic hyperinsulinaemia in anaesthetized rats. Pressor doses of AII (50 and 400 ng/kg per min) had dose-dependent hypertensive and hyperglycaemic effects during glucose clamp studies. Glucose turnover measurements showed that hepatic glucose output (HGO) increased equally at both pressor doses compared with either saline infusion or AII infusion at a dose without a pressor effect (20 ng/kg per min); however, glucose disposal increased significantly only at 50 ng/kg per min. Infusion of the AII receptor antagonist, saralasin, did not itself alter glucose output or disposal significantly, but it abolished the effects of a simultaneous infusion of AII. It is concluded that pressor doses of AII increase HGO by a receptor-mediated mechanism that is not related to the pressor response to the hormone. The hyperglycaemic reaction to this metabolic effect of AII is partially offset by increased glucose disposal at lower doses. The physiological significance of these metabolic actions of AII remains to be established, but they raise the possibility that AII could potentially play a role in glucose homeostasis in vivo. PMID:8699145

  20. Total lymphoid irradiation in rat heart albgrafts: dose, fractionation, and combination with cyclosporin-A. [X-ray

    SciTech Connect

    Rynasiewicz, J.J.; Sutherland, D.E.R.; Kawahara, K.; Kim, T.; Najarian, J.S.

    1981-03-01

    The survival or organ allografts is prolonged in mice and rats treated with fractionated, high-dose total lymphoid irradiation (TLI). We have studied the effect of TLI, alone or in combination with donor bone marrow or pharmacologic immunosuppression (cyclosporin-A: CY-A), on the survival of heterotopic rat heart allografts. Specifically, we evaluated the generalized immunosuppressive effect of TLI as a function of accumulated dose and fractionation schedule. In addition, TLI and CY-A were used individually in schedules that by themselves gave only moderate graft prolongation and then subsequently in sequential combination.

  1. Single fraction multimodal image guided focal salvage high-dose-rate brachytherapy for recurrent prostate cancer

    PubMed Central

    Rischke, Hans-Christian; Meyer, Philipp Tobias; Knobe, Sven; Volgeova-Neher, Natalja; Kollefrath, Michael; Jilg, Cordula Annette; Grosu, Anca Ligia; Baltas, Dimos; Kroenig, Malte

    2016-01-01

    Purpose We present a novel method for treatment of locally recurrent prostate cancer (PCa) following radiation therapy: focal, multimodal image guided high-dose-rate (HDR) brachytherapy. Material and methods We treated two patients with recurrent PCa after primary (#1) or adjuvant (#2) external beam radiation therapy. Multiparametric magnetic resonance imaging (mpMRI), choline, positron emission tomography combined with computed tomography (PET/CT), or prostate-specific membrane antigen (PSMA)-PET combined with CT identified a single intraprostatic lesion. Positron emission tomography or magnetic resonance imaging – transrectal ultrasound (MRI-TRUS) fusion guided transperineal biopsy confirmed PCa within each target lesion. We defined a PET and mpMRI based gross tumor volume (GTV). A 5 mm isotropic margin was applied additionally to each lesion to generate a planning target volume (PTV), which accounts for technical fusion inaccuracies. A D90 of 18 Gy was intended in one fraction to each PTV using ultrasound guided HDR brachytherapy. Results Six month follow-up showed adequate prostate specific antygen (PSA) decline in both patients (ΔPSA 83% in patient 1 and ΔPSA 59.3% in patient 2). Follow-up 3-tesla MRI revealed regressive disease in both patients and PSMA-PET/CT showed no evidence of active disease in patient #1. No acute or late toxicities occurred. Conclusions Single fraction, focal, multimodal image guided salvage HDR brachytherapy for recurrent prostate cancer is a feasible therapy for selected patients with single lesions. This approach has to be evaluated in larger clinical trials. PMID:27504134

  2. Fractional-Dose Inactivated Poliovirus Vaccine Immunization Campaign - Telangana State, India, June 2016.

    PubMed

    Bahl, Sunil; Verma, Harish; Bhatnagar, Pankaj; Haldar, Pradeep; Satapathy, Asish; Kumar, K N Arun; Horton, Jennifer; Estivariz, Concepcion F; Anand, Abhijeet; Sutter, Roland

    2016-01-01

    Wild poliovirus type 2 was declared eradicated in September 2015 (1). In April 2016, India, switched from use of trivalent oral poliovirus vaccine (tOPV; containing types 1, 2, and 3 polio vaccine viruses), to bivalent OPV (bOPV; containing types 1 and 3), as part of a globally synchronized initiative to withdraw Sabin poliovirus type 2 vaccine. Concurrently, inactivated poliovirus vaccine (IPV) was introduced into India's routine immunization program to maintain an immunity base that would mitigate the number of paralytic cases in the event of epidemic transmission of poliovirus type 2 (2,3). After cessation of use of type 2 Sabin vaccine, any reported isolation of vaccine-derived poliovirus type 2 (VDPV2) would be treated as a public health emergency and might need outbreak response with monovalent type 2 oral vaccine, IPV, or both (4). In response to identification of a VDPV2 isolate from a sewage sample collected in the southern state of Telangana in May 2016, India conducted a mass vaccination campaign in June 2016 using an intradermal fractional dose (0.1 ml) of IPV (fIPV). Because of a global IPV supply shortage, fIPV, which uses one fifth of regular intramuscular (IM) dose administered intradermally, has been recommended as a response strategy for VDPV2 (5). Clinical trials have demonstrated that fIPV is highly immunogenic (6,7). During the 6-day campaign, 311,064 children aged 6 weeks-3 years were vaccinated, achieving an estimated coverage of 94%. With appropriate preparation, an emergency fIPV response can be promptly and successfully implemented. Lessons learned from this campaign can be applied to successful implementation of future outbreak responses using fIPV. PMID:27559683

  3. Unexpected radiation laryngeal necrosis after carbon ion therapy using conventional dose fractionation for laryngeal cancer.

    PubMed

    Demizu, Yusuke; Fujii, Osamu; Nagano, Fumiko; Terashima, Kazuki; Jin, Dongcun; Mima, Masayuki; Oda, Naoharu; Takeuchi, Kaoru; Takeda, Makiko; Ito, Kazuyuki; Fuwa, Nobukazu; Okimoto, Tomoaki

    2015-11-01

    Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy.

  4. Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach.

    PubMed

    Nissenbaum, M; Browde, S; Bezwoda, W R; de Moor, N G; Derman, D P

    1984-01-01

    Fifty-eight patients with advanced head and neck cancer were entered into a randomised trial comparing chemotherapy (DDP + bleomycin) alone, multiple daily fractionated radiation therapy, and multimodality therapy consisting of chemotherapy plus multiple fractionated radiation therapy. Multimodal therapy gave a significantly higher response rate (69%) than either single-treatment modality. The use of a multiple daily dose fractionation allowed radiation therapy to be completed over 10 treatment days, and the addition of chemotherapy to the radiation treatment did not significantly increase toxicity. Patients receiving multimodal therapy also survived significantly longer (median 50 weeks) than those receiving single-modality therapy (median 24 weeks).

  5. Subanesthetic doses of ketamine transiently decrease serotonin transporter activity: a PET study in conscious monkeys.

    PubMed

    Yamamoto, Shigeyuki; Ohba, Hiroyuki; Nishiyama, Shingo; Harada, Norihiro; Kakiuchi, Takeharu; Tsukada, Hideo; Domino, Edward F

    2013-12-01

    Subanesthetic doses of ketamine, an N-methyl-D-aspartic acid (NMDA) antagonist, have a rapid antidepressant effect which lasts for up to 2 weeks. However, the neurobiological mechanism regarding this effect remains unclear. In the present study, the effects of subanesthetic doses of ketamine on serotonergic systems in conscious monkey brain were investigated. Five young monkeys underwent four positron emission tomography measurements with [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile ([(11)C]DASB) for the serotonin transporter (SERT), during and after intravenous infusion of vehicle or ketamine hydrochloride in a dose of 0.5 or 1.5 mg/kg for 40 min, and 24 h post infusion. Global reduction of [(11)C]DASB binding to SERT was observed during ketamine infusion in a dose-dependent manner, but not 24 h later. The effect of ketamine on the serotonin 1A receptor (5-HT1A-R) and dopamine transporter (DAT) was also investigated in the same subjects studied with [(11)C]DASB. No significant changes were observed in either 5-HT1A-R or DAT binding after ketamine infusion. Microdialysis analysis indicated that ketamine infusion transiently increased serotonin levels in the extracellular fluid of the prefrontal cortex. The present study demonstrates that subanesthetic ketamine selectively enhanced serotonergic transmission by inhibition of SERT activity. This action coexists with the rapid antidepressant effect of subanesthetic doses of ketamine. Further studies are needed to investigate whether the transient combination of SERT and NMDA reception inhibition enhances each other's antidepressant actions. PMID:23880871

  6. Serum triiodothyronine 7-15 years after fractionated low dose radioiodine therapy of thyrotoxicosis.

    PubMed

    Herrmann, J; Schaps, D; Rusche, H J; Berger, M; Krüskemper, H L; von zur Hühlen, A; Hackenberg, K; Reinwein, D

    1975-03-01

    In 189 of 334 patients, who had been treated with fractionated doses of radioiodine for Graves' disease 7-15 years ago, the serum concentrations of triiodothyronine have been estimated in additition to the following parameters: Protein bound 127-iodine (PB-127-I), free thyroxine index, cholesterol- and TSH-level in serum, tendon reflex time and clinical index according to Billewitz et al. (1969). In forty-one of the 189 sera the free T4 (AFT4) and free T3 (AFT3) concentrations were measured as well. The following hormonal and clinical patterns were observed: (1) Euthyroidism, with all parameters within the normal range in 148 patients (equals 78-4%). (2) Hypothyroidism with low serum T3, PBI, AFT4, AFT3 and elevated TSH six subjects (equals 3-2%). (3) Persistent hyperthyroidism with increased thyroid hormone concentrations and low TSH in seven cases (equals 3-7%). (4) In twenty-eight clinically euthyroid patients (equals 14-8%) TSH was elevated with normal PBI and AFT4. Twenty of these subjects had a low normal T3 and in nine the T3 was clearly in the hypothyroid range (40 plus or minus 12 mug/dl). (5) The constellation of normal T3, low T4 and elevated TSH, which has been frequently found after radioiodine therapy, has been seen in only moderate form in ten cases.

  7. Supplementation of the black rice outer layer fraction to rabbits decreases atherosclerotic plaque formation and increases antioxidant status.

    PubMed

    Ling, Wen Hua; Wang, Lin Llin; Ma, Jing

    2002-01-01

    The influence of the supplementation of black and white rice outer layer fractions on atherosclerotic plaque formation induced by hypercholesterolemia was investigated in rabbits. Male rabbits (n = 32) were randomly divided into four groups. They were fed nonpurified diet (normal group), a lard (3.5 g/100 g) with high cholesterol (0.5 g/100 g) diet (HC group); the HC diet with 5 g/100 g white rice outer layer fraction (WRF group); or the HC diet with 5 g/100 g black rice outer layer fraction (BRF) for 2 mo. Blood samples were collected for determination of lipid concentration and oxidative and antioxidative status variables, and aortae were taken for the assessment of atherosclerotic plaques. The atherosclerotic plaque area in rabbits fed the BRF diet was 66% lower than that of the HC or WRF rabbits (P < 0.001). Supplementation of the black rice outer layer significantly (P < 0.05) lowered aortic 8-hydroxy-2'-deoxyguanosine (8-OHdG) (-52%, -44%) compared with the WRF or HC diets (P < 0.05). There were no differences in aortic 8-OHdG levels between rabbits fed the BRF and normal diets. The BRF diet significantly (P < 0.05) decreased the malondialdehyde (MDA) level of serum (-37%) and aortic artery (-50%) compared with the WRF diet. There were no differences in the concentrations of serum total cholesterol (TC), LDL cholesterol (LDL-C), HDL-C or the ratio of apoprotein (apo)I/apoB among the HC, WRF and BRF groups. Similarly, there were no differences in the serum vitamin E concentration and erythrocyte and aorta superoxide dismutase (SOD) activities among rabbits fed these diets. The serum concentration of most fatty acids except 18:1 did not differ between the WRF and the BRF groups. We conclude that the inhibition of atherosclerotic plaque formation derived from the black rice outer layer fraction in rabbits might be mediated by antioxidative or anti-inflammatory effects. PMID:11773502

  8. SU-E-T-94: Daily Fraction Dose Recalculation Based On Rigid Registration Using Cone Beam CT

    SciTech Connect

    Bosse, C; Tuohy, R; Mavroidis, P; Shi, Z; Crownover, R; Papanikolaou, N; Stathakis, S

    2014-06-01

    Purpose: To calculate the daily fraction dose for a CBCT recalculation based on rigid registration and compare it to the planned CT dose. Methods: For this study, 30 patients that were previously treated (10 SBRT lung, 10 prostate and 10 abdomen) were considered. The daily CBCT images were imported into the Pinnacle treatment planning system from Mosaic. The prescribing physician contoured the regions of interest (ROI) on each CBCT and then dose was computed on each CBCT. Each CBCT dose distribution was then compared against the plan. The evaluation was based on isodose line comparison and Dose Volume Histogram comparison. Results: In the case of lung patients the dose differences between daily dose and plan dose were considered small. The PTV coverage was not compromised and the dose to the organs at risk had negligible differences. Larger differences were observed for prostate and abdomen patients. In these cases, although the PTV doses did not change on a daily basis, the doses to the organs at risk had significant differences. For a prostate patient, the bladder dose at 35% volume was 2714.444 cGy for the CT plan and 2844.747, 2801.556, 3552.37, and 2970.968 cGy for subsequent CBCTs. For the PTV on a SBRT patient, however, the CT plan had a dose at 35% volume of 6917.71 cGy and 6815.385, 6892.5, 6896.25, and 6922.9 cGy for the CBCTs. Conclusion: Daily dose validation is feasible using CBCT and treatment planning system. It provides means to evaluate the course of treatment for the patient undergoing radiation therapy and can assist in the decision of the need of adaptation of the treatment plan.

  9. Assessment of the unattached fraction of indoor radon progeny and its contribution to dose: a pilot study in China.

    PubMed

    Guo, Qiuju; Zhang, Lei; Guo, Lu

    2012-12-01

    The unattached fraction of radon progeny (f(p)) is one of the most important factors for accurate evaluation of the effective dose from a unit of radon exposure, and it may vary greatly in different environments. For precise evaluation of the indoor radon exposure dose and the influence of unattached radon progeny, a pilot survey of f(p) in different environments was carried out in China with a portable and integrating monitor. The dose conversion factors for radon progeny are calculated with LUDEP(®) code, and the dose contributions from the unattached and the attached radon progenies were simultaneously evaluated based on the results of field measurements. The results show that even though the concentrations of radon progeny vary significantly among different indoor environments, the variations of f(p) seem relatively small (9.3-16.9%). The dose contribution from unattached radon progeny is generally larger (30.2-46.2%) in an indoor environment.

  10. Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose–volume histograms

    SciTech Connect

    Sugano, Yasutaka; Mizuta, Masahiro; Takao, Seishin; Shirato, Hiroki; Sutherland, Kenneth L.; Date, Hiroyuki

    2015-11-15

    Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.

  11. Decreasing Temporal Lobe Dose With Five-Field Intensity-Modulated Radiotherapy for Treatment of Pituitary Macroadenomas

    SciTech Connect

    Parhar, Preeti K.; Duckworth, Tamara; Shah, Parinda; DeWyngaert, J. Keith; Narayana, Ashwatha; Formenti, Silvia C.; Shah, Jinesh N.

    2010-10-01

    Purpose: To compare temporal lobe dose delivered by three pituitary macroadenoma irradiation techniques: three-field three-dimensional conformal radiotherapy (3D-CRT), three-field intensity-modulated radiotherapy (3F IMRT), and a proposed novel alternative of five-field IMRT (5F IMRT). Methods and Materials: Computed tomography-based external beam radiotherapy planning was performed for 15 pituitary macroadenoma patients treated at New York University between 2002 and 2007 using: 3D-CRT (two lateral, one midline superior anterior oblique [SAO] beams), 3F IMRT (same beam angles), and 5F IMRT (same beam angles with additional right SAO and left SAO beams). Prescription dose was 45 Gy. Target volumes were: gross tumor volume (GTV) = macroadenoma, clinical target volume (CTV) = GTV, and planning target volume = CTV + 0.5 cm. Structure contouring was performed by two radiation oncologists guided by an expert neuroradiologist. Results: Five-field IMRT yielded significantly decreased temporal lobe dose delivery compared with 3D-CRT and 3F IMRT. Temporal lobe sparing with 5F IMRT was most pronounced at intermediate doses: mean V25Gy (% of total temporal lobe volume receiving {>=}25 Gy) of 13% vs. 28% vs. 29% for right temporal lobe and 14% vs. 29% vs. 30% for left temporal lobe for 5F IMRT, 3D-CRT, and 3F IMRT, respectively (p < 10{sup -7} for 5F IMRT vs. 3D-CRT and 5F IMRT vs. 3F IMRT). Five-field IMRT plans did not compromise target coverage, exceed normal tissue dose constraints, or increase estimated brain integral dose. Conclusions: Five-field IMRT irradiation technique results in a statistically significant decrease in the dose to the temporal lobes and may thus help prevent neurocognitive sequelae in irradiated pituitary macroadenoma patients.

  12. Glucose and insulin do not decrease in a dose-dependent manner after increasing doses of mixed fibers that are consumed in muffins for breakfast.

    PubMed

    Willis, Holly J; Thomas, William; Eldridge, Alison L; Harkness, Laura; Green, Hilary; Slavin, Joanne L

    2011-01-01

    Conventional wisdom suggests that fiber consumption leads to lower postprandial glucose and insulin response. We hypothesized that increasing doses of mixed, viscous fiber would lower glucose and insulin levels in a dose-dependent manner. Healthy men (n = 10) and women (n = 10) with a body mass index of 24 ± 2 (mean ± SEM) participated in this double-blind, crossover study. On 4 separate visits, fasting subjects consumed an approximately 2093 kJ (500 calorie) muffin with 0, 4, 8, or 12 g of mixed fibers. Blood was drawn to measure glucose and insulin at regular intervals throughout a 3-hour test period. Area under the curve (AUC) glucose was significantly lower after 0 g of fiber than after 4, 8, or 12 g of fiber (arbitrary AUC units ± SEM: 25.3 ± 5.2 vs 44.6 ± 7.7, 49.7 ± 7.9, 51.5 ± 6.6, respectively; P < .006). Area under the curve glucose increased with increasing fiber doses (P for trend = .0003). Area under the curve insulin was higher after the 4-g dose than after the 0-, 8-, and 12-g doses (arbitrary AUC units ± SEM: 84.4 ± 8.0 vs 60.1 ± 6.5, 69.4 ± 8.7, 69.7 ± 8.5, respectively; P < .05); it did not change in a dose-dependent manner. Area under the curve glucose and AUC insulin did not correlate with each other. Glucose and insulin did not decrease in a dose-dependent manner after 0, 4, 8, and 12 g of mixed fibers were consumed in muffins for breakfast. The lack of differences was largely based on the individual variation in glucose response. Caution should be used when making general claims about the expected impact of fiber on glucose and insulin levels.

  13. Health-Related Quality of Life After Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Prostate Cancer

    SciTech Connect

    Morton, Gerard C.; Loblaw, D. Andrew; Chung, Hans; Tsang, Gail; Sankreacha, Raxa; Deabreu, Andrea; Zhang Liying; Mamedov, Alexandre; Cheung, Patrick; Batchelar, Deidre; Danjoux, Cyril; Szumacher, Ewa

    2011-08-01

    Purpose: To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change. Methods and Materials: Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received high-dose-rate brachytherapy as a single 15-Gy implant, followed by external beam radiotherapy to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]). The proportion of patients developing a clinically significant difference in the EPIC domain score (minimally important difference of >0.5 standard deviation) was determined and correlated with the baseline clinical and dosimetric factors. The study accrued 125 patients, with a median follow-up of 24 months. Results: By 24 months, 23% had Grade 2 urinary toxicity and only 5% had Grade 2 bowel toxicity, with no Grade 3 toxicity. The proportion of patients reporting a significant decrease in EPIC urinary, bowel, sexual, and hormonal domain scores was 53%, 51%, 45%, and 40% at 12 months and 57%, 65%, 51%, and 30% at 24 months, respectively. The proportion with a >1 standard deviation decrease in the EPIC urinary, bowel, sexual, and hormonal domain scores was 38%, 36%, 24%, and 20% at 12 months and 46%, 48%, 19%, and 8% at 24 months, respectively. On multivariate analysis, the dose to 10% of the urethra was associated with a decreasing EPIC urinary domain score (p = .0089) and, less strongly (p = .0312) with a decreasing hormonal domain score. No association was found between the prostate volume, bladder dose, or high-dose volume and urinary health-related quality of life. A high baseline International Index of Erectile Function score was associated (p = .0019) with a decreasing sexual domain score. The optimal maximal dose

  14. Early micro-rheological consequences of single fraction total body low-dose photon irradiation in mice.

    PubMed

    Szluha, Kornelia; Lazanyi, Kornelia; Furka, Andrea; Kiss, Ferenc; Szabo, Imre; Pintye, Eva; Miko, Iren; Nemeth, Norbert

    2014-01-01

    Despite of the studies on widespread biological effects of irradiation, surprisingly only little number of papers can be found dealing with its in vivo hemorheological impact. Furthermore, other studies suggested that low-dose irradiation might differ from high-dose in more than linear ways. On Balb/c Jackson female adult mice hematological and hemorheological impacts of total body irradiation were investigated 1 hour following 0.002, 0.005, 0.01, 0.02, 0.05 and 0.1 Gy dose irradiation. In case of 0.01 Gy further groups were analyzed 30 minutes, 2, 4, 6, 24 and 48 h after irradiation. According to the results, it seems that the dose-dependent changes of blood micro-rheological parameters are not linear. The irradiation dose of 0.01 Gy acted as a point of 'inflexion', because by this dose we found the most expressed changes in hematological parameters, as well as in red blood cell aggregation, deformability and osmoscan data. The time-dependent changes showed progressive decrease in pH, rise in lactate concentration, further decrease in erythrocyte aggregation index and deformability, with moderate shifting of the optimal osmolarity point and modulation in membrane stability. As conclusion, low-dose total body irradiation may cause micro-rheological changes, being non-linearly correlated with the irradiation dose.

  15. Decreasing radiation doses in digital subtraction angiographies consecutively performed by trainees.

    PubMed

    Xu, Gelin; Zhao, Wenxin; Zheng, Ling; Fan, Xinying; Yin, Qin; Liu, Xinfeng

    2012-01-01

    Digital subtraction angiography (DSA) performed by trainees may be related to increased radiation exposure. This study was aimed to investigate and quantify this learning effect, with fluoroscopy time and dose-area product (DAP) as parameters. We collected procedure data of the first to the fortieth cerebral DSA consecutively performed by 13 trainees in a training centre. DAP, procedure time, fluoroscopy time, number of cine-frames of the first 20 DSA procedures performed by these trainees were compared with that of the second 20 procedures. There was no significant difference concerning the procedure time between the first and the second 20 procedures (56.3 ± 29.5 vs 51.5 ± 20.2 min, p = 0.113). Numbers of cine-frames were very similar between the first and the second 20 procedures (750.7 ± 290.3 vs 744.5 ± 188.7, p = 0.830). Fluoroscopy time of the first 20 procedures was significantly longer than that of the second 20 procedures (17.8 ± 15.4 vs 12.6 ± 9.0, p = 0.001). DAP of the first 20 procedures was significantly higher than that of the second 20 procedures (6.4 ± 4.9 vs 3.8 ± 1.8, p < 0.001). DAP was correlated significantly with the performer's experience (R = -0.288, p < 0.001). There exists a learning effect of radiation exposure during cerebral DSA procedures performed by trainees. The learning effect is significant during the first 20 procedures, and becomes insignificant after 20 procedures. Insufficient catheter skills in novice trainees may be one reason for this effect. PMID:21303782

  16. Differential sensitivity of two predominant stromal progenitor cell subpopulations in bone marrow to single and fractionated radiation doses

    SciTech Connect

    Kolesnikova, A.I.; Konoplyannikov, A.G.; Hendry, J.H.

    1995-12-01

    The sensitivity of fibroblastoid precursor cells in rat bone marrow to single and fractionated doses of {gamma} rays delivered in vivo was measured. In vitro colonies were classified as being compact or diffuse, and the progenitor cells for both types were slowly cycling in vivo (survival levels after exposure to hydroxyurea were 90 {+-} 6% and 93 {+-} 11%, respectively). The progenitor cells forming diffuse colonies were more resistant (D{sub o} = 1.39 Gy) than those forming compact colonies (D{sub o} = 0.76 Gy). The fractionation sensitivities were characterized by an {alpha}/{beta} ratio of 12.7 {+-} 5.5 Gy for diffuse colonies and 4.5 {+-} 3.0 Gy for compact colonies, respectively. The progenitor cells forming diffuse colonies may contribute more to long-term regeneration after high doses in vivo. 15 refs., 2 figs., 1 tab.

  17. Experimental dosing of wetlands with coagulants removes mercury from surface water and decreases mercury bioaccumulation in fish.

    PubMed

    Ackerman, Joshua T; Kraus, Tamara E C; Fleck, Jacob A; Krabbenhoft, David P; Horwath, William R; Bachand, Sandra M; Herzog, Mark P; Hartman, C Alex; Bachand, Philip A M

    2015-05-19

    Mercury pollution is widespread globally, and strategies for managing mercury contamination in aquatic environments are necessary. We tested whether coagulation with metal-based salts could remove mercury from wetland surface waters and decrease mercury bioaccumulation in fish. In a complete randomized block design, we constructed nine experimental wetlands in California's Sacramento-San Joaquin Delta, stocked them with mosquitofish (Gambusia affinis), and then continuously applied agricultural drainage water that was either untreated (control), or treated with polyaluminum chloride or ferric sulfate coagulants. Total mercury and methylmercury concentrations in surface waters were decreased by 62% and 63% in polyaluminum chloride treated wetlands and 50% and 76% in ferric sulfate treated wetlands compared to control wetlands. Specifically, following coagulation, mercury was transferred from the filtered fraction of water into the particulate fraction of water which then settled within the wetland. Mosquitofish mercury concentrations were decreased by 35% in ferric sulfate treated wetlands compared to control wetlands. There was no reduction in mosquitofish mercury concentrations within the polyaluminum chloride treated wetlands, which may have been caused by production of bioavailable methylmercury within those wetlands. Coagulation may be an effective management strategy for reducing mercury contamination within wetlands, but further studies should explore potential effects on wetland ecosystems.

  18. Experimental dosing of wetlands with coagulants removes mercury from surface water and decreases mercury bioaccumulation in fish

    USGS Publications Warehouse

    Ackerman, Joshua T.; Kraus, Tamara E.C.; Fleck, Jacob A.; Krabbenhoft, David P.; Horwarth, William R.; Bachand, Sandra M.; Herzog, Mark; Hartman, Christopher; Bachand, Philip A.M.

    2015-01-01

    Mercury pollution is widespread globally, and strategies for managing mercury contamination in aquatic environments are necessary. We tested whether coagulation with metal-based salts could remove mercury from wetland surface waters and decrease mercury bioaccumulation in fish. In a complete randomized block design, we constructed nine experimental wetlands in California's Sacramento-San Joaquin Delta, stocked them with mosquitofish (Gambusia affinis), and then continuously applied agricultural drainage water that was either untreated (control), or treated with polyaluminum chloride or ferric sulfate coagulants. Total mercury and methylmercury concentrations in surface waters were decreased by 62% and 63% in polyaluminum chloride treated wetlands and 50% and 76% in ferric sulfate treated wetlands compared to control wetlands. Specifically, following coagulation, mercury was transferred from the filtered fraction of water into the particulate fraction of water which then settled within the wetland. Mosquitofish mercury concentrations were decreased by 35% in ferric sulfate treated wetlands compared to control wetlands. There was no reduction in mosquitofish mercury concentrations within the polyaluminum chloride treated wetlands, which may have been caused by production of bioavailable methylmercury within those wetlands. Coagulation may be an effective management strategy for reducing mercury contamination within wetlands, but further studies should explore potential effects on wetland ecosystems.

  19. Electron paramagnetic resonance (EPR) oxygen image hypoxic fraction plus radiation dose strongly correlates with tumor cure in FSa fibrosarcomas

    PubMed Central

    Elas, Martyna; Bell, Rebecca; Hleihel, Danielle; Barth, Eugene D.; McFaul, Colin; Haney, Chad R.; Bielanska, Joanna; Pustelny, Katarzyna; Ahn, Kang-Hyun; Pelizzari, Charles A.; Kocherginsky, Masha; Halpern, Howard J.

    2008-01-01

    Purpose Tumor hypoxia has long been known to produce resistance to radiation. In this study, electron paramagnetic resonance (EPR) oxygen imaging was investigated for its power to predict the success of tumor control depending on tumor oxygenation level and radiation therapy dose. Methods and Materials Thirty-four EPR oxygen images were obtained from the legs of C3H mice bearing 0.5 ml FSa fibrosarcomas under both normal (air breathing) and clamped tumor conditions. Under the same conditions as those during which the images were obtained, tumors were irradiated to a variety doses near the FSa TCD50. Tumor tissue was distinguished from normal tissue using co-registration of the EPR oxygen images with spin-echo MRI images of the tumor and/or stereotactic localization. Tumor voxel statistics in the EPR oxygen image included mean and median pO2, and the fraction of tumor voxels below the specified pO2 values of 3, 6 and 10 torr. Bivariate logistic regression analysis using radiation dose and each of the EPR oxygen image statistics determined which best separated treatment failure from success. Results and Conclusions TCD50 measurements were similar to those found in the literature for this syngeneic tumor. Bivariate analysis of 34 tumors demonstrated that tumor cure correlated with dose (p=0.004) and with <10 torr hypoxic fraction (p=0.023). Together, radiation dose and EPR image hypoxic fraction separate the population of FSa fibrosarcomas which are cured from those which fail, thus predicting curability. PMID:18474313

  20. SU-E-J-176: Characterization of Inter-Fraction Breast Variability and the Implications On Delivered Dose

    SciTech Connect

    Sudhoff, M; Lamba, M; Kumar, N; Ward, A; Elson, H

    2015-06-15

    Purpose: To systematically characterize inter-fraction breast variability and determine implications on delivered dose. Methods: Weekly port films were used to characterize breast setup variability. Five evenly spaced representative positions across the contour of each breast were chosen on the electronic port film in reference to graticule, and window and level was set such that the skin surface of the breast was visible. Measurements from the skin surface to treatment field edge were taken on each port film at each position and compared to the planning DRR, quantifying the variability. The systematic measurement technique was repeated for all port films for 20 recently treated breast cancer patients. Measured setup variability for each patient was modeled as a normal distribution. The distribution was randomly sampled from the model and applied as isocentric shifts in the treatment planning computer, representing setup variability for each fraction. Dose was calculated for each shifted fraction and summed to obtain DVHs and BEDs that modeled the dose with daily setup variability. Patients were categorized in to relevant groupings that were chosen to investigate the rigorousness of immobilization types, treatment techniques, and inherent anatomical difficulties. Mean position differences and dosimetric differences were evaluated between planned and delivered doses. Results: The setup variability was found to follow a normal distribution with mean position differences between the DRR and port film between − 8.6–3.5 mm with sigma range of 5.3–9.8 mm. Setup position was not found to be significantly different than zero. The mean seroma or whole breast PTV dosimetric difference, calculated as BED, ranged from a −0.23 to +1.13Gy. Conclusion: A systematic technique to quantify and model setup variability was used to calculate the dose in 20 breast cancer patients including variable setup. No statistically significant PTV or OAR BED differences were found between

  1. Investigating the Implications of a Variable RBE on Proton Dose Fractionation Across a Clinical Pencil Beam Scanned Spread-Out Bragg Peak

    PubMed Central

    Marshall, Thomas I.; Chaudhary, Pankaj; Michaelidesová, Anna; Vachelová, Jana; Davídková, Marie; Vondráček, Vladimir; Schettino, Giuseppe; Prise, Kevin M.

    2016-01-01

    Purpose To investigate the clinical implications of a variable relative biological effectiveness (RBE) on proton dose fractionation. Using acute exposures, the current clinical adoption of a generic, constant cell killing RBE has been shown to underestimate the effect of the sharp increase in linear energy transfer (LET) in the distal regions of the spread-out Bragg peak (SOBP). However, experimental data for the impact of dose fractionation in such scenarios are still limited. Methods and Materials Human fibroblasts (AG01522) at 4 key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subjected to various fractionation regimens with an interfraction period of 24 hours at Proton Therapy Center in Prague, Czech Republic. Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and parameterized using a linear quadratic formalism. Results Significant variations in the cell killing RBE for fractionated exposures along the proton dose profile were observed. RBE increased sharply toward the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect was more pronounced at smaller doses per fraction. Experimental survival fractions were adequately predicted using a linear quadratic formalism assuming full repair between fractions. Data were also used to validate a parameterized variable RBE model based on linear α parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimens. Conclusions The RBE-weighted absorbed dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE, particularly in fractionation regimens with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, our study provides an RBE dataset that can be used

  2. A decrease in lung cancer mortality following the introduction of low-dose chest CT screening in Hitachi, Japan.

    PubMed

    Nawa, Takeshi; Nakagawa, Tohru; Mizoue, Tetsuya; Kusano, Suzushi; Chonan, Tatsuya; Hayashihara, Kenji; Suito, Tetsushi; Endo, Katsuyuki

    2012-12-01

    Recent US clinical trial demonstrated that CT screening prevents lung cancer death among high risk individuals. However, it remains unclear whether wide implementation of low-dose CT screening for lung cancer can decrease mortality in the community. Among residents in Hitachi City (Japan), where nearly 40% of inhabitants aged 50-69 years were estimated to have participated in the screening at least once from 1998 through 2009, the trend of lung cancer mortality was described in relation to the timing of implementation of the CT screening. Cancer mortality data were obtained from regional cancer registry and standardized mortality ratio (SMR) of lung cancer was calculated for each 5-year period during 1995-2009. In both men and women aged 60 years or older, age-specific lung cancer mortality rates were generally lower during 2005-2009 as compared with those during 1995-2004. For combined men and women aged 50-79 years, SMR was nearly unity prior to or during introductory phase of CT screening and during early period of implementation; however, it was significantly decreased during 2005-2009, well after the implementation of CT screening, with SMR (95% confidence interval) being 0.76 (0.67-0.86). Results suggest that wide implementation of low-dose chest CT screening may decrease lung cancer mortality in the community 4-8 years after introduction of the screening.

  3. A comprehensive study on decreasing the kilovoltage cone-beam CT dose by reducing the projection number.

    PubMed

    Lu, Bo; Lu, Haibin; Palta, Jatinder

    2010-01-01

    The objective of this study was to evaluate the effect of kilovoltage cone-beam computed tomography (CBCT) on registration accuracy and image qualities with a reduced number of planar projections used in volumetric imaging reconstruction. The ultimate goal is to evaluate the possibility of reducing the patient dose while maintaining registration accuracy under different projection-number schemes for various clinical sites. An Elekta Synergy Linear accelerator with an onboard CBCT system was used in this study. The quality of the Elekta XVI cone-beam three-dimensional volumetric images reconstructed with a decreasing number of projections was quantitatively evaluated by a Catphan phantom. Subsequently, we tested the registration accuracy of imaging data sets on three rigid anthropomorphic phantoms and three real patient sites under the reduced projection-number (as low as 1/6th) reconstruction of CBCT data with different rectilinear shifts and rota-tions. CBCT scan results of the Catphan phantom indicated the CBCT images got noisier when the number of projections was reduced, but their spatial resolution and uniformity were hardly affected. The maximum registration errors under the small amount transformation of the reference CT images were found to be within 0.7 mm translation and 0.3 masculine rotation. However, when the projection number was lower than one-fourth of the full set with a large amount of transformation of reference CT images, the registration could easily be trapped into local minima solutions for a nonrigid anatomy. We concluded, by using projection-number reduction strategy under conscientious care, imaging-guided localization procedure could achieve a lower patient dose without losing the registration accuracy for various clinical sites and situations. A faster scanning time is the main advantage compared to the mA decrease-based, dose-reduction method.

  4. Cumulative dose on fractional delivery of tomotherapy to periodically moving organ: A phantom QA suggestion

    SciTech Connect

    Shin, Eunhyuk; Han, Youngyih; Park, Hee-Chul; Sung Kim, Jin; Hwan Ahn, Sung; Suk Shin, Jung; Gyu Ju, Sang; Ho Choi, Doo; Lee, Jaiki

    2013-01-01

    This study was conducted to evaluate the cumulative dosimetric error that occurs in both target and surrounding normal tissues when treating a moving target in multifractional treatment with tomotherapy. An experiment was devised to measure cumulative error in multifractional treatments delivered to a horseshoe-shaped clinical target volume (CTV) surrounding a cylinder shape of organ at risk (OAR). Treatments differed in jaw size (1.05 vs 2.5 cm), pitch (0.287 vs 0.660), and modulation factor (1.5 vs 2.5), and tumor motion characteristics differing in amplitude (1 to 3 cm), period (3 to 5 second), and regularity (sinusoidal vs irregular) were tested. Treatment plans were delivered to a moving phantom up to 5-times exposure. Dose distribution on central coronal plane from 1 to 5 times exposure was measured with GAFCHROMIC EBT film. Dose differences occurring across 1 to 5 times exposure of treatment and between treatment plans were evaluated by analyzing measurements of gamma index, gamma index histogram, histogram changes, and dose at the center of the OAR. The experiment showed dose distortion due to organ motion increased between multiexposure 1 to 3 times but plateaued and remained constant after 3-times exposure. In addition, although larger motion amplitude and a longer period of motion both increased dosimetric error, the dose at the OAR was more significantly affected by motion amplitude rather than motion period. Irregularity of motion did not contribute significantly to dosimetric error when compared with other motion parameters. Restriction of organ motion to have small amplitude and short motion period together with larger jaw size and small modulation factor (with small pitch) is effective in reducing dosimetric error. Pretreatment measurements for 3-times exposure of treatment to a moving phantom with patient-specific tumor motion would provide a good estimation of the delivered dose distribution.

  5. Stereotactic body radiotherapy for patients with oligometastases from colorectal cancer: risk-adapted dose prescription with a maximum dose of 83–100 Gy in five fractions

    PubMed Central

    Takeda, Atsuya; Sanuki, Naoko; Tsurugai, Yuichiro; Oku, Yohei; Aoki, Yousuke

    2016-01-01

    We previously reported that the local control of pulmonary metastases from colorectal cancer (CRC) following stereotactic body radiotherapy (SBRT) with moderate prescription dose was relatively worse. We investigated the treatment outcomes and toxicities of patients with oligometastases from CRC treated by SBRT using risk-adapted, very high- and convergent-dose regimens. Among patients referred for SBRT from August 2011 to January 2015, those patients were extracted who had liver or pulmonary metastases from CRC, and they were treated with a total dose of 50–60 Gy in five fractions prescribed to the 60% isodose line of the maximum dose covering the surface of the planning target volume. Concurrent administration of chemotherapy was not admitted during SBRT, while neoadjuvant or adjuvant chemotherapy was allowed. A total of 21 patients (12 liver, 9 lung) with 28 oligometastases were evaluated. The median follow-up duration was 27.5 months (range: 6.5–43.3 months). Four patients were treated with SBRT as a series of initial treatments, and 17 patients were treated after recurrent oligometastases. The local control rates at 1 and 2 years from the start of SBRT were 100%. The disease-free and actuarial overall survival rates were 62% and 55%, and 79% and 79%, respectively. No severe toxicities (≥grade 3) occurred during follow-up. The outcomes following high-dose SBRT were excellent. This treatment can provide an alternative to the surgical resection of oligometastases from CRC. Prospective studies are needed to validate the effectiveness of SBRT. PMID:26983981

  6. Sci—Thur AM: YIS - 11: Estimation of Bladder-Wall Cumulative Dose in Multi-Fraction Image-Based Gynaecological Brachytherapy Using Deformable Point Set Registration

    SciTech Connect

    Zakariaee, R; Brown, C J; Hamarneh, G; Parsons, C A; Spadinger, I

    2014-08-15

    Dosimetric parameters based on dose-volume histograms (DVH) of contoured structures are routinely used to evaluate dose delivered to target structures and organs at risk. However, the DVH provides no information on the spatial distribution of the dose in situations of repeated fractions with changes in organ shape or size. The aim of this research was to develop methods to more accurately determine geometrically localized, cumulative dose to the bladder wall in intracavitary brachytherapy for cervical cancer. The CT scans and treatment plans of 20 cervical cancer patients were used. Each patient was treated with five high-dose-rate (HDR) brachytherapy fractions of 600cGy prescribed dose. The bladder inner and outer surfaces were delineated using MIM Maestro software (MIM Software Inc.) and were imported into MATLAB (MathWorks) as 3-dimensional point clouds constituting the “bladder wall”. A point-set registration toolbox for MATLAB, Coherent Point Drift (CPD), was used to non-rigidly transform the bladder-wall points from four of the fractions to the coordinate system of the remaining (reference) fraction, which was chosen to be the emptiest bladder for each patient. The doses were accumulated on the reference fraction and new cumulative dosimetric parameters were calculated. The LENT-SOMA toxicity scores of these patients were studied against the cumulative dose parameters. Based on this study, there was no significant correlation between the toxicity scores and the determined cumulative dose parameters.

  7. SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

    SciTech Connect

    Ding, C; Hrycushko, B; Jiang, S; Meyer, J; Timmerman, R

    2014-06-01

    Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm{sup 3}) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan, the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.

  8. Evaluation of Biologic Effective Dose and Schedule of Fractionation for Preoperative Radiotherapy for Rectal Cancer: Meta-Analyses and Meta-Regression;Rectal cancer; Preoperative radiotherapy; Biologic effective dose; Meta-analysis

    SciTech Connect

    Arruda Viani, Gustavo; Stefano, Eduardo Jose; Vendito Soares, Francisco; Afonso, Sergio Luis

    2011-07-15

    Purpose: To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone. Methods and Materials: A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy{sub 10} and a short RT schedule; Group 2, RCTs with BED >30 Gy{sub 10} and a long RT schedule; Group 3, RCTs with BED {<=}30 Gy{sub 10} and a short RT schedule; and Group 4, RCTs with BED {<=}30 Gy{sub 10} and a long RT schedule. Results: Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy{sub 10} of BED. Conclusion: Our data have shown that RT with a BED of >30 Gy{sub 10} is more efficient in reducing local recurrence and mortality rates than a BED of {<=}30 Gy{sub 10}, independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy{sub 10} should be recommended for sphincter preservation.

  9. SU-E-T-548: How To Decrease Spine Dose In Patients Who Underwent Sterotactic Spine Radiosurgery?

    SciTech Connect

    Acar, H; Altinok, A; Kucukmorkoc, E; Kucuk, N; Caglar, H

    2014-06-01

    Purpose: Stereotactic radiosurgery for spine metastases involves irradiation using a single high dose fraction. The purpose of this study was to dosimetrically compare stereotactic spine radiosurgery(SRS) plans using a recently new volumetric modulated arc therapy(VMAT) technique against fix-field intensity-modulated radiotherapy(IMRT). Plans were evaluated for target conformity and spinal cord sparing. Methods: Fifteen previously treated patients were replanned using the Eclipse 10.1 TPS AAA calculation algorithm. IMRT plans with 7 fields were generated. The arc plans used 2 full arc configurations. Arc and IMRT plans were normalized and prescribed to deliver 16.0 Gy in a single fraction to 90% of the planning target volume(PTV). PTVs consisted of the vertebral body expanded by 3mm, excluding the PRV-cord, where the cord was expanded by 2mm.RTOG 0631 recommendations were applied for treatment planning. Partial spinal cord volume was defined as 5mm above and below the radiosurgery target volume. Plans were compared for conformity and gradient index as well as spinal cord sparing. Results: The conformity index values of fifteen patients for two different treatment planning techniques were shown in table 1. Conformity index values for 2 full arc planning (average CI=0.84) were higher than that of IMRT planning (average CI=0.79). The gradient index values of fifteen patients for two different treatment planning techniques were shown in table 2. Gradient index values for 2 full arc planning (average GI=3.58) were higher than that of IMRT planning (average GI=2.82).The spinal cord doses of fifteen patients for two different treatment planning techniques were shown in table 3. D0.35cc, D0.03cc and partial spinal cord D10% values in 2 full arc plannings (average D0.35cc=819.3cGy, D0.03cc=965.4cGy, 10%partial spinal=718.1cGy) were lower than IMRT plannings (average D0.35cc=877.4cGy, D0.03c=1071.4cGy, 10%partial spinal=805.1cGy). Conclusions: The two arc VMAT technique is

  10. Attached, unattached fraction of progeny concentrations and equilibrium factor for dose assessments from (222)Rn and (220)Rn.

    PubMed

    Singh, Parminder; Saini, Komal; Mishra, Rosaline; Sahoo, Bijay Kumar; Bajwa, Bikramjit Singh

    2016-08-01

    In this study, measurements of indoor radon ((222)Rn), thoron ((220)Rn) and their equilibrium equivalent concentration (EEC) were carried out in 96 dwellings from 22 different villages situated in Hamirpur district, Himachal Pradesh, India, by using LR-115 type II-based pinhole twin cup dosimeters and deposition-based progeny sensors (DRPS/DTPS). The annual average indoor (222)Rn and (220)Rn concentrations observed in these dwellings were 63.82 and 89.59 Bq/m(3), respectively, while the average EEC (attached + unattached) for (222)Rn and (220)Rn was 29.28 and 2.74 Bq/m(3). For (222)Rn (f Rn) and (220)Rn (f Tn), the average values of unattached fraction were 0.11 and 0.09, respectively. The equilibrium factors for radon (F Rn) and thoron (F Tn) varied from 0.12 to 0.77 with an average of 0.50, and from 0.01 to 0.34 with an average of 0.05, respectively. The annual inhalation dose due to mouth and nasal breathing was calculated using dose conversion factors and unattached fractions. The indoor annual effective doses for (222)Rn (AEDR) and (220)Rn (AEDT) were found to be 1.92 and 0.83 mSv a(-1), respectively. The values of (222)Rn/(220)Rn concentrations and annual effective doses obtained in the present study are within the safe limits as recommended by the International Commission on Radiological Protection for indoor dwelling exposure conditions. PMID:27289385

  11. Attached, unattached fraction of progeny concentrations and equilibrium factor for dose assessments from (222)Rn and (220)Rn.

    PubMed

    Singh, Parminder; Saini, Komal; Mishra, Rosaline; Sahoo, Bijay Kumar; Bajwa, Bikramjit Singh

    2016-08-01

    In this study, measurements of indoor radon ((222)Rn), thoron ((220)Rn) and their equilibrium equivalent concentration (EEC) were carried out in 96 dwellings from 22 different villages situated in Hamirpur district, Himachal Pradesh, India, by using LR-115 type II-based pinhole twin cup dosimeters and deposition-based progeny sensors (DRPS/DTPS). The annual average indoor (222)Rn and (220)Rn concentrations observed in these dwellings were 63.82 and 89.59 Bq/m(3), respectively, while the average EEC (attached + unattached) for (222)Rn and (220)Rn was 29.28 and 2.74 Bq/m(3). For (222)Rn (f Rn) and (220)Rn (f Tn), the average values of unattached fraction were 0.11 and 0.09, respectively. The equilibrium factors for radon (F Rn) and thoron (F Tn) varied from 0.12 to 0.77 with an average of 0.50, and from 0.01 to 0.34 with an average of 0.05, respectively. The annual inhalation dose due to mouth and nasal breathing was calculated using dose conversion factors and unattached fractions. The indoor annual effective doses for (222)Rn (AEDR) and (220)Rn (AEDT) were found to be 1.92 and 0.83 mSv a(-1), respectively. The values of (222)Rn/(220)Rn concentrations and annual effective doses obtained in the present study are within the safe limits as recommended by the International Commission on Radiological Protection for indoor dwelling exposure conditions.

  12. Assessing the reproducibility of fractional rates of protein synthesis in muscle tissue measured using the flooding dose technique.

    PubMed

    McCarthy, Ian D; Brown, James

    2016-07-01

    The flooding dose technique of Garlick et al. (1980) has become the main method for measuring tissue and whole-animal rates of protein synthesis in ectotherms. However, single tissue samples are used to determine rates of protein synthesis and no studies have examined the pattern of flooding in large tissues such as the white muscle in fishes, which can comprise up to 55% of the wet body mass of a fish and which is poorly perfused. The present study has examined, for the first time, the patterns of flooding and measured rates of protein synthesis in five different regions of the white muscle in the Arctic charr Salvelinus alpinus ranging in size from 25g to 1.6kg following a flooding dose injection of L-[(3)H]-phenylalanine. The results indicate that the degree of flooding (i.e. free pool specific radioactivity relative to that of the injection solution) and elevation in free phenylalanine concentrations can vary between regions but the calculated fractional rates of protein synthesis were similar in four of the five regions studied. The variability in rates of protein synthesis increased with body size with greater variability observed between regions for fish >1kg in body mass. For consistency between studies, it is recommended that samples are taken from the epaxial muscle in the region below the dorsal fin when measuring fractional rates of white muscle synthesis in fishes. PMID:26970581

  13. Monte Carlo calculation of VMAT and helical tomotherapy dose distributions for lung stereotactic treatments with intra-fraction motion

    NASA Astrophysics Data System (ADS)

    Belec, J.; Clark, B. G.

    2013-05-01

    The aim of this study is to calculate realistic dose distributions that include the continuous deformation of organs and continuous motion of machine using 4D Monte Carlo methods for both volumetric modulated arc therapy and helical tomotherapy treatments. As part of a previous study, we presented a method to perform position-probability-sampled Monte Carlo dose calculations in the BEAMnrc and DOSXZYnrc user codes of EGSnrc. In this study, the DOSXYZnrc user code was further modified to account for the continuous intra-fraction deformation of the patient geometry. We implemented in the user code a method to update the transport grid densities as a function of time and map the energy deposited in the time dependent transport grid back to a reference grid. We provide information on the measurements performed to validate the implementation of this method and present an example of the application of the method for lung stereotactic treatments with intra-fraction motion. The results show that breathing motion is properly addressed with the internal target volume method for the cases studied.

  14. Assessing the reproducibility of fractional rates of protein synthesis in muscle tissue measured using the flooding dose technique.

    PubMed

    McCarthy, Ian D; Brown, James

    2016-07-01

    The flooding dose technique of Garlick et al. (1980) has become the main method for measuring tissue and whole-animal rates of protein synthesis in ectotherms. However, single tissue samples are used to determine rates of protein synthesis and no studies have examined the pattern of flooding in large tissues such as the white muscle in fishes, which can comprise up to 55% of the wet body mass of a fish and which is poorly perfused. The present study has examined, for the first time, the patterns of flooding and measured rates of protein synthesis in five different regions of the white muscle in the Arctic charr Salvelinus alpinus ranging in size from 25g to 1.6kg following a flooding dose injection of L-[(3)H]-phenylalanine. The results indicate that the degree of flooding (i.e. free pool specific radioactivity relative to that of the injection solution) and elevation in free phenylalanine concentrations can vary between regions but the calculated fractional rates of protein synthesis were similar in four of the five regions studied. The variability in rates of protein synthesis increased with body size with greater variability observed between regions for fish >1kg in body mass. For consistency between studies, it is recommended that samples are taken from the epaxial muscle in the region below the dorsal fin when measuring fractional rates of white muscle synthesis in fishes.

  15. High-dose-rate brachytherapy delivered in two fractions as monotherapy for low-risk prostate cancer

    PubMed Central

    Alwers, Elizabeth; Cifuentes, Javier; Bobadilla, Ivan; Torres, Felipe; Arbelaez, Juan; Gaitan, Armando; Cortes, Helber; Acevedo, Yenny; Quintero, Paulo; Vasquez, Jaider

    2015-01-01

    Purpose High-dose-rate (HDR) brachytherapy has been accepted as an effective and safe method to treat prostate cancer. The aim of this study was to describe acute toxicity following HDR brachytherapy to the prostate, and to examine the association between dosimetric parameters and urinary toxicity in low-risk prostate cancer patients. Material and methods Patients with low-risk prostate cancer were given HDR brachytherapy as monotherapy in two 12.5 Gy fractions. Planning objectives for the planning target volume (PTV) were V100% ≥ 90% and V150% ≤ 35%. Planning objectives for organs at risk were V75% ≤ 1 cc for the bladder, rectum and perineum, and V125% ≤ 1 cc for the urethra. Toxicity was assessed three months after treatment using the Common Terminology Criteria for Adverse Events. Results Seventy-three patients were included in the analysis. Thirty-three patients (45%) reported having any type of toxicity in the three months following HDR brachytherapy. Most toxicity cases (26%) were grade 1 urinary toxicity. Mean coverage index was 0.89 and mean V100 was 88.85. Doses administered to the urethra were associated with urinary toxicity. Patients who received more than 111.3% of the prescribed dose in 1 cc of the urethra were four times more likely to have urinary toxicity compared to patients receiving less than 111.3% (OR = 4.71, 95% CI: 1.43-15.6; p = 0.011). Conclusions High-dose-rate brachytherapy administered as monotherapy for prostate cancer proved to be a safe alternative treatment for patients with low-risk prostate cancer. Urinary toxicity was associated with the dose administered to 1 cc and 0.1 cc of the urethra and was remarkably inferior to the reported toxicity in similar studies. PMID:25829931

  16. Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model

    PubMed Central

    2013-01-01

    Background Several treatment alternatives are available for primary breast cancer, although those for metastatic disease or inflammation associated with tumor progression are ineffective. Therefore, there is a great need for new therapeutic alternatives capable of generating an immune response against residual tumor cells, thus contributing to eradication of micrometastases and cancer stem cells. The use of complex natural products is an excellent therapeutic alternative widely used by Chinese, Hindu, Egyptian, and ancestral Latin-American Indian populations. Methods The present study evaluated cytotoxic, antitumor, and tumor progression activities of a gallotannin-rich fraction derived from Caesalpinia spinosa (P2Et). The parameters evaluated in vitro were mitochondrial membrane depolarization, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and clonogenic activity. The parameters evaluated in vivo were tumor growth, leukocyte number, metastatic cell number, and cytokine production by flow cytometry. Results The in vitro results showed that the P2Et fraction induced apoptosis with mitochondrial membrane potential loss, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and decreased clonogenic capacity of 4T1 cells. In vivo, the P2Et fraction induced primary tumor reduction in terms of diameter and weight in BALB/c mice transplanted with 4T1 cells and decreased numbers of metastatic cells, mainly in the spleen. Furthermore, decreases in the number of peripheral blood leukocytes (leukemoid reaction) and interleukin 6 (IL-6) serum levels were found, which are events associated with a poor prognosis. The P2Et fraction exerts its activity on the primary tumor, reduces cell migration to distant organs, and decreases IL-6 serum levels, implying tumor microenvironment mechanisms. Conclusions Overall, the P2Et fraction lessens risk factors associated with tumor progression and diminishes primary tumor size, showing

  17. The Impact of Radiation Dose and Fractionation on Outcomes for Limited-Stage Small-Cell Lung Cancer

    SciTech Connect

    Tomita, Natsuo; Kodaira, Takeshi; Hida, Toyoaki; Tachibana, Hiroyuki; Nakamura, Tatsuya; Nakahara, Rie; Inokuchi, Haruo

    2010-03-15

    Purpose: To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients and to compare the outcomes among three groups in which the total radiation doses were 45 Gy with accelerated hyperfractionation (AHF), <54 Gy with standard fractionation (SF), and >=54 Gy with SF. Methods and Materials: LS-SCLC patients that had been treated with chemoradiotherapy between 1997 and 2007 at Aichi Cancer Center Hospital were reviewed in this study. Of the 127 eligible patients, there were 37 patients in the AHF group, 29 in the SF <54 Gy group, and 61 in the SF >=54 Gy group. Results: Fifty-five patients (43%) were alive at the time of this analysis, and the median follow-up time of the surviving patients was 33 months. The median survival times were 30.0 months (95% confidence interval [CI] 16.3-43.7) for the AHF group, 14.0 months (CI 6.6-21.4) for the SF <54 Gy group, and 41.0 months (CI 33.9-48.1) for the SF >= 54 Gy group. As for the local control rates, and the overall and progression-free survival rates, all outcomes were significantly lower in the SF <54 Gy group than in the other two groups, although no significant difference was found between the AHF and SF >=54 Gy groups. Conclusions: These results suggest the importance of a high dose of radiation when using once-daily regimen. This study will support future prospective studies to establish optimal radiation doses and fractionation.

  18. [The dose-response of unstable chromosome exchanges in lymphocytes of cancer patients undergone whole-body fractionated gamma-rays exposure at the total dose 1.15 Gy].

    PubMed

    Semenov, A V; Vorobtsova, I E; Zharinov, G M

    2010-01-01

    The dose-response of unstable chromosome exchanges (UCE) in lymphocytes of 4 cancer patients undergone whole-body fractionated gamma-rays exposure (at the daily dose of 0.115 Gy up to the total dose 1.15 Gy) was compared with corresponding dose-response for lymphocytes of the same patients, irradiated in vitro at the same dose range. In vivo irradiation yielded lower frequency of UCE on the dose unit than in vitro irradiation. It was shown that the in vivo dose-response curve gives more adequate dose estimation than in vitro one. This curve could be used for reconstruction of absorbed dose in the cases of analogous character of in-controlled irradiation of people.

  19. Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia.

    PubMed

    Halhali, Ali; Díaz, Lorenza; Avila, Euclides; Ariza, Ana Carolina; Garabédian, Michèle; Larrea, Fernando

    2007-03-01

    During preeclampsia several alterations of calcium metabolism have been described, the most common of them is hypocalciuria, which pathophysiology is still unclear. In order to assess the contribution of calciotropic hormones to urinary calcium excretion, a cross-sectional study was done including 26 preeclamptic Mexican women (PE group) and 26 normotensive control pregnant women (NT group). Total and fractional urinary calcium excretion were significantly lower (P<0.0001) in the PE group than in the NT group (82+/-7 versus 171+/-7 mg/24h and 0.62+/-0.38 versus 1.38+/-0.71%, respectively), without significant differences in creatinine clearance, urinary sodium excretion and phosphate tubular reabsorption. In addition, serum 1,25-(OH)(2)D and IGF-I levels were significantly (P<0.05) lower in the PE than in NT group (43+/-9 versus 50+/-9 pg/mL and 195+/-67 versus 293+/-105 ng/mL, respectively), without significant differences in serum PTH levels. In the NT group, association analysis showed that total and fractional urinary calcium excretions positively correlated with serum levels of 1,25-(OH)(2)D (P<0.01) and IGF-I (P<0.001). In the PE group, total urinary calcium excretion positively correlated only with serum 1,25-(OH)(2)D (P<0.05). In conclusion, the results obtained in this study confirm that PE is associated with hypocalciuria and suggest that 1,25-(OH)(2)D and/or IGF-I may be involved in the regulation of urinary calcium excretion.

  20. DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS

    EPA Science Inventory

    DEHP (di-n-ethylhexyl phthalate), when administered during sexual differentiation, induces dose dependent decreases in fetal testis gene expression and steroid hormone synthesis.
    Vickie S. Wilson, Christy Lambright, Johnathan Furr, Kathy Bobseine, Carmen Wood, Gary Held, and ...

  1. Plants increase arsenic in solution but decrease the non-specifically bound fraction in the rhizosphere of an alkaline, naturally rich soil.

    PubMed

    Obeidy, Carole; Bravin, Matthieu N; Bouchardon, Jean-Luc; Conord, Cyrille; Moutte, Jacques; Guy, Bernard; Faure, Olivier

    2016-04-01

    We aimed at determining the major physical-chemical processes that drive arsenic (As) dynamic in the rhizosphere of four species (Holcus lanatus, Dittrichia viscosa, Lotus corniculatus, Plantago lanceolata) tested for phytostabilization. Experiments were performed with an alkaline soil naturally rich in As. Composition of the soil solution of planted and unplanted pots was monitored every 15 days for 90 days, with a focus on the evolution of As concentrations in solution and in the non-specifically bound (i.e. easily exchangeable) fraction. The four species similarly increased As concentration in solution, but decreased As concentration in the non-specifically bound fraction. The major part (60%) of As desorbed from the non-specifically bound fraction in planted pots was likely redistributed on the less available fractions of As on the solid phase. A second part (35%) of desorbed As was taken up by plants. The minor part (5%) of desorbed As supplied As increase in solution. To conclude, plants induced a substantial redistribution of As on the less available fractions in the rhizosphere, as expected in phytostabilization strategies. Plants however concomitantly increased As concentration in the rhizosphere solution which may contribute to As transfer through plant uptake and leaching.

  2. Plants increase arsenic in solution but decrease the non-specifically bound fraction in the rhizosphere of an alkaline, naturally rich soil.

    PubMed

    Obeidy, Carole; Bravin, Matthieu N; Bouchardon, Jean-Luc; Conord, Cyrille; Moutte, Jacques; Guy, Bernard; Faure, Olivier

    2016-04-01

    We aimed at determining the major physical-chemical processes that drive arsenic (As) dynamic in the rhizosphere of four species (Holcus lanatus, Dittrichia viscosa, Lotus corniculatus, Plantago lanceolata) tested for phytostabilization. Experiments were performed with an alkaline soil naturally rich in As. Composition of the soil solution of planted and unplanted pots was monitored every 15 days for 90 days, with a focus on the evolution of As concentrations in solution and in the non-specifically bound (i.e. easily exchangeable) fraction. The four species similarly increased As concentration in solution, but decreased As concentration in the non-specifically bound fraction. The major part (60%) of As desorbed from the non-specifically bound fraction in planted pots was likely redistributed on the less available fractions of As on the solid phase. A second part (35%) of desorbed As was taken up by plants. The minor part (5%) of desorbed As supplied As increase in solution. To conclude, plants induced a substantial redistribution of As on the less available fractions in the rhizosphere, as expected in phytostabilization strategies. Plants however concomitantly increased As concentration in the rhizosphere solution which may contribute to As transfer through plant uptake and leaching. PMID:26707185

  3. Acute personalized habitual caffeine doses improve attention and have selective effects when considering the fractionation of executive functions.

    PubMed

    Lanini, Juliana; Galduróz, José Carlos Fernandes; Pompéia, Sabine

    2016-01-01

    Caffeine is widely used, often consumed with food, and improves simple and complex/executive attention under fasting conditions. We investigated whether these cognitive effects are observed when personalized habitual doses of caffeine are ingested by caffeine consumers, whether they are influenced by nutriments and if various executive domains are susceptible to improvement. This was a double-blind, placebo-controlled study including 60 young, healthy, rested males randomly assigned to one of four treatments: placebo fasting, caffeine fasting, placebo meal and caffeine meal. Caffeine doses were individualized for each participant based on their self-reported caffeine consumption at the time of testing (morning). The test battery included measures of simple and sustained attention, executive domains (inhibiting, updating, shifting, dual tasking, planning and accessing long-term memory), control measures of subjective alterations, glucose and insulin levels, skin conductance, heart rate and pupil dilation. Regardless of meal intake, acute habitual doses of caffeine decreased fatigue, and improved simple and sustained attention and executive updating. This executive effect was not secondary to the habitual weekly dose consumed, changes in simple and sustained attention, mood, meal ingestion and increases in cognitive effort. We conclude that the morning caffeine "fix" has positive attentional effects and selectively improved executive updating whether or not caffeine is consumed with food.

  4. Acute personalized habitual caffeine doses improve attention and have selective effects when considering the fractionation of executive functions.

    PubMed

    Lanini, Juliana; Galduróz, José Carlos Fernandes; Pompéia, Sabine

    2016-01-01

    Caffeine is widely used, often consumed with food, and improves simple and complex/executive attention under fasting conditions. We investigated whether these cognitive effects are observed when personalized habitual doses of caffeine are ingested by caffeine consumers, whether they are influenced by nutriments and if various executive domains are susceptible to improvement. This was a double-blind, placebo-controlled study including 60 young, healthy, rested males randomly assigned to one of four treatments: placebo fasting, caffeine fasting, placebo meal and caffeine meal. Caffeine doses were individualized for each participant based on their self-reported caffeine consumption at the time of testing (morning). The test battery included measures of simple and sustained attention, executive domains (inhibiting, updating, shifting, dual tasking, planning and accessing long-term memory), control measures of subjective alterations, glucose and insulin levels, skin conductance, heart rate and pupil dilation. Regardless of meal intake, acute habitual doses of caffeine decreased fatigue, and improved simple and sustained attention and executive updating. This executive effect was not secondary to the habitual weekly dose consumed, changes in simple and sustained attention, mood, meal ingestion and increases in cognitive effort. We conclude that the morning caffeine "fix" has positive attentional effects and selectively improved executive updating whether or not caffeine is consumed with food. PMID:26621326

  5. RBE values and repair characteristics for colo-rectal injury after caesium 137 gamma-ray and neutron irradiation. II. Fractionation up to ten doses.

    PubMed

    Terry, N H; Denekamp, J

    1984-07-01

    Early and late colo-rectal damage in mice have been assessed after 137Cs gamma irradiation and 3 MeV neutrons given as 1,2,5 or 10 fractions. Damage was measured by early changes in body weight, the late production of short faecal pellets and the pattern of lethality after irradiation. The data have been analysed in terms of the time course of expression of damage, fractionation effects and the RBE for neutrons over a wide range of doses per fraction (0.5-12.5 Gy neutrons, 3.5-33.5 Gy gamma rays). An initial epithelial denudation led to an early loss of weight, maximal at 11-17 days after irradiation. A dose-dependent weight reduction persisted over the animals' life-time. Deaths after localised pelvic gamma irradiation were progressive with no sharp demarcation between early or late phases of injury. The time course for lethality was qualitatively similar after neutrons. Beyond six months the rectum became constricted by fibrosis and a higher proportion of small faecal pellets was observed. At 6-15 months relatively shallow dose-response curves were obtained for this change. The sparing effect of fractionation was marked for the gamma-irradiated mice and almost absent after neutrons. A very high repair increment (11 Gy) was seen with two gamma-ray fractions of 20 Gy. At lower doses per fraction the proportion of each gamma-ray fraction recovered was 50-69% for all assays, i.e., similar to that for other normal tissues. There was a slight enhancement in the sparing effect for the late compared with the early assays over the lower dose range. The RBE was strongly dependent on dose per fraction because of the lack of reparable damage after neutrons. The RBE for both early and late effects was 5.0 at a neutron dose per fraction of 1 Gy. Extrapolation of the RBE data to lower doses, using the linear quadratic model, predicts a higher RBE for late (7.4-12.7) than for early damage (5.7-8.5) if gamma-ray doses below 5 Gy are used.

  6. Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

    SciTech Connect

    Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho

    2015-08-14

    We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

  7. Dose Evaluation of Fractionated Schema and Distance From Tumor to Spinal Cord for Spinal SBRT with Simultaneous Integrated Boost: A Preliminary Study.

    PubMed

    Yang, Hao; Cai, Bo-ning; Wang, Xiao-shen; Cong, Xiao-hu; Xu, Wei; Wang, Jin-yuan; Yang, Jun; Xu, Shou-ping; Ju, Zhong-jian; Ma, Lin

    2016-02-23

    BACKGROUND This study investigated and quantified the dosimetric impact of the distance from the tumor to the spinal cord and fractionation schemes for patients who received stereotactic body radiation therapy (SBRT) and hypofractionated simultaneous integrated boost (HF-SIB). MATERIAL AND METHODS Six modified planning target volumes (PTVs) for 5 patients with spinal metastases were created by artificial uniform extension in the region of PTV adjacent spinal cord with a specified minimum tumor to cord distance (0-5 mm). The prescription dose (biologic equivalent dose, BED) was 70 Gy in different fractionation schemes (1, 3, 5, and 10 fractions). For PTV V100, Dmin, D98, D95, and D1, spinal cord dose, conformity index (CI), V30 were measured and compared. RESULTS PTV-to-cord distance influenced PTV V100, Dmin, D98, and D95, and fractionation schemes influenced Dmin and D98, with a significant difference. Distances of ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm from PTV to spinal cord meet dose requirements in 1, 3, 5, and 10 fractionations, respectively. Spinal cord dose, CI, and V30 were not impacted by PTV-to-cord distance and fractionation schemes. CONCLUSIONS Target volume coverage, Dmin, D98, and D95 were directly correlated with distance from the spinal cord for spine SBRT and HF-SIB. Based on our study, ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm distance from PTV to spinal cord meets dose requirements in 1, 3, 5 and 10 fractionations, respectively.

  8. Decrease of concentration and colloidal fraction of organic carbon and trace elements in response to the anomalously hot summer 2010 in a humic boreal lake.

    PubMed

    Shirokova, L S; Pokrovsky, O S; Moreva, O Yu; Chupakov, A V; Zabelina, S A; Klimov, S I; Shorina, N V; Vorobieva, T Ya

    2013-10-01

    The colloidal distribution and size fractionation of organic carbon (OC), major elements and trace elements (TE) were studied in a seasonally stratified, organic-rich boreal lake, Lake Svyatoe, located in the European subarctic zone (NW Russia, Arkhangelsk region). This study took place over the course of 4 years in both winter and summer periods using an in situ dialysis technique (1 kDa, 10 kDa and 50 kDa) and traditional frontal filtration and ultrafiltration (5, 0.22 and 0.025 μm). We observed a systematic difference in dissolved elements and colloidal fractions between summer and winter periods with the highest proportion of organic and organo-ferric colloids (1 kDa-0.22 μm) observed during winter periods. The anomalously hot summer of 2010 in European Russia produced surface water temperatures of approximately 30°C, which were 10° above the usual summer temperatures and brought about crucial changes in element speciation and size fractionation. In August 2010, the concentration of dissolved organic carbon (DOC) decreased by more than 30% compared to normal period, while the relative proportion of organic colloids decreased from 70-80% to only 20-30% over the full depth of the water column. Similarly, the proportion of colloidal Fe decreased from 90-98% in most summers and winters to approximately 60-70% in August 2010. During this hot summer, measurable and significant (>30% compared to other periods) decreases in the colloidal fractions of Ca, Mg, Sr, Ba, Al, Ti, Ni, As, V, Co, Y, all rare earth elements (REEs), Zr, Hf, Th and U were also observed. In addition, dissolved (<0.22 μm) TE concentrations decreased by a factor of 2 to 6 compared to previously investigated periods. The three processes most likely responsible for such a crucial change in element biogeochemistry with elevated water temperature are 1) massive phytoplankton bloom, 2) enhanced mineralization (respiration) of allochthonous dissolved organic matter by heterotrophic aerobic

  9. MR spectroscopy and diffusion tensor imaging of the brain in congenital muscular dystrophy with merosin deficiency: metabolite level decreases, fractional anisotropy decreases, and apparent diffusion coefficient increases in the white matter.

    PubMed

    Sijens, P E; Fock, J M; Meiners, L C; Potze, J H; Irwan, R; Oudkerk, M

    2007-06-01

    Brain magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in one patient with merosin-deficient congenital muscular dystrophy (MDCMD) revealed significant metabolite (choline, creatine, N-acetyl aspartate) level reductions, fractional anisotropy (FA) reduction and increased apparent diffusion coefficient (ADC) in the white matter (p<0.01, all). In the gray matter, the MRS properties did not differ significantly from those in controls. The ADC and FA, however, differed significantly as in the white matter, although the differences were less pronounced. This is the first quantitative MR study of the brain in a patient with MDCMD, which revealed that the concentrations of all MRS measured metabolites were decreased only in the white matter. This observation, combined with the DTI observed ADC increases and FA decrease, indicated a presence of vasogenic edema in the white matter.

  10. A Phase I Dose-Escalation Study of Fractionated Stereotactic Radiosurgery in Combination With Gefitinib in Patients With Recurrent Malignant Gliomas

    SciTech Connect

    Schwer, Amanda L.; Damek, Denise M.; Kavanagh, Brian D.; Gaspar, Laurie E.; Lillehei, Kevin; Stuhr, Kelly; Chen Changhu

    2008-03-15

    Purpose: To determine the maximum tolerated dose (MTD) of fractionated stereotactic radiosurgery (SRS) with gefitinib in patients with recurrent malignant gliomas. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had pathologically proved recurrent anaplastic astrocytoma or glioblastoma. Patients started gefitinib (250 mg/day) 7 days before SRS and continued for 1 year or until disease progression. SRS was delivered in three fractions over 3 days. The planning target volume (PTV) was the T1-weighted MRI postcontrast enhancing lesion + 2 mm. The first cohort received an SRS dose of 18 Gy, and subsequent cohorts received higher doses up to the maximum dose of 36 Gy. Dose-limiting toxicity (DLT) was any Grade 3 toxicity. The MTD was exceeded if 2 of 6 patients in a cohort experienced DLT. Results: Characteristics of the 15 patients enrolled were: 9 men, 6 women; median age, 47 years (range, 23-65 years); 11 glioblastoma, 4 AA; median prior RT dose, 60 Gy (range, 54-61.2 Gy); median interval since RT, 12 months (range, 3-57 months); median PTV, 41 cc (range, 12-151 cc). Median follow-up time was 7 months (range, 2-28 months). Median time on gefitinib was 5 months (range, 2-12 months). No patient experienced a DLT, and the SRS dose was escalated from 18 to 36 Gy. Grade 1-2 gefitinib-related dermatitis and diarrhea were common (10 and 7 patients, respectively). Conclusion: Fractionated SRS to a dose of 36 Gy in three fractions is well tolerated with gefitinib at daily dose of 250 mg. Further studies of SRS and novel molecular targeted agents are warranted in this challenging clinical setting.

  11. A polyphenol-rich fraction obtained from table grapes decreases adiposity, insulin resistance and markers of inflammation and impacts gut microbiota in high-fat-fed mice.

    PubMed

    Collins, Brian; Hoffman, Jessie; Martinez, Kristina; Grace, Mary; Lila, Mary Ann; Cockrell, Chase; Nadimpalli, Anuradha; Chang, Eugene; Chuang, Chia-Chi; Zhong, Wei; Mackert, Jessica; Shen, Wan; Cooney, Paula; Hopkins, Robin; McIntosh, Michael

    2016-05-01

    The objective of this study was to determine if consuming an extractable or nonextractable fraction of table grapes reduced the metabolic consequences of consuming a high-fat, American-type diet. Male C57BL/6J mice were fed a low fat (LF) diet, a high fat (HF) diet, or an HF diet containing whole table grape powder (5% w/w), an extractable, polyphenol-rich (HF-EP) fraction, a nonextractable, polyphenol-poor (HF-NEP) fraction or equal combinations of both fractions (HF-EP+NEP) from grape powder for 16weeks. Mice fed the HF-EP and HF-EP+NEP diets had lower percentages of body fat and amounts of white adipose tissue (WAT) and improved glucose tolerance compared to the HF-fed controls. Mice fed the HF-EP+NEP diet had lower liver weights and triglyceride (TG) levels compared to the HF-fed controls. Mice fed the HF-EP+NEP diets had higher hepatic mRNA levels of hormone sensitive lipase and adipose TG lipase, and decreased expression of c-reactive protein compared to the HF-fed controls. In epididymal (visceral) WAT, the expression levels of several inflammatory genes were lower in mice fed the HF-EP and HF-EP+NEP diets compared to the HF-fed controls. Mice fed the HF diets had increased myeloperoxidase activity and impaired localization of the tight junction protein zonula occludens-1 in ileal mucosa compared to the HF-EP and HF-NEP diets. Several of these treatment effects were associated with alterations in gut bacterial community structure. Collectively, these data demonstrate that the polyphenol-rich, EP fraction from table grapes attenuated many of the adverse health consequences associated with consuming an HF diet.

  12. Radiation dose reduction to the breast in thoracic CT: Comparison of bismuth shielding, organ-based tube current modulation, and use of a globally decreased tube current

    SciTech Connect

    Wang Jia; Duan Xinhui; Christner, Jodie A.; Leng Shuai; Yu Lifeng; McCollough, Cynthia H.

    2011-11-15

    Purpose: The purpose of this work was to evaluate dose performance and image quality in thoracic CT using three techniques to reduce dose to the breast: bismuth shielding, organ-based tube current modulation (TCM) and global tube current reduction. Methods: Semi-anthropomorphic thorax phantoms of four different sizes (15, 30, 35, and 40 cm lateral width) were used for dose measurement and image quality assessment. Four scans were performed on each phantom using 100 or 120 kV with a clinical CT scanner: (1) reference scan; (2) scan with bismuth breast shield of an appropriate thickness; (3) scan with organ-based TCM; and (4) scan with a global reduction in tube current chosen to match the dose reduction from bismuth shielding. Dose to the breast was measured with an ion chamber on the surface of the phantom. Image quality was evaluated by measuring the mean and standard deviation of CT numbers within the lung and heart regions. Results: Compared to the reference scan, dose to the breast region was decreased by about 21% for the 15-cm phantom with a pediatric (2-ply) shield and by about 37% for the 30, 35, and 40-cm phantoms with adult (4-ply) shields. Organ-based TCM decreased the dose by 12% for the 15-cm phantom, and 34-39% for the 30, 35, and 40-cm phantoms. Global lowering of the tube current reduced breast dose by 23% for the 15-cm phantom and 39% for the 30, 35, and 40-cm phantoms. In phantoms of all four sizes, image noise was increased in both the lung and heart regions with bismuth shielding. No significant increase in noise was observed with organ-based TCM. Decreasing tube current globally led to similar noise increases as bismuth shielding. Streak and beam hardening artifacts, and a resulting artifactual increase in CT numbers, were observed for scans with bismuth shields, but not for organ-based TCM or global tube current reduction. Conclusions: Organ-based TCM produces dose reduction to the breast similar to that achieved with bismuth shielding for

  13. The consistency of Fletcher-Suit applicator geometry and of the rectal probe’s position in high dose rate brachytherapy treatment fraction of cervix carcinoma

    PubMed Central

    2009-01-01

    Purpose The dose values computed with the treatment planning system and the in vivo dose measurements with semiconductor detectors in rectum during the high dose rate brachytherapy treatment fraction of the cervix carcinoma are occasionally significantly different. We’ve investigated the consistency of the Fletcher-Suit applicator geometry and the in vivo rectal probe’s position stability during the high dose rate brachytherapy treatment fraction. Material and methods The patient lied in a lithotomic position during a biplane reconstruction images, throughout the treatment planning and dose administration. We obtained post-treatment reconstruction images and prepared a post-treatment plan. The amount of 14 treatment fractions of 10 patients were considered in the study. Two methods were applied: evaluation of the difference of reconstructed pre-treatment and post-treatment applicator points and rectal probe’s detectors being relevant to the co-ordinate system fixed to the applicator, and estimation of applicators and rectal probe’s reallocation with respect to the pelvic bones with registration of pre- and post-treatment reconstruction images. Results We’ve experienced good consistency in the Fletcher-Suit applicator geometry in all treatment fractions. 70% of them presented small variation in the rectal probe’s position, while the rest showed significant shift in the applicator or rectal probe’s position with regard to the pelvic bones.

  14. High-Dose Spatially Fractionated GRID Radiation Therapy (SFGRT): A Comparison of Treatment Outcomes With Cerrobend vs. MLC SFGRT

    SciTech Connect

    Neuner, Geoffrey; Mohiuddin, Majid M.; Vander Walde, Noam; Goloubeva, Olga; Ha, Jonathan; Yu, Cedric X.; Regine, William F.

    2012-04-01

    Purpose: Spatially fractionated GRID radiotherapy (SFGRT) using a customized Cerrobend block has been used to improve response rates in patients with bulky tumors. The clinical efficacy of our own multileaf collimator (MLC) technique is unknown. We undertook a retrospective analysis to compare clinical response rates attained using these two techniques. Methods and Materials: Seventy-nine patients with bulky tumors (median diameter, 7.6 cm; range, 4-30 cm) treated with SFGRT were reviewed. Between 2003 and late 2005, the Cerrobend block technique (n = 39) was used. Between late 2005 and 2008, SFGRT was delivered using MLC-shaped fields (n = 40). Dose was prescribed to dmax (depth of maximum dose) and was typically 15 Gy. Eighty percent of patients in both groups received external beam radiotherapy in addition to SFGRT. The two-sided Fisher-Freeman-Halton test was used to compare pain and mass effect response rates between the two groups. Results: Sixty-one patients (77%) were treated for palliative intent and 18 (23%) for curative intent. The majority of patients had either lung or head-and-neck primaries in both groups; the most frequent site of SFGRT application was the neck. The majority of patients complained of either pain (65%) or mass effect (58%) at intake. Overall response rates for pain and mass response were no different between the Cerrobend and MLC groups: pain, 75% and 74%, respectively (p = 0.50), and mass effect, 67% and 73%, respectively (p = 0.85). The majority of toxicities were Grade 1 or 2, and only 3 patients had late Grade 3-4 toxicities. Conclusions: MLC-based and Cerrobend-based SFGRT have comparable and encouraging response rates when used either in the palliative or curative setting. MLC-based SGFRT should allow clinics to more easily adopt this novel treatment approach for the treatment of bulky tumors.

  15. Validation of contour-driven thin-plate splines for tracking fraction-to-fraction changes in anatomy and radiation therapy dose mapping

    NASA Astrophysics Data System (ADS)

    Schaly, B.; Bauman, G. S.; Battista, J. J.; Van Dyk, J.

    2005-02-01

    The goal of this study is to validate a deformable model using contour-driven thin-plate splines for application to radiation therapy dose mapping. Our testing includes a virtual spherical phantom as well as real computed tomography (CT) data from ten prostate cancer patients with radio-opaque markers surgically implanted into the prostate and seminal vesicles. In the spherical mathematical phantom, homologous control points generated automatically given input contour data in CT slice geometry were compared to homologous control point placement using analytical geometry as the ground truth. The dose delivered to specific voxels driven by both sets of homologous control points were compared to determine the accuracy of dose tracking via the deformable model. A 3D analytical spherically symmetric dose distribution with a dose gradient of ~10% per mm was used for this phantom. This test showed that the uncertainty in calculating the delivered dose to a tissue element depends on slice thickness and the variation in defining homologous landmarks, where dose agreement of 3-4% in high dose gradient regions was achieved. In the patient data, radio-opaque marker positions driven by the thin-plate spline algorithm were compared to the actual marker positions as identified in the CT scans. It is demonstrated that the deformable model is accurate (~2.5 mm) to within the intra-observer contouring variability. This work shows that the algorithm is appropriate for describing changes in pelvic anatomy and for the dose mapping application with dose gradients characteristic of conformal and intensity modulated radiation therapy.

  16. Inter fractional dose variation during intensity-modulated radiation therapy for cervical cancer assessed by weekly CT evaluation

    SciTech Connect

    Han, Youngyih; Shin, Eun Hyuk; Huh, Seung Jae . E-mail: sjhuh@smc.samsung.co.kr; Lee, Jung Eun; Park, Won

    2006-06-01

    Purpose: To investigate the inter fractional dose variation of a small-bowel displacement system (SBDS)-assisted intensity-modulated radiation therapy (IMRT) for the treatment of cervical cancer. Methods: Four computed tomography (CT) scans were carried out in 10 patients who received radiotherapy for uterine cervical cancer. The initial CT was taken by use of the SBDS, before the beginning of radiotherapy, and 3 additional CT scans with the SBDS were done in subsequent weeks. IMRT was planned by use of the initial CT, and the subsequent images were fused with the initial CT set. Dose-volume histogram (DVH) changes of the targets (planning target volume [PTV] = clinical target volume [CTV] + 1.5 cm) and of the critical organs were evaluated after obtaining the volumes of each organ on 4 CT sets. Results: No significant differences were found in PTV volumes. Changes on the DVH of the CTVs were not significant, whereas DVH changes of the PTVs at 40% to 100% of the prescription dose level were significant (V{sub 90%}; 2nd week: p = 0.0091, 3rd week: p = 0.0029, 4th week: p = 0.0050). The changes in the small-bowel volume included in the treatment field were significant. These were 119.5 cm{sup 3} (range, 26.9-251.0 cm{sup 3}), 126 cm{sup 3} (range, 38.3-336 cm{sup 3}), 161.9 cm{sup 3} (range, 37.7-294.6 cm{sup 3}), and 149.1 cm{sup 3} (range, 38.6-277.8 cm{sup 3}) at the 1st, 2nd, 3rd, and 4th weeks, respectively, and were significantly correlated with the DVH change in the small bowel, which were significant at the 3rd (V{sub 80%}; p = 0.0230) and 4th (V{sub 80%}; p = 0.0263) weeks. The bladder-volume change correlated to the large volume change (>20%) of the small-bowel volume. Conclusions: Significant DVH differences for the small bowel can result because of interfractional position variations, whereas the DVH differences of the CTV were not significant. Strict bladder-filling control and an accurate margin for the PTV, as well as image-guided position verification

  17. Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial☆, ☆

    PubMed Central

    Stevens, Allen D.; Hernandez, Caleb; Jones, Seth; Moreira, Maria E.; Blumen, Jason R.; Hopkins, Emily; Sande, Margaret; Bakes, Katherine; Haukoos, Jason S.

    2016-01-01

    Background Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients where dosing often requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared to conventional medication administration, in simulated prehospital pediatric resuscitation scenarios. Methods We performed a prospective, block-randomized, cross-over study, where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled, color-coded-syringes (intervention) or their own medication kits stocked with conventional ampoules (control). Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed. The ambulance patient compartment and the intravenous medication port were video recorded. Data were extracted from video review by blinded, independent reviewers. Results Median time to delivery of all doses for the intervention and control groups was 34 (95% CI: 28–39) seconds and 42 (95% CI: 36–51) seconds, respectively (difference = 9 [95% CI: 4–14] seconds). Using the conventional method, 62 doses were administered with 24 (39%) critical dosing errors; using the prefilled, color-coded syringe method, 59 doses were administered with 0 (0%) critical dosing errors (difference = 39%, 95% CI: 13–61%). Conclusions A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations. PMID:26247145

  18. Hypolipidemic Effect of a Blue-Green Alga (Nostoc commune) Is Attributed to Its Nonlipid Fraction by Decreasing Intestinal Cholesterol Absorption in C57BL/6J Mice.

    PubMed

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Weller, Curtis L; Carr, Timothy P; Park, Young-Ki; Lee, Ji-Young

    2015-11-01

    We previously demonstrated that Nostoc commune var. sphaeroids Kützing (NO), a blue-green alga (BGA), exerts a hypolipidemic effect in vivo and its lipid extract regulates the expression of genes involved in cholesterol and lipid metabolism in vitro. The objective of this study was to investigate whether the hypolipidemic effect of NO is attributed to an algal lipid or a delipidated fraction in vivo compared with Spirulina platensis (SP). Male C57BL/6J mice were fed an AIN-93M diet containing 2.5% or 5% of BGA (w/w) or a lipid extract equivalent to 5% of BGA for 4 weeks to measure plasma and liver lipids, hepatic gene expression, intestinal cholesterol absorption, and fecal sterol excretion. Plasma total cholesterol (TC) was significantly lower in 2.5% and 5% NO-fed groups, while plasma triglyceride (TG) levels were decreased in the 5% NO group compared with controls. However, neither NO organic extract (NOE) nor SP-fed groups altered plasma lipids. Hepatic mRNA levels of sterol regulatory element-binding protein 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), carnitine palmitoyltransferase-1α, and acyl-CoA oxidase 1 were induced in 5% NO-fed mice, while there were no significant changes in hepatic lipogenic gene expression between groups. NO, but not NOE and SP groups, significantly decreased intestinal cholesterol absorption. When HepG2 cells and primary mouse hepatocytes were incubated with NOE and SP organic extract (SPE), there were marked decreases in protein levels of HMGR, low-density lipoprotein receptor, and fatty acid synthase. In conclusion, the nonlipid fraction of NO exerts TC and TG-lowering effects primarily by inhibiting intestinal cholesterol absorption and by increasing hepatic fatty acid oxidation, respectively. PMID:26161942

  19. Differences in rates of decrease of environmental radiation dose rates by ground surface property in Fukushima City after the Fukushima Daiichi nuclear power plant accident.

    PubMed

    Kakamu, Takeyasu; Kanda, Hideyuki; Tsuji, Masayoshi; Kobayashi, Daisuke; Miyake, Masao; Hayakawa, Takehito; Katsuda, Shin-ichiro; Mori, Yayoi; Okouchi, Toshiyasu; Hazama, Akihiro; Fukushima, Tetsuhito

    2013-01-01

    After the Great East Japan Earthquake on 11 March 2011, the environmental radiation dose in Fukushima City increased. On 11 April, 1 mo after the earthquake, the environmental radiation dose rate at various surfaces in the same area differed greatly by surface property. Environmental radiation measurements continue in order to determine the estimated time to 50% reduction in environmental radiation dose rates by surface property in order to make suggestions for decontamination in Fukushima. The measurements were carried out from 11 April to 11 November 2011. Forty-eight (48) measurement points were selected, including four kinds of ground surface properties: grass (13), soil (5), artificial turf (7), and asphalt (23). Environmental radiation dose rate was measured at heights of 100 cm above the ground surface. Time to 50% reduction of environmental radiation dose rates was estimated for each ground surface property. Radiation dose rates on 11 November had decreased significantly compared with those on 11 April for all surface properties. Artificial turf showed the longest time to 50% reduction (544.32 d, standard error: 96.86), and soil showed the shortest (213.20 d, standard error: 35.88). The authors found the environmental radiation dose rate on artificial materials to have a longer 50% reduction time than that on natural materials. These results contribute to determining an order of priority for decontamination after nuclear disasters.

  20. Decrease in survival and fecundity of Glossina palpalis gambiensis vanderplank 1949 (Diptera: Glossinidae) fed on cattle treated with single doses of ivermectin

    PubMed Central

    2013-01-01

    Background Human and Animal Trypanosomes are major problems for the socio-economic growth of developing countries like Burkina Faso. Ivermectin is currently used to treat humans in mass drug administration programs in Africa, and is also commonly used for veterinary purposes. In this study, we tested the effect of ivermectin injected into cattle on the survival and fecundity of Glossina palpalis gambiensis, the main vector of human and animal trypanosomes in West Africa. Methods Three cows (local zebu*baoulé crossbreds) were used, and received either no ivermectin (for the control), or ivermectin at therapeutic dose (0.2 mg/kg) and 10 times the therapeutic dose (2 mg/kg) respectively. G. palpalis gambiensis were fed on the cattle for their first bloodmeal, and then either on cattle or on membrane for subsequent meals. Results Our results showed that survival of Glossina palpalis gambiensis was significantly decreased when they were fed on cattle treated with ivermectin. This decrease in survival ranged from 21% to 83.7% for the therapeutic dose (0.2 mg/kg), up to 8 days after treatment. The effects of a dose of 2 mg/kg were higher with a 78.3% to 93.9% decrease in survival, until 14 days after injection. The therapeutic dose of ivermectin also decreased fecundity, and delayed the first larviposition, but there was no significant effect on hatching rate. Conclusion Ivermectin injected into cattle may constitute an additional potential tool for the control of Glossina palpalis gambiensis and possibly other vector species. Further studies will be needed to assess its effect on trypanosome transmission, and to define more precisely the adequate dose to be used for control purposes. PMID:23741989

  1. Blue-violet light irradiation dose dependently decreases carotenoids in human skin, which indicates the generation of free radicals.

    PubMed

    Vandersee, Staffan; Beyer, Marc; Lademann, Juergen; Darvin, Maxim E

    2015-01-01

    In contrast to ultraviolet and infrared irradiation, which are known to facilitate cutaneous photoaging, immunosuppression, or tumour emergence due to formation of free radicals and reactive oxygen species, potentially similar effects of visible light on the human skin are still poorly characterized. Using a blue-violet light irradiation source and aiming to characterize its potential influence on the antioxidant status of the human skin, the cutaneous carotenoid concentration was measured noninvasively in nine healthy volunteers using resonance Raman spectroscopy following irradiation. The dose-dependent significant degradation of carotenoids was measured to be 13.5% and 21.2% directly after irradiation at 50 J/cm² and 100 J/cm² (P < 0.05). The irradiation intensity was 100 mW/cm². This is above natural conditions; the achieved doses, though, are acquirable under natural conditions. The corresponding restoration lasted 2 and 24 hours, respectively. The degradation of cutaneous carotenoids indirectly shows the amount of generated free radicals and especially reactive oxygen species in human skin. In all volunteers the cutaneous carotenoid concentration dropped down in a manner similar to that caused by the infrared or ultraviolet irradiations, leading to the conclusion that also blue-violet light at high doses could represent a comparably adverse factor for human skin.

  2. Blue-Violet Light Irradiation Dose Dependently Decreases Carotenoids in Human Skin, Which Indicates the Generation of Free Radicals

    PubMed Central

    Vandersee, Staffan; Beyer, Marc; Lademann, Juergen; Darvin, Maxim E.

    2015-01-01

    In contrast to ultraviolet and infrared irradiation, which are known to facilitate cutaneous photoaging, immunosuppression, or tumour emergence due to formation of free radicals and reactive oxygen species, potentially similar effects of visible light on the human skin are still poorly characterized. Using a blue-violet light irradiation source and aiming to characterize its potential influence on the antioxidant status of the human skin, the cutaneous carotenoid concentration was measured noninvasively in nine healthy volunteers using resonance Raman spectroscopy following irradiation. The dose-dependent significant degradation of carotenoids was measured to be 13.5% and 21.2% directly after irradiation at 50 J/cm² and 100 J/cm² (P < 0.05). The irradiation intensity was 100 mW/cm². This is above natural conditions; the achieved doses, though, are acquirable under natural conditions. The corresponding restoration lasted 2 and 24 hours, respectively. The degradation of cutaneous carotenoids indirectly shows the amount of generated free radicals and especially reactive oxygen species in human skin. In all volunteers the cutaneous carotenoid concentration dropped down in a manner similar to that caused by the infrared or ultraviolet irradiations, leading to the conclusion that also blue-violet light at high doses could represent a comparably adverse factor for human skin. PMID:25741404

  3. Cardiosphere-derived cells reverse heart failure with preserved ejection fraction (HFpEF) in rats by decreasing fibrosis and inflammation

    PubMed Central

    Gallet, Romain; de Couto, Geoffrey; Simsolo, Eli; Valle, Jackelyn; Sun, Baiming; Liu, Weixin; Tseliou, Eleni; Zile, Michael R.; Marbán, Eduardo

    2016-01-01

    Background The pathogenesis of HFpEF is unclear, but fibrosis, inflammation and hypertrophy have been put forth as likely contributors. CDCs are heart-derived cell products with anti-fibrotic and anti-inflammatory properties. Objectives We questioned whether allogeneic rat CDCs might be able to decrease manifestations of HFpEF in hypertensive rats. Methods Starting at 7 weeks of age, Dahl salt-sensitive rats were fed a high-salt diet for 6–7 weeks and randomized to receive intracoronary CDCs or placebo. Dahl rats fed normal chow served as controls. Results High-salt rats developed hypertension, left ventricular (LV) hypertrophy and diastolic dysfunction, without impairment of ejection fraction. Four weeks after treatment, diastolic dysfunction resolved in CDC-treated rats but not in placebo. The improved LV relaxation was associated with lower LV end-diastolic pressure, decreased lung congestion and enhanced survival in CDC-treated rats. Histology and echocardiography revealed no decrease in cardiac hypertrophy after CDC treatment, consistent with the finding of sustained, equally-elevated blood pressure in CDC- and placebo-treated rats. Nevertheless, CDC treatment decreased LV fibrosis and inflammatory infiltrates. Serum inflammatory cytokines were likewise decreased after CDC treatment. Whole-transcriptome analysis revealed major HFpEF-related, CDC-reversed changes in numerous transcripts, including many involved in inflammation and/or fibrosis. Conclusion CDCs normalized LV relaxation and LV diastolic pressure while improving survival in a rat model of HFpEF. The benefits of CDCs occurred despite persistent hypertension and cardiac hypertrophy. By selectively reversing inflammation and fibrosis, CDCs may be beneficial in the treatment of HFpEF. PMID:27104217

  4. Measurement of patient imaging dose for real-time kilovoltage x-ray intra-fraction tumour position monitoring in prostate patients

    PubMed Central

    Crocker, James K; Ng, Jin Aun; Keall, Paul J; Booth, Jeremy T

    2012-01-01

    The dose for image-based motion monitoring of prostate tumours during radiotherapy delivery has not been established. This study aimed to provide quantitative analysis and optimisation of the fluoroscopic patient imaging dose during radiotherapy for IMRT and VMAT treatments using standard and hypofractionated treatment schedules. Twenty-two patients with type T1c N0/M0 prostate cancer and three implanted fiducial markers were considered. Minimum field sizes encompassing all fiducial markers plus a 7.5mm motion margin were determined for each treatment beam, each patient and the complete cohort. Imaging doses were measured for different field sizes and depths in a phantom at 75kV and 120kV. Based on these measurements, the patient imaging doses were then estimated according to beam-on time for clinical settings. The population minimum field size was 5.3 × 6.1cm2, yielding doses of 406mGy and 185mGy over the course of an IMRT treatment for 75kV (10 mAs) and 120kV (1.04 mAs) imaging, respectively at 1Hz. The imaging dose was reduced by an average of 28% and 32% by adopting patient specific and treatment-beam specific field sizes respectively. Standard fractionation VMAT imaging doses were 37% lower than IMRT doses over a complete treatment. Hypofractionated IMRT SBRT and VMAT SBRT imaging doses were 58% and 76% lower than IMRT doses respectively. The patient dose for kilovoltage intrafraction monitoring of the prostate was quantified. Tailoring imaging field sizes to specific patients yielded a significant reduction in the imaging dose, as did adoption of faster treatment modalities such as VMAT. PMID:22517054

  5. High dose of N-acetylcysteine increase H₂O₂ and MDA levels and decrease GSH level of HUVECs exposed with malaria serum.

    PubMed

    Fitri, L E; Sardjono, T W; Simamora, D; Sumarno, R P; Setyawati, S K

    2011-04-01

    Dysfunction of endothelial cells in severe malaria may result from excessive activation of tumor necrosis factor (TNF)-α which leads to an increase in production of reactive oxygen species (ROS) and decrease of antioxidant level of endothelial cells. To investigate the effect of N-acetylcysteine (NAC) on hydrogen peroxide (H2O2), malondialdehyde (MDA) and glutathione (GSH) levels produced by endothelial cells exposed with serum of malaria falciparum patient, an in vitro model of human umbilical vein endothelial cells (HUVECs) culture was used. Sample groups were normal HUVECs (group A), HUVECs that was exposed with malaria serum without any treatment (group B), HUVECs that were exposed with malaria serum and treated with NAC 2 μM (group C), HUVECs that were exposed with malaria serum and treated with NAC 4 μM (group D), and HUVECs that were exposed with malaria serum and treated with NAC 8 μM (group E). The level of MDA was measured by thio-barbituric acid reaction assay and H2O2 level was measured by NWLSS Hydrogen Peroxyde/Peroxydase Assay kit. The level of GSH was determined by using NWLSS Glutathione Assay kit. The level of H2O2 and MDA decreased after administration of low dose of NAC. Unfortunately, increased H2O2 and MDA levels were found on HUVECs treated with high dose of NAC (8 μM). There was a positive correlation between NAC dose and H2O2 level (r= 0,603) and between NAC dose and MDA level (r= 0,721). A significant decreased level of GSH was found on HUVECs treated with high dose of NAC (p = 0,023). It can be concluded that the use of high dose of NAC as supportive therapy in severe malaria infection must be taken carefully.

  6. SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

    SciTech Connect

    Yu, V; Nguyen, D; Pajonk, F; Kaprealian, T; Kupelian, P; Steinberg, M; Low, D; Sheng, K

    2015-06-15

    Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to explore the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work

  7. Recovery capacity of glial progenitors after in vivo fission-neutron or X irradiation: age dependence, fractionation and low-dose-rate irradiations.

    PubMed

    Philippo, H; Winter, E A M; van der Kogel, A J; Huiskamp, R

    2005-06-01

    Previous experiments on the radiosensitivity of O-2A glial progenitors determined for single-dose fission-neutron and X irradiation showed log-linear survival curves, suggesting a lack of accumulation of recovery of sublethal damage. In the present study, we addressed this question and further characterized the radiobiological properties of these glial stem cells by investigating the recovery capacity of glial stem cells using either fractionated or protracted whole-body irradiation. Irradiations were performed on newborn, 2-week-old or 12-week-old rats. Fractionated irradiations (four fractions) were performed with 24-h intervals, followed by cell isolations 16- 24 h after the last irradiation. Single-dose irradiations were followed by cell isolation 16-24 h after irradiation or delayed cell isolation (4 days after irradiation) of the O-2A progenitor cells from either spinal cord (newborns) or optic nerve (2- and 12-week-old rats). Results for neonatal progenitor cell survival show effect ratios for both fractionated fission-neutron and X irradiation of the order of 1.8 when compared with single-dose irradiation. A similar ratio was found after single-dose irradiation combined with delayed plating. Comparable results were observed for juvenile and adult optic nerve progenitors, with effect ratios of the order of 1.2. The present investigation clearly shows that fractionated irradiation regimens using X rays or fission neutrons and CNS tissue from rats of various ages results in an increase in O-2A progenitor cell survival while repair is virtually absent. This recovery of the progenitor pool after irradiation can be observed at all ages but is greatest in the neonatal spinal cord and can probably be attributed to repopulation. PMID:15913395

  8. Single dose disposition of chloroquine in kwashiorkor and normal children--evidence for decreased absorption in kwashiorkor.

    PubMed

    Walker, O; Dawodu, A H; Salako, L A; Alván, G; Johnson, A O

    1987-04-01

    The single dose disposition of chloroquine was studied in five children with kwashiorkor and six normal control children after an oral dose of 10 mg kg-1 of chloroquine base. Plasma concentrations of chloroquine and its main metabolite were assayed by high performance liquid chromatography (h.p.l.c.). Chloroquine was detectable for up to 21 days in all the subjects. Chloroquine was detectable in all the subjects within 30 min after giving the drug except in one subject. Peak levels were reached between 0.5 and 8 h in all the subjects (with no significant difference in the tmax between the two groups of children). Peak plasma chloroquine concentrations in the children with kwashiorkor varied from 9 ng ml-1 to 95 ng ml-1 (mean 40 +/- 34 ng ml-1). Peak chloroquine concentrations in the controls varied between 69 ng ml-1 and 330 ng ml-1 (mean 134 +/- 99 ng ml-1). The mean AUC in the kwashiorkor children was significantly lower than the mean AUC in the control children (P less than 0.001). Peak plasma desethylchloroquine concentrations in the children with kwashiorkor varied between 3 and 13 ng ml-1 (mean 6 +/- 9 ng ml-1) while in the controls the concentrations varied between 14 and 170 ng ml-1 (mean 50 +/- 61 ng ml-1). There was no significant difference in the half-life of chloroquine between the kwashiorkor children and the normal control children. The possible influence of a different binding and distribution pattern of chloroquine in kwashiorkor could not be assessed in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Image Registration of Cone-Beam Computer Tomography and Preprocedural Computer Tomography Aids in Localization of Adrenal Veins and Decreasing Radiation Dose in Adrenal Vein Sampling

    SciTech Connect

    Busser, Wendy M. H. Arntz, Mark J.; Jenniskens, Sjoerd F. M.; Deinum, Jaap; Hoogeveen, Yvonne L.; Lange, Frank de; Schultze Kool, Leo J.

    2015-08-15

    PurposeWe assessed whether image registration of cone-beam computed tomography (CT) (CBCT) and contrast-enhanced CT (CE-CT) images indicating the locations of the adrenal veins can aid in increasing the success rate of first-attempts adrenal vein sampling (AVS) and therefore decreasing patient radiation dose.Materials and Methods CBCT scans were acquired in the interventional suite (Philips Allura Xper FD20) and rigidly registered to the vertebra in previously acquired CE-CT. Adrenal vein locations were marked on the CT image and superimposed with live fluoroscopy and digital-subtraction angiography (DSA) to guide the AVS. Seventeen first attempts at AVS were performed with image registration and retrospectively compared with 15 first attempts without image registration performed earlier by the same 2 interventional radiologists. First-attempt AVS was considered successful when both adrenal vein samples showed representative cortisol levels. Sampling time, dose-area product (DAP), number of DSA runs, fluoroscopy time, and skin dose were recorded.ResultsWithout image registration, the first attempt at sampling was successful in 8 of 15 procedures indicating a success rate of 53.3 %. This increased to 76.5 % (13 of 17) by adding CBCT and CE-CT image registration to AVS procedures (p = 0.266). DAP values (p = 0.001) and DSA runs (p = 0.026) decreased significantly by adding image registration guidance. Sampling and fluoroscopy times and skin dose showed no significant changes.ConclusionGuidance based on registration of CBCT and previously acquired diagnostic CE-CT can aid in enhancing localization of the adrenal veins thereby increasing the success rate of first-attempt AVS with a significant decrease in the number of used DSA runs and, consequently, radiation dose required.

  10. Effet de la dose d'irradiation sur la fraction tocophérolique d'huiles végétales

    NASA Astrophysics Data System (ADS)

    Chaouch, A.; El Fartah, S.; Pouliquen-Sonaglia, I.; Lesgards, G.; Raffi, J.; Trihi, M.

    1999-01-01

    Tocopherols, minor components of vegetable oils, are very important due to their high antioxydant power; we studied separation and quantification of tocopherol fraction with regard to the irradiation dose, using liquid chromatography combined with electrochemical detection. Dans les huiles végétales, les tocophérols sont des constituants mineurs très importants grâce à leur pouvoir antioxydant très élevé. Notre travail s'est porté sur la séparation et la quantification de la fraction tocophérolique et son évolution en fonction des différentes doses d'ionisation par la technique C.L.H.P. / détection électrochimique.

  11. K-Ras mutant fraction in A/J mouse lung increases as a function of benzo[a]pyrene dose

    EPA Science Inventory

    K-Ras mutant fraction (MF) was measured to examine the default assumption of low dose linearity in the benzo[a]pyrene (B[a]P) mutational response. Groups of ten male A/J mice (7-9 weeks-old) received a single i.p. injection of 0, 0.05, 0.5, 5, or 50 mg/kg B[a]P, and were sacrifi...

  12. Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

    SciTech Connect

    Jebsen, Nina L.; Engellau, Jacob; Engström, Katarina; Bauer, Henrik C.; Monge, Odd R.; Muren, Ludvig P.; Eide, Geir E.; Trovik, Clement S.; Bruland, Øyvind S.

    2013-08-01

    Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.

  13. Single-Dose and Fractionated Irradiation Promote Initiation and Progression of Atherosclerosis and Induce an Inflammatory Plaque Phenotype in ApoE{sup -/-} Mice

    SciTech Connect

    Hoving, Saske; Heeneman, Sylvia; Gijbels, Marion J.J.; Poele, Johannes A.M. te; Russell, Nicola S.; Daemen, Mat J.A.P.; Stewart, Fiona A.

    2008-07-01

    Purpose: Increased risk of atherosclerosis and stroke has been demonstrated in patients receiving radiotherapy for Hodgkin's lymphoma and head-and-neck cancer. We previously showed that 14 Gy to the carotid arteries of hypercholesterolemic ApoE{sup -/-} mice resulted in accelerated development of macrophage-rich, inflammatory atherosclerotic lesions. Here we investigate whether clinically relevant fractionated irradiation schedules and lower single doses also predispose to an inflammatory plaque phenotype. Methods and Materials: ApoE{sup -/-} mice were given 8 or 14 Gy, or 20 x 2.0 Gy in 4 weeks to the neck, and the carotid arteries were subsequently examinated for presence of atherosclerotic lesions, plaque size, and phenotype. Results: At 4 weeks, early atherosclerotic lesions were found in 44% of the mice after single doses of 14 Gy but not in age-matched controls. At 22 to 30 weeks after irradiation there was a twofold increase in the mean number of carotid lesions (8-14 Gy and 20 x 2.0 Gy) and total plaque burden (single doses only), compared with age-matched controls. The majority of lesions seen at 30 to 34 weeks after fractionated irradiation or 14-Gy single doses were granulocyte rich (100% and 63%, respectively), with thrombotic features (90% and 88%), whereas these phenotypes were much less common in age-matched controls or after a single dose of 8 Gy. Conclusions: We showed that fractionated irradiation accelerated the development of atherosclerosis in ApoE{sup -/-} mice and predisposed to the formation of an inflammatory, thrombotic plaque phenotype.

  14. Response of 9L rat brain tumor multicellular spheroids to single and fractionated doses of 1,3-bis(2-chloroethyl)-1-nitrosourea.

    PubMed

    Sano, Y; Hoshino, T; Barker, M; Deen, D F

    1984-02-01

    the overall cytotoxicity produced by fractionated BCNU protocols. Although spheroids did not shrink during or after exposure to BCNU, growth was retarded by treatment with all doses and schedules. An optimum time point for growth delay measurement could not be determined from the data. However, correlations between cell survival and growth delay were obtained with arbitrarily chosen end point volumes of four and ten times the volume at the time of treatment. PMID:6692362

  15. Progressive Neurodegeneration or Endogenous Compensation in an Animal Model of Parkinson's Disease Produced by Decreasing Doses of Alpha-Synuclein

    PubMed Central

    Koprich, James B.; Johnston, Tom H.; Huot, Philippe; Reyes, M. Gabriela; Espinosa, Maria; Brotchie, Jonathan M.

    2011-01-01

    The pathological hallmarks of Parkinson's disease (PD) are degeneration of dopamine (DA) neurons of the substantia nigra (SN) and the presence of alpha-synuclein (α-syn)-rich Lewy bodies in DA cells that remain. To model these aspects of the disease, we previously showed that high titer (5.1×10exp12 gp/ml) AAV1/2 driven expression of A53T α-syn in the SN of rats caused nigrostriatal pathology including a loss of DA neurons, but also with toxicity in the GFP control group. In the current study, we evaluate the effects of two lower titers by dilution of the vector (1∶3 [1.7×10exp12] and 1∶10 [5.1×10exp11]) to define a concentration that produced pathology specific for α-syn. In GFP and empty vector groups there were no behavioural or post-mortem changes at 3 or 6 weeks post-administration at either vector dose. Dilution of the AAV1/2 A53T α-syn (1∶3) produced significant paw use asymmetry, reductions in striatal tyrosine hydroxylase (TH), and increases in DA turnover at 3 weeks in the absence of overt pathology. By 6 weeks greater evidence of pathology was observed and included, reductions in SN DA neurons, striatal DA, TH and DA-transporter, along with a sustained behavioural deficit. In contrast, the 1∶10 AAV1/2 A53T α-syn treated animals showed normalization between 3 and 6 weeks in paw use asymmetry, reductions in striatal TH, and increased DA turnover. Progression of dopaminergic deficits using the 1∶3 titer of AAV1/2 A53Tα-syn provides a platform for evaluating treatments directed at preventing and/or reversing synucleinopathy. Use of the 1∶10 titer of AAV1/2 A53T α-syn provides an opportunity to study mechanisms of endogenous compensation. Furthermore, these data highlight the need to characterize the titer of vector being utilized, when using AAV to express pathogenic proteins and model disease process, to avoid producing non-specific effects. PMID:21408191

  16. Solutions that enable ablative radiotherapy for large liver tumors: Fractionated dose painting, simultaneous integrated protection, motion management, and computed tomography image guidance.

    PubMed

    Crane, Christopher H; Koay, Eugene J

    2016-07-01

    The emergence and success of stereotactic body radiation therapy (SBRT) for the treatment of lung cancer have led to its rapid adoption for liver cancers. SBRT can achieve excellent results for small liver tumors. However, the vast majority of physicians interpret SBRT as meaning doses of radiation (range, 4-20 Gray [Gy]) that may not be ablative but are delivered within about 1 week (ie, in 3-6 fractions). Adherence to this approach has limited the effectiveness of SBRT for large liver tumors (>7 cm) because of the need to reduce doses to meet organ constraints. The prognosis for patients who present with large liver tumors is poor, with a median survival ≤12 months, and most of these patients die from tumor-related liver failure. Herein, the authors present a comprehensive solution to achieve ablative SBRT doses for patients with large liver tumors by using a combination of classic, modern, and novel concepts of radiotherapy: fractionation, dose painting, motion management, image guidance, and simultaneous integrated protection. The authors discuss these concepts in the context of large, inoperable liver tumors and review how this approach can substantially prolong survival for patients, most of whom otherwise have a very poor prognosis and few effective treatment options. Cancer 2016;122:1974-86. © 2016 American Cancer Society. PMID:26950735

  17. Low doses of hyperbaric oxygenation effectively decrease the size of necrotic zone in rats with experimental myocardial infarction.

    PubMed

    Dotsenko, E A; Nikulina, N V; Salivonchik, D P; Lappo, O G; Gritsuk, A I; Bastron, A S

    2015-04-01

    We studied the effect of a single session of hyperbaric oxygenation on the size of risk, ischemic, and necrotic zones in rat myocardium after irreversible occlusion of the coronary artery and excessive oxygen pressure of 0.02 and 0.1 MPa. Myocardium infarction was reproduced by ligation of the left coronary artery. The size of the risk, ischemic, and necrotic zones was planimetrically evaluated. Hyperbaric oxygenation (60-min session) was performed 3 h after artery occlusion at excessive oxygen pressure of 0.02 and 0.1 MPa. In rats not exposed to hyperbaric oxygenation, the risk zone median was 31.7% of the left ventricle weight, while after the session it did not exceed 25%. In spontaneous course of myocardium infarction, the ischemia to necrosis zone ratio was 1.7:1, while under conditions of hyperbaric oxygenation at oxygen pressure of 0.1 and 0.02 MPa, the these values were 0.6:1 and 2:1, respectively. Excessive oxygen pressure of 0.02 mPa is better than traditionally used 0.1 MPa, because it promotes redistribution of the ischemic and necrotic areas in the risk zone: the area of necrotic zone decreased at the expense of the ischemic zone. Hyperbaric oxygenation produces a positive effect on the myocardium under conditions of total occlusion of the coronary artery. PMID:25900609

  18. Differences in Clinical Results After LINAC-Based Single-Dose Radiosurgery Versus Fractionated Stereotactic Radiotherapy for Patients With Vestibular Schwannomas

    SciTech Connect

    Combs, Stephanie E.; Welzel, Thomas; Schulz-Ertner, Daniela; Huber, Peter E.; Debus, Juergen

    2010-01-15

    Purpose: To evaluate the outcomes of patients with vestibular schwannoma (VS) treated with fractionated stereotactic radiotherapy (FSRT) vs. those treated with stereotactic radiosurgery (SRS). Methods and Materials: This study is based on an analysis of 200 patients with 202 VSs treated with FSRT (n = 172) or SRS (n = 30). Patients with tumor progression and/or progression of clinical symptoms were selected for treatment. In 165 out of 202 VSs (82%), RT was performed as the primary treatment for VS, and for 37 VSs (18%), RT was conducted for tumor progression after neurosurgical intervention. For patients receiving FSRT, a median total dose of 57.6 Gy was prescribed, with a median fractionation of 5 x 1.8 Gy per week. For patients who underwent SRS, a median single dose of 13 Gy was prescribed to the 80% isodose. Results: FSRT and SRS were well tolerated. Median follow-up time was 75 months. Local control was not statistically different for both groups. The probability of maintaining the pretreatment hearing level after SRS with doses of <=13 Gy was comparable to that of FSRT. The radiation dose for the SRS group (<=13 Gy vs. >13 Gy) significantly influenced hearing preservation rates (p = 0.03). In the group of patients treated with SRS doses of <=13 Gy, cranial nerve toxicity was comparable to that of the FSRT group. Conclusions: FSRT and SRS are both safe and effective alternatives for the treatment of VS. Local control rates are comparable in both groups. SRS with doses of <=13 Gy is a safe alternative to FSRT. While FSRT can be applied safely for the treatment of VSs of all sizes, SRS should be reserved for smaller lesions.

  19. Early depression of Ankrd2 and Csrp3 mRNAs in the polyribosomal and whole tissue fractions in skeletal muscle with decreased voluntary running.

    PubMed

    Roberts, Michael D; Childs, Thomas E; Brown, Jacob D; Davis, J Wade; Booth, Frank W

    2012-04-01

    The wheel-lock (WL) model for depressed ambulatory activity in rats has shown metabolic maladies ensuing within 53-173 h after WL begins. We sought to determine if WL beginning after 21-23 days of voluntary running in growing female Wistar rats affected the mRNA profile in the polyribosomal fraction from plantaris muscle shortly following WL. In experiment 1, WL occurred at 0200 and muscles were harvested at 0700 daily at 5 h (WL5h, n = 4), 29 h (WL29h, n = 4), or 53 h (WL53h, n = 4) after WL. Affymetrix Rat Gene 1.0 ST Arrays were used to test the initial question as to whether WL affects mRNA occupancy on skeletal muscle polyribosomes. Using a false discovery rate of 15%, no changes in mRNAs in the polyribosomal fraction were observed at WL29h and eight mRNAs (of over 8,200 identified targets) were altered at WL53h compared with WL5h. Interestingly, two of the six downregulated genes included ankyrin repeat domain 2 (Ankrd2) and cysteine-rich protein 3/muscle LIM protein (Csrp3), both of which encode mechanical stretch sensors and RT-PCR verified their WL-induced decline. In experiment 2, whole muscle mRNA and protein levels were analyzed for Ankrd2 and Csrp3 from the muscles of WL5h (4 original samples + 2 new), WL29h (4 original), WL53h (4 original + 2 new), as well as WL173 h (n = 6 new) and animals that never ran (SED, 4-5 new). Relative to WL5h controls, whole tissue Ankrd2 and Csrp3 mRNAs were lower (P < 0.05) at WL53h, WL173h, and SED; Ankrd2 protein tended to decrease at WL53h (P = 0.054) and Csrp3 protein was less in WL173h and SED rats (P < 0.05). In summary, unique early declines in Ankrd2 and Csrp3 mRNAs were identified with removal of voluntary running, which was subsequently followed by declines in Csrp3 protein levels during longer periods of wheel lock.

  20. Metformin as an initial adjunct to low-dose liraglutide enhances the weight-decreasing potential of liraglutide in obese polycystic ovary syndrome: Randomized control study

    PubMed Central

    JENSTERLE, MOJCA; GORICAR, KATJA; JANEZ, ANDREJ

    2016-01-01

    Liraglutide (LIRA) treatment is associated with the dose-dependent reduction of weight. Higher doses are more effective than lower doses, although higher doses are also more poorly tolerated. Metformin may enhance the weight-lowering potential of LIRA via the stimulatory modulation of incretin in addition to its direct beneficial effects in PCOS. The aim of the present study was to evaluate whether metformin as an adjunct to low-dose LIRA affects body weight with increased efficacy compared with low-dose LIRA alone in obese patients with PCOS. In a 12-week study, 44 obese women with PCOS were randomly offered either combined treatment (COMBO) with 1,000 mg metformin twice a day and 1.2 mg LIRA once a day, or treatment with 1.2 mg LIRA alone. The primary outcome of treatment was an alteration in the levels of obesity. A total of 43 patients [aged 30.3±4.4 years; body mass index (BMI) 37.2±4.5 kg/m2; mean ± standard deviation] completed the study. The subjects treated with COMBO lost on average 6.2±2.4 kg compared with a 3.8±3.5 kg weight loss in the patients treated with LIRA alone (P=0.024). The BMI decreased by 2.2±0.8 kg/m2 in patients treated with COMBO and by 1.4±1.2 kg/m2 in patients treated with LIRA alone (P=0.024). A clinically significant ≥5% weight reduction was achieved in 59.1% of patients treated with COMBO and 42.9% of patients treated with LIRA alone. Reductions in glucose levels following oral glucose tolerance testing, as well as in androstenedione levels in the COMBO group were significantly greater compared with those in the LIRA group. The side effects were mild and transient in the two treatment groups. A combination of metformin and low-dose LIRA was more effective than low-dose LIRA alone in reducing body weight in obese patients with PCOS. PMID:27073422

  1. Radiation for Hodgkin's Lymphoma in Young Female Patients: A New Technique to Avoid the Breasts and Decrease the Dose to the Heart

    SciTech Connect

    Dabaja, Bouthaina S.; Rebueno, Neal C.S.; Mazloom, Ali; Thorne, Scott; Perrin, Kelly J.; Tolani, Naresh; Das, Pragnan; Delclos, Marc E.; Iyengar, Puneeth; Reed, Valerie K.; Horace, Patrecia; Salehpour, Mohammad R.

    2011-02-01

    Purpose: To demonstrate how, in young female patients with Hodgkin's lymphoma, using an inclined board technique can further decrease the volume of breasts and heart in the treatment field. Methods and Materials: An inclined board was constructed with the ability to mount an Aquaplast face mask, a Vacu-Lock, and a hip stopper. Eight female patients with early-stage Hodgkin's lymphoma were planned and compared using the conventional flat position and the inclined board position. All patients on the inclined board were planned with 90{sup o} degree table position and 15{sup o} gantry angle rotation to compensate for the beam divergence resulting from the patient's position on the inclined board. Dose-volume histograms were generated, as well as the mean V30 and V5 of both breasts and heart using both treatment positions. Results: The mean value of V30 of the right breast, left breast, and heart decreased from 3%, 3%, and 13%, respectively, using the flat position to 0, 0.4%, and 5%, respectively, using the inclined board. The mean value of V5 of the right breast, left breast, and heart decreased from 6%, 13%, and 36%, respectively, using the flat position to 2%, 8%, and 29%, respectively, using the inclined board. Conclusions: Compared with conventional flat positioning, this simple device and technique allows better sparing of the breasts and the heart while maintaining comparable target coverage and total lung dose.

  2. Outcome of Patients Treated With a Single-Fraction Dose of Palliative Radiation for Cutaneous T-Cell Lymphoma

    SciTech Connect

    Thomas, Tarita O.; Agrawal, Priya; Guitart, Joan; Rosen, Steven T.; Querfeld, Christiane; Kuzel, Timothy M.

    2013-03-01

    Purpose: Cutaneous T-cell lymphoma (CTCL) is a radiosensitive tumor. Presently, treatment with radiation is given in multiple fractions. The current literature lacks data that support single-fraction treatment for CTCL. This retrospective review assesses the clinical response in patients treated with a single fraction of radiation. Methods and Materials: This study reviewed the records of 58 patients with CTCL, primarily mycosis fungoides, treated with a single fraction of palliative radiation therapy (RT) between October 1991 and January 2011. Patient and tumor characteristics were reviewed. Response rates were compared using Fisher's exact test and multiple logistic regressions. Survival rates were determined using the Kaplan-Meier method. Cost-effectiveness analysis was performed to assess the cost of a single vs a multifractionated treatment regimen. Results: Two hundred seventy individual lesions were treated, with the majority (97%) treated with ≥700 cGy; mean follow-up was 41.3 months (range, 3-180 months). Response rate by lesion was assessed, with a complete response (CR) in 255 (94.4%) lesions, a partial response in 10 (3.7%) lesions, a partial response converted to a CR after a second treatment in 4 (1.5%) lesions, and no response in 1 (0.4%) lesion. The CR in lower extremity lesions was lower than in other sites (P=.0016). Lesions treated with photons had lower CR than those treated with electrons (P=.017). Patients with lesions exhibiting large cell transformation and tumor morphology had lower CR (P=.04 and P=.035, respectively). Immunophenotype did not impact response rate (P=.23). Overall survival was significantly lower for patients with Sézary syndrome (P=.0003) and erythroderma (P<.0001). The cost of multifractionated radiation was >200% higher than that for single-fraction radiation. Conclusions: A single fraction of 700 cGy-800 cGy provides excellent palliation for CTCL lesions and is cost effective and convenient for the patient.

  3. Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

    SciTech Connect

    Matsuyama, Tomohiko; Kogo, Kasei; Oya, Natsuo

    2013-03-15

    Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy{sub 10}. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.

  4. Pifithrin-alpha decreases the radioprotective efficacy of a Podophyllum hexandrum Himalayan mayapple fraction REC-2006 in HepG2 cells.

    PubMed

    Singh, Pankaj Kumar; Kumar, Raj; Sharma, Ashok; Arora, Rajesh; Jain, Swatantra Kumar; Sharma, Rakesh Kumar

    2009-07-09

    Inhibition of the tumour suppressor p53 by PFT (pifithrin-alpha) promotes p53-mediated apoptosis and protects against doxorubicin-induced apoptosis. The present study was carried out to evaluate the effect of PFT on the radioprotective potential of Podophyllum hexandrum fraction (REC-2006) in HepG2 (p53++) cell line. REC-2006 (10-5 microg/ml) treatment at 2 h before irradiation (10 Gy) rendered 80+/-3% protection in HepG2 cells, whereas PFT debilitated the radioprotective potential of REC-2006. REC-2006 increased the expression of Hsp70 (heat-shock protein 70), HSF1 (heat-shock factor 1) and Bcl-2 in irradiated HepG2 cells, whereas PFT when treated with REC-2006 decreased the expression of Hsp70, HSF1 and Bcl-2 in HepG2 cells. REC-2006 facilitated post-irradiation DNA repair by pausing cell-cycle progression at G1- and G2-phase, whereas no such cell-cycle arrest was observed in irradiated HepG2 cells pretreated with PFT in irradiated HepG2 cells. No change was observed in Mdm2 (murine double minute 2) and Ras-GAP (Ras-GTPase-activating protein) expression with or without PFT treatment. Decrease in the expression of caspase 3 and Bax was observed in HepG2 cells when REC-2006 treatment was given 2 h before irradiation; however, PFT treatment increased the expression of Bax leading to apoptosis. It can be concluded that p53 expression plays a major role in the REC-2006-mediated protection against acute irradiation in HepG2 cells. PFT treatment reduced the radioprotective efficacy of REC-2006 by inhibiting the expression of HSF1 and Hsp70 and thereby the expression of Bcl-2, by up-regulating the cell-cycle-regulatory proteins and therefore reducing the span of time for DNA repair and also by inducing Bax-mediated apoptosis. PFT did not, however, show any effect on p53 regulating protein (Mdm2) and pro-survival protein (Ras-GAP).

  5. Estimation of EEC, unattached fraction and equilibrium factor for the assessment of radiological dose using pin-hole cup dosimeters and deposition based progeny sensors.

    PubMed

    Bangotra, Pargin; Mehra, Rohit; Kaur, Kirandeep; Kanse, Sandeep; Mishra, Rosaline; Sahoo, B K

    2015-10-01

    High concentration of radon ((222)Rn), thoron ((220)Rn) and their decay products in environment may increase the risk of radiological exposure to the mankind. The (222)Rn, (220)Rn concentration and their separate attached and unattached progeny concentration in units of EEC have been measured in the dwellings of Muktsar and Mansa districts of Punjab (India), using Pin-hole cup dosimeters and deposition based progeny sensors (DTPS/DRPS). The indoor (222)Rn and (220)Rn concentration was found to vary from 21 Bqm(-3) to 94 Bqm(-3) and 17 Bqm(-3) to 125 Bqm(-3). The average EEC (attached + unattached) of (222)Rn and (220)Rn was 25 Bqm(-3) and 1.8 Bqm(-3). The equilibrium factor for (222)Rn and (220)Rn in studied area was 0.47 ± 0.13 and 0.05 ± 0.03. The equilibrium factor and unattached fraction of (222)Rn and (220)Rn has been calculated separately. Dose conversion factors (DCFs) of different models have been calculated from unattached fraction for the estimation of annual effective dose in the studied area. From the experimental data a correlation relationship has been observed between unattached fraction (f(p)(Rn)) and equilibrium factor (F(Rn)). The present work also aims to evaluate an accurate expression among available expression in literature for the estimation of f(p)(Rn). PMID:26117280

  6. [Mesothelioma incidence decreases parallel to asbestos exposure decrement or interruption: a confirmation of a dose-response relationship, with implications in public health].

    PubMed

    Merler, Enzo

    2007-01-01

    On the basis of the available evidence, several groups of experts and investigators identified a dose-response relationship between exposure to commercial types of asbestos fibres and mesothelioma risk. The first mathematical model was proposed by Peto et al. It was derived from a conceptualisation of the multistage theory of cancer and provides an interpretation of the risk for the occurrence of mesothelioma in cohorts of exposed workers. In the study described in this paper, the author reviewed the data suggesting a decrease in mesotheliomas rate follosing reduction or interruption of exposure. Descriptive analyses and the few available long-term cohort studies indicate a decrease in risk. This is supported also by the fact that even the most biopersistent asbestos fibres are eliminated from the lungs. Indeed, a slow but effective reduction of risk has been demonstrated in the cohort of Wittenoom workers in Australia, previously exposed to crocidolite.

  7. Perinatal exposure to low-dose methylmercury induces dysfunction of motor coordination with decreases in synaptophysin expression in the cerebellar granule cells of rats.

    PubMed

    Fujimura, Masatake; Cheng, Jinping; Zhao, Wenchang

    2012-06-29

    Methylmercury (MeHg) is an environmental pollutant that is toxic to the developing central nervous system (CNS) in children, even at low exposure levels. Perinatal exposure to MeHg is known to induce neurological symptoms with neuropathological changes in the CNS. However, the relationship between the neurological symptoms and neuropathological changes induced in offspring as a result of exposure to low-dose MeHg is not well defined. In the present study, neurobehavioral analyses revealed that exposure to a low level of MeHg (5 ppm in drinking water) during developmental caused a significant deficit in the motor coordination of rats in the rotating rod test. In contrast, general neuropathological findings, including neuronal cell death and the subsequent nerve inflammation, were not observed in the region of the cerebellum responsible for regulating motor coordination. Surprisingly, the expression of synaptophysin (SPP), a marker protein for synaptic formation, significantly decreased in cerebellar granule cells. These results showed that perinatal exposure to low-dose MeHg causes neurobehavioral impairment without general neuropathological changes in rats. We demonstrated for the first time that exposure to low-dose MeHg during development induces the dysfunction of motor coordination due to changes of synaptic homeostasis in cerebellar granule cells.

  8. Experimentally induced, synergistic late effects of a single dose of radiation and aging: significance in LKS fraction as compared with mature blood cells.

    PubMed

    Hirabayashi, Yoko; Tsuboi, Isao; Nakachi, Kei; Kusunoki, Yoichiro; Inoue, Tohru

    2015-03-01

    The number of murine mature blood cells recovered within 6 weeks after 2-Gy whole-body irradiation at 6 weeks of age, whereas in the case of the undifferentiated hematopoietic stem/progenitor cell (HSC/HPC) compartment [cells in the lineage-negative, c-kit-positive and stem-cell-antigen-1-positive (LKS) fraction], the numerical differences between mice with and without irradiation remained more than a year, but conclusively the cells showed numerical recovery. When mice were exposed to radiation at 6 months of age, acute damages of mature blood cells were rather milder probably because of their maturation with age; but again, cells in the LKS fraction were specifically damaged, and their numerical recovery was significantly delayed probably as a result of LKS-specific cellular damages. Interestingly, in contrast to the recovery of the number of cells in the LKS fraction, their quality was not recovered, which was quantitatively assessed on the basis of oxidative-stress-related fluorescence intensity. To investigate why the recovery in the number of cells in the LKS fraction was delayed, expression levels of genes related to cellular proliferation and apoptosis of cells in the bone marrow and LKS fraction were analyzed by real-time polymerase chain reaction (RT-PCR). In the case of 21-month-old mice after radiation exposure, Ccnd1, PiK3r1 and Fyn were overexpressed solely in cells in the LKS fraction. Because Ccnd1and PiK3r1 upregulated by aging were further upregulated by radiation, single-dose radiation seemed to induce the acceleration of aging, which is related to the essential biological responses during aging based on a lifetime-dependent relationship between a living creature and xenobiotic materials.

  9. Two-fraction high-dose-rate brachytherapy within a single day combined with external beam radiotherapy for prostate cancer: single institution experience and outcomes

    PubMed Central

    Liu, Junyang; Kaidu, Motoki; Sasamoto, Ryuta; Ayukawa, Fumio; Yamana, Nobuko; Sato, Hiraku; Tanaka, Kensuke; Kawaguchi, Gen; Ohta, Atsushi; Maruyama, Katsuya; Abe, Eisuke; Kasahara, Takashi; Nishiyama, Tsutomu; Tomita, Yoshihiko; Aoyama, Hidefumi

    2016-01-01

    We investigated the outcomes of treatment for patients with localized prostate cancer (PCa) treated with 3D conformal radiation therapy (3D-CRT) followed by two-fraction high-dose-rate brachytherapy within a single day (2-fr.-HDR-BT/day) at a single institution. A total of 156 consecutive Asian males (median age, 67 years) were enrolled. To compare our findings with those of other studies, we analyzed our results using the D'Amico classification, assigning the patients to low- (n =5; 3.2%), intermediate- (n =36; 23.1%) and high-risk (n =115; 73.7%) groups (Stage T3 PCa patients were classified as high-risk). One patient in the D'Amico low-risk group (20%), 13 intermediate-risk patients (36.1%) and 99 high-risk patients (86.1%) underwent androgen deprivation therapy. We administered a prescription dose of 39 Gy in 13 fractions of 3D-CRT combined with 18 Gy of HDR-BT in two 9-Gy fractions delivered within a single day. We did not distinguish between risk groups in determining the prescription dose. The median follow-up period was 38 months. Of the 156 patients, one died from primary disease and five died from other diseases. The 3-year overall survival (OS) rates were 100%, 100% and 93.7%, and the 3-year ‘biochemical no evidence of disease (bNED)’ rates were 100%, 100% and 96.9% for the D'Amico low-, intermediate- and high-risk groups, respectively. No patient developed ≥ Grade 3 early toxicity. The Grade 3 late genitourinary toxicity rate was 2.6%, and no ≥ Grade 3 late gastrointestinal toxicity occurred. The efficacy and safety of this study were satisfactory, and longer-term follow-up is necessary. PMID:26983988

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

    PubMed

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

    2014-04-01

    Gemtuzumab ozogamicin (fGO), a humanized anti-CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥ 6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m², days 1, 4, 7) with standard-dose cytarabine (200 mg/m² /day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty-four patients (median age 68 years) received fGO with cytarabine. Median follow-up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two-year overall survival (OS) was 51% (95% CI: 28-69) and 2 years relapse-free survival (RFS) was 51% (95%CI: 25-72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse. PMID:24375467

  11. Fractional randomness

    NASA Astrophysics Data System (ADS)

    Tapiero, Charles S.; Vallois, Pierre

    2016-11-01

    The premise of this paper is that a fractional probability distribution is based on fractional operators and the fractional (Hurst) index used that alters the classical setting of random variables. For example, a random variable defined by its density function might not have a fractional density function defined in its conventional sense. Practically, it implies that a distribution's granularity defined by a fractional kernel may have properties that differ due to the fractional index used and the fractional calculus applied to define it. The purpose of this paper is to consider an application of fractional calculus to define the fractional density function of a random variable. In addition, we provide and prove a number of results, defining the functional forms of these distributions as well as their existence. In particular, we define fractional probability distributions for increasing and decreasing functions that are right continuous. Examples are used to motivate the usefulness of a statistical approach to fractional calculus and its application to economic and financial problems. In conclusion, this paper is a preliminary attempt to construct statistical fractional models. Due to the breadth and the extent of such problems, this paper may be considered as an initial attempt to do so.

  12. The serum levels of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction

    PubMed Central

    Wang, Shu-Jin; Qu, Zhong-Sen; Zhang, Qing-De; Li, Liang; Wang, Feng; Zhang, Bin; Wu, Bang-Li; Zhao, Yu-Wu

    2015-01-01

    To investigate the effect of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction. 112 cases of uremia complicated with cerebral infarction were randomly divided into the peritoneal dialysate with urokinase treatment group (66 cases) and the conventional treatment group (46 cases). At the same time, 50 cases of healthy people who were more than 45 years old were enrolled in the control group. The basic treatment in both treatment groups was the same. In urokinase therapy group based on the conventional treatment, urokinase was added into peritoneal dialysis fluid, and changes of serum MMP-9, MMP-2 and vWF were observed by drawing blood at different time points within 8 weeks. The changes of serum MMP-2, MMP-9 and vWF were detected by enzyme-linked immunosorbent assay. At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2, vWF were significantly higher (P<0.05, P<0.05, P<0.01). Conventional antiplatelet therapy in brain protection only reduce MMP-9 to the normal range (P>0.05) within 8 weeks. But the MMP-2 and vWF cannot be reduced to the normal range (P<0.01, P<0.01). Low doses of urokinase can reduce MMP-9 (7 d) and MMP-2 (14 d) to the normal range (P>0.05, P>0.05) at the early stage and decrease the vWF to a normal range within 8 weeks (P>0.05). At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2 and vWF increased significantly. Low doses of urokinase dialysis can reduce serum MMP-9, MMP-2, and vWF in acute uremia complicated with cerebral infarction without recurrence of cerebral infarction and cerebral hemorrhagic transformation, indicating that low dose of urokinase peritoneal dialysis may have a certain effect on the early treatment of this disease. PMID:26550224

  13. Feasibility study of stereotactic body radiotherapy for peripheral lung tumors with a maximum dose of 100 Gy in five fractions and a heterogeneous dose distribution in the planning target volume.

    PubMed

    Takeda, Atsuya; Oku, Yohei; Sanuki, Naoko; Eriguchi, Takahisa; Aoki, Yousuke; Enomoto, Tatsuji; Kaneko, Takeshi; Nishimura, Shuichi; Kunieda, Etsuo

    2014-09-01

    We evaluated toxicity and outcomes for patients with peripheral lung tumors treated with stereotactic body radiation therapy (SBRT) in a dose-escalation and dose-convergence study. A total of 15 patients were enrolled. SBRT was performed with 60 Gy in 5 fractions (fr.) prescribed to the 60% isodose line of maximum dose, which was 100 Gy in 5 fr., covering the planning target volume (PTV) surface (60 Gy/5 fr. - (60%-isodose)) using dynamic conformal multiple arc therapy (DCMAT). The primary endpoint was radiation pneumonitis (RP) ≥ Grade 2 within 6 months. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Using dose-volumetric analysis, the trial regimen of 60 Gy/5 fr. - (60%-isodose) was compared with our institutional conventional regimen of 50 Gy/5 fr. - (80%-isodose). The enrolled consecutive patients had either a solitary peripheral tumor or two ipsilateral tumors. The median follow-up duration was 22.0 (12.0-27.0) months. After 6 months post-SBRT, the respective number of RP Grade 0, 1 and 2 cases was 5, 9 and 1. In the Grade 2 RP patient, the image showed an organizing pneumonia pattern at 6.0 months post-SBRT. No other toxicity was found. At last follow-up, there was no evidence of recurrence of the treated tumors. The target volumes of 60 Gy/ 5 fr. - (60%-isodose) were irradiated with a significantly higher dose than those of 50 Gy/5 fr. - (80%-isodose), while the former dosimetric parameters of normal lung were almost equivalent to the latter. SBRT with 60 Gy/5 fr. - (60%-isodose) using DCMAT allowed the delivery of very high and convergent doses to peripheral lung tumors with feasibility in the acute and subacute phases. Further follow-up is required to assess for late toxicity.

  14. Proteomic analysis of post-nuclear supernatant fraction and percoll-purified membranes prepared from brain cortex of rats exposed to increasing doses of morphine

    PubMed Central

    2014-01-01

    ; Aspartate aminotransferase, ↓2.2×] origin. Surprisingly, the immunoblot analysis of the same PM resolved by 2D-ELFO indicated that the “active”, morphine-induced pool of Gβ subunits represented just a minor fraction of the total signal of Gβ which was decreased 1.2x only. The dominant signal of Gβ was unchanged. Conclusion Brain cortex of rats exposed to increasing doses of morphine is far from being adapted. Significant up-regulation of proteins functionally related to oxidative stress and apoptosis suggests a major change of energy metabolism resulting in the state of severe brain cell “discomfort” or even death. PMID:24528483

  15. Standard-Fractionated Radiotherapy for Optic Nerve Sheath Meningioma: Visual Outcome Is Predicted by Mean Eye Dose

    SciTech Connect

    Abouaf, Lucie; Girard, Nicolas; Lefort, Thibaud; D'hombres, Anne; Tilikete, Caroline; Vighetto, Alain; Mornex, Francoise

    2012-03-01

    Purpose: Radiotherapy has shown its efficacy in controlling optic nerve sheath meningiomas (ONSM) tumor growth while allowing visual acuity to improve or stabilize. However, radiation-induced toxicity may ultimately jeopardize the functional benefit. The purpose of this study was to identify predictive factors of poor visual outcome in patients receiving radiotherapy for ONSM. Methods and Materials: We conducted an extensive analysis of 10 patients with ONSM with regard to clinical, radiologic, and dosimetric aspects. All patients were treated with conformal radiotherapy and subsequently underwent biannual neuroophthalmologic and imaging assessments. Pretreatment and posttreatment values of visual acuity and visual field were compared with Wilcoxon's signed rank test. Results: Visual acuity values significantly improved after radiotherapy. After a median follow-up time of 51 months, 6 patients had improved visual acuity, 4 patients had improved visual field, 1 patient was in stable condition, and 1 patient had deteriorated visual acuity and visual field. Tumor control rate was 100% at magnetic resonance imaging assessment. Visual acuity deterioration after radiotherapy was related to radiation-induced retinopathy in 2 patients and radiation-induced mature cataract in 1 patient. Study of radiotherapy parameters showed that the mean eye dose was significantly higher in those 3 patients who had deteriorated vision. Conclusions: Our study confirms that radiotherapy is efficient in treating ONSM. Long-term visual outcome may be compromised by radiation-induced side effects. Mean eye dose has to be considered as a limiting constraint in treatment planning.

  16. A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II

    PubMed Central

    Regan, Jessica A.; Mauro, Adolfo Gabriele; Carbone, Salvatore; Marchetti, Carlo; Gill, Rabia; Mezzaroma, Eleonora; Valle Raleigh, Juan; Salloum, Fadi N.; Van Tassell, Benjamin W.; Abbate, Antonio

    2015-01-01

    Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ∼50% of patients with HF, the mechanisms of disease are poorly understood, and therapies are generally ineffective in reducing HF progression. Animal models of HFpEF not due to pressure or volume overload are lacking, therefore limiting in-depth understanding of the pathophysiological mechanisms and the development of novel therapies. We hypothesize that a continuous infusion of low-dose angiotensin II (ATII) is sufficient to induce left ventricular (LV) diastolic dysfunction and HFpEF, without increasing blood pressure or inducing LV hypertrophy or dilatation. Osmotic pumps were implanted subcutaneously in 8-wk-old male mice assigned to the ATII (0.2 mg·kg−1·day−1) or volume-matched vehicle (N = 8/group) for 4 wk. We measured systolic and diastolic arterial blood pressures through a tail-cuff transducer, LV dimensions and ejection fraction through echocardiography, and LV relaxation through pulsed-wave Doppler and LV catheterization. Myocardial fibrosis and cardiomyocyte cross-sectional area were measured. ATII infusion had no effects on systemic arterial blood pressure. ATII induced significant impairment in LV diastolic function, as measured by an increase (worsening) in LV isovolumetric relaxation time, myocardial performance index, isovolumetric relaxation time constant, and LV end-diastolic pressure without altering LV dimensions, mass, or ejection fraction. Chronic infusion of low-dose ATII recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF. PMID:26188021

  17. High-Dose-Rate Brachytherapy of a Single Implant With Two Fractions Combined With External Beam Radiotherapy for Hormone-Naive Prostate Cancer

    SciTech Connect

    Sato, Morio Mori, Takashi; Shirai, Shintaro; Kishi, Kazushi; Inagaki, Takeshi; Hara, Isao

    2008-11-15

    Purpose: To evaluate the preliminary outcomes of high-dose-rate (HDR) brachytherapy of a single implant with two fractions and external beam radiotherapy (EBRT) for hormone-naive prostate cancer. Methods and Materials: Between March 2000 and Sept 2003, a total of 53 patients with tumor Stage T1c-T3b N0 M0 prostate cancer were treated with HDR brachytherapy boost doses (7.5 Gy/fraction) and 50-Gy EBRT during a 5.5-week period. Median follow-up was 61 months. Patients were divided into groups with localized (T1c-T2b) and advanced disease (T3a-T3b). We used the American Society for Therapeutic Radiology and Oncology (ASTRO) definition for biochemical failure. According to recommendations of the Radiation Therapy Oncology Group-ASTRO Phoenix Consensus Conference, biochemical failure-free control rates (BF-FCRs) at 3 years were investigated as 2 years short of the median follow-up. Results: Between April 2000 and Sept 2007, Common Terminology Criteria for Adverse Events Version 2.0 late Grade 2 genitourinary and gastrointestinal toxicity rates were 0% and 3.8%, respectively. Erectile preservation was 25% at 5 years. Overall survival was 88.1% and cause-specific survival was 100%. At 3 years, ASTRO BF-FCRs of the localized and advanced groups were 100% and 42%, respectively (p = 0.001). Conclusions: The HDR brachytherapy of a single implant with two fractions plus EBRT is effective in treating patients with localized hormone-naive prostate cancer, with the least genitourinary and gastrointestinal toxicities; however, longer median BF-FCR follow-up is required to assess these findings.

  18. Three or Four Fractions of 4-5 Gy per Week in Postoperative High-Dose-Rate Brachytherapy for Endometrial Carcinoma

    SciTech Connect

    Rovirosa, Angeles; Ascaso, Carlos; Sanchez-Reyes, Alberto; Herreros, Antonio; Abellana, Rosa; Pahisa, Jaume; Lejarcegui, Jose Antonio; Biete, Albert

    2011-10-01

    Purpose: To evaluate the results of high-dose-rate brachytherapy (HDRBT) using a schedule of three or four fractions per week, when possible, in 89 patients on local control and toxicity in postoperative treatment of endometrial carcinoma. The effect of the overall HDRBT treatment time (OTT) on toxicity was also evaluated. Patients and Methods: Federation Internationale de Gynecologie Obstetrique Stage: 24 IB, 45 IC, 4 IIA, 6 IIB, 4 IIIA, 2 IIIB, and 4 IIIC. Radiotherapy: Group 1-67 of 89 patients received external beam irradiation (EBI; 44-50 Gy) plus HDRBT (3 fractions of 4-6 Gy); Group 2-22 of 89 patients received HDRBT alone (6 fractions of 4-5 Gy). OTT: Group 1-HDRBT was completed in a median of 5 days in 32 patients and in >5 days in 35; Group 2-HDRBT was completed in <15 days in 11 patients and in {>=}16 days in 11. Toxicity was evaluated using Radiation Therapy Oncology Group scores and the bioequivalent dose (BED) study was performed in vaginal mucosa surface. Statistics included Student's t test, chi-square test, and receiving operator curves. Results: With a mean follow-up of 31 months (range, 6-70), 1 of 89 patients had vaginal relapse. Early toxicity appeared in 8 of 89 (9%) patients and was resolved. Late toxicity appeared in 13/89 (14%): vaginal nine Grade 1, three Grade 2, one Grade 4; bladder two Grade 2; rectal three Grade 1, one Grade 2. No differences were found in relation to OTT in Groups 1 and 2. Mean BED was 88.48 Gy in Group 1 and 165.28 Gy in Group 2. Cases with Grade 2 late vaginal toxicity received >75 Gy after EBI and >165 Gy in Group 2. Conclusions: Three fractions of 4-5 Gy in 3-5 days after EBI or 6 fractions in <15 days in patients receiving HDRBT alone was a safe treatment in relation to toxicity and local control. Vaginal surface BED less than 75 Gy after EBI and less than 160 Gy in HDRBT alone may be safe to avoid G2 toxicity.

  19. Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

    SciTech Connect

    Horton, Janet K.; Blitzblau, Rachel C.; Yoo, Sua; Geradts, Joseph; Chang, Zheng; Baker, Jay A.; Georgiade, Gregory S.; Chen, Wei; Siamakpour-Reihani, Sharareh; Wang, Chunhao; Broadwater, Gloria; Groth, Jeff; Palta, Manisha; Dewhirst, Mark; Barry, William T.; Duffy, Eileen A.; and others

    2015-07-15

    Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should

  20. High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

    SciTech Connect

    Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy

    2012-07-01

    Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy Multiplication-Sign 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy Multiplication-Sign 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of {<=}12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable

  1. Fractionation of a tumor-initiating UV dose introduces DNA damage-retaining cells in hairless mouse skin and renders subsequent TPA-promoted tumors non-regressing.

    PubMed

    van de Glind, Gerline; Rebel, Heggert; van Kempen, Marika; Tensen, Kees; de Gruijl, Frank

    2016-02-16

    Sunburns and especially sub-sunburn chronic UV exposure are associated with increased risk of squamous cell carcinomas (SCCs). Here we focus on a possible difference in tumor initiation from a single severe-sunburn dose (on day 1, 21 hairless mice) and from an equal dose fractionated into very low sub-sunburn doses not causing any (growth-promoting) epidermal hyperplasia (40 days daily exposure, n=20). From day 47 all mice received 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications (2x/wk) for 20 weeks to promote tumor development within the lifetime of the animals. After the sub-sunburn regimen sparse DNA damage-retaining basal cells (quiescent stem cells, QSCs) remained in the non-hyperplastic epidermis. These cells were forced to divide by TPA. After discontinuation of TPA tumors regressed and disappeared in the 'sunburn group' but persisted and grew in the 'sub-sunburn group' (0.06 vs 2.50 SCCs and precursors ≥4 mm/mouse after 280 days, p=0.03). As the tumors carried no mutations in p53, H/K/N-Ras and Notch1/2, these 'usual suspects' were not involved in the UV-driven tumor initiation. Although we could not selectively eliminate QSCs (unknown phenotype) to establish causality, our data suggest that forcing specifically DNA damage-retaining QSCs to divide--with high mutagenic risk--gives rise to persisting (mainly 'in situ') skin carcinomas. PMID:26797757

  2. Posttraumatic Stress Disorder After High-Dose-Rate Brachytherapy for Cervical Cancer With 2 Fractions in 1 Application Under Spinal/Epidural Anesthesia: Incidence and Risk Factors

    SciTech Connect

    Kirchheiner, Kathrin; Czajka-Pepl, Agnieszka; Scharbert, Gisela; Wetzel, Léonore; Sturdza, Alina; Dörr, Wolfgang; Pötter, Richard

    2014-06-01

    Purpose: To investigate the psychological consequences of high-dose-rate brachytherapy with 2 fractions in 1 application under spinal/epidural anesthesia in the treatment of locally advanced cervical cancer. Methods and Materials: In 50 patients with locally advanced cervical cancer, validated questionnaires were used for prospective assessment of acute and posttraumatic stress disorder (ASD/PTSD) (Impact of Event Scale–Revision), anxiety/depression (Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30/Cervical Cancer 24), physical functioning (World Health Organization performance status), and pain (visual analogue scale), before and during treatment and 1 week and 3 months after treatment. Qualitative interviews were recorded in open format for content analysis. Results: Symptoms of ASD occurred in 30% of patients 1 week after treatment; and of PTSD in 41% 3 months after treatment in association with this specific brachytherapy procedure. Pretreatment predictive variables explain 82% of the variance of PTSD symptoms. Helpful experiences were the support of the treatment team, psychological support, and a positive attitude. Stressful factors were pain, organizational problems during treatment, and immobility between brachytherapy fractions. Conclusions: The specific brachytherapy procedure, as performed in the investigated mono-institutional setting with 2 fractions in 1 application under spinal/epidural anesthesia, bears a considerable risk of traumatization. The source of stress seems to be not the brachytherapy application itself but the maintenance of the applicator under epidural anesthesia in the time between fractions. Patients at risk may be identified before treatment, to offer targeted psycho-social support. The patients' open reports regarding helpful experiences are an encouraging feedback for the treatment team; the reported stressful factors

  3. 30 Gy or 34 Gy? Comparing 2 Single-Fraction SBRT Dose Schedules for Stage I Medically Inoperable Non-Small Cell Lung Cancer

    SciTech Connect

    Videtic, Gregory M.M. Stephans, Kevin L.; Woody, Neil M.; Reddy, Chandana A.; Zhuang, Tingliang; Magnelli, Anthony; Djemil, Toufik

    2014-09-01

    Purpose: To review outcomes of 2 single-fraction lung stereotactic body radiation therapy (SBRT) schedules used for medically inoperable early stage lung cancer. Methods and Materials: Patients in our institution have been treated on and off protocols using single-fraction SBRT (30 Gy and 34 Gy, respectively). All patients had node-negative lung cancer measuring ≤5 cm and lying ≥2 cm beyond the trachea-bronchial tree and were treated on a Novalis/BrainLAB system with the ExactTrac positioning system for daily image guidance. Results: For the interval from 2009 to 2012, 80 patients with 82 lesions were treated with single-fraction lung SBRT. Fifty-five patients (69%) and 25 patients (31%) received 30 Gy and 34 Gy, respectively. In a comparison of 30 Gy and 34 Gy cohorts, patient and tumor characteristics were balanced and median follow-up in months was 18.7 and 17.8, respectively. The average heterogeneity-corrected mean doses to the target were 33.75 Gy and 37.94 Gy for the 30-Gy and 34-Gy prescriptions, respectively. Comparing 30-Gy and 34-Gy cohorts, 92.7% and 84.0% of patients, respectively, experienced no toxicity (P was not significant), and had neither grade 3 nor higher toxicities. For the 30-Gy and 34-Gy patients, rates of 1-year local failure, overall survival, and lung cancer-specific mortality were 2.0% versus 13.8%, 75.0% versus 64.0%, and 2. 1% versus 16.0%, respectively (P values for differences were not significant). Conclusions: This is the largest single-fraction lung SBRT series yet reported. and it confirms the safety, efficacy, and minimal toxicity of this schedule for inoperable early stage lung cancer.

  4. Comparative study of dose distributions and cell survival fractions for 1H, 4He, 12C and 16O beams using Geant4 and Microdosimetric Kinetic model

    NASA Astrophysics Data System (ADS)

    Burigo, Lucas; Pshenichnov, Igor; Mishustin, Igor; Bleicher, Marcus

    2015-04-01

    Depth and radial dose profiles for therapeutic 1H, 4He, 12C and 16O beams are calculated using the Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT). 4He and 16O ions are presented as alternative options to 1H and 12C broadly used for ion-beam cancer therapy. Biological dose profiles and survival fractions of cells are estimated using the modified Microdosimetric Kinetic model. Depth distributions of cell survival of healthy tissues, assuming 10% and 50% survival of tumor cells, are calculated for 6 cm SOBPs at two tumor depths and for different tissues radiosensitivities. It is found that the optimal ion choice depends on (i) depth of the tumor, (ii) dose levels and (iii) the contrast of radiosensitivities of tumor and surrounding healthy tissues. Our results indicate that 12C and 16O ions are more appropriate to spare healthy tissues in the case of a more radioresistant tumor at moderate depths. On the other hand, a sensitive tumor surrounded by more resistant tissues can be better treated with 1H and 4He ions. In general, 4He beam is found to be a good candidate for therapy. It better spares healthy tissues in all considered cases compared to 1H. Besides, the dose conformation is improved for deep-seated tumors compared to 1H, and the damage to surrounding healthy tissues is reduced compared to heavier ions due to the lower impact of nuclear fragmentation. No definite advantages of 16O with respect to 12C ions are found in this study.

  5. A moderate dose of caffeine ingestion does not change energy expenditure but decreases sleep time in physically active males: a double-blind randomized controlled trial.

    PubMed

    Júdice, Pedro B; Magalhães, João P; Santos, Diana A; Matias, Catarina N; Carita, Ana Isabel; Armada-Da-Silva, Paulo A S; Sardinha, Luís B; Silva, Analiza M

    2013-01-01

    Research on the effect of caffeine on energy expenditure (EE), physical activity (PA), and total sleep time (TST) during free-living conditions using objective measures is scarce. We aimed to determine the impact of a moderate dose of caffeine on TST, resting EE (REE), physical activity EE (PAEE), total EE (TEE), and daily time spent in sedentary, light, moderate, and vigorous intensity activities in a 4-day period and the acute effects on heart rate (HR) and EE in physically active males. Using a double-blind crossover trial (ClinicalTrials.gov ID: NCT01477294) with two conditions (4 days each with 3-day washout) randomly ordered as caffeine (5 mg/kg of body mass/day) and placebo (maltodextrin) administered twice per day (2.5 mg/kg), 30 nonsmoker males, low-caffeine users (<100 mg/day), aged 20-39, were followed. Body composition was assessed by dual-energy X-ray absorptiometry. PA was assessed by accelerometry, while a combined HR and movement sensor estimated EE and HR on the second hour after the first administration dose. REE was assessed by indirect calorimetry, and PAEE was calculated as [TEE - (REE + 0.1TEE)]. TST and daily food records were obtained. Repeated measures ANOVA and ANCOVA were used. After a 4-day period, adjusting for fat-free mass, PAEE, and REE, TST was reduced (p = 0.022) under caffeine intake, while no differences were found between conditions for REE, PAEE, TEE, and PA patterns. Also, no acute effects on HR and EE were found between conditions. Though a large individual variability was observed, our findings revealed no acute or long-term effects of caffeine on EE and PA but decreased TST during free-living conditions in healthy males.

  6. A Prospective Cohort Study to Compare Treatment Results Between 2 Fractionation Schedules of High-Dose-Rate Intracavitary Brachytherapy (HDR-ICBT) in Patients With Cervical Cancer

    SciTech Connect

    Huang, Eng-Yen; Sun, Li-Min; Lin, Hao; Lan, Jen-Hong; Chanchien, Chan-Chao; Huang, Yu-Jie; Wang, Chang-Yu; Wang, Chong-Jong

    2013-01-01

    Purpose: To compare the treatment results of 2 fractionation schedules for high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. Methods and Materials: From June 2001 through January 2008, 267 patients with stage IB-IVA cervical cancer were enrolled in the study. All patients underwent 4-field pelvic irradiation and HDR-ICBT. The median central and parametrial doses were 39.6 Gy and 45 Gy, respectively. Patient underwent either 6 Gy Multiplication-Sign 4 (HDR-4) (n=144) or 4.5 Gy Multiplication-Sign 6 (HDR-6) (n=123) to point A of ICBT using {sup 192}Ir isotope twice weekly. The rates of overall survival, locoregional failure, distant metastasis, proctitis, cystitis, and enterocolitis were compared between HDR-4 and HDR-6. Results: There were no significant differences in the demographic data between HDR-4 and HDR-6 except for total treatment time. The 5-year proctitis rates were 23.0% and 21.5% in HDR-4 and HDR-6 (P=.399), respectively. The corresponding rates of grade 2-4 proctitis were 18.7% and 9.6% (P=.060). The corresponding rates of grades 3-4 proctitis were 5.2% and 1.3% (P=.231). Subgroup analysis revealed that HDR-4 significantly increased grade 2-4 proctitis in patients aged {>=}62 years old (P=.012) but not in patients aged <62 years (P=.976). The rates of overall survival, locoregional failure, distant metastasis, cystitis, and enterocolitis were not significantly different between HDR-4 and HDR-6 schedules. Conclusion: The small fraction size of HDR-ICBT is associated with grade 2 proctitis without compromise of prognosis in elderly patients. This schedule is suggested for patients who tolerate an additional 2 applications of HDR-ICBT.

  7. Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiation Therapy in the Treatment of Intermediate-Risk Prostate Cancer - Long Term Results

    SciTech Connect

    Cury, Fabio L.; Duclos, Marie; Aprikian, Armen; Patrocinio, Horacio; Kassouf, Wassim; Shenouda, George; Faria, Sergio; David, Marc; Souhami, Luis

    2012-03-15

    Purpose: We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single-fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HypoRT). Methods and Materials: Patients were treated exclusively with HDRB and HypoRT. HDRB delivered a dose of 10 Gy to the prostate surface and HypoRT consisted of 50 Gy delivered in 20 daily fractions. The first 121 consecutive patients with a minimum of 2 years posttreatment follow-up were assessed for toxicity and disease control. Results: The median follow-up was 65.2 months. No acute Grade III or higher toxicity was seen. Late Grade II gastrointestinal toxicity was seen in 9 patients (7.4%) and Grade III in 2 (1.6%). Late Grade III genitourinary toxicity was seen in 2 patients (1.6%). After a 24-month follow-up, a rebiopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. Negative biopsies were found in 40 patients (91%). The 5-year biochemical relapse-free survival rate was 90.7% (95% CI, 84.5-96.9%), with 13 patients presenting biochemical failure. Among them, 9 were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 5 years were 100% and 98.8% (95% CI, 96.4-100%), respectively. Conclusion: The combination of HDRB and HypoRT is well tolerated, with acceptable toxicity rates. Furthermore, results from rebiopsies revealed an encouraging rate of local control. These results confirm that the use of conformal RT techniques, adapted to specific biological tumor characteristics, have the potential to improve the therapeutic ratio in intermediate-risk PC patients.

  8. In-vitro and in-vivo evidence of dose-dependent decrease of uropathogenic Escherichia coli virulence after consumption of commercial Vaccinium macrocarpon (cranberry) capsules.

    PubMed

    Lavigne, J-P; Bourg, G; Combescure, C; Botto, H; Sotto, A

    2008-04-01

    This study evaluated the antibacterial efficacy of the consumption of cranberry capsules vs. placebo in the urine of healthy volunteers. A first double-blind, randomised, crossover trial involved eight volunteers who had followed three regimens, with or without cranberry, with a wash-out period of at least 6 days between each regimen. Twelve hours after consumption of cranberry or placebo hard capsules, the first urine of the morning was collected. Different Escherichia coli strains were cultured in the urine samples. Urinary antibacterial adhesion activity was measured in vitro using the human T24 epithelial cell-line, and in vivo using the Caenorhabditis elegans killing model. With the in-vitro model, 108 mg of cranberry induced a significant reduction in bacterial adherence to T24 cells as compared with placebo (p <0.001). A significant dose-dependent decrease in bacterial adherence in vitro was noted after the consumption of 108 and 36 mg of cranberry (p <0.001). The in-vivo model confirmed that E. coli strains had a reduced ability to kill C. elegans after growth in the urine of patients who consumed cranberry capsules. Overall, these in-vivo and in-vitro studies suggested that consumption of cranberry juice represents an interesting new strategy to prevent recurrent urinary tract infection.

  9. Manganese accumulation in membrane fractions of primary astrocytes is associated with decreased γ-aminobutyric acid (GABA) uptake, and is exacerbated by oleic acid and palmitate.

    PubMed

    Fordahl, Steve C; Erikson, Keith M

    2014-05-01

    Manganese (Mn) exposure interferes with GABA uptake; however, the effects of Mn on GABA transport proteins (GATs) have not been identified. We sought to characterize how Mn impairs GAT function in primary rat astrocytes. Astrocytes exposed to Mn (500 μM) had significantly reduced (3)H-GABA uptake despite no change in membrane or cytosolic GAT3 protein levels. Co-treatment with 100 μM oleic or palmitic acids (both known to be elevated in Mn neurotoxicity), exacerbated the Mn-induced decline in (3)H-GABA uptake. Mn accumulation in the membrane fraction of astrocytes was enhanced with fatty acid administration, and was negatively correlated with (3)H-GABA uptake. Furthermore, control cells exposed to Mn only during the experimental uptake had significantly reduced (3)H-GABA uptake, and the addition of GABA (50 μM) blunted cytosolic Mn accumulation. These data indicate that reduced GAT function in astrocytes is influenced by Mn and fatty acids accumulating at or interacting with the plasma membrane.

  10. Pasta supplemented with isolated lupin protein fractions reduces body weight gain and food intake of rats and decreases plasma glucose concentration upon glucose overload trial.

    PubMed

    Capraro, Jessica; Magni, Chiara; Scarafoni, Alessio; Caramanico, Rosita; Rossi, Filippo; Morlacchini, Mauro; Duranti, Marcello

    2014-02-01

    The supplementation of foods with biologically active compounds can be a powerful approach for improving diet and well being. In this study we separately included in pasta matrices a concentrate of γ-conglutin, a glucose-lowering protein from Lupinus albus seeds, an isolate of the other main lupin storage proteins and ovalbumin, at a ratio corresponding to 125 mg of pure protein in 100 g of pasta. With these products we fed rats made hyperglycaemic, for 3 weeks. Among the most relevant changes measured in body and blood parameters were: (i) a significant reduction in food intake of rats fed γ-conglutin concentrate supplemented pasta and a significant limitation in the body weight increase in rats fed α, β and δ-conglutin isolate supplemented pasta, while the food conversion indices were unchanged; (ii) a reduction in glycaemia upon glucose overload trial, especially in the γ-conglutin concentrate supplemented pasta fed animals, at a dose of 45 mg per kg body weight. The correlations among the measured parameters are discussed. Overall, the results evidence the potentiality of supplementing traditional foods with exogenous nutraceutical seed proteins to control body weight gain and glycaemia.

  11. Decreased forelimb ability in mice intracerebroventricularly injected with low dose 6-hydroxidopamine: A model on the dissociation of bradykinesia from hypokinesia.

    PubMed

    Ribeiro, Renata Pietsch; Santos, Danúbia Bonfanti; Colle, Dirleise; Naime, Aline Aita; Gonçalves, Cinara Ludvig; Ghizoni, Heloisa; Hort, Mariana Appel; Godoi, Marcelo; Dias, Paulo Fernando; Braga, Antonio Luiz; Farina, Marcelo

    2016-05-15

    Bradykinesia and hypokinesia represent well-known motor symptoms of Parkinson's disease (PD). While bradykinesia (slow execution of movements) is present in less affected PD patients and aggravates as the disease severity increases, hypokinesia (reduction of movement) seems to emerge prominently only in the more affected patients. Here we developed a model based on the central infusion of low dose (40μg) 6-hydroxydopamine (6-OHDA) in mice in an attempt to discriminate bradykinesia (accessed through forelimb inability) from hypokinesia (accessed through locomotor and exploratory activities). The potential beneficial effects of succinobucol against 6-OHDA-induced forelimb inability were also evaluated. One week after the beginning of treatment with succinobucol (i.p. injections, 10mg/kg/day), mice received a single i.c.v. infusion of 6-OHDA (40μg/site). One week after 6-OHDA infusion, general locomotor/exploratory activities (open field test), muscle strength (grid test), forelimb skill (single pellet task), as well as striatal biochemical parameters related to oxidative stress and cellular homeostasis (glutathione peroxidase, glutathione reductase and NADH dehydrogenases activities, lipid peroxidation and TH levels), were evaluated. 6-OHDA infusions did not change locomotor/exploratory activities and muscle strength, as well as the evaluated striatal biochemical parameters. However, 6-OHDA infusions caused significant reductions (50%) in the single pellet reaching task performance, which detects forelimb skill inability and can be used to experimentally identify bradykinesia. Succinobucol partially protected against 6-OHDA-induced forelimb inability. The decreased forelimb ability with no changes in locomotor/exploratory behavior indicates that our 6-OHDA-based protocol represents a useful tool to mechanistically study the dissociation of bradykinesia and hypokinesia in PD.

  12. Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Men With Intermediate-Risk Prostate Cancer: Analysis of Short- and Medium-Term Toxicity and Quality of Life

    SciTech Connect

    Morton, Gerard C.; Loblaw, D. Andrew; Sankreacha, Raxa

    2010-07-01

    Purpose: To determine the short- and medium-term effects of a single high-dose-rate brachytherapy fraction of 15Gy and hypofractionated external beam radiation therapy for prostate cancer. Methods and Materials: Eligible patients had localized prostate cancer with a Gleason score of 7 and a prostate-specific antigen (PSA) concentration of <20 ng/ml or a Gleason score of 6 with a PSA concentration of 10 to 20 ng/ml. Patients received high-dose-rate brachytherapy as a single 15-Gy dose, followed by external beam radiation therapy at 37.5Gy in 15 fractions, and were followed prospectively for toxicity (using Common Terminology Criteria for Adverse Events version 3.0), urinary symptoms (using the International Prostate Symptom Score [IPSS]), erectile function (with the International Index of Erectile Function [IIEF]), and health-related quality of life (with the Expanded Prostate Cancer Index Composite [EPIC]). Clinical examinations and PSA measurements were performed at every visit, and prostate biopsies were repeated at 2 years. The trial accrued 125 patients, with a median follow-up of 1.14 years. Results: Acute grade 2 and 3 genitourinary toxicity occurred in 62% and 1.6% of patients, respectively, and acute grade 2 gastrointestinal toxicity occurred in 6.5% of patients. No grade 3 late toxicity has occurred: 47% of patients had grade 2 genitourinary and 10% of patients had grade 2 gastrointestinal toxicity. Median IPSSs rose from 5 at baseline to 12 at 1 month and returned to 7 at 3 months. Of the total number of patients who were initially potent (IIEF, >21), 8% of patients developed mild to moderate dysfunction, and 27% of patients developed severe erectile dysfunction. Baseline EPIC bowel, urinary, and sexual bother scores decreased by 9, 7, and 19 points, respectively, at 1 year. No patient has experienced biochemical failure, and 16 of the first 17 biopsy results showed no malignancy. Conclusions: Treatment is well tolerated in the short and medium term, with

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

    PubMed

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

    2015-04-01

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

  14. Value of Combined PET/CT for Radiation Planning in CT-Guided Percutaneous Interstitial High-Dose-Rate Single-Fraction Brachytherapy for Colorectal Liver Metastases

    SciTech Connect

    Steffen, Ingo G.; Wust, Peter; Ruehl, Ricarda

    2010-07-15

    Purpose: To determine the additional value of fluorodeoxyglucose-positron emission tomography (PET) for clinical target volume definition in the planning of computed tomography (CT)-guided interstitial brachytherapy for liver metastases. Patients and Methods: A total of 19 patients with liver metastases from colorectal cancer treated in 25 sessions were included in the present study. All patients had undergone fluorodeoxyglucose-PET for patient evaluation before interstitial CT-guided brachytherapy. A contrast-enhanced CT scan of the upper abdomen was obtained for radiation planning. The clinical target volume (CTV) was defined by a radiation oncologist and radiologist. After registration of the CT scan with the PET data set, the target volume was defined again using the fusion images. Results: PET revealed one additional liver lesion that was not visible on CT. The median CT-CTV (defined using CT and magnetic resonance imaging) was 68 cm{sup 3} (range 4-260). The PET/CT-CTV (median, 78 cm{sup 3}; range, 4-273) was significantly larger, with a median gain of 24.5% (interquartile range, 2.1-71.5%; p = .022). An increased CTV was observed in 15 cases and a decrease in 6; in 4 cases, the CT-CTV and PET/CT-CTV were equal. Incomplete dose coverage of PET/CT-CTVs was indicative of early local progression (p = .004); however, CT-based radiation plans did not show significant differences in the local control rates when stratified by dose coverage. Conclusion: Retrospective implementation of fluorodeoxyglucose-PET for CTV specification for CT-guided brachytherapy for colorectal liver metastases revealed a significant change in the CTVs. Additional PET-positive tumor regions with incomplete dose coverage could explain unexpected early local progression.

  15. Fractionated doses of oral etoposide in the treatment of patients with aids-related kaposi sarcoma: a clinical and pharmacologic study to improve therapeutic index.

    PubMed

    Sprinz, E; Caldas, A P; Mans, D R; Cancela, A; DiLeone, L; Dalla Costa, T; Schwartsmann, G

    2001-04-01

    The purpose of this study was to examine the antitumor activity, toxic effects, and plasma pharmacokinetics of fractionated doses of oral etoposide aiming at the achievement of prolonged safe and active plasma drug levels in patients with AIDS-related Kaposi sarcoma (KS). This was designed as a phase II trial in which consecutive patients with progressing AIDS-KS after at least 3 months of active antiretroviral therapy received oral etoposide at the dose of 20 mg/m2 every 8 hours daily for 7 days every 21 days, with the study of its plasma pharmacokinetics. Eligible patients were 18 to 60 years old, with a histopathologically confirmed diagnosis of AIDS-related KS, human immunodeficiency virus-positive test, progressing after at least 3 months of active antiretroviral therapy, World Health Organization (WHO) performance status 0 to 3, New York University staging IIA or greater, no active infection except oral candidiasis, normal bone marrow, liver, and renal function, and who signed an informed consent. Objective tumor responses were evaluated after at least one full treatment course according to a modified WHO criteria, and toxicity was evaluated weekly and graded using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) criteria. For the pharmacokinetic study, plasma was obtained from patients during the first drug administration immediately before and at various time points thereafter. Etoposide was measured after extraction from plasma by a standard high-performance liquid chromatography. Twenty-one patients were accrued for the study, and 18 of them met the eligibility criteria. They were all men, with median age of 36 years old (range: 25-50 years), median WHO performance status 0 (range: 0-3) median CD4+ count (cells/mm3) 67 (range: 8-443), prior AIDS diagnosis in 10 of 18 cases, NYU staging IIA (1 patient), IIB (1), IIIA (7), IIIB (1), IVA (4), and IVB (4) sites of disease: mucocutaneous only (5), mucocutaneous/lymph nodes (5), mucocutaneous

  16. Case control study to assess the possibility of decrease the risk of osteoradionecrosis in relation to the dose of radiation absorbed by the jaw

    PubMed Central

    Carini, Fabrizio; Bucalo, Concetta; Saggese, Vito; Monai, Dario; Porcaro, Gianluca

    2012-01-01

    Summary Aims the assessment of the limit dose for the organs at risk in external radiotherapy is a fundamental step to guarantee an optimal risk-benefit ratio. The aim of this study was to assess, through contouring the single dental cavities, the absorbed radiation dose on irradiated alveolar bones during the treatment of cervico-facial tumours, so as to test the correlation between the absorbed dose of radiation at alveolar level and the level of individual surgical risk for osteonecrosis. Materials and methods we selected 45 out of 89 patients on the basis of different exclusion criteria. Nine of these patients showed evidence of osteoradionecrosis. The patients were treated either with 3D conformational radiation therapy (3D-CRT) or with intensity-modulated radiation therapy (IMRT), there after alveolar bones were contoured using computed axial tomography (CAT scans) carried out following oncological and dental treatment. The dose-volume histograms (DVH) were obtained on the basis of such data, which included those relating to the dental cavities in addition to those inherent to the tumours and the organs at risk. Results all patients, irrespective of type of treatment, received an average of 60 to 70 grays in 30/35 sittings. The patients treated with IMRT showed higher variation in absorbed radiation dose than those treated with 3D-CRT. The alveolar encirclement allowed the assessment of the absorbed radiation dose, and consequently it also allowed to assess the individual surgical risk for osteonecrosis in patients with head and neck tumours who underwent radiography treatment. Conclusions the study of DVH allows the assessment of limit dose and the detection of the areas at greater risk for osteoradionecrosis before dental surgery. PMID:23285316

  17. A single acute dose of pinitol from a naturally-occurring food ingredient decreases hyperglycaemia and circulating insulin levels in healthy subjects.

    PubMed

    Hernández-Mijares, Antonio; Bañuls, Celia; Peris, Jose E; Monzó, Nuria; Jover, Ana; Bellod, Lorena; Victor, Victor M; Rocha, Milagros

    2013-11-15

    A limited amount of research suggests that oral ingestion of pinitol (3-O-methyl-d-chiro-inositol) positively influences glucose tolerance in humans. This study assessed the effects of different doses of pinitol supplementation on glucose tolerance, insulin sensitivity and plasma pinitol concentrations. Thirty healthy subjects underwent two one-day trials in which they consumed a nutritive beverage (Fruit Up®) containing 2.5, 4.0 or 6.0g of pinitol and a corresponding placebo equivalent in both energy and carbohydrates. Blood samples were collected frequently over the 240-min test period. The pinitol-enriched beverage reduced serum glucose and insulin at 45 and 60min, but only at a dose of 6.0g. Plasma pinitol concentrations, maximum concentration and AUC increased according to the dose administered. The results show that a single dose of pinitol from a naturally-occurring food ingredient at the highest dose administered acutely influences indices of whole-body glucose tolerance and insulin sensitivity in healthy subjects.

  18. Use of 120 Kilovolt Tube Potential for Digital Subtraction Angiography and Fluoroscopy in an Image-Intensifier Angiographic System: Decrease of Skin Dose in Transarterial Chemoembolization Therapy for Hepatocellular Carcinoma

    SciTech Connect

    Irie, Toshiyuki Satou, Ryuta

    2007-09-15

    In an image-intensifier angiographic system, the tube potential is commonly regulated in ranges from 75 to 90 kV for digital subtraction angiography (DSA) and fluoroscopy in transarterial chemoembolization therapy (TACE) for hepatocellular carcinoma. The purpose of this study was to investigate whether or not a 120-kV tube potential could be used for DSA and fluoroscopy in TACE to decrease the skin dose. Forty-three patients administered TACE were randomly allocated into two groups: TACE was performed using standard-kilovoltage (75- to 90-kV) DSA and fluoroscopy modes (group A; n = 20) or using high-kilovoltage (120-kV) modes (group B; n = 23). The peak skin dose was compared between the groups. One case in group A was excluded from the study because the HCC nodule was not depicted on DSA. The peak skin dose (mGy) for group A was 383.6 {+-} 176.5 and that for group B was 265.1 {+-} 145.1. The peak skin dose was decreased by 31% in the 120-kV mode, a statistically significant difference (t-test, p = 0.022). We conclude that the use of 120 kV tube potential for DSA and fluoroscopy may be one option for performing TACE while decreasing the skin dose.

  19. Validation of the flooding dose technique to determine fractional rates of protein synthesis in a model bivalve species, the blue mussel (Mytilus edulis L.).

    PubMed

    McCarthy, Ian D; Nicholls, Ruth; Malham, Shelagh K; Whiteley, Nia M

    2016-01-01

    For the first time, use of the flooding dose technique using (3)H-Phenylalanine is validated for measuring whole-animal and tissue-specific rates of protein synthesis in the blue mussel Mytilus edulis (61mm shell length; 4.0g fresh body mass). Following injection, the phenylalanine-specific radioactivities in the gill, mantle and whole-animal free pools were elevated within one hour and remained elevated and stable for up to 6h following injection of (3)H-phenylalanine into the posterior adductor muscle. Incorporation of (3)H-phenylalanine into body protein was linear over time following injection and the non-significant intercepts for the regressions suggested incorporation into body protein occurred rapidly after injection. These results validate the technique for measuring rates of protein synthesis in mussels. There were no differences in the calculated rates following 1-6h incubation in gill, mantle or whole-animal and fractional rates of protein synthesis from the combined time course data were 9.5±0.8%d(-1) for the gill, 2.5±0.3%d(-1) for the mantle and 2.6±0.3%d(-1) for the whole-animal, respectively (mean values±SEM). The whole-animal absolute rate of protein synthesis was calculated as 18.9±0.6mg protein day(-1). The use of this technique in measuring one of the major components of maintenance metabolism and growth will provide a valuable and convenient tool in furthering our understanding of the protein metabolism and energetics of this keystone marine invertebrate and its ability to adjust and respond to fluctuations, such as that expected as a result of climate change.

  20. Prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat-cell carcinoma of the lung

    SciTech Connect

    Perez, C.A.; Stanley, K.; Rubin, P.; Kramer, S.; Brady, L.; Perez-Tamayo, R.; Brown, G.S.; Concannon, J.; Rotman, M.; Seydel, H.G.

    1980-06-01

    Analysis is presented of a prospective randomized study involving 365 patients with histologically proven unresectable non-oat-cell carcinoma of the lung treated with deffinitive radiotherapy. The patients were radomized to one of four treatment regimens: 4000 rad split course, or 4000, 5000, or 6000-rad continuous courses in five fractions per week. Ninety to 100 patients were accessioned to each group. The one-year survival rate is 50% and the two-year survival rate, 25%. The patients treated with the split course have the lowest survival rate in comparison with the other groups. The complete and partial local regression of tumor was 49% in patients treated with 4000 rad and 55% in the groups treated with 5000 and 6000 rad. For patients who achieved complete regression of the tumor following irradiation, the two-year survival rate is 40%, in contrast to 20% for those with partial regression, and no survivors among the patients with stable or progressive disease. The incidence of intrathoracic recurrence was 33% for patients treated with 6000 rad, 39% for those receiving 5000 rad, and 44 to 49% for those treated with a 4000-rad split or continuous course. At present, the data stongly suggest that patients treated with 5000 or 6000 rad have a better response, tumor control, and survival rate than those receiving lower doses. Patients with high performance status or with tumors in earlier stages have a two-year survival rate of approx. 40%, in comparison with 20% for other patients. The various irradiation regimens have been well tolerated, with complications being slightly higher in the 4000-rad split course group and in the 6000-rad continuous course group. The most frequent complications have been pneumonitis, pulmonary fibrosis, and dyspagia due to transient esophagitis. Further investigation will be necessary before the optimal management of patients with bronchogenic carcinoma by irradiation is established.

  1. Bezafibrate at clinically relevant doses decreases serum/liver triglycerides via down-regulation of sterol regulatory element-binding protein-1c in mice: a novel peroxisome proliferator-activated receptor alpha-independent mechanism.

    PubMed

    Nakajima, Takero; Tanaka, Naoki; Kanbe, Hiroki; Hara, Atsushi; Kamijo, Yuji; Zhang, Xiaowei; Gonzalez, Frank J; Aoyama, Toshifumi

    2009-04-01

    The triglyceride-lowering effect of bezafibrate in humans has been attributed to peroxisome proliferator-activated receptor (PPAR) alpha activation based on results from rodent studies. However, the bezafibrate dosages used in conventional rodent experiments are typically higher than those in clinical use (> or =50 versus < or =10 mg/kg/day), and thus it remains unclear whether such data can be translated to humans. Furthermore, because bezafibrate is a pan-PPAR activator, the actual contribution of PPARalpha to its triglyceride-lowering properties remains undetermined. To address these issues, bezafibrate at clinically relevant doses (10 mg/kg/day; low) was administered to wild-type and Ppara-null mice, and its effects were compared with those from conventionally used doses (100 mg/kg/day; high). Pharmacokinetic analyses showed that maximum plasma concentration and area under the concentration-time curve in bezafibrate-treated mice were similar to those in humans at low doses, but not at high doses. Low-dose bezafibrate decreased serum/liver triglycerides in a PPARalpha-independent manner by attenuation of hepatic lipogenesis and triglyceride secretion. It is noteworthy that instead of PPAR activation, down-regulation of sterol regulatory element-binding protein (SREBP)-1c was observed in mice undergoing low-dose treatment. High-dose bezafibrate decreased serum/liver triglycerides by enhancement of hepatic fatty acid uptake and beta-oxidation via PPARalpha activation, as expected. In conclusion, clinically relevant doses of bezafibrate exert a triglyceride-lowering effect by suppression of the SREBP-1c-regulated pathway in mice and not by PPARalpha activation. Our results may provide novel information about the pharmacological mechanism of bezafibrate action and new insights into the treatment of disorders involving SREBP-1c. PMID:19124612

  2. Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model?

    PubMed

    Little, M P

    2010-05-01

    In this paper we review the evidence for departure from linearity for malignant and non-malignant disease and in the light of this assess likely mechanisms, and in particular the potential role for non-targeted effects. Excess cancer risks observed in the Japanese atomic bomb survivors and in many medically and occupationally exposed groups exposed at low or moderate doses are generally statistically compatible. For most cancer sites the dose-response in these groups is compatible with linearity over the range observed. The available data on biological mechanisms do not provide general support for the idea of a low dose threshold or hormesis. This large body of evidence does not suggest, indeed is not statistically compatible with, any very large threshold in dose for cancer, or with possible hormetic effects, and there is little evidence of the sorts of non-linearity in response implied by non-DNA-targeted effects. There are also excess risks of various types of non-malignant disease in the Japanese atomic bomb survivors and in other groups. In particular, elevated risks of cardiovascular disease, respiratory disease and digestive disease are observed in the A-bomb data. In contrast with cancer, there is much less consistency in the patterns of risk between the various exposed groups; for example, radiation-associated respiratory and digestive diseases have not been seen in these other (non-A-bomb) groups. Cardiovascular risks have been seen in many exposed populations, particularly in medically exposed groups, but in contrast with cancer there is much less consistency in risk between studies: risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well known (but unobserved) risk factors. In the absence of a convincing mechanistic explanation of epidemiological evidence that is, at present, less than persuasive, a cause-and-effect interpretation of the reported

  3. Dietary peptides from the non-digestible fraction of Phaseolus vulgaris L. decrease angiotensin II-dependent proliferation in HCT116 human colorectal cancer cells through the blockade of the renin-angiotensin system.

    PubMed

    Luna-Vital, Diego A; Liang, Katie; González de Mejía, Elvira; Loarca-Piña, Guadalupe

    2016-05-18

    This study aimed to determine the ability of peptides present in the non-digestible fraction (NDF) of common beans to decrease angiotensin II (AngII) through the blockade of RAS and its effect on the proliferation of HCT116 human colorectal cancer cells. Pure synthesized peptides GLTSK and GEGSGA and the peptide fractions (PF) of cultivars Azufrado Higuera and Bayo Madero were used. The cells were pretreated with pure peptides, PF or AGT at their IC50 or IC25 values, in comparison with the simultaneous treatment of peptides and AGT. For western blot and microscopy analysis, 100 μM and 0.5 mg mL(-1) were used for pure peptides and PF treatments, respectively. According to the ELISA tests, GLTSK and GEGSGA decreased (p < 0.05) the conversion rate of AGT to angiotensin I (AngI) by 38 and 28%, respectively. All the peptides tested reduced (p < 0.05) the conversion rate of AngI to AngII from 38 to 50%. When the cells were pretreated with both pure peptides and PF before exposure to AGT, the effectiveness inhibiting cell proliferation was higher than the simultaneous treatment suggesting their preventive effects. GLTSK and GEGSGA interacted with the catalytic site of renin, the angiotensin-I converting enzyme, and the AngII receptor, mainly through hydrogen bonds, polar, hydrophobic and cation-π interactions according to molecular docking. Through confocal microscopy, it was determined that GLTSK and GEGSGA caused the decrease (p < 0.05) of AngII-dependent STAT3 nuclear activation in HCT116 cells by 66 and 23%, respectively. The results suggest that peptides present in the common bean NDF could potentially ameliorate the effects of RAS overexpression in colorectal cancer. PMID:27156533

  4. Lung cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with lung cancer mortality in the atomic bomb survivors study

    SciTech Connect

    Howe, G.R.

    1995-06-01

    Current lung cancer risk estimates after exposure to low-linear energy transfer radiation such as X rays are based on studies of people exposed to such radiation at high dose rates, for example the atomic bomb survivors. Radiobiology and animal experiments suggest that risks from exposure at low to moderate dose rates, for example medical diagnostic procedures, may be overestimated by such risk models, but data for humans to examine this issue are limited. In this paper we report on lung cancer mortality between 1950 and 1987 in a cohort of 64,172 Canadian tuberculosis patients, of whom 39% were exposed to highly fractionated multiple chest fluoroscopies leading to a mean lung radiation dose of 1.02 Sv received at moderate dose rates. These data have been used to estimate the excess relative risk per sievert of lung cancer mortality, and this is compared directly to estimates derived from 75,991 atomic bomb survivors. Based on 1,178 lung cancer deaths in the fluoroscopy study, there was no evidence of any positive association between risk and dose, with the relative risk at 1 Sv being 1.00 (95% confidence interval 0.94, 1.07), which contrasts with that based on the atomic bomb survivors, 1.60 (1.27, 1.99). The difference in effect between the two studies almost certainly did not arise by chance (P = 0.0001). This study provides strong support from data for humans for a substantial fractionation/dose-rate effect for low-linear energy transfer radiation and lung cancer risk. This implies that lung cancer risk from exposures to such radiation at present-day dose rates is likely to be lower than would be predicted by current radiation risk models based on studies of high-dose-rate exposures. 25 refs., 8 tabs.

  5. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation.

    PubMed

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Liza S; Osipov, Andrian N; Zhuravleva, Veronika F; Pankratova, Galina V; Porokhovnik, Lev N; Veiko, Natalia N

    2015-09-01

    The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism's cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1×Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab DNA and TM values may provide the information about the human organism's cell resistivity to chronic exposure to the low-dose IR and about the development of the adaptive response in the organism that is aimed, firstly, at the effective cfDNA elimination from the blood circulation, and, secondly - at survival of the cells, including the cells with the damaged DNA. PMID:26113293

  6. Decrease of D2 receptor binding but increase in D2-stimulated G-protein activation, dopamine transporter binding and behavioural sensitization in brains of mice treated with a chronic escalating dose 'binge' cocaine administration paradigm.

    PubMed

    Bailey, A; Metaxas, A; Yoo, J H; McGee, T; Kitchen, I

    2008-08-01

    Understanding the neurobiology of the transition from initial drug use to excessive drug use has been a challenge in drug addiction. We examined the effect of chronic 'binge' escalating dose cocaine administration, which mimics human compulsive drug use, on behavioural responses and the dopaminergic system of mice and compared it with a chronic steady dose (3 x 15 mg/kg/day) 'binge' cocaine administration paradigm. Male C57BL/6J mice were injected with saline or cocaine in an escalating dose paradigm for 14 days. Locomotor and stereotypy activity were measured and quantitative autoradiographic mapping of D(1) and D(2) receptors, dopamine transporters and D(2)-stimulated [(35)S]GTPgammaS binding was performed in the brains of mice treated with this escalating and steady dose paradigm. An initial sensitization to the locomotor effects of cocaine followed by a dose-dependent increase in the duration of the locomotor effect of cocaine was observed in the escalating but not the steady dose paradigm. Sensitization to the stereotypy effect of cocaine and an increase in cocaine-induced stereotypy score was observed from 3 x 20 to 3 x 25 mg/kg/day cocaine. There was a significant decrease in D(2) receptor density, but an increase in D(2)-stimulated G-protein activity and dopamine transporter density in the striatum of cocaine-treated mice, which was not observed in our steady dose paradigm. Our results document that chronic 'binge' escalating dose cocaine treatment triggers profound behavioural and neurochemical changes in the dopaminergic system, which might underlie the transition from drug use to compulsive drug use associated with addiction, which is a process of escalation.

  7. [The estimation of appropriateness of chromosomal aberration assay as a biological dosimetry based on cytogenetic investigation of lung cancer patients given non-uniform fractional exposures to high doses of therapeutic 60Co gamma-rays].

    PubMed

    Khvostunov, I K; Kursova, L V; Shepel', N N; Ragulin, Iu A; Sevan'kaev, A V; Gulidov, I A; Glazyrin, D A; Ivanova, I N

    2012-01-01

    The objective of this study was to investigate in vivo the dose response of radiation induced chromosomal aberrations in human blood lymphocytes of lung cancer patients given non-uniform fractional exposures to high doses of therapeutic 60Co gamma-rays delivered synchronously with polychemotherapy. The chromosome aberration analysis was carried out in peripheral blood lymphocytes of 13 lung cancer patients who manifested II to IV developmental clinical stage. During the course of radiotherapy they received the accumulated tumor dose ranged 47.5 to 70 Gy. The yield ofdicentrics, centric rings and fragments was measured in the blood samples taken before treatment, after the first day and after the complete course of radiotherapy. Based on cytogenetic measurements of 3 patients, the average tumor dose after the first day was estimated to be 2.1 to 3.0 Gy given that the corresponding physical dose was (1.0 Gy + 1.5 Gy). The quotient of the individual dose estimated by the frequency of aberrations to the physical dose after the complete course of radiotherapy was calculated for all 13 patients. The mean quotient was shown to be equal to 93 +/- 9% ranged 50 to 154%.

  8. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study.

    PubMed

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600mg/kg body weight/day for 28days. In the subgranular zone (SGZ), 600mg/kg CPZ increased the number of cleaved caspase-3(+) apoptotic cells. At ≥120mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥120mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥120mg/kg decreased phosphorylated TRKB(+) interneurons, although the number of reelin(+) interneurons was unchanged. At 600mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells.

  9. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

    SciTech Connect

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

  10. Meta-analysis: low-dose intake of vitamin E combined with other vitamins or minerals may decrease all-cause mortality.

    PubMed

    Jiang, Shan; Pan, Zhenyu; Li, Hui; Li, Fenglan; Song, Yanyan; Qiu, Yu

    2014-01-01

    It has been suggested that vitamin E alone or combined with other vitamins or minerals can prevent oxidative stress and slow oxidative injury-related diseases, such as cardiovascular disease and cancer. A comprehensive search of PubMed/MEDLINE, EMBASE and the Cochrane Library was performed. Relative risk was used as an effect measure to compare the intervention and control groups. A total of 33 trials were included in the meta-analysis. Neither vitamin E intake alone (RR=1.01; 95% CI, 0.97 to 1.04; p=0.77) nor vitamin E intake combined with other agents (RR=0.97; 95% CI, 0.89 to 1.06; p=0.55) was correlated with all-cause mortality. Subgroup analyses revealed that low-dose vitamin E supplementation combined with other agents is associated with a statistically significant reduction in all-cause mortality (RR=0.92; 95% CI, 0.86 to 0.98; p=0.01), and vitamin E intake combined with other agents is associated with a statistically significant reduction in mortality rates among individuals without probable or confirmed diseases (RR=0.92; 95% CI, 0.86 to 0.99; p=0.02). Neither vitamin E intake alone nor combined with other agents is associated with a reduction in all-cause mortality. But a low dose (<400 IU/d) of vitamin E combined with other agents is correlated with a reduction in all-cause mortality, and vitamin E intake combined with other agents is correlated with a reduction in the mortality rate among individuals without probable or confirmed diseases.

  11. Single-fraction high-dose-rate brachytherapy using real-time transrectal ultrasound based planning in combination with external beam radiotherapy for prostate cancer: dosimetrics and early clinical results

    PubMed Central

    Lauche, Olivier; Delouya, Guila; Taussky, Daniel; Menard, Cynthia; Béliveau-Nadeau, Dominic; Hervieux, Yannick; Larouche, Renée

    2016-01-01

    Purpose To validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT) boost for prostate cancer using real-time transrectal ultrasound (TRUS) based planning. Material and methods From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions) was performed before (31%) or after (69%) HDRBT boost. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS) and the common terminology criteria for adverse events (CTCAE) v3.0. Results All dose-planning objectives were achieved in 90% of patients. Prostate D90 ≥ 105% and ≤ 115% was achieved in 99% of patients, prostate V150 ≤ 40% in 99%, prostate V200 < 11% in 96%, urethra D10 < 120% for 99%, urethra V125 = 0% in 100%, and rectal V75 < 1 cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed ≥ grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didn't receive ADT, cumulative percentage of patients with PSA ≤ 1 ng/ml at 4 and 18 months was respectively 23% and 66%. Conclusions Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities. PMID:27257413

  12. Comparison of internal doses calculated using the specific absorbed fractions of the average adult Japanese male phantom with those of the reference computational phantom-adult male of ICRP publication 110

    NASA Astrophysics Data System (ADS)

    Manabe, Kentaro; Sato, Kaoru; Endo, Akira

    2014-03-01

    In order to study the effects of body sizes and masses of organs and tissues on internal dose assessment, the values corresponding to effective dose coefficients for intakes of radionuclides were calculated using the specific absorbed fractions (SAFs) of two phantoms: the average adult Japanese male phantom (JM-103) and the reference computational phantom-adult male (RCP-AM) of the International Commission on Radiological Protection. SAFs were evaluated using the phantoms and Monte Carlo radiation transport code MCNPX or were taken from published data. As a result of a comparison for 2894 cases of 923 radionuclides, the maximum discrepancy in the effective dose coefficients between the JM-103 and RCP-AM was about 40%. However, the discrepancies were smaller than 10% in 97% of all cases.

  13. Split-course radiation therapy of carcinoma of the nasopharynx: results of a national collaborative clinical trial of the Radiation Therapy Oncology Group. [Comparative effectiveness of fractionated and split-dose radiotherapy and complications

    SciTech Connect

    Marcial, V.A.; Hanley, J.A.; Chang, C.; Davis, L.W.; Moscol, J.A.

    1980-04-01

    The initial results of a prospective randomized collaborative therapeutic trial of split-course radiotherapy in carcinoma of the nasopharynx are reported. The split-course therapy consisted of two irradiation courses, each delivering 3000 rad in 2 weeks, in 10 fractions of 300 rad. The courses were separated by a rest period of 3 weeks. Continuous radiation therapy consisted of 30 fractions of 220 rad each, for a total dose of 6600 rad. One hundred and nine patients were eligible for analysis with a minimal follow-up period of 1 year. No statistically significant differences were observed in the two therapeutic groups with regard to acute toxicity (normal tissue reactions, completion of therapy, and need of hospitalization during radiotherapy), late toxicity, incidence of distant metastases, patients who became free of clinically detectable tumor in the primary and neck sites at last follow-up or at death, and survival after therapy.

  14. Protection of mouse jejunal crypt cells by WR-2721 after small doses of radiation.

    PubMed

    Travis, E L; Thames, H D; Tucker, S L; Watkins, T L; Kiss, I

    1986-05-01

    The ability of WR-2721 to protect jejunal crypt cells after single doses and multifractionated doses of radiation was studied. Effective dose survival curves for jejunal crypt cells were constructed over the dose range of 230 to 1600 cGy. WR-2721 was given 30 minutes before each fraction, in a regimen consisting of 200 mg/kg before the first radiation fraction, followed at 3 hr intervals by 100 mg/kg for a total of 12 drug doses for the largest number of fractions. Fractionation protocols were designed with common dose fractions in regimens with different fraction numbers, allowing a test of the hypothesis of equal effect per fraction and an estimate of the initial number of clonogens per crypt in both the drug treated and non-drug treated mice. The hypothesis of equal effect per fraction could not be rejected in either the drug or non-drug treated mice. An average number of 137 clonogens per crypt was estimated for the non-drug treated mice and 81 clonogens per crypt in the drug treated mice; the difference between these two values was not significant. The protection factor decreased with decreasing dose ranging from a high of 1.47 (95% C.L. = 1.44 to 1.50) after a single dose of 2000 cGy to a low of 1.21 (95% C.L. = 1.08 to 1.37) after 200 cGy. Analysis of the data using either the linear quadratic (LQ) or two-component (TC) model of cell survival showed that WR-2721 was not dose-modifying over the dose range tested. Analysis using the LQ model showed that both beta and alpha were modified by WR-2721, by 50% and 20% respectively. These data indicate that protection by WR-2721 can be expected to decrease with dose although there is some protection after clinically relevant doses. PMID:3011713

  15. Is the in vivo dosimetry with the OneDosePlusTM system able to detect intra-fraction motion? A retrospective analysis of in vivo data from breast and prostate patients

    PubMed Central

    2012-01-01

    Background The OneDosePlusTM system, based on MOSFET solid-state radiation detectors and a handheld dosimetry reader, has been used to evaluate intra-fraction movements of patients with breast and prostate cancer. Methods An Action Threshold (AT), defined as the maximum acceptable discrepancy between measured dose and dose calculated with the Treatment Planning System (TPS) (for each field) has been determined from phantom data. To investigate the sensitivity of the system to direction of the patient movements, fixed displacements have been simulated in phantom. The AT has been used as an indicator to establish if patients move during a treatment session, after having verified the set-up with 2D and/or 3D images. Phantom tests have been performed matching different linear accelerators and two TPSs (TPS1 and TPS2). Results The ATs have been found to be very similar (5.0% for TPS1 and 4.5% for TPS2). From statistical data analysis, the system has been found not sensitive enough to reveal displacements smaller than 1 cm (within two standard deviations). The ATs applied to in vivo treatments showed that among the twenty five patients treated for breast cancer, only four of them moved during each measurement session. Splitting data into medial and lateral field, two patients have been found to move during all these sessions; the others, instead, moved only in the second part of the treatment. Patients with prostate cancer have behaved better than patients with breast cancer. Only two out of twenty five moved in each measurement session. Conclusions The method described in the paper, easily implemented in the clinical practice, combines all the advantages of in vivo procedures using the OneDosePlusTM system with the possibility of detecting intra-fraction patient movements. PMID:22716260

  16. Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study

    PubMed Central

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Kamran Samani, Roghayeh; Mohebbi, Shokoufeh

    2016-01-01

    Objective Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. Materials and Methods This experimental study irradiated three groups of target cells for one, two and three times with60Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. Results RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. Conclusion The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy).

  17. Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study

    PubMed Central

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Kamran Samani, Roghayeh; Mohebbi, Shokoufeh

    2016-01-01

    Objective Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. Materials and Methods This experimental study irradiated three groups of target cells for one, two and three times with60Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. Results RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. Conclusion The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy). PMID:27602316

  18. High Dose-Per-Fraction Irradiation of Limited Lung Volumes Using an Image-Guided, Highly Focused Irradiator: Simulating Stereotactic Body Radiotherapy Regimens in a Small-Animal Model

    SciTech Connect

    Cho, Jaeho; Kodym, Reinhard; Seliounine, Serguei

    2010-07-01

    Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.

  19. DMLC tracking and gating can improve dose coverage for prostate VMAT

    SciTech Connect

    Colvill, E.; Poulsen, P. R.; Booth, J. T.; O’Brien, R. T.; Keall, P. J.; Ng, J. A.

    2014-09-15

    Purpose: To assess and compare the dosimetric impact of dynamic multileaf collimator (DMLC) tracking and gating as motion correction strategies to account for intrafraction motion during conventionally fractionated prostate radiotherapy. Methods: A dose reconstruction method was used to retrospectively assess the dose distributions delivered without motion correction during volumetric modulated arc therapy fractions for 20 fractions of five prostate cancer patients who received conventionally fractionated radiotherapy. These delivered dose distributions were compared with the dose distributions which would have been delivered had DMLC tracking or gating motion correction strategies been implemented. The delivered dose distributions were constructed by incorporating the observed prostate motion with the patient's original treatment plan to simulate the treatment delivery. The DMLC tracking dose distributions were constructed using the same dose reconstruction method with the addition of MLC positions from Linac log files obtained during DMLC tracking simulations with the observed prostate motions input to the DMLC tracking software. The gating dose distributions were constructed by altering the prostate motion to simulate the application of a gating threshold of 3 mm for 5 s. Results: The delivered dose distributions showed that dosimetric effects of intrafraction prostate motion could be substantial for some fractions, with an estimated dose decrease of more than 19% and 34% from the planned CTVD{sub 99%} and PTV D{sub 95%} values, respectively, for one fraction. Evaluation of dose distributions for DMLC tracking and gating deliveries showed that both interventions were effective in improving the CTV D{sub 99%} for all of the selected fractions to within 4% of planned value for all fractions. For the delivered dose distributions the difference in rectum V{sub 65%} for the individual fractions from planned ranged from −44% to 101% and for the bladder V{sub 65

  20. Repair in mouse lung between multiple small doses of X rays

    SciTech Connect

    Travis, E.L.; Parkins, C.S.; Down, J.D.; Fowler, J.F.; Thames, H.D.

    1983-05-01

    Multiple fraction experiments have been carried out to determine the response of mouse lung to repeated small doses of 240 kV X rays down to 150 rad/fraction using breathing rate and lethality to assess damage. Two experimental approaches were used to measure the effect of small doses in vivo: (1) multiple equal doses and (2) multiple priming doses followed by a large test dose. Analysis was performed using the multitarget two-component model and the linear test dose. The amount of repair was calculated as a function of either dose per fraction (F/sub R/) or total dose (F/sub rec/). Both F/sub R/ and F/sub rec/ increased with decreasing dose per fraction but the change in F/sub R/ was small. The advantage of F/sub rec/ was that it varied more rapidly with dose per fraction than F/sub R/, so that possible differences between tissue repair capabilities are more visible on plots of repair as a function of dose per fraction. F/sub R/ and F/sub rec/ both decreased with the level of single-dose isoeffect injury; thus neither parameter is acceptable for comparing repair capability of different normal tissues with widely differing single-dose end point levels. Beta/alpha values were calculated and found to be a more acceptable index of repair capability than either F/sub R/ or F/sub rec/ because unlike those two parameters, ..beta../..cap alpha.. varied little with level of damage. Beta/alpha values of 1.7 to 4.2 krad/sup -1/ were obtained for both lung death and increased breathing rate and are clearly intermediate between the lower ..beta../..cap alpha.. ratios for acute reactions, i.e., skin and intestine, and the higher values for late reactions in kidney and spinal cord.

  1. Helical tomotherapy superficial dose measurements

    SciTech Connect

    Ramsey, Chester R.; Seibert, Rebecca M.; Robison, Benjamin; Mitchell, Martha

    2007-08-15

    Helical tomotherapy is a treatment technique that is delivered from a 6 MV fan beam that traces a helical path while the couch moves linearly into the bore. In order to increase the treatment delivery dose rate, helical tomotherapy systems do not have a flattening filter. As such, the dose distributions near the surface of the patient may be considerably different from other forms of intensity-modulated delivery. The purpose of this study was to measure the dose distributions near the surface for helical tomotherapy plans with a varying separation between the target volume and the surface of an anthropomorphic phantom. A hypothetical planning target volume (PTV) was defined on an anthropomorphic head phantom to simulate a 2.0 Gy per fraction IMRT parotid-sparing head and neck treatment of the upper neck nodes. A total of six target volumes were created with 0, 1, 2, 3, 4, and 5 mm of separation between the surface of the phantom and the outer edge of the PTV. Superficial doses were measured for each of the treatment deliveries using film placed in the head phantom and thermoluminescent dosimeters (TLDs) placed on the phantom's surface underneath an immobilization mask. In the 0 mm test case where the PTV extends to the phantom surface, the mean TLD dose was 1.73{+-}0.10 Gy (or 86.6{+-}5.1% of the prescribed dose). The measured superficial dose decreases to 1.23{+-}0.10 Gy (61.5{+-}5.1% of the prescribed dose) for a PTV-surface separation of 5 mm. The doses measured by the TLDs indicated that the tomotherapy treatment planning system overestimates superficial doses by 8.9{+-}3.2%. The radiographic film dose for the 0 mm test case was 1.73{+-}0.07 Gy, as compared to the calculated dose of 1.78{+-}0.05 Gy. Given the results of the TLD and film measurements, the superficial calculated doses are overestimated between 3% and 13%. Without the use of bolus, tumor volumes that extend to the surface may be underdosed. As such, it is recommended that bolus be added for these

  2. SU-F-BRF-12: Investigating Dosimetric Effects of Inter-Fraction Deformation in Lung Cancer Stereotactic Body Radiotherapy (SBRT)

    SciTech Connect

    Jia, J; Tian, Z; Gu, X; Yan, H; Jia, X; Jiang, S

    2014-06-15

    Purpose: We studied dosimetric effects of inter-fraction deformation in lung stereotactic body radiotherapy (SBRT), in order to investigate the necessity of adaptive re-planning for lung SBRT treatments. Methods: Six lung cancer patients with different treatment fractions were retrospectively investigated. All the patients were immobilized and localized with a stereotactic body frame and were treated under cone-beam CT (CBCT) image guidance at each fraction. We calculated the actual delivered dose of the treatment plan using the up-to-date patient geometry of each fraction, and compared the dose with the intended plan dose to investigate the dosimetric effects of the inter-fraction deformation. Deformable registration was carried out between the treatment planning CT and the CBCT of each fraction to obtain deformed planning CT for more accurate dose calculations of the delivered dose. The extent of the inter-fraction deformation was also evaluated by calculating the dice similarity coefficient between the delineated structures on the planning CT and those on the deformed planning CT. Results: The average dice coefficients for PTV, spinal cord, esophagus were 0.87, 0.83 and 0.69, respectively. The volume of PTV covered by prescription dose was decreased by 23.78% on average for all fractions and all patients. For spinal cord and esophagus, the volumes covered by the constraint dose were increased by 4.57% and 3.83%. The maximum dose was also increased by 4.11% for spinal cord and 4.29% for esophagus. Conclusion: Due to inter-fraction deformation, large deterioration was found in both PTV coverage and OAR sparing, which demonstrated the needs for adaptive re-planning of lung SBRT cases to improve target coverage while reducing radiation dose to nearby normal tissues.

  3. Stereotactic Body Radiotherapy for Primary Lung Cancer at a Dose of 50 Gy Total in Five Fractions to the Periphery of the Planning Target Volume Calculated Using a Superposition Algorithm

    SciTech Connect

    Takeda, Atsuya; Sanuki, Naoko; Kunieda, Etsuo Ohashi, Toshio; Oku, Yohei; Takeda, Toshiaki; Shigematsu, Naoyuki; Kubo, Atsushi

    2009-02-01

    Purpose: To retrospectively analyze the clinical outcomes of stereotactic body radiotherapy (SBRT) for patients with Stages 1A and 1B non-small-cell lung cancer. Methods and Materials: We reviewed the records of patients with non-small-cell lung cancer treated with curative intent between Dec 2001 and May 2007. All patients had histopathologically or cytologically confirmed disease, increased levels of tumor markers, and/or positive findings on fluorodeoxyglucose positron emission tomography. Staging studies identified their disease as Stage 1A or 1B. Performance status was 2 or less according to World Health Organization guidelines in all cases. The prescribed dose of 50 Gy total in five fractions, calculated by using a superposition algorithm, was defined for the periphery of the planning target volume. Results: One hundred twenty-one patients underwent SBRT during the study period, and 63 were eligible for this analysis. Thirty-eight patients had Stage 1A (T1N0M0) and 25 had Stage 1B (T2N0M0). Forty-nine patients were not appropriate candidates for surgery because of chronic pulmonary disease. Median follow-up of these 49 patients was 31 months (range, 10-72 months). The 3-year local control, disease-free, and overall survival rates in patients with Stages 1A and 1B were 93% and 96% (p = 0.86), 76% and 77% (p = 0.83), and 90% and 63% (p = 0.09), respectively. No acute toxicity was observed. Grade 2 or higher radiation pneumonitis was experienced by 3 patients, and 1 of them had fatal bacterial pneumonia. Conclusions: The SBRT at 50 Gy total in five fractions to the periphery of the planning target volume calculated by using a superposition algorithm is feasible. High local control rates were achieved for both T2 and T1 tumors.

  4. Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer

    PubMed Central

    Warner, Andrew; Pickles, Tom; Crook, Juanita; Martin, Andre-Guy; Souhami, Luis; Catton, Charles; Lukka, Himu

    2015-01-01

    Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II “Phoenix” definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database. Methods and Materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy  (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates. Results: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT. Conclusions: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and

  5. Fraction Reduction through Continued Fractions

    ERIC Educational Resources Information Center

    Carley, Holly

    2011-01-01

    This article presents a method of reducing fractions without factoring. The ideas presented may be useful as a project for motivated students in an undergraduate number theory course. The discussion is related to the Euclidean Algorithm and its variations may lead to projects or early examples involving efficiency of an algorithm.

  6. Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer.

    PubMed

    Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

    2016-01-01

    To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D90 of 34Gy in 8.5Gy per fraction, and 145Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2Gy per fraction, EQD2) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The Dmean (EQD2) of rectum decreased 22.36Gy in HDR and 17.01Gy in LDR from 30.24Gy in VMAT, respectively. The Dmean (EQD2) of bladder decreased 6.91Gy in HDR and 2.53Gy in LDR from 13.46Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD2) was 80.26, 70.23, and 104.91Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR.

  7. Studies on the immunomodulatory activity of flavonoidal fraction of Tephrosia purpurea.

    PubMed

    Damre, A S; Gokhale, A B; Phadke, A S; Kulkarni, K R; Saraf, M N

    2003-04-01

    The flavonoid fraction of Tephrosia purpurea (FFTP) was studied for its effect on cellular and humoral functions and on macrophage phagocytosis in mice. Oral administration of FFTP (10-40 mg/kg) significantly inhibited sheep red blood cells (SRBC)-induced delayed-type hypersensitivity reactions. It also produced a significant, dose-related decrease in sheep erythrocyte-specific haemagglutination antibody titre. However, the fraction failed to show a significant change in the macrophage phagocytic activity. The results obtained indicate the ability of the flavonoidal fraction of T. purpurea to modulate both the cell-mediated and the humoral components of the immune system.

  8. Synchronized dynamic dose reconstruction

    SciTech Connect

    Litzenberg, Dale W.; Hadley, Scott W.; Tyagi, Neelam; Balter, James M.; Ten Haken, Randall K.; Chetty, Indrin J.

    2007-01-15

    Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined.

  9. Maximizing Tumor Immunity With Fractionated Radiation

    SciTech Connect

    Schaue, Doerthe; Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H.

    2012-07-15

    Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-{gamma} enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4{sup +}CD25{sup hi}Foxp3{sup +} T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.

  10. Brush border intestinal enzymes after multiple daily fractionation

    SciTech Connect

    Becciolini, A.; Giache, V.; Balzi, M.; Morrone, A.

    1987-03-01

    The modifications in brush border enzyme activity of the epithelial cell of the small intestine were studied after multiple daily fractionation (MDF) of 3 Gy X and 3 Gy X 2 X 2 (12 h split). Disaccharase and dipeptidase activities changed in the same way after irradiation. The results show that both total doses caused the three known phases of increase, decrease, and a return to normal. With MDF, activity at the end of irradiation was similar to or greater than that of controls and remained higher longer than a single dose of 8 Gy. However, the return to normal occurred sooner than after a single dose of 8 Gy. After 11 days, circadian oscillations of brush border enzyme activity appeared similar to those of controls in many segments of the intestine, reaching the highest activity during the night and the lowest in the afternoon.

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  12. soil organic matter fractionation

    NASA Astrophysics Data System (ADS)

    Osat, Maryam; Heidari, Ahmad

    2010-05-01

    studies were carried out to illustrate the relationship between clay mineral series and organic matter. According to the results the amount of organic carbon increases by decreasing size fractions and reaches to its maximum in <250μ classes, also 2:1 and expanding clays which have the ability to maintain larger amounts of organic carbon were the dominant clay minerals. Chemical fractionation of soil organic matter to humic acid and fulvic acid shows that there is a better correlation between humic acid contents and soil organic matter (R2 = 0.86) than fulvic acid and organic matter (R2=0.5). The amount of humic and fulvic acids varies in different size fractions and reaches to its minimum in the E fraction in all three stages. The relationships between fulvic and humic acids with organic matter content, demonstrating that at the lower organic matter content, humification is slow, thus humic acid content is rather low than the fulvic acid content. By increasing the organic matter content biological activity increases and followed by humification process proceeds so that the humic acid content locates over the fulvic acid content.

  13. Radiation Dose-Volume Effects of Optic Nerves and Chiasm

    SciTech Connect

    Mayo, Charles; Martel, Mary K.; Marks, Lawrence B.; Flickinger, John; Nam, Jiho; Kirkpatrick, John

    2010-03-01

    Publications relating radiation toxicity of the optic nerves and chiasm to quantitative dose and dose-volume measures were reviewed. Few studies have adequate data for dose-volume outcome modeling. The risk of toxicity increased markedly at doses >60 Gy at {approx}1.8 Gy/fraction and at >12 Gy for single-fraction radiosurgery. The evidence is strong that radiation tolerance is increased with a reduction in the dose per fraction. Models of threshold tolerance were examined.

  14. Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

    PubMed Central

    HARRIS, SIMON J.; WILCE, PETER; BEDI, KULDIP S.

    2000-01-01

    Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4–9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged ∼ 171 mg/dl and in the ETHD animals ∼ 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection of ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of ∼ 145000–165000 axons in MRC, SC and ETLD animals. About 4% of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axons (P < 0.05) of which about 2.8% were myelinated. By 30 d of age there was a total of between 75000–90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (∼ 77%) than in the other groups (about 98%). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9. PMID:11117631

  15. Radiobiology of hypofractionated stereotactic radiotherapy: what are the optimal fractionation schedules?

    PubMed Central

    Shibamoto, Yuta; Miyakawa, Akifumi; Otsuka, Shinya; Iwata, Hiromitsu

    2016-01-01

    In hypofractionated stereotactic radiotherapy (SRT), high doses per fraction are usually used and the dose delivery pattern is different from that of conventional radiation. The daily dose is usually given intermittently over a longer time compared with conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. In in vivo tumors, however, this decrease in effect may be counterbalanced by rapid reoxygenation. Another issue related to hypofractionated SRT is the mathematical model for dose evaluation and conversion. The linear–quadratic (LQ) model and biologically effective dose (BED) have been suggested to be incorrect when used for hypofractionation. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when used for tumor responses in vivo, since it does not take reoxygenation into account. Correction of the errors, estimated at 5–20%, associated with the use of BED is necessary when it is used for SRT. High fractional doses have been reported to exhibit effects against tumor vasculature and enhance host immunity, leading to increased antitumor effects. This may be an interesting topic that should be further investigated. Radioresistance of hypoxic tumor cells is more problematic in hypofractionated SRT, so trials of hypoxia-targeted agents are encouraged in the future. In this review, the radiobiological characteristics of hypofractionated SRT are summarized, and based on the considerations, we would like to recommend 60 Gy in eight fractions delivered three times a week for lung tumors larger than 2 cm in diameter. PMID:27006380

  16. [High dose rate brachytherapy].

    PubMed

    Aisen, S; Carvalho, H A; Chavantes, M C; Esteves, S C; Haddad, C M; Permonian, A C; Taier, M do C; Marinheiro, R C; Feriancic, C V

    1992-01-01

    The high dose rate brachytherapy uses a single source os 192Ir with 10Ci of nominal activity in a remote afterloading machine. This technique allows an outpatient treatment, without the inconveniences of the conventional low dose rate brachytherapy such as use of general anesthesia, rhachianesthesia, prolonged immobilization, and personal exposition to radiation. The radiotherapy department is now studying 5 basic treatment schemes concerning carcinomas of the uterine cervix, endometrium, lung, esophagus and central nervous system tumors. With the Micro Selectron HDR, 257 treatment sessions were done in 90 patients. Mostly were treated with weekly fractions, receiving a total of three to four treatments each. No complications were observed neither during nor after the procedure. Doses, fraction and ideal associations still have to be studied, so that a higher therapeutic ratio can be reached.

  17. Evaluation of the antipsychotic potential of aqueous fraction of Securinega virosa root bark extract in mice.

    PubMed

    Magaji, M G; Mohammed, M; Magaji, R A; Musa, A M; Abdu-Aguye, I; Hussaini, I M

    2014-03-01

    Securinega virosa (Roxb ex. Willd) Baill. is a plant which is commonly used in African traditional medicine in management of mental illness. Previous study showed that the crude methanolic root bark extract of the plant possesses antipsychotic activity. In this study, the antipsychotic potential of the residual aqueous fraction of the plant was evaluated using two experimental models, apomorphine induced stereotypic climbing behaviour and swim induced grooming, all in mice. The effect of the fraction on haloperidol-induced catalepsy was also evaluated. The fraction significantly reduced the mean climbing score at the highest dose tested (500 mg/kg). In the swim-induced grooming test, the fraction significantly and dose-dependently (125-500 mg/kg) decreased the mean number and mean duration of swim-induced grooming activity in mice. Similarly, the standard haloperidol (1 mg/kg) significantly (p < 0.001) decreased the mean grooming episodes and duration. However, the fraction did not significantly potentiate haloperidol-induced catalepsy. These results suggest that the residual aqueous fraction of methanol root bark extract of Securinega virosa contains biological active principle with antipsychotic potential.

  18. [Fractionated P-bilirubins].

    PubMed

    Schou, C S; Mortensen, H

    1989-08-14

    A diazo-based dry film technique for the estimation of different bilirubins in plasma is now available. This procedure separates bilirubins from icteric sera into three separate fractions: bilirubin (unconjugated), bilirubin-glucuronides (mono + diglucuronide) and bilirubin-albumin. In newborns with prolonged jaundice classification of hyperbilirubinemia is of importance for choice of treatment. While binding of bilirubin and bilirubin-glucuronides to albumin is non covalent, reversible, bilirubin-albumin appears to be firmly associated with albumin by covalent bonds. This causes delayed clearance of this bilirubin fraction from plasma as the half-life of albumin is approximately 18 days. Hence the substance concentration of bilirubin-albumin will decrease at a slower rate than will bilirubin and bilirubin-glucuronide, despite hepatobiliary recovery. Bilirubin-albumin may therefore prove of value in the differentiation between different clinical entities with hyperbilirubinemia. PMID:2773134

  19. Peripheral doses from pediatric IMRT

    SciTech Connect

    Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David

    2006-07-15

    Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 to 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged

  20. The Radiation Dose-Response of the Human Spinal Cord

    SciTech Connect

    Schultheiss, Timothy E.

    2008-08-01

    Purpose: To characterize the radiation dose-response of the human spinal cord. Methods and Materials: Because no single institution has sufficient data to establish a dose-response function for the human spinal cord, published reports were combined. Requisite data were dose and fractionation, number of patients at risk, number of myelopathy cases, and survival experience of the population. Eight data points for cervical myelopathy were obtained from five reports. Using maximum likelihood estimation correcting for the survival experience of the population, estimates were obtained for the median tolerance dose, slope parameter, and {alpha}/{beta} ratio in a logistic dose-response function. An adequate fit to thoracic data was not possible. Hyperbaric oxygen treatments involving the cervical cord were also analyzed. Results: The estimate of the median tolerance dose (cervical cord) was 69.4 Gy (95% confidence interval, 66.4-72.6). The {alpha}/{beta} = 0.87 Gy. At 45 Gy, the (extrapolated) probability of myelopathy is 0.03%; and at 50 Gy, 0.2%. The dose for a 5% myelopathy rate is 59.3 Gy. Graphical analysis indicates that the sensitivity of the thoracic cord is less than that of the cervical cord. There appears to be a sensitizing effect from hyperbaric oxygen treatment. Conclusions: The estimate of {alpha}/{beta} is smaller than usually quoted, but values this small were found in some studies. Using {alpha}/{beta} = 0.87 Gy, one would expect a considerable advantage by decreasing the dose/fraction to less than 2 Gy. These results were obtained from only single fractions/day and should not be applied uncritically to hyperfractionation.

  1. Commercial SNF Accident Release Fractions

    SciTech Connect

    J. Schulz

    2004-11-05

    The purpose of this analysis is to specify and document the total and respirable fractions for radioactive materials that could be potentially released from an accident at the repository involving commercial spent nuclear fuel (SNF) in a dry environment. The total and respirable release fractions are used to support the preclosure licensing basis for the repository. The total release fraction is defined as the fraction of total commercial SNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. Radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses; this subset of the total release fraction is referred to as the respirable release fraction. Accidents may involve waste forms characterized as: (1) bare unconfined intact fuel assemblies, (2) confined intact fuel assemblies, or (3) canistered failed commercial SNF. Confined intact commercial SNF assemblies at the repository are contained in shipping casks, canisters, or waste packages. Four categories of failed commercial SNF are identified: (1) mechanically and cladding-penetration damaged commercial SNF, (2) consolidated/reconstituted assemblies, (3) fuel rods, pieces, and debris, and (4) nonfuel components. It is assumed that failed commercial SNF is placed into waste packages with a mesh screen at each end (CRWMS M&O 1999). In contrast to bare unconfined fuel assemblies, the

  2. Biological doses with template distribution patterns

    SciTech Connect

    Harrop, R.; Haymond, H.R.; Nisar, A.; Syed, A.N.M.; Feder, B.H.; Neblett, D.L.

    1981-02-01

    Consideration of radiation dose rate effects emphasizes advantages of the template method for lateral distribution of multiple sources in treatment of laterally infiltrating gynecologic cancer, when compared to a conventional technique with colpostats. Biological doses in time dose fractionation (TDF), ret and reu units are calculated for the two treatment methods. With the template method the lateral dose (point B) is raised without significantly increasing the doses to the rectum and bladder, that is, relatively, the calculated biological doses at point A and B are more nearly equivalent and the doses to the rectum and bladder are significantly lower than the dose to point B.

  3. Rigidity spectrum of Forbush decrease

    NASA Technical Reports Server (NTRS)

    Sakakibara, S.; Munakata, K.; Nagashima, K.

    1985-01-01

    Using data from neutron monitors and muon telescopes at surface and underground stations, the average rigidity spectrum of Forbush decreases (Fds) during the period of 1978-1982 were obtained. Thirty eight Ed-events are classified into two groups Hard Fd and Soft Fd according to size of Fd at Sakashita station. It is found that a spectral form of fractional-power type (P to the-gamma sub 1 (P+P sub c) to the -gamma sub2) is more suitable for the present purpose than that of power-exponential type or of power type with an upper limiting rigidity. The best fitted spectrum of fractional-power type is expressed by gamma sub1 = 0.37, gamma sub2 = 0.89 and P subc = 10 GV for Hard Fd and gamma sub1 = 0.77, gamma sub2 = 1.02 and P sub c - 14GV for Soft Fd.

  4. [The effectiveness of fractionated exposure of sarcoma M-1 to gamma-radiation and fast neutrons].

    PubMed

    Iuzhakov, V V; Sevan'kaeva, L E; Ul'ianenko, S E; Iakovleva, N D; Kuznetsova, M N; Tsyganova, M G; Fomina, N K; Ingel', I E; Lychagin, A A

    2013-01-01

    The effectiveness of fractionated exposure to gamma- and neutron radiation in their separate and combined use on the growth and functional morphology of mutant p53 sarcoma M-1 in rats was studied. Investigation techniques included immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic activity and apoptotic death of tumor cells, as well as computer analysis of microscopic images. The antitumor efficacy of different types of radiation is shown to be determined by different levels of apoptosis induction, reduced proliferation and cellularity. Neutron radiation of the impulse generator has a marked damaging effect on the vasculature and the development of tumor necrosis. Fractionated irradiation at equal daily doses led to the decrease in the relative effectiveness of radio-inactivation of tumor cells. After 9 fractions of irradiation, the calculated value of the RBE of fast neutrons normalized to the input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7 and 3.1, respectively. In the mode of daily superfractionation with splitting the dose in two fractions, the effectiveness of the combined exposure corresponded to the additive effect of gamma- and neutron radiation with a tendency toward synergism. There are reasons to believe that high resistance of sarcoma M-1 to the ionizing radiation impact is due not only to a fraction of hypoxic cells, but also the mutant status of p53 gene.

  5. Effects of split-dose X irradiation on rat salivary gland function

    SciTech Connect

    Vissink, A.; s-Gravenmade, E.J.; Ligeon, E.E.; Konings, A.W. )

    1991-07-01

    The effect of a single local dose of 15 Gy on salivary gland function in male Albino Wistar rats was compared with the effect of two doses of 7.5 Gy. The intervals chosen were 0-24 h and 1 week. Before and 1-30 days after the last radiation dose, samples of parotid and submandibular saliva were collected simultaneously after stimulation of the glands with pilocarpine. Irradiation with the single dose resulted in an increased lag phase and potassium concentration, and a decreased flow rate and sodium concentration. The rate of secretion of amylase was decreased during Days 1-6, increased at Day 10, and was decreased again at Day 30. With two dose fractions, substantial dose-sparing effects on lag phase, flow rate, and secretion of amylase were observed for both the very early (0-6 days postirradiation) and later (6-30 days postirradiation) effects. These effects were maximal when the interval between the fractions was 6 h. A significant dose-sparing effect on electrolytes was observed for the later effects only, again with a maximum for the 6-h interval. The dose-sparing observed for the very early effects cannot be explained satisfactorily by repair of sublethal damage (SLD), redistribution of cells over the cell cycle, or repopulation of salivary gland tissue between the doses. In contrast to the earlier dose-sparing effects, the split-dose recovery seen for later damage may be attributed, in part, to SLD repair in providing for greater reproductive survival of intercalated ductal cells and enhanced tissue regeneration.

  6. Hypofractionation Results in Reduced Tumor Cell Kill Compared to Conventional Fractionation for Tumors With Regions of Hypoxia

    SciTech Connect

    Carlson, David J.; Keall, Paul J.; Loo, Billy W.; Chen, Zhe J.; Brown, J. Martin

    2011-03-15

    Purpose: Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation. Methods and Materials: A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions. Results: Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10{sup 5} over a distance of 130 {mu}m. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of {approx}10{sup 3} as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively. Conclusions: Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia.

  7. Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

    NASA Astrophysics Data System (ADS)

    Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

    Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for γ-radiation. When total doses of 96 or 247 cGy of neutrons or γ rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and γ-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or γ rays, a significant age- and radiation-related deficiency

  8. Filling the gap in central shielding: three-dimensional analysis of the EQD2 dose in radiotherapy for cervical cancer with the central shielding technique

    PubMed Central

    Tamaki, Tomoaki; Ohno, Tatsuya; Noda, Shin-ei; Kato, Shingo; Nakano, Takashi

    2015-01-01

    This study aimed to provide accurate dose distribution profiles of radiotherapy for cervical cancer when treated with the central shielding technique by analysing the composite 3D EQD2 dose distribution of external beam radiotherapy (EBRT) plus intracavitary brachytherapy (ICBT). On a phantom, four patterns of the combinations of whole pelvis irradiation (WP) (4 fields), pelvis irradiation with central shielding technique (CS) [anterior–posterior/posterior–anterior (AP-PA fields), shielding width of 3 or 4 cm] and ICBT using Point-A prescription were created: 30 Gy/15 fractions + 20 Gy/10 fractions + 24 Gy/4 fractions [Plan (30 + 20 + 24)], 40 Gy/20 fractions + 10 Gy/5 fractions + 18 Gy/3 fractions [Plan (40 + 10 + 18)], 40 Gy/20 fractions + 10 Gy/5 fractions + 24 Gy/4 fractions [Plan (40 + 10 + 24)] and 45 Gy/25 fractions + 0 Gy + 28 Gy/4 fractions [Plan (45 + 0 + 28)]. The composite EQD2 dose distributions of the complete treatment were analysed. The Point-A dose of Plan (30 + 20 + 24), Plan (40 + 10 + 18), Plan (40 + 10 + 24) and Plan (45 + 0 + 28) were 78.0 Gy (CS 3 cm)/71.8 Gy (CS 4 cm), 72.1 Gy (CS 3 cm)/69.0 Gy (CS 4 cm), 80.1 Gy (CS 3 cm)/77.0 Gy (CS 4 cm) and 84.1 Gy, whereas it has been previously reported to be 62 Gy, 64 Gy, 72 Gy and 84 Gy, respectively. For all the treatment plans with CS, equivalent or wider coverage of 60 Gy (EQD2) was achieved in the right–left direction, while coverage in the anterior–posterior direction decreased in plans with CS. There were no irregularly ‘cold’ regions around the central target. The use of CS in radiotherapy for cervical cancer resulted in tumor coverage in the lateral direction with doses higher than the previously reported Point-A doses. PMID:26062811

  9. Evaluation of nonrigid registration models for interfraction dose accumulation in radiotherapy

    SciTech Connect

    Janssens, Guillaume; Orban de Xivry, Jonathan; Fekkes, Stein; Dekker, Andre; Macq, Benoit; Lambin, Philippe; Elmpt, Wouter van

    2009-09-15

    Purpose: Interfraction dose accumulation is necessary to evaluate the dose distribution of an entire course of treatment by adding up multiple dose distributions of different treatment fractions. This accumulation of dose distributions is not straightforward as changes in the patient anatomy may occur during treatment. For this purpose, the accuracy of nonrigid registration methods is assessed for dose accumulation based on the calculated deformations fields. Methods: A phantom study using a deformable cubic silicon phantom with implanted markers and a cylindrical silicon phantom with MOSFET detectors has been performed. The phantoms were deformed and images were acquired using a cone-beam CT imager. Dose calculations were performed on these CT scans using the treatment planning system. Nonrigid CT-based registration was performed using two different methods, the Morphons and Demons. The resulting deformation field was applied on the dose distribution. For both phantoms, accuracy of the registered dose distribution was assessed. For the cylindrical phantom, also measured dose values in the deformed conditions were compared with the dose values of the registered dose distributions. Finally, interfraction dose accumulation for two treatment fractions of a patient with primary rectal cancer has been performed and evaluated using isodose lines and the dose volume histograms of the target volume and normal tissue. Results: A significant decrease in the difference in marker or MOSFET position was observed after nonrigid registration methods (p<0.001) for both phantoms and with both methods, as well as a significant decrease in the dose estimation error (p<0.01 for the cubic phantom and p<0.001 for the cylindrical) with both methods. Considering the whole data set at once, the difference between estimated and measured doses was also significantly decreased using registration (p<0.001 for both methods). The patient case showed a slightly underdosed planning target volume

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  11. Effect of acute and fractionated irradiation on hippocampal neurogenesis.

    PubMed

    Park, Min-Kyoung; Kim, Seolhwa; Jung, Uhee; Kim, Insub; Kim, Jin Kyu; Roh, Changhyun

    2012-08-08

    Ionizing radiation has become an inevitable health concern emanating from natural sources like space travel and from artificial sources like medical therapies. In general, exposure to ionizing radiation such as γ-rays is one of the methods currently used to stress specific model systems. In this study, we elucidated the long-term effect of acute and fractionated irradiation on DCX-positive cells in hippocampal neurogenesis. Groups of two-month-old C57BL/6 female mice were exposed to whole-body irradiation at acute dose (5 Gy) or fractional doses (1 Gy × 5 times and 0.5 Gy × 10 times). Six months after exposure to γ-irradiation, the hippocampus was analyzed. Doublecortin (DCX) immunohistochemistry was used to measure changes of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). The number of DCX-positive cells was significantly decreased in all acute and fractionally irradiation groups. The long-term changes in DCX-positive cells triggered by radiation exposure showed a very different pattern to the short-term changes which tended to return to the control level in previous studies. Furthermore, the number of DCX-positive cells was relatively lower in the acute irradiation group than the fractional irradiation groups (approximately 3.6-fold), suggesting the biological change on hippocampal neurogenesis was more susceptible to being damaged by acute than fractional irradiation. These results suggest that the exposure to γ-irradiation as a long-term effect can trigger biological responses resulting in the inhibition of hippocampal neurogenesis.

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

    SciTech Connect

    Viel, Francis; Duzenli, Cheryl; Camborde, Marie-Laure; Strgar, Vincent; Horwood, Ron; Atwal, Parmveer; Gete, Ermias; Karan, Tania

    2014-08-15

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

  13. Exploratory Study of the Prognostic Value of Microenvironmental Parameters During Fractionated Irradiation in Human Squamous Cell Carcinoma Xenografts

    SciTech Connect

    Yaromina, Ala; Kroeber, Theresa; Meinzer, Andreas; Boeke, Simon; Thames, Howard; Baumann, Michael; Zips, Daniel

    2011-07-15

    Purpose: To explore the prognostic value of microenvironmental parameters for local tumor control determined before and during fractionated irradiation. Methods and Materials: Six human squamous cell carcinoma (hSCC) lines were transplanted subcutaneously into the right hind leg of nude mice. Tumors were irradiated with 30 fractions within 6 weeks. Local tumor control was determined 120 days after irradiation. Radiation response was quantified as dose to cure 50% of tumors (TCD{sub 50}). In parallel, untreated and irradiated tumors were excised after injection of pimonidazole (hypoxia marker) and Hoechst 33342 (perfusion marker) for histological evaluation. Results: Pimonidazole hypoxia decreased during fractionated irradiation in the majority of tumor lines. Fraction of perfused vessels and vascular area showed modest changes during fractionated irradiation. Histological parameters before treatment and after three and five fractions did not significantly correlate with TCD{sub 50} after irradiation with 30 fractions within 6 weeks (p > 0.05). Hypoxic volume and perfused vessels after 10 fractions showed a significant association with local tumor control after fractionated irradiation (p = 0.018 and p = 0.019, respectively). None of these parameters remained statistically significant when the p value was adjusted for multiple comparisons. Conclusions: The results from this exploratory study suggest that determination of microenvironmental parameters during treatment provides better prognostic information for the outcome after fractionated radiotherapy than pretreatment parameters, which warrants further investigation and confirmation in experimental and clinical studies.

  14. Matrix fractional systems

    NASA Astrophysics Data System (ADS)

    Tenreiro Machado, J. A.

    2015-08-01

    This paper addresses the matrix representation of dynamical systems in the perspective of fractional calculus. Fractional elements and fractional systems are interpreted under the light of the classical Cole-Cole, Davidson-Cole, and Havriliak-Negami heuristic models. Numerical simulations for an electrical circuit enlighten the results for matrix based models and high fractional orders. The conclusions clarify the distinction between fractional elements and fractional systems.

  15. Characteristics of dose-response relationships for late radiation effects: an analysis of skin telangiectasia and of head and neck morbidity.

    PubMed

    Turesson, I

    1991-03-01

    The dose-response characteristics were analysed for late skin telangiectasia in patients for 1, 2 and 5 fractions per week and 3 to 4 dose levels per schedule. Altogether 286 fields were used. Skin telangiectasia was scored on an arbitrary scale and dose-response analysis was performed at 10 year's follow-up for various degrees of telangiectasia, score greater than or equal to 1 to greater than or equal to 4. The following parameters were determined for each schedule and the equivalent single dose-response curves for each endpoint using probit analysis: the ED50, the absolute steepness, measured as the probit width, K, the relative steepness, K/ED50, and the normalised effect gradient, gamma 50. The inverse radiosensitivity, Doeff or Do, was estimated using the Poisson and LQ-models for tissue response. The alpha/beta value was found to be independent of the degree of telangiectasia used as endpoint. The absolute steepness of the dose-incidence curve increased with increasing dose per fraction and was correlated to the degree of damage. The relative steepness was independent of the dose per fraction when the dose-response curve was generated by a fixed dose per fraction, and was less than if generated by a fixed number of fractions. The relative steepness increased with higher degree of damage. Doeff decreased with increasing dose per fraction, and also with higher degree of telangiectasia. The highest steepness determined for telangiectasia score greater than or equal to 4 (partially confluent or more) at 10 years corresponded to K = 0.8 Gy, K/ED50 = 5%, gamma 50 = 7 and Do = 0.7 Gy. The dose-response characteristics found for late skin telangiectasia score greater than or equal to 2 to greater than or equal to 4 were consistent with those determined for necrosis and fatal complications 5 years after radiotherapy to head and neck tumours in our department.

  16. Actual Dose Variation of Parotid Glands and Spinal Cord for Nasopharyngeal Cancer Patients During Radiotherapy

    SciTech Connect

    Han Chunhui Chen Yijen; Liu An; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

    2008-03-15

    Purpose: For intensity-modulated radiotherapy of nasopharyngeal cancer, accurate dose delivery is crucial to the success of treatment. This study aimed to evaluate the significance of daily image-guided patient setup corrections and to quantify the parotid gland volume and dose variations for nasopharyngeal cancer patients using helical tomotherapy megavoltage computed tomography (CT). Methods and Materials: Five nasopharyngeal cancer patients who underwent helical tomotherapy were selected retrospectively. Each patient had received 70 Gy in 35 fractions. Daily megavoltage CT scans were registered with the planning CT images to correct the patient setup errors. Contours of the spinal cord and parotid glands were drawn on the megavoltage CT images at fixed treatment intervals. The actual doses delivered to the critical structures were calculated using the helical tomotherapy Planned Adaptive application. Results: The maximal dose to the spinal cord showed a significant increase and greater variation without daily setup corrections. The significant decrease in the parotid gland volume led to a greater median dose in the later phase of treatment. The average parotid gland volume had decreased from 20.5 to 13.2 cm{sup 3} by the end of treatment. On average, the median dose to the parotid glands was 83 cGy and 145 cGy for the first and the last treatment fractions, respectively. Conclusions: Daily image-guided setup corrections can eliminate significant dose variations to critical structures. Constant monitoring of patient anatomic changes and selective replanning should be used during radiotherapy to avoid critical structure complications.

  17. SU-E-J-181: Effect of Prostate Motion On Combined Brachytherapy and External Beam Dose Based On Daily Motion of the Prostate

    SciTech Connect

    Narayana, V; McLaughlin, P; Ealbaj, J

    2015-06-15

    Purpose: In this study, the adequacy of target expansions on the combined external beam and implant dose was examined based on the measured daily motion of the prostate. Methods: Thirty patients received an I–125 prostate implant prescribed to dose of 90Gy. This was followed by external beam to deliver a dose of 90Gyeq (external beam equivalent) to the prostate over 25 to 30 fractions. An ideal IMRT plan was developed by optimizing the external beam dose based on the delivered implant dose. The implant dose was converted to an equivalent external beam dose using the linear quadratic model. Patients were set up on the treatment table by daily orthogonal imaging and aligning the marker seeds in the prostate. Orthogonal images were obtained at the end of treatment to assess prostate intrafraction motion. Based on the observed motion of the markers between the initial and final images, 5 individual plans showing the actual dose delivered to the patient were calculated. A final true dose distribution was established based on summing the implant dose and the 5 external beam plans. Dose to the prostate, seminal vesicles, lymphnodes and normal tissues, rectal wall, urethra and lower sphincter were calculated and compared to ideal. On 18 patients who were sexually active, dose to the corpus cavernosum and internal pudendal artery was also calculated. Results: The average prostate motion in 3 orthogonal directions was less than 1 mm with a standard deviation of less than +2 mm. Dose and volume parameters showed that there was no decrease in dose to the targets and a marginal decrease in dose to in normal tissues. Conclusion: Dose delivered by seed implant moves with the prostate, decreasing the impact of intrafractions dose movement on actual dose delivered. Combined brachytherapy and external beam dose delivered to the prostate was not sensitive to prostate motion.

  18. Calcium kinetics with microgram stable isotope doses and saliva sampling

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Wastney, M. E.; Nyquist, L. E.; Shih, C. Y.; Wiesmann, H.; Nillen, J. L.; Lane, H. W.

    1996-01-01

    Studies of calcium kinetics require administration of tracer doses of calcium and subsequent repeated sampling of biological fluids. This study was designed to develop techniques that would allow estimation of calcium kinetics by using small (micrograms) doses of isotopes instead of the more common large (mg) doses to minimize tracer perturbation of the system and reduce cost, and to explore the use of saliva sampling as an alternative to blood sampling. Subjects received an oral dose (133 micrograms) of 43Ca and an i.v. dose (7.7 micrograms) of 46Ca. Isotopic enrichment in blood, urine, saliva and feces was well above thermal ionization mass spectrometry measurement precision up to 170 h after dosing. Fractional calcium absorptions determined from isotopic ratios in blood, urine and saliva were similar. Compartmental modeling revealed that kinetic parameters determined from serum or saliva data were similar, decreasing the necessity for blood samples. It is concluded from these results that calcium kinetics can be assessed with micrograms doses of stable isotopes, thereby reducing tracer costs and with saliva samples, thereby reducing the amount of blood needed.

  19. Metals in air pollution particles decrease whole-blood coagulation time.

    PubMed

    Sangani, Rahul G; Soukup, Joleen M; Ghio, Andrew J

    2010-07-01

    The mechanism underlying procoagulative effects of air pollution particle exposure is not known. The authors tested the postulate that (1) the water-soluble components of an air pollution particle could affect whole-blood coagulation time and (2) metals included in this fraction were responsible for this effect. Exposure to the water-soluble fraction of particulate matter (PM), at doses as low as 50 ng/ml original particle, significantly diminished the whole-blood coagulation time. Inclusion of deferoxamine prolonged coagulation time following the exposures to the water-soluble fraction, whereas equivalent doses of ferroxamine had no effect. Except for nickel, all metal sulfates shortened the whole-blood coagulation time. Iron and zinc were two metals with the greatest capacity to reduce the coagulation time, with an effect observed at 10 ng/ml. Finally, in contrast to the anticoagulants citrate and EDTA, their iron complexes were found to be procoagulative. The authors conclude that metals in the water-soluble fraction of air pollution particles decrease whole-blood coagulation time. These metals can potentially contribute to procoagulative effects observed following human exposures to air pollution particles.

  20. Initialized Fractional Calculus

    NASA Technical Reports Server (NTRS)

    Lorenzo, Carl F.; Hartley, Tom T.

    2000-01-01

    This paper demonstrates the need for a nonconstant initialization for the fractional calculus and establishes a basic definition set for the initialized fractional differintegral. This definition set allows the formalization of an initialized fractional calculus. Two basis calculi are considered; the Riemann-Liouville and the Grunwald fractional calculi. Two forms of initialization, terminal and side are developed.

  1. Fractional kinetics in multi-compartmental systems.

    PubMed

    Dokoumetzidis, Aristides; Magin, Richard; Macheras, Panos

    2010-10-01

    Fractional calculus, the branch of calculus dealing with derivatives of non-integer order (e.g., the half-derivative) allows the formulation of fractional differential equations (FDEs), which have recently been applied to pharmacokinetics (PK) for one-compartment models. In this work we extend that theory to multi-compartmental models. Unlike systems defined by a single ordinary differential equation (ODE), considering fractional multi-compartmental models is not as simple as changing the order of the ordinary derivatives of the left-hand side of the ODEs to fractional orders. The latter may produce inconsistent systems which violate mass balance. We present a rationale for fractionalization of ODEs, which produces consistent systems and allows processes of different fractional orders in the same system. We also apply a method of solving such systems based on a numerical inverse Laplace transform algorithm, which we demonstrate that is consistent with analytical solutions when these are available. As examples of our approach, we consider two cases of a basic two-compartment PK model with a single IV dose and multiple oral dosing, where the transfer from the peripheral to the central compartment is of fractional order α < 1, accounting for anomalous kinetics and deep tissue trapping, while all other processes are of the usual order 1. Simulations with the studied systems are performed using the numerical inverse Laplace transform method. It is shown that the presence of a transfer rate of fractional order produces a non-exponential terminal phase, while multiple dose and constant infusion systems never reach steady state and drug accumulation carries on indefinitely. The IV fractional system is also fitted to PK data and parameter values are estimated. In conclusion, our approach allows the formulation of systems of FDEs, mixing different fractional orders, in a consistent manner and also provides a method for the numerical solution of these systems. PMID

  2. Tempered fractional calculus

    NASA Astrophysics Data System (ADS)

    Sabzikar, Farzad; Meerschaert, Mark M.; Chen, Jinghua

    2015-07-01

    Fractional derivatives and integrals are convolutions with a power law. Multiplying by an exponential factor leads to tempered fractional derivatives and integrals. Tempered fractional diffusion equations, where the usual second derivative in space is replaced by a tempered fractional derivative, govern the limits of random walk models with an exponentially tempered power law jump distribution. The limiting tempered stable probability densities exhibit semi-heavy tails, which are commonly observed in finance. Tempered power law waiting times lead to tempered fractional time derivatives, which have proven useful in geophysics. The tempered fractional derivative or integral of a Brownian motion, called a tempered fractional Brownian motion, can exhibit semi-long range dependence. The increments of this process, called tempered fractional Gaussian noise, provide a useful new stochastic model for wind speed data. A tempered fractional difference forms the basis for numerical methods to solve tempered fractional diffusion equations, and it also provides a useful new correlation model in time series.

  3. Tempered fractional calculus

    SciTech Connect

    Sabzikar, Farzad; Meerschaert, Mark M.; Chen, Jinghua

    2015-07-15

    Fractional derivatives and integrals are convolutions with a power law. Multiplying by an exponential factor leads to tempered fractional derivatives and integrals. Tempered fractional diffusion equations, where the usual second derivative in space is replaced by a tempered fractional derivative, govern the limits of random walk models with an exponentially tempered power law jump distribution. The limiting tempered stable probability densities exhibit semi-heavy tails, which are commonly observed in finance. Tempered power law waiting times lead to tempered fractional time derivatives, which have proven useful in geophysics. The tempered fractional derivative or integral of a Brownian motion, called a tempered fractional Brownian motion, can exhibit semi-long range dependence. The increments of this process, called tempered fractional Gaussian noise, provide a useful new stochastic model for wind speed data. A tempered fractional difference forms the basis for numerical methods to solve tempered fractional diffusion equations, and it also provides a useful new correlation model in time series.

  4. Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Redfield, Margaret M.; Anstrom, Kevin J.; Levine, James A.; Koepp, Gabe A.; Borlaug, Barry A.; Chen, Horng H.; LeWinter, Martin M.; Joseph, Susan M.; Shah, Sanjiv J.; Semigran, Marc J.; Felker, G. Michael; Cole, Robert T.; Reeves, Gordon R.; Tedford, Ryan J.; Tang, W.H. Wilson; McNulty, Steven E.; Velazquez, Eric J.; Shah, Monica R.; Braunwald, Eugene

    2015-01-01

    BACKGROUND Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro–brain natriuretic peptide (NT-proBNP). RESULTS In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (−381 accelerometer units; 95% confidence interval [CI], −780 to 17; P = 0.06) and a significant decrease in hours of activity per day (−0.30 hours; 95% CI, −0.55 to −0.05; P = 0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (−439 accelerometer units; 95% CI, −792 to −86; P = 0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. CONCLUSIONS Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did

  5. The extent, time course, and fraction size dependence of mouse spinal cord recovery from radiation injury

    SciTech Connect

    Lavey, R.S.; Taylor, M.G.; Tward, J.D.

    1994-10-15

    This experiment was designed to assess: (a) the influence of fraction size and time interval between fractions on the tolerance of the spinal cord to high cumulative doses of radiation; and (b) the influence of the long-term recovery process on the tolerance of the spinal cord to reirradiation. The T10-L2 level of the spinal cord of C3Hf mice was irradiated using a conventionally fractionated regimen of 2.0 Gy once daily, a prolonged fractionated regimen of 1.2 Gy once daily, a hyperfractionated regimen of 1.2 Gy twice daily, or a single dose of 12 Gy followed 0-190 days later by a second dose of 5-20 Gy. Mice in the multifractionated regimen groups were given a single 15 Gy top-up- dose 24 h after reaching a cumulative fractionated dose of 24-70 Gy. Hind limb strength was measured weekly for 2 years after the completion of irradiation. Paralysis occurred in a bimodal time distribution, with peaks at 5-10 months and 15-23 months after the completion of irradiation. The cumulative radiation dose was directly associated with the incidence of paralysis in each radiation schedule (p<0.0001) and inversely associated with the time to onset of paralysis in the 1.2 Gy b.i.d. (p = 0.0001) and 2.0 Gy q.d. schedules (p = 0.03). The median latency of paralysis in each group was inversely associated with the incidence of paralysis in that group (p =<0.001). Decreasing the fraction size from 2.0 to 1.2 Gy once daily markedly increased the radiation tolerance of the spinal cord (p <0.0001), consistent with a very small alpha-beta value of -0.30 Gy ({approximately}95% confidence interval -0.72, +0.18) in the linear-quadratic model. Decreasing the time interval from 24 h to alternating 8 and 16 h periods produced an offsetting diminuation in cord tolerance (p <0.0001). 36 refs., 5 figs., 6 tabs.

  6. Multiple anatomy optimization of accumulated dose

    SciTech Connect

    Watkins, W. Tyler Siebers, Jeffrey V.; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.

    2014-11-01

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

  7. Multiple anatomy optimization of accumulated dose

    PubMed Central

    Watkins, W. Tyler; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.; Siebers, Jeffrey V.

    2014-01-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated. PMID:25370619

  8. Influence of trichlorfon and fractionated irradiation on hydroproteolytic activity of pancreas and intestinal tissues of rats.

    PubMed

    Koćmierska-Grodzka, D

    1976-03-01

    Investigations into the hydroproteolytic activity of pancreas and intestinal tissues (small intestine and colon) of rats after fractionated irradiation (5 X 150 R) were carried out. There was found marked postirradiation enhancement of lipase activity in pancreas and duodenal part of intestine and increase of B-glucuronidase and acid phosphatase activity in nearly all parts of the examined intestinal tissues. Fractionated irradiation resulted in an increase of pancreatic catheptic (proteolytic) activity causing simultaneous decrease of proteolytic activity in intestine and colon. Preventive administration of Trichlorfon (ten days before irradiation) in the dose of 10 mg or 30 mg/kg evoked modification of hydroproteolytic activity in intestinal tissues of healthy and irradiated rats. Trichlorfon applied in the dose of 30 mg/kg exerted antilipolytic and anticatheptic effects in pancreas and intestinal tissues of irradiated rats. PMID:1258099

  9. TEMPERED FRACTIONAL CALCULUS

    PubMed Central

    MEERSCHAERT, MARK M.; SABZIKAR, FARZAD; CHEN, JINGHUA

    2014-01-01

    Fractional derivatives and integrals are convolutions with a power law. Multiplying by an exponential factor leads to tempered fractional derivatives and integrals. Tempered fractional diffusion equations, where the usual second derivative in space is replaced by a tempered fractional derivative, govern the limits of random walk models with an exponentially tempered power law jump distribution. The limiting tempered stable probability densities exhibit semi-heavy tails, which are commonly observed in finance. Tempered power law waiting times lead to tempered fractional time derivatives, which have proven useful in geophysics. The tempered fractional derivative or integral of a Brownian motion, called a tempered fractional Brownian motion, can exhibit semi-long range dependence. The increments of this process, called tempered fractional Gaussian noise, provide a useful new stochastic model for wind speed data. A tempered difference forms the basis for numerical methods to solve tempered fractional diffusion equations, and it also provides a useful new correlation model in time series. PMID:26085690

  10. Insulin-Like Growth Factor-1 Preserves Salivary Gland Function After Fractionated Radiation

    SciTech Connect

    Limesand, Kirsten H.; Avila, Jennifer L.; Victory, Kerton; Chang, Hui-Hua; Shin, Yoon Joo; Grundmann, Oliver; Klein, Rob R.

    2010-10-01

    Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVB mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.

  11. Long term results of comparison of concurrent low-dose daily cisplatin versus the standard weekly cisplatin with six fractions per week radiotherapy in locally advanced head neck cancer

    PubMed Central

    Gupta, Pramod Kumar; Lal, Punita; Bajpai, Ranjeet; Goel, Anshu; Yadav, Rajan; Verma, Mranalini; Kumar, Shaleen

    2016-01-01

    Aim and Objective: Weekly administration of cisplatin (cis-diamminedichloroplatinum [CDDP]) appears more feasible and substantially more popular than the 3 weekly schedules due to better compliance. Different concurrent cisplatin schedules have been attempted including a daily schedule. We did a comparison of two consecutive single arm studies, i.e., use of weekly cisplatin versus daily cisplatin when used with concurrently with a moderately accelerated radiotherapy (RT) schedule. Patients and Methods: Two prospective feasibility, safety and efficacy studies were carried out consecutively within the department. The weekly CDDP study was done from August 2003 to August 2005 and daily CDDP study was conducted from November 2005 to June 2007. Both studies included locally advanced stage III and IV squamous cell carcinoma of the head and neck region with RT dose of 70 Gy. Concurrent single-agent cisplatin was administered weekly (35 mg/m2) in the first and daily (6 mg/m2) in the second study. Results: Weekly cisplatin study had 68 and daily CDDP study had 52 patients. The median follow-up in the two studies was 93 and 63 months, respectively. Compliance in the two studies was comparable. Acute Grade III/IV mucositis and dysphagia were significantly higher in weekly cisplatin study. Late Grade II/III toxicities such as xerostomia, dysphagia, ototoxicity and nephrotoxicity were similar. The 5 years locoregional control was 18% and 25% and 5 years overall survival rate was 32% and 31% in weekly and daily cisplatin studies, respectively. Conclusions: Modest acceleration along with either weekly or daily cisplatin, whichever is possible in one's setup, is do-able, provided due attention is paid to patient selection and supportive care. PMID:27275456

  12. Ramipril-induced decrease in renal lithium excretion in the rat.

    PubMed Central

    Barthelmebs, M.; Grima, M.; Imbs, J. L.

    1995-01-01

    1. The interaction of ramipril, an inhibitor of angiotensin I converting enzyme, with renal lithium handling was analysed in conscious normotensive Wistar rats and compared with the known increase in renal tubular lithium reabsorption induced by the non-steroidal anti-inflammatory drug, indomethacin. 2. The rats were treated for five days with ramipril (1 mg kg-1 day-1 orally), indomethacin (2.5 mg kg-1 day-1 intramuscularly) or their solvents. Lithium chloride (16.7 mg kg-1 intraperitonealy) was given as a single dose on the fifth day and renal functions were measured. 3. Ramipril induced a decrease in renal lithium clearance which was correlated with the decrease in the quantity of filtered lithium and the increase in the tubular fractional reabsorption of the metal. Ramipril also reduced the systolic blood pressure of the rats by about 15 mmHg. 4. In the absence of any effect on creatinine clearance or systolic blood pressure, indomethacin increased renal fractional lithium reabsorption and led to an increase in plasma lithium levels, as previously reported by our group. 5. In conclusions, our results indicate that ramipril decreases renal lithium excretion in Wistar rats, when given orally at a dose of 1 mg kg-1 day-1 over five days. PMID:8564243

  13. [Effects of Low and Sublethal Doses of γ-Radiation on Mesenchymal and Neural Stem Cells from Mouse Brain].

    PubMed

    Posypanova, G A; Moskaleva, E Yu; Rodina, A V; Semochkina, Yu P; Ratushnjak, M G; Perevozchikova, V G

    2016-01-01

    Mesenchymal stem cells (MSC) exist in the brain in addition to the neural stem cells (NSC). The aim of this work was to investigate the sensitivity of mouse brain MSC (MSC(BR)) to sublethal doses of γ-radiation in comparison with the sensitivity of bone marrow MSC (MSC(BM)) and NSC and to study the effects of γ-irradiation at low doses on these cells. Cells were exposed to γ-radiation (137Cs) at the doses of 10 to 200 mGy at a dose rate of 10 mGy/min; higher doses were achieved at the dose rates of 200 and 500 mGy/min (60Co). The survival of cells was assessed by counting living cells after staining with trypan blue in the Goryaev's chamber or using the MTT test for NSC growing as neurospheres. SP fraction was measured using flow cytometry after incubation with rhodamine-123. Exposure to the doses in the range of 10 to 500 mGy stimulated cell proliferation. The maximum decrease in the cells number was seen on the seventh day after irradiation and it was practically the same for the MSC(BR) and MSC(BM). NCS were more radiosensitive than MSC. Exposure to the doses of 100 to 500 mGy stimulated cells proliferation of all SCs except of MSC(BM). It was shown that the size of SP fraction of MSC(BR) was diminished after γ-irradiation at low doses. Thus, the stimulation of cell proliferation after γ-irradiation at low doses is accompanied by the redistribution of distinct cell subpopulations: the decrease in the SP fraction and the increase in the general population of cells were observed.

  14. [Effects of Low and Sublethal Doses of γ-Radiation on Mesenchymal and Neural Stem Cells from Mouse Brain].

    PubMed

    Posypanova, G A; Moskaleva, E Yu; Rodina, A V; Semochkina, Yu P; Ratushnjak, M G; Perevozchikova, V G

    2016-01-01

    Mesenchymal stem cells (MSC) exist in the brain in addition to the neural stem cells (NSC). The aim of this work was to investigate the sensitivity of mouse brain MSC (MSC(BR)) to sublethal doses of γ-radiation in comparison with the sensitivity of bone marrow MSC (MSC(BM)) and NSC and to study the effects of γ-irradiation at low doses on these cells. Cells were exposed to γ-radiation (137Cs) at the doses of 10 to 200 mGy at a dose rate of 10 mGy/min; higher doses were achieved at the dose rates of 200 and 500 mGy/min (60Co). The survival of cells was assessed by counting living cells after staining with trypan blue in the Goryaev's chamber or using the MTT test for NSC growing as neurospheres. SP fraction was measured using flow cytometry after incubation with rhodamine-123. Exposure to the doses in the range of 10 to 500 mGy stimulated cell proliferation. The maximum decrease in the cells number was seen on the seventh day after irradiation and it was practically the same for the MSC(BR) and MSC(BM). NCS were more radiosensitive than MSC. Exposure to the doses of 100 to 500 mGy stimulated cells proliferation of all SCs except of MSC(BM). It was shown that the size of SP fraction of MSC(BR) was diminished after γ-irradiation at low doses. Thus, the stimulation of cell proliferation after γ-irradiation at low doses is accompanied by the redistribution of distinct cell subpopulations: the decrease in the SP fraction and the increase in the general population of cells were observed. PMID:27245003

  15. Antidepressant-like effects of the ethyl acetate soluble fraction of the root bark of Morus alba on the immobility behavior of rats in the forced swim test.

    PubMed

    Lim, Dong Wook; Kim, Yun Tai; Park, Ji-Hae; Baek, Nam-In; Han, Daeseok

    2014-06-12

    In this study, the antidepressant-like effects of Morus alba fractions in rats were investigated in the forced swim test (FST). Male Wistar rats (9-week-old) were administered orally the M. alba ethyl acetate (EtOAc 30 and 100 mg/kg) and M. alba n-butanol fractions (n-BuOH 30 and 100 mg/kg) every day for 7 consecutive days. On day 7, 1 h after the final administration of the fractions, the rats were exposed to the FST. M. alba EtOAc fraction at the dose of 100 mg/kg induced a decrease in immobility behavior (p < 0.01) with a concomitant increase in both climbing (p < 0.05) and swimming (p < 0.05) behaviors when compared with the control group, and M. alba EtOAc fraction at the dose of 100 mg/kg decreased the hypothalamic-pituitary-adrenal (HPA) axis response to the stress, as indicated by an attenuated corticosterone response and decreased c-fos immunoreactivity in the hippocampal and hypothalamic paraventricular nucleus (PVN) region. These findings demonstrated that M. alba EtOAc fraction have beneficial effects on depressive behaviors and restore both altered c-fos expression and HPA activity.

  16. Impact of variable RBE on proton fractionation

    SciTech Connect

    Dasu, Alexandru; Toma-Dasu, Iuliana

    2013-01-15

    Purpose: To explore the impact of variable proton relative biological effectiveness (RBE) on dose fractionation for clinically relevant situations. A generic RBE = 1.1 is generally used for isoeffect calculations, while experimental studies showed that proton RBE varies with tissue type, dose, and linear energy transfer (LET). Methods: An analytical expression for the LET and {alpha}/{beta} dependence of the linear-quadratic (LQ) model has been used for proton simulations in parallel with the assumption of a generic RBE = 1.1. Calculations have been performed for ranges of LET values and fractionation sensitivities to describe clinically relevant cases, such as the treatment of head and neck and prostate tumors. Isoeffect calculations were compared with predictions from a generic RBE value and reported clinical results. Results: The generic RBE = 1.1 appears to be a reasonable estimate for the proton RBE of rapidly growing tissues irradiated with low LET radiation. However, the use of a variable RBE predicts larger differences for tissues with low {alpha}/{beta} (both tumor and normal) and at low doses per fraction. In some situations these differences may appear in contrast to the findings from photon studies highlighting the importance of accurate accounting for the radiobiological effectiveness of protons. Furthermore, the use of variable RBE leads to closer predictions to clinical results. Conclusions: The LET dependence of the RBE has a strong impact on the predicted effectiveness of fractionated proton radiotherapy. The magnitude of the effect is modulated by the fractionation sensitivity and the fractional dose indicating the need for accurate analyses both in the target and around it. Care should therefore be employed for changing clinical fractionation patterns or when analyzing results from clinical studies for this type of radiation.

  17. Impact of Prolonged Fraction Delivery Times Simulating IMRT on Cultured Nasopharyngeal Carcinoma Cell Killing

    SciTech Connect

    Zheng Xiaokang; Chen Longhua; Wang Wenjun; Ye Feng; Liu Jiabing; Li Qisheng; Sun Henwen

    2010-12-01

    Purpose: To determine the impact of prolonged fraction delivery times (FDTs) simulating intensity-modulated radiotherapy (IMRT) on cultured nasopharyngeal carcinoma (NPC) cell killing. Methods and Material: Cultured NPC cell lines CNE1 and CNE2 were used in this study. The biological effectiveness of fractionated irradiation protocols simulating conventional external beam radiotherapy and IMRT (FDT of 15, 36, and 50 minutes) was estimated with standard colony assay, and the differences in cell surviving fractions after irradiation with different protocols were tested by use of the paired t test. The impact degree of prolonged FDTs (from 8 to 50 minutes) on cell killing was also assessed by the dose-modifying factors, which were estimated by comparing the effectiveness of intermittently delivered 2 Gy with that of continuously delivered 1.5 to 2 Gy. Results: The cell surviving fractions of both CNE1 and CNE2 after fractionated irradiation simulating IMRT were higher than those simulating conventional external beam radiotherapy (p < 0.05). The dose-modifying factors for a fraction dose of 2 Gy increased from 1.05 to 1.18 for CNE1 and from 1.05 to 1.11 for CNE2 with the FDT being prolonged from 15 to 50 minutes. Conclusions: This study showed that the prolonged FDTs simulating IMRT significantly decreased the cell killing in both CNE1 and CNE2 cell lines, and these negative effects increased with the FDT being prolonged from 15 to 50 minutes. These effects, if confirmed by in vivo and clinical studies, need to be considered in designing IMRT treatments for NPC.

  18. Statistics of the doses absorbed by workers

    NASA Astrophysics Data System (ADS)

    Parisi, A.

    1982-10-01

    A statistical analysis of the distribution of the doses by individual workers is presented to assess existing norms. A log-normal distribution is assumed for the individual doses. A reference distribution is introduced, characterized by log-normal distribution of annual doses, average 0,5 rem (10% of the limit) and 0.1% of the individuals that will absorb more than 5 rem. Expressions are given for the probability of finding a dose in a given interval and for the fraction of the collective dose due to doses from a given interval. An example using data from medical professions in the United States shows that the fraction of workers with annual doses larger than 5 rem is not contained within the 0.1% recommended limit, and that the level of risk is not uniform between professions.

  19. Radiation dose estimates for radiopharmaceuticals

    SciTech Connect

    Stabin, M.G.; Stubbs, J.B.; Toohey, R.E.

    1996-04-01

    Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.

  20. [Effect of Nano Zeolite on Chemical Fractions of Cd in Soil and Its Uptake by Cabbage].

    PubMed

    Xiong, Shi-juan; Xu, Wei-hong; Xie, Wen-wen; Chen, Rong; Chen, Yong-qin; Chi, Sun-lin; Chen, Xu- gen; Zhang, Jin-zhong; Xiong, Zhi-ting; Wang, Zheng-yin; Xie, De-ti

    2015-12-01

    Incubation experiments were carried out to investigate the influence of different nano zeolite (NZ) and ordinary zeolite (OZ) levels(0, 5, 10 and 20 g · kg⁻¹) on the change trends in fraction distribution coefficient (FDC) of Cd when exposed to different Cadmium (Cd) levels (1, 5, 10 and 15 mg · kg⁻¹), and pot experiments were carried out to investigate their influence on soil Cd fraction and Cd uptake by cabbage. The results in incubation experiments showed that the application of nano zeolite as well as ordinary zeolite effectively decreased the FDC of exchangeable Cd and increased the FDC of Fe-Mn oxide fraction. The FDC of soil Cd from 0 d to 28 d was deceased at first, then increased and tended to be stable, and finally increased. At the end of incubation, the FDC of soil exchangeable Cd decreased from 72.0%-88.0% to 30.0%-66.4%. Exchangeable fraction Cd was the most dominant Cd fraction in soil during the whole incubation. The results in pot experiment indicated that the application of nano zeolite and ordinary zeolite decreased the concentration and FDC of soil exchangeable Cd, and concurrently the concentration and FDC of Cd in carbonate, Fe-Mn oxide, organic matter and residual fraction were increased. The lowest EX-Cd was observed in the treatment with high dose of nano zeolite (20 g · kg⁻¹). The FDC of exchangeable Cd showed significant negative relationship with the soil pH (P < 0.05), and was concurrently extremely positively correlated with Cd concentration in shoot and root of cabbage (P < 0.01). Soil pH increased by 1.8%-45.5% and 6.1%-54.3% in the presence of zeolite when exposed to 5 mg · kg⁻¹ 1 and Cd, respectively; FDC of exchangeable Cd decreased by 16.3%-47.7% and 16.2%-46.7%; Cd concentration in each tissues of cabbage decreased by 1.0%-75.0% and 3.8%-53.2%, respectively. Moreover, the reduction effect of nano zeolite on soil and plant Cd was better than that of ordinary zeolite. The growth of cabbage was stimulated by low and

  1. [Effect of Nano Zeolite on Chemical Fractions of Cd in Soil and Its Uptake by Cabbage].

    PubMed

    Xiong, Shi-juan; Xu, Wei-hong; Xie, Wen-wen; Chen, Rong; Chen, Yong-qin; Chi, Sun-lin; Chen, Xu- gen; Zhang, Jin-zhong; Xiong, Zhi-ting; Wang, Zheng-yin; Xie, De-ti

    2015-12-01

    Incubation experiments were carried out to investigate the influence of different nano zeolite (NZ) and ordinary zeolite (OZ) levels(0, 5, 10 and 20 g · kg⁻¹) on the change trends in fraction distribution coefficient (FDC) of Cd when exposed to different Cadmium (Cd) levels (1, 5, 10 and 15 mg · kg⁻¹), and pot experiments were carried out to investigate their influence on soil Cd fraction and Cd uptake by cabbage. The results in incubation experiments showed that the application of nano zeolite as well as ordinary zeolite effectively decreased the FDC of exchangeable Cd and increased the FDC of Fe-Mn oxide fraction. The FDC of soil Cd from 0 d to 28 d was deceased at first, then increased and tended to be stable, and finally increased. At the end of incubation, the FDC of soil exchangeable Cd decreased from 72.0%-88.0% to 30.0%-66.4%. Exchangeable fraction Cd was the most dominant Cd fraction in soil during the whole incubation. The results in pot experiment indicated that the application of nano zeolite and ordinary zeolite decreased the concentration and FDC of soil exchangeable Cd, and concurrently the concentration and FDC of Cd in carbonate, Fe-Mn oxide, organic matter and residual fraction were increased. The lowest EX-Cd was observed in the treatment with high dose of nano zeolite (20 g · kg⁻¹). The FDC of exchangeable Cd showed significant negative relationship with the soil pH (P < 0.05), and was concurrently extremely positively correlated with Cd concentration in shoot and root of cabbage (P < 0.01). Soil pH increased by 1.8%-45.5% and 6.1%-54.3% in the presence of zeolite when exposed to 5 mg · kg⁻¹ 1 and Cd, respectively; FDC of exchangeable Cd decreased by 16.3%-47.7% and 16.2%-46.7%; Cd concentration in each tissues of cabbage decreased by 1.0%-75.0% and 3.8%-53.2%, respectively. Moreover, the reduction effect of nano zeolite on soil and plant Cd was better than that of ordinary zeolite. The growth of cabbage was stimulated by low and

  2. On voxel-by-voxel accumulated dose for prostate radiation therapy using deformable image registration

    PubMed Central

    Yu, Jialu; Hardcastle, Nicholas; Jeong, Kyoungkeun; Bender, Edward T.; Ritter, Mark A.; Tomé, Wolfgang A.

    2015-01-01

    Since delivered dose is rarely the same with planned, we calculated the delivered total dose to ten prostate radiotherapy patients treated with rectal balloons using deformable dose accumulation (DDA) and compared it with the planned dose. The patients were treated with TomoTherapy using two rectal balloon designs: five patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM balloon (balloon B). Prostate and rectal wall contours were outlined on each pre-treatment MVCT for all patients. Delivered fractional doses were calculated using the MVCT taken immediately prior to delivery. Dose grids were accumulated to the last MVCT using DDA tools in Pinnacle3 ™ (v9.100, Philips Radiation Oncology Systems, Fitchburg, USA). Delivered total doses were compared with planned doses using prostate and rectal wall DVHs. The rectal NTCP was calculated based on total delivered and planned doses for all patients using the Lyman model. For 8/10 patients, the rectal wall NTCP calculated using the delivered total dose was less than planned, with seven patients showing a decrease of more than 5% in NTCP. For 2/10 patients studied, the rectal wall NTCP calculated using total delivered dose was 2% higher than planned. This study indicates that for patients receiving hypofractionated radiotherapy for prostate cancer with a rectal balloon, total delivered doses to prostate is similar with planned while delivered dose to rectal walls may be significantly different from planned doses. 8/10 patients show significant correlation between rectal balloon anterior-posterior positions and some VD values. PMID:24354754

  3. Impact of Drug Therapy, Radiation Dose, and Dose Rate on Renal Toxicity Following Bone Marrow Transplantation

    SciTech Connect

    Cheng, Jonathan C.; Schultheiss, Timothy E. Wong, Jeffrey Y.C.

    2008-08-01

    Purpose: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). Methods and Materials: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age {>=}18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Results: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. Conclusion: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function.

  4. Effect of edema, relative biological effectiveness, and dose heterogeneity on prostate brachytherapy

    SciTech Connect

    Wang, Jian Z.; Mayr, Nina A.; Nag, Subir; Montebello, Joseph; Gupta, Nilendu; Samsami, Nina; Kanellitsas, Christos

    2006-04-15

    Many factors influence response in low-dose-rate (LDR) brachytherapy of prostate cancer. Among them, edema, relative biological effectiveness (RBE), and dose heterogeneity have not been fully modeled previously. In this work, the generalized linear-quadratic (LQ) model, extended to account for the effects of edema, RBE, and dose heterogeneity, was used to assess these factors and their combination effect. Published clinical data have shown that prostate edema after seed implant has a magnitude (ratio of post- to preimplant volume) of 1.3-2.0 and resolves exponentially with a half-life of 4-25 days over the duration of the implant dose delivery. Based on these parameters and a representative dose-volume histogram (DVH), we investigated the influence of edema on the implant dose distribution. The LQ parameters ({alpha}=0.15 Gy{sup -1} and {alpha}/{beta}=3.1 Gy) determined in earlier studies were used to calculate the equivalent uniform dose in 2 Gy fractions (EUD{sub 2}) with respect to three effects: edema, RBE, and dose heterogeneity for {sup 125}I and {sup 103}Pd implants. The EUD{sub 2} analysis shows a negative effect of edema and dose heterogeneity on tumor cell killing because the prostate edema degrades the dose coverage to tumor target. For the representative DVH, the V{sub 100} (volume covered by 100% of prescription dose) decreases from 93% to 91% and 86%, and the D{sub 90} (dose covering 90% of target volume) decrease from 107% to 102% and 94% of prescription dose for {sup 125}I and {sup 103}Pd implants, respectively. Conversely, the RBE effect of LDR brachytherapy [versus external-beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy] enhances dose effect on tumor cell kill. In order to balance the negative effects of edema and dose heterogeneity, the RBE of prostate brachytherapy was determined to be approximately 1.2-1.4 for {sup 125}I and 1.3-1.6 for {sup 103}Pd implants. These RBE values are consistent with the RBE data published in the

  5. [Mechanism of injury of air-dry pea seeds under the influence of low doses of gamma-radiation].

    PubMed

    Veselova, T V; Veselovskiĭ, V A

    2012-01-01

    The aim of this work was to determine which processes in air-dry seeds result in bimodal changes of the pea seed quality under the influence of low doses of gamma-radiation. Pea seeds (cv. "Nemchinovsky-85", harvest 2006, 82% germination persentage) were exposed to gamma-radiation at doses of 3, 10 and 100 Gy The germination percentage decreased to 45% four days after irradiation at the dose of 3 Gy, rised up to 87% at doses of 10 Gy, while the dose of 100 Gy killed the most part of seeds. Seed fractions differing in quality were selected using the metod of Room temperature phosphorecsence (RTP): strong seed frasction I from non-irradiated seeds; weak seed fraction II from the seeds irradiated at a dose of 3 Gy; dead seeds from the seeds irradiated at a dose of 100 Gy. ThermoChemiLuminecnsece (TCL) of seed powders and cotyledons was used. It was shown that the increase of the TCL level in the temperature range from 50 to 110 degreesC was associated with the lipid peroxidation products. The TCL level of seeds subjected to gamma-irradiation at a dose of 3 Gy was similar to that of non-irradiated seeds in the temperature range 50 to 100 degreesC. Therefore, lipid peroxidation was not the cause of the abnormal seedling appearance. The TCL level within this temperature range was increased only in seeds subjected to y-irradiation at a dose of 100 Gy. The TCL level at 150 degreesC was in proportion with the exogenous glucose amount. The increased TCL level of seeds subjected to y-irradiation at a dose of 3 Gy at 150 degreesC resulted from the increase of the glucose content. This means that the transition from the fraction of strong seeds into the fraction of weak ones was the result of the activation of hydrolysis processes. Decrease in the water content of seeds testified to utilization of bound water in this process. The decrease of the glucose content in the "improved" seeds subjected to gamma-irradiation at a dose of 10 Gy most probably indicates the participation of

  6. Fractionated proton beam irradiation of pituitary adenomas

    SciTech Connect

    Ronson, Brian B.; Schulte, Reinhard W.; Han, Khanh P.; Loredo, Lilia N.; Slater, James M.; Slater, Jerry D. . E-mail: jdslater@dominion.llumc.edu

    2006-02-01

    Purpose: Various radiation techniques and modalities have been used to treat pituitary adenomas. This report details our experience with proton treatment of these tumors. Methods and Materials: Forty-seven patients with pituitary adenomas treated with protons, who had at least 6 months of follow-up, were included in this analysis. Forty-two patients underwent a prior surgical resection; 5 were treated with primary radiation. Approximately half the tumors were functional. The median dose was 54 cobalt-gray equivalent. Results: Tumor stabilization occurred in all 41 patients available for follow-up imaging; 10 patients had no residual tumor, and 3 had greater than 50% reduction in tumor size. Seventeen patients with functional adenomas had normalized or decreased hormone levels; progression occurred in 3 patients. Six patients have died; 2 deaths were attributed to functional progression. Complications included temporal lobe necrosis in 1 patient, new significant visual deficits in 3 patients, and incident hypopituitarism in 11 patients. Conclusion: Fractionated conformal proton-beam irradiation achieved effective radiologic, endocrinological, and symptomatic control of pituitary adenomas. Significant morbidity was uncommon, with the exception of postradiation hypopituitarism, which we attribute in part to concomitant risk factors for hypopituitarism present in our patient population.

  7. High-dose mode of mortality in Tribolium: A model system for study of radiation injury and repair in non-proliferative tissues

    SciTech Connect

    Cheng, Chihing Christina.

    1989-01-01

    With appropriate doses of ionizing radiation, both the acute, or lethal-midlethal, dose-independent pattern of mortality, and the hyperacute, dose-dependent pattern, were demonstrated within a single insect genus (Tribolium). This demonstration provides resolution of apparently contradictory reports of insect radiation responses in terms of doses required to cause lethality and those based on survival time as a function of dose. A dose-dependent mortality pattern was elicited in adult Tribolium receiving high doses, viz., 300 Gy or greater; its time course was complete in 10 days, before the dose-independent pattern of mortality began. Visual observations of heavily-irradiated Tribolium suggested neural and/or neuromuscular damage, as had been previously proposed by others for lethally-irradiated wasps, flies, and mosquitoes. Results of experiments using fractionated high doses supported the suggestion that the hyperacute or high-dose mode of death is the result of damage to nonproliferative tissues. Relative resistance of a strain to the hyperacute or high-dose mode of death was not correlated with resistance to the midlethal mode, which is believed to be the result of damage to the proliferative cells of the midgut. Using the high-dose mode of death as a model of radiation damage to nonproliferative tissues, the effects of age, and of a moderate priming dose were assessed. Beetles showed age-related increase in sensitivity to the high-dose mode of death, suggesting a decline in capacity to repair radiation damage to postmitotic tissue. This correlated with a decrease (50%) in the amount of repair reflected in the sparing effect of dose-fractionation (SDF) between the age of 1 to 3 months. The age related increase in radiosensitivity was reduced by a moderate priming dose (40 or 65 Gy) given at a young age.

  8. Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

    PubMed Central

    Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

    2014-01-01

    Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

  9. Dose to medium versus dose to water as an estimator of dose to sensitive skeletal tissue

    NASA Astrophysics Data System (ADS)

    Walters, B. R. B.; Kramer, R.; Kawrakow, I.

    2010-08-01

    The purpose of this study is to determine whether dose to medium, Dm, or dose to water, Dw, provides a better estimate of the dose to the radiosensitive red bone marrow (RBM) and bone surface cells (BSC) in spongiosa, or cancellous bone. This is addressed in the larger context of the ongoing debate over whether Dm or Dw should be specified in Monte Carlo calculated radiotherapy treatment plans. The study uses voxelized, virtual human phantoms, FAX06/MAX06 (female/male), incorporated into an EGSnrc Monte Carlo code to perform Monte Carlo dose calculations during simulated irradiation by a 6 MV photon beam from an Elekta SL25 accelerator. Head and neck, chest and pelvis irradiations are studied. FAX06/MAX06 include precise modelling of spongiosa based on µCT images, allowing dose to RBM and BSC to be resolved from the dose to bone. Modifications to the FAX06/MAX06 user codes are required to score Dw and Dm in spongiosa. Dose uncertainties of ~1% (BSC, RBM) or ~0.5% (Dm, Dw) are obtained after up to 5 days of simulations on 88 CPUs. Clinically significant differences (>5%) between Dm and Dw are found only in cranial spongiosa, where the volume fraction of trabecular bone (TBVF) is high (55%). However, for spongiosa locations where there is any significant difference between Dm and Dw, comparisons of differential dose volume histograms (DVHs) and average doses show that Dw provides a better overall estimate of dose to RBM and BSC. For example, in cranial spongiosa the average Dm underestimates the average dose to sensitive tissue by at least 5%, while average Dw is within ~1% of the average dose to sensitive tissue. Thus, it is better to specify Dw than Dm in Monte Carlo treatment plans, since Dw provides a better estimate of dose to sensitive tissue in bone, the only location where the difference is likely to be clinically significant.

  10. Dividing Fractions: A Pedagogical Technique

    ERIC Educational Resources Information Center

    Lewis, Robert

    2016-01-01

    When dividing one fraction by a second fraction, invert, that is, flip the second fraction, then multiply it by the first fraction. To multiply fractions, simply multiply across the denominators, and multiply across the numerators to get the resultant fraction. So by inverting the division of fractions it is turned into an easy multiplication of…

  11. The unattached fraction of radon decay products: Potential effects of in-home air cleaners on lung cancer risk

    SciTech Connect

    Brady, P.A.

    1991-01-01

    Radon decay products are a factor in the development of lung cancer. Because of their efficient deposition within the lung, the fraction of decay products not attached to particulate (i.e., the unattached fraction) is very important in lung dosimetry. This study simulated the use of two in-home air cleaning devices to reduce airborne particulate concentrations, measure the effect on the unattached fraction, and estimate the radon lung cancer risk. Radon was released into a chamber having a volume-to-surface-area ratio similar to a small home. At radon-decay product equilibrium, radon and airborne particle concentrations were measured, and the concentration of the unattached fraction was estimated. The effect of particle concentration on the unattached fraction was then determined. The average unattached fractions corresponding to the particle concentration ranges expected for the air cleaning devices were used to calculate the annual alpha radiation dose and annual radon lung cancer for men, women and children at rest and under light activity. The annual doses and related risks were compared to those used in the models published by the Environmental Protection Agency. For particulate concentrations of a home with no particulate generating activities (e.g., smoking, cooking), the electronic air cleaner is predicted to reduce the unattached fraction from seven percent (the value used by the NCRP and confirmed in this study) to four percent. These conditions represent the maximum reduction in the unattached fraction. The decrease in the unattached fraction is tentatively attributed to an increase in plateout. Based on these results, a reduction of less than ten percent in the calculated annual lung cancer risk is found in all cases.

  12. Dose Rate Effects in Linear Bipolar Transistors

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  13. Antinociceptive Activity of the Chloroform Fraction of Dioclea virgata (Rich.) Amshoff (Fabaceae) in Mice

    PubMed Central

    Mota, Vanine Gomes; de Carvalho, Fabíola Lélis; de Morais, Liana Clébia Soares Lima; Bhattacharyya, Jnanabrata; de Almeida, Reinaldo Nóbrega; de Alencar, Jacicarlos Lima

    2011-01-01

    Acute treatment with the chloroform fraction of Dioclea virgata (Rich.) Amshoff (CFDv) in mice produced decreased ambulation and sedation in the behavioral pharmacological screening. Doses of 125 and 250 mg/kg CFDv decreased latency of sleep onset in the test of sleeping time potentiation. In the open field, animals treated with CFDv reduced ambulation and rearing (250 mg/kg), as well as defecation (125; 250 mg/kg). Regarding the antinociceptive activity, CFDv (125, 250, 500 mg/kg) increased latency to first writhing and decreased the number of writhings induced by acetic acid. In the formalin test, CFDv (250 mg/kg) decreased paw licking time in the first and second phases indicating antinociceptive activity that can be mediated both peripherally and at the central level. CFDv did not affect motor coordination until 120 minutes after treatment. CFDv shows psychopharmacological effects suggestive of CNS-depressant drugs with promising antinociceptive activity. PMID:21776190

  14. Utirik Atoll Dose Assessment

    SciTech Connect

    Robison, W.L.; Conrado, C.L.; Bogen, K.T

    1999-10-06

    radionuclides. However, we continually see {sup 137}Cs in the groundwater at all contaminated atolls; the turnover time of the groundwater is about 5 y. The {sup 137}Cs can only get to the groundwater by leaching through the soil column when a portion of the soluble fraction of {sup 137}Cs inventory in the soil is transported to the groundwater when rainfall is heavy enough to cause recharge of the aquifer. This process is causing a loss of {sup 137}Cs out of the root zone of the plants that provides an environmental loss constant ({lambda}{sub env}) in addition to radiological decay {lambda}{sub rad}. Consequently, there is an effective rate of loss, {lambda}{sub eff} = {lambda}{sub rad} + {lambda}{sub env} that is the sum of the radiological and environmental-loss decay constants. We have had, and continue to have, a vigorous program to determine the rate of the environmental loss process. What we do know at this time is that the loss of {sup 137}Cs over time is greater than the estimate based on radiological decay only, and that the actual dose received by the Utirik people over 30-, 50-, or 70-y will be less than those presented in this report.

  15. Determination of the uncertainties in radiation doses from ingestion of strontium-90

    NASA Astrophysics Data System (ADS)

    Apostoaei, Andrei Iulian

    Quantification of the uncertainties in the internal dosimetry is important because it can impact the outcome of dose reconstruction, risk assessment or epidemiological studies. This research focused on determination of the uncertainties in the dose factors from a single ingestion of 90Sr by adults, and analyzed the changes with age and the effect of gender. The uncertainties in the estimated dose factors are a factor of 6 for the bone surface, 5 for the red bone marrow, 2.5 for bladder and stomach, 2.2 for the small intestine, 2.1 for the upper large intestine and 2.7 for the lower large intestine. For the rest of the organs the uncertainty is a factor of 3. Only four parameters of the biokinetic model showed an age-dependency within the adult age group: the fractional transfers of strontium from plasma to cortical and trabecular bone, and the removal rates from the cortical and trabecular bone, respectively. When age-dependent biokinetic parameters were used, the estimated dose-factors are very close to the dose factors obtained using age-independent kinetics (within 40%). Thus, the dose factors based on age-independent parameters should suffice for most practical purposes. The dose factors and the associated uncertainties were also calculated as a function of age-at-exposure and attained age. These age dependent curves can be used for estimating doses from continuous intakes, or doses delivered over a limited portion of time. In addition to the committed dose, an expected dose is also estimated in this work. The expected dose is calculated using the dose rate weighted by the probability of surviving up to the age when the dose-rate is delivered. For exposure at young ages the expected dose and the committed dose are similar, but the committed dose decreases to zero when exposure occurs close to age 70, while the expected dose has elevated values pass age 70. No gender differences were found for bone surface, for red bone marrow, and the large intestine. The doses

  16. Impact of Dose on Local Failure Rates After Image-Guided Reirradiation of Recurrent Paraspinal Metastases

    SciTech Connect

    Damast, Shari; Wright, Jean; Bilsky, Mark; Hsu, Meier; Zhang Zhigang; Lovelock, Michael; Cox, Brett; Zatcky, Joan; Yamada, Yoshiya

    2011-11-01

    Purpose: To examine the impact of dose on local failure (LF) rates in the re-treatment of recurrent paraspinal metastases with image-guided intensity-modulated radiotherapy (IG-IMRT). Methods and Materials: The records of patients with in-field recurrence after previous spine radiation (median dose, 30 Gy) who received salvage IG-IMRT with either five 4-Gy (20-Gy group, n = 42) or five 6-Gy (30-Gy group, n = 55) daily fractions between January 2003 and August 2008 were reviewed. Institutional practice was 20 Gy before April 2006, when it changed to 30 Gy. A total of 47 cases (48%) were treated adjuvantly, after surgery to decompress epidural disease. LF after IG-IMRT was defined radiographically. Results: The median follow-up was 12.1 months (range, 0.2-63.6 months). The 1-year cumulative incidences of LF after 20 Gy and 30 Gy IG-IMRT were 45% and 26%, respectively (p = 0.04). Of all treatment characteristics examined (20-Gy vs. 30-Gy dose group, dose to 95% of the planned and gross target volume, tumor size, histology, receipt of surgery, and interval between first and second radiation), only dose group had a significant impact on actuarial LF incidence (p = 0.04; unadjusted HR, 0.51; 95% CI, 0.27-0.96). There was no incidence of myelopathy. Conclusions: A significant decrease in LF after IG-IMRT with five 6-Gy fractions compared with five 4-Gy fractions was observed without increased risk of myelopathy. Until prospective data comparing stereotactic hypofractionated and single-fraction regimens become available, when reirradiating recurrent paraspinal metastases with IG-IMRT, administration of five 6-Gy daily fractions is reasonable.

  17. Clinical Study of the Necessity of Replanning Before the 25th Fraction During the Course of Intensity-Modulated Radiotherapy for Patients With Nasopharyngeal Carcinoma

    SciTech Connect

    Wang Wei; Yang Haihua; Hu Wei; Shan Guoping; Ding Weijun; Yu Changhui; Wang Biyun; Wang Xufeng; Xu Qianyi

    2010-06-01

    Purpose: To quantify the target and normal structures on dose distributing variations during intensity-modulated radiotherapy (IMRT) and to assess the value of replanning for nasopharyngeal carcinoma (NPC) patients. Methods and Materials: Twenty-eight NPC patients treated with IMRT were recruited. The IMRT was delivered in 33 fractions, to 70 to 76Gy, to the gross tumor volume (GTV). Before the 25th fraction of IMRT, a new simulation computed tomography (CT) scan was acquired for all patients. According to the dose constraint criterion in the Radiation Therapy Oncology Group (RTOG) 0225 protocol, the replanning was generated on the new simulation CT. With the Quality Assessment Center of a CORVUS 6.3 treatment planning system, a phantom plan was generated for each patient by applying the beam configurations of the initial plan to the anatomy of the new simulation CT. The dose-volume histograms of the phantom plan were compared with the replanning. Results: The percentage of prescription dose delivered to the clinical target volume (CTV1) was significantly increased by 4.91% +- 10.89%, whereas the maximum dose to the spinal cord, mean dose to the left parotid, and V30 to the right parotid were significantly decreased by 5.00 +- 9.23Gy, 4.23 +- 10.03Gy, and 11.47% +- 18.89% respectively in the replanning, compared with the phantom plan (p < 0.05). Based on the dose constraint criterion in the RTOG0225 protocol, 50% of phantom plans (14/28) were out of limit for the dose to the normal critical structures, whereas no plan was out of limit in replanning (p < 0.001). Conclusion: Replanning for patients with NPC before the 25th fraction during IMRT helps to ensure adequate dose to the target volumes and safe doses to critical normal structures.

  18. Assessing dose rate distributions in VMAT plans.

    PubMed

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

    2016-04-21

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

  19. An Appetite for Fractions

    ERIC Educational Resources Information Center

    Wilkerson, Trena L.; Bryan, Tommy; Curry, Jane

    2012-01-01

    This article describes how using candy bars as models gives sixth-grade students a taste for learning to represent fractions whose denominators are factors of twelve. Using paper models of the candy bars, students explored and compared fractions. They noticed fewer different representations for one-third than for one-half. The authors conclude…

  20. (Carbon isotope fractionation inplants)

    SciTech Connect

    O'Leary, M.H.

    1990-01-01

    The objectives of this research are: To develop a theoretical and experimental framework for understanding isotope fractionations in plants; and to develop methods for using this isotope fractionation for understanding the dynamics of CO{sub 2} fixation in plants. Progress is described.

  1. The Future of Fractions

    ERIC Educational Resources Information Center

    Usiskin, Zalman P.

    2007-01-01

    In the 1970s, the movement to the metric system (which has still not completely occurred in the United States) and the advent of hand-held calculators led some to speculate that decimal representation of numbers would render fractions obsolete. This provocative proposition stimulated Zalman Usiskin to write "The Future of Fractions" in 1979. He…

  2. Preoperative Single Fraction Partial Breast Radiotherapy for Early-Stage Breast Cancer

    SciTech Connect

    Palta, Manisha; Yoo, Sua; Adamson, Justus D.; Prosnitz, Leonard R.; Horton, Janet K.

    2012-01-01

    Purpose: Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. Methods and Materials: A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A 'virtual plan' was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. Results: The median breast volume was 1,713 cm{sup 3} (range: 1,014-2,140), and the median clinical target volume was 44 cm{sup 3} (range: 26-73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42) and 53% (range: 24-65) in the institutional historical controls treated with postoperative external beam PBI (p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm{sup 3} of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Conclusion: Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing.

  3. Fractionated Grid Therapy in Treating Cervical Cancers: Conventional Fractionation or Hypofractionation?

    SciTech Connect

    Zhang Hualin Wang, Jian Z.; Mayr, Nina; Kong Xiang; Yuan Jiankui; Gupta, Nilendu; Lo, Simon; Grecula, John; Montebello, Joseph; Martin, Douglas; Yuh, William

    2008-01-01

    Purpose: To evaluate the conventionally fractionated and hypofractionated grid therapy in debulking cervical cancers using the linear quadratic (LQ) model. Methods and Materials: A Monte Carlo technique was used to calculate the dose distribution of a commercially available grid in a 6-MV photon beam. The LQ model was used to evaluate the therapeutic outcome of both the conventionally fractionated (2 Gy/fraction) and hypofractionated (15 Gy/fraction) grid therapy regimens to debulk cervical cancers with different LQ parameters. The equivalent open-field dose (EOD) to the cancer cells and therapeutic ratio (TR) were defined by comparing grid therapy with the open debulking field. The clinical outcomes from 114 patients were used to verify our theoretical model. Results: The cervical cancer and normal tissue cell survival statistics for grid therapy in two regimens were calculated. The EODs and TRs were derived. The EOD was only a fraction of the prescribed dose. The TR was dependent on the prescribed dose and the LQ parameters of both the tumor and normal tissue cells. The grid therapy favors the acutely responding tumors inside radiosensitive normal tissues. Theoretical model predictions were consistent with the clinical outcomes. Conclusions: Grid therapy provided a pronounced therapeutic advantage in both the hypofractionated and conventionally fractionated regimens compared with that seen with single fraction, open debulking field regimens, but the true therapeutic advantage exists only in the hypofractionated grid therapy. The clinical outcomes and our study indicated that a course of open-field radiotherapy is necessary to control tumor growth fully after a grid therapy.

  4. Minimizing metastatic risk in radiotherapy fractionation schedules

    NASA Astrophysics Data System (ADS)

    Badri, Hamidreza; Ramakrishnan, Jagdish; Leder, Kevin

    2015-11-01

    Metastasis is the process by which cells from a primary tumor disperse and form new tumors at distant anatomical locations. The treatment and prevention of metastatic cancer remains an extremely challenging problem. This work introduces a novel biologically motivated objective function to the radiation optimization community that takes into account metastatic risk instead of the status of the primary tumor. In this work, we consider the problem of developing fractionated irradiation schedules that minimize production of metastatic cancer cells while keeping normal tissue damage below an acceptable level. A dynamic programming framework is utilized to determine the optimal fractionation scheme. We evaluated our approach on a breast cancer case using the heart and the lung as organs-at-risk (OAR). For small tumor α /β values, hypo-fractionated schedules were optimal, which is consistent with standard models. However, for relatively larger α /β values, we found the type of schedule depended on various parameters such as the time when metastatic risk was evaluated, the α /β values of the OARs, and the normal tissue sparing factors. Interestingly, in contrast to standard models, hypo-fractionated and semi-hypo-fractionated schedules (large initial doses with doses tapering off with time) were suggested even with large tumor α/β values. Numerical results indicate the potential for significant reduction in metastatic risk.

  5. Assessing dose rate distributions in VMAT plans

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  6. Fractional calculus in bioengineering.

    PubMed

    Magin, Richard L

    2004-01-01

    Fractional calculus (integral and differential operations of noninteger order) is not often used to model biological systems. Although the basic mathematical ideas were developed long ago by the mathematicians Leibniz (1695), Liouville (1834), Riemann (1892), and others and brought to the attention of the engineering world by Oliver Heaviside in the 1890s, it was not until 1974 that the first book on the topic was published by Oldham and Spanier. Recent monographs and symposia proceedings have highlighted the application of fractional calculus in physics, continuum mechanics, signal processing, and electromagnetics, but with few examples of applications in bioengineering. This is surprising because the methods of fractional calculus, when defined as a Laplace or Fourier convolution product, are suitable for solving many problems in biomedical research. For example, early studies by Cole (1933) and Hodgkin (1946) of the electrical properties of nerve cell membranes and the propagation of electrical signals are well characterized by differential equations of fractional order. The solution involves a generalization of the exponential function to the Mittag-Leffler function, which provides a better fit to the observed cell membrane data. A parallel application of fractional derivatives to viscoelastic materials establishes, in a natural way, hereditary integrals and the power law (Nutting/Scott Blair) stress-strain relationship for modeling biomaterials. In this review, I will introduce the idea of fractional operations by following the original approach of Heaviside, demonstrate the basic operations of fractional calculus on well-behaved functions (step, ramp, pulse, sinusoid) of engineering interest, and give specific examples from electrochemistry, physics, bioengineering, and biophysics. The fractional derivative accurately describes natural phenomena that occur in such common engineering problems as heat transfer, electrode/electrolyte behavior, and sub

  7. Fractional calculus in bioengineering.

    PubMed

    Magin, Richard L

    2004-01-01

    Fractional calculus (integral and differential operations of noninteger order) is not often used to model biological systems. Although the basic mathematical ideas were developed long ago by the mathematicians Leibniz (1695), Liouville (1834), Riemann (1892), and others and brought to the attention of the engineering world by Oliver Heaviside in the 1890s, it was not until 1974 that the first book on the topic was published by Oldham and Spanier. Recent monographs and symposia proceedings have highlighted the application of fractional calculus in physics, continuum mechanics, signal processing, and electromagnetics, but with few examples of applications in bioengineering. This is surprising because the methods of fractional calculus, when defined as a Laplace or Fourier convolution product, are suitable for solving many problems in biomedical research. For example, early studies by Cole (1933) and Hodgkin (1946) of the electrical properties of nerve cell membranes and the propagation of electrical signals are well characterized by differential equations of fractional order. The solution involves a generalization of the exponential function to the Mittag-Leffler function, which provides a better fit to the observed cell membrane data. A parallel application of fractional derivatives to viscoelastic materials establishes, in a natural way, hereditary integrals and the power law (Nutting/Scott Blair) stress-strain relationship for modeling biomaterials. In this review, I will introduce the idea of fractional operations by following the original approach of Heaviside, demonstrate the basic operations of fractional calculus on well-behaved functions (step, ramp, pulse, sinusoid) of engineering interest, and give specific examples from electrochemistry, physics, bioengineering, and biophysics. The fractional derivative accurately describes natural phenomena that occur in such common engineering problems as heat transfer, electrode/electrolyte behavior, and sub

  8. Effect of methoxychlor on the antioxidant system in mitochondrial and microsome-rich fractions of rat testis.

    PubMed

    Latchoumycandane, C; Mathur, P P

    2002-07-01

    Methoxychlor, an environmental contaminant, which is widely used as a pesticide in many countries, has been shown to induce reproductive abnormalities in male rats. The precise nature and mechanism of action of methoxychlor on the male reproductive system is not clear. In the present study, we have sought to investigate the induction of oxidative stress in the testis of rat after exposure to methoxychlor. Methoxychlor (1, 10, and 100 mg kg(-1) body weight per day) was administered orally to the rats for 45 days. After 24 h of the last treatment the animals were killed using anesthetic ether. The body weight of the animals administered with methoxychlor did not show any significant change. The weights of the testis, epididymis, seminal vesicles and ventral prostate decreased significantly in 100 mg dose but remained unchanged in 1 and 10 mg doses. Mitochondrial and microsome-rich fractions of the testis were obtained by the method of differential centrifugation. The activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase decreased significantly in the animals treated with methoxychlor in a dose-dependent manner in the mitochondrial and microsome-rich fractions of rat testis. The levels of hydrogen peroxide generation (H(2)O(2)) and lipid peroxidation increased in mitochondrial and microsome-rich fractions of the testis of the rats treated with methoxychlor. The results suggested that the low to medium doses of methoxychlor elicit depletion of antioxidant enzymes and concomitant increase in the levels of H(2)O(2) and lipid peroxidation differentially in mitochondrial and microsome-rich fractions of rat testis. In conclusion, the adverse effect of methoxychlor on male reproduction could be due to the induction of oxidative stress in testis.

  9. Stable Chlorine Isotope Fractionation

    NASA Astrophysics Data System (ADS)

    Sharp, Z.

    2006-12-01

    Chlorine isotope partitioning between different phases is not well understood. Pore fluids can have δ37Cl values as low as -8‰, with neoform sediments having strongly positive values. Most strikingly, volcanic gases have δ37Cl values that cover a range in excess of 14‰ (Barnes et al., this meeting). The large range is difficult to explain in terms of equilibrium fractionation, which, although calculated to be very large for Cl in different oxidation states, should be less than 2‰ between chloride species (Schauble et al., 2003, GCA). To address the discrepancy between Nature and theory, we have measured Cl isotope fractionation for selected equilibrium and disequilibrium experiments in order to identify mechanisms that might lead to large fractionations. 1) NaCl (s,l) NaCl (v): NaCl was sealed in an evacuated silica tube and heated at one end, causing vaporization and reprecipitation of NaCl (v) at the cool end of the tube. The fractionation is 0.2‰ at 700°C (halite-vapor) and 0.7‰ at 800°C (liquid-vapor), respectively. The larger fractionation at higher temperature may be related to equilibrium fractionation between liquid and gas vs. `stripping' of the solid in the lower T experiments. 2) Sodalite NaCl(l): Nepheline and excess NaCl were sealed in a Pt crucible at 825°C for 48 hrs producing sodalite. The measured newly-formed sodalite-NaCl fractionation is -0.2‰. 3) Volatilization of HCl: Dry inert gas was bubbled through HCl solutions and the vapor was collected in a downstream water trap. There was no fractionation for 12.4M HCl (HCl fuming) vapor at 25°C. For a 1 M boiling HCl solution, the HCl-vapor fractionation was ~9‰. The difference is probably related to the degree of dissociation in the acid, with HCl dissolved in water for the highly acidic solutions, and dissociated H3O+ and Cl- for lower concentrations. The HCl volatilization experiments are in contrast to earlier vapor-liquid experiments in NaCl-H2O system, where fractionation was

  10. Intracellular Cadmium Isotope Fractionation

    NASA Astrophysics Data System (ADS)

    Horner, T. J.; Lee, R. B.; Henderson, G. M.; Rickaby, R. E.

    2011-12-01

    Recent stable isotope studies into the biological utilization of transition metals (e.g. Cu, Fe, Zn, Cd) suggest several stepwise cellular processes can fractionate isotopes in both culture and nature. However, the determination of fractionation factors is often unsatisfactory, as significant variability can exist - even between different organisms with the same cellular functions. Thus, it has not been possible to adequately understand the source and mechanisms of metal isotopic fractionation. In order to address this problem, we investigated the biological fractionation of Cd isotopes within genetically-modified bacteria (E. coli). There is currently only one known biological use or requirement of Cd, a Cd/Zn carbonic anhydrase (CdCA, from the marine diatom T. weissfloggii), which we introduce into the E. coli genome. We have also developed a cleaning procedure that allows for the treating of bacteria so as to study the isotopic composition of different cellular components. We find that whole cells always exhibit a preference for uptake of the lighter isotopes of Cd. Notably, whole cells appear to have a similar Cd isotopic composition regardless of the expression of CdCA within the E. coli. However, isotopic fractionation can occur within the genetically modified E. coli during Cd use, such that Cd bound in CdCA can display a distinct isotopic composition compared to the cell as a whole. Thus, the externally observed fractionation is independent of the internal uses of Cd, with the largest Cd isotope fractionation occurring during cross-membrane transport. A general implication of these experiments is that trace metal isotopic fractionation most likely reflects metal transport into biological cells (either actively or passively), rather than relating to expression of specific physiological function and genetic expression of different metalloenzymes.

  11. Effect of almond consumption on the serum fatty acid profile: a dose-response study.

    PubMed

    Nishi, Stephanie; Kendall, Cyril W C; Gascoyne, Ana-Maria; Bazinet, Richard P; Bashyam, Balachandran; Lapsley, Karen G; Augustin, Livia S A; Sievenpiper, John L; Jenkins, David J A

    2014-10-14

    Consumption of almonds has been shown to be associated with a decreased risk of CHD, which may be related to their fatty acid (FA) composition. However, the effect of almond consumption on the serum FA composition is not known. Therefore, in the present study, we investigated whether almond consumption would alter the serum FA profile and risk of CHD, as calculated using Framingham's 10-year risk score, in a dose-dependent manner in hyperlipidaemic individuals when compared with a higher-carbohydrate control group using dietary interventions incorporating almonds. A total of twenty-seven hyperlipidaemic individuals consumed three isoenergetic (mean 1770 kJ/d) supplements during three 1-month dietary phases: (1) full-dose almonds (50-100 g/d); (2) half-dose almonds with half-dose muffins; (3) full-dose muffins. Fasting blood samples were obtained at weeks 0 and 4 for the determination of FA concentrations. Almond intake (g/d) was found to be inversely associated with the estimated Framingham 10-year CHD risk score (P= 0·026). In both the half-dose and full-dose almond groups, the proportions of oleic acid (OA) and MUFA in the TAG fraction (half-almond: OA P= 0·003; MUFA P= 0·004; full-almond: OA P< 0·001; MUFA P< 0·001) and in the NEFA fraction (half-almond: OA P= 0·01; MUFA P= 0·04; full-almond: OA P= 0·12; MUFA P= 0·06) increased. The estimated Framingham 10-year CHD risk score was inversely associated with the percentage change of OA (P= 0·011) and MUFA (P= 0·016) content in the TAG fraction. The proportions of MUFA in the TAG and NEFA fractions were positively associated with changes in HDL-cholesterol concentrations. Similarly, the estimated Framingham 10-year CHD risk score was inversely associated with the percentage change of OA (P= 0·069) and MUFA content in the NEFA fraction (P= 0·009). In conclusion, the results of the present study indicate that almond consumption increases OA and MUFA content in serum TAG and NEFA fractions

  12. Dose rate mapping of VMAT treatments

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  13. Dose rate mapping of VMAT treatments

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  14. Dose rate mapping of VMAT treatments.

    PubMed

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

    2016-06-01

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

  15. Chromatographic methods of fractionation.

    PubMed

    Friesen, A D

    1987-01-01

    Chromatography's functional versatility, separation efficiency, gentle non-denaturing separating process and ease of automation and scale-up make it attractive for industrial scale protein purification. The Winnipeg Rh Institute's new Plasma Fractionation facility is an example of the use of chromatography for the large scale purification of plasma protein fractions. The fractionation facility has a capacity to process 800 litres of plasma per batch into blood clotting factor VIII and IX, albumin and intravenous immune serum globulin (i.v. ISG). Albumin and i.v. ISG are purified using ion exchange columns of DEAE-Sepharose (230 litre size), DEAE-Biogel (150 litre size) and CM-Sepharose (150 litre size). The chromatographic process is automated using a Modicon 584 Programmable Logic Controller to regulate valves, pumps and sensors which control plasma flow during fractionation. The stainless steel tanks and piping are automatically cleaned-in-place. The high degree of automation and cleaning provides efficient operation and sanitary processing. Chromatographic methods (DEAE-Sepharose and metal chelation) are also being used at the pilot scale to purify the human blood products superoxide dismutase and hemoglobin from outdated red blood cells. Characterization of the protein fractions produced by chromatography has shown them to be of equal or higher quality than fractions produced by other techniques.

  16. A Practical Guide for the Treatment of Symptomatic Heart Failure with Reduced Ejection Fraction (HFrEF)

    PubMed Central

    Reed, Brent N; Sueta, Carla A

    2015-01-01

    This review will outline the management of patients with symptomatic systolic heart failure or heart failure with reduced ejec-tion fraction (HFrEF), i.e., those with structural heart disease and previous or current symptoms. Determination of volume status and appropriate diuretic administration is important in heart failure management. Inhibition of the renin-angiotensin-aldosterone and sympathetic nervous systems improves survival and decreases hospitalizations in patients with systolic or reduced ejection fraction HF (HFrEF). Beta blockers and aldosterone antagonists improve ejection fraction. Indications for additional agents including nitrates plus hydralazine, digoxin, statins, omega 3 polyunsaturated fatty acids, anticoagulants, and antiarrhythmics will be discussed. Choice of agents, dose-related effects, strategies to minimize adverse effects, and medications to avoid will be presented. PMID:24251455

  17. 21 years of Biologically Effective Dose

    PubMed Central

    Fowler, J F

    2010-01-01

    In 1989 the British Journal of Radiology published a review proposing the term biologically effective dose (BED), based on linear quadratic cell survival in radiobiology. It aimed to indicate quantitatively the biological effect of any radiotherapy treatment, taking account of changes in dose-per-fraction or dose rate, total dose and (the new factor) overall time. How has it done so far? Acceptable clinical results have been generally reported using BED, and it is in increasing use, although sometimes mistaken for “biologically equivalent dose”, from which it differs by large factors, as explained here. The continuously bending nature of the linear quadratic curve has been questioned but BED has worked well for comparing treatments in many modalities, including some with large fractions. Two important improvements occurred in the BED formula. First, in 1999, high linear energy transfer (LET) radiation was included; second, in 2003, when time parameters for acute mucosal tolerance were proposed, optimum overall times could then be “triangulated” to optimise tumour BED and cell kill. This occurs only when both early and late BEDs meet their full constraints simultaneously. New methods of dose delivery (intensity modulated radiation therapy, stereotactic body radiation therapy, protons, tomotherapy, rapid arc and cyberknife) use a few large fractions and obviously oppose well-known fractionation schedules. Careful biological modelling is required to balance the differing trends of fraction size and local dose gradient, as explained in the discussion “How Fractionation Really Works”. BED is now used for dose escalation studies, radiochemotherapy, brachytherapy, high-LET particle beams, radionuclide-targeted therapy, and for quantifying any treatments using ionising radiation. PMID:20603408

  18. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    SciTech Connect

    Levy, R.P.

    1991-01-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examining the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute [gamma]-radiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. It was concluded that oligodendrocytes in irradiated cultures had significantly lower functional capacity than did unirradiated controls. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. At DIC 14, the group irradiated in a single fraction had significantly lower oligodendrocyte counts than any group given split doses; all irradiated cultures had marked depression of MBP synthesis, but to significant differences referable to time interval between doses. At DIC 21, cultures irradiated at intervals of 0 h to 2 h had similar oligodendrocyte counts to one another, but these counts were significantly lower than in cultures irradiated at intervals of 4 h to 6 h; MBP levels remained depressed at DIC 21 for all irradiated cultures. The oligodendrocyte response to dose rate (0.03 to 1.97 Gy/min) was evaluated at DIC 14 and DIC 21. Exposure at 0.03 Gy/min suppressed oligodendrocyte counts at DIC 21 less than did higher dose rates in 5-Gy irradiated cultures.

  19. Deviation of negatively charged protein fractions in the trochophore and veliger larvae by the larvicidal action of baygon in freshwater pulmonate Gyraulus convexiusculus (Planorbidae).

    PubMed

    Bhide, Mangla; Gupta, Priyamvada

    2006-10-01

    In the present investigation egg capsules of Gyraulus convexiusculus were treated with different concentrations of baygon. A dose and duration dependent deviations in the number of negatively charged protein fractions in the trochophore and veliger larval stages were observed. It resulted into anomalies in the morphogenesis and organogenesis of corresponding larval stages. Most of the protein bands showed the decrease in the protein positive intensities in comparison to control. This suggested that baygon causes larval toxicity in Gyraulus convexiusculus.

  20. Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant

    SciTech Connect

    Singh, Anurag K. . E-mail: singan@mail.nih.gov; Karimpour, Shervin E.; Savani, Bipin N.; Guion, Peter M.S.; Hope, Andrew J.; Mansueti, John R.; Ning, Holly; Altemus, Rosemary M. Ph.D.; Wu, Colin O.; Barrett, A. John

    2006-10-01

    Purpose: To determine the value of pulmonary function tests (PFTs) done before peripheral blood stem cell transplant (PBSCT) in predicting mortality after total body irradiation (TBI) performed with or without dose reduction to the lung. Methods and Materials: From 1997 to 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. With regimen A (n = 85), patients were treated without lung dose reduction to 13.6 gray (Gy). In regimen B (n = 35), total body dose was decreased to 12 Gy (1.5 Gy twice per day for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In regimen C (n = 26), lung dose was reduced to 6 Gy. All patients received PFTs before treatment, 90 days after treatment, and annually. Results: Median follow-up was 44 months (range, 12-90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV{sub 1}) and a diffusion capacity of carbon dioxide (DLCO) <100% predicted. In this group, there was a 20% improvement in one-year overall survival with lung dose reduction (70 vs. 50%, log-rank test p = 0.042). Conclusion: Among those with combined ventilation/diffusion capacity deficits, lung dose reduction during TBI significantly improved survival.

  1. Effect of particle size in the TL response of natural quartz sensitized with high gamma dose

    NASA Astrophysics Data System (ADS)

    Carvalho, A. B., Jr.; Guzzo, P. L.; Sullasi, H. L.; Khoury, H. J.

    2010-11-01

    The aim of this study is to investigate the effect of particle size in the thermoluminescence (TL) response of natural quartz sensitized with high gamma dose. For this, fragments of a single crystal taken from the Solonópole district (Brazil) were crushed and classified into ten size fractions ranging from 38 μm to 5 mm. Aliquots of each size fraction were sensitized with 25 kGy of gamma dose of 60Co and heat-treated in a muffle furnace at 400oC. The non-sensitized samples were exposed to test doses between 50 Gy and 5 kGy and the sensitized samples were exposed to a unique test dose equal to 50 mGy. For non-sensitized samples, the TL peak near 325 °C increases with the particle size decreasing. However, in the case of sensitized samples, the TL output near 280 °C increases with the increasing of particle size up to mean grain size equal to 308 μm. Above 308 μm, an abrupt reduction in the TL intensity was noticed. These effects are discussed in relation to the specific surface area and the different interaction of high gamma doses with fine and coarse particles of quartz.

  2. Modeling of dose to tumor and normal tissue from intraperitoneal radioimmunotherapy with alpha and beta emitters

    SciTech Connect

    Roeske, J.C.; Chen, G.T.; Atcher, R.W.; Pelizzari, C.A.; Rotmensch, J.; Haraf, D.; Montag, A.; Weichselbaum, R.R. )

    1990-12-01

    Dose distributions for normal and tumor tissues from intraperitoneally administered radiolabeled antibodies have been calculated for 90-Yttrium (90Y), 131-Iodine (131I), and 211-Astatine (211At). The dose calculations use data on the activity of intraperitoneal fluid administered, the percent injected dose/gm uptake by tumor, biological half life, and a model for diffusion of antibody/radionuclide complex into peritoneal tissues. Calculations are performed for planar and hemispherical tumor shapes, ranging in size to establish the influence of geometry on dose distribution. Calculations for tumor geometry obtained from biopsies are also performed. When the activity is concentrated on or near the tumor surface, the maximum dose to a planar tumor for a 20 mci administration of 90Y is approximately 60 Gy, and falls rapidly to 50% of this value within 1 mm. However, for a hemispherical tumor, the dose is a maximum of 26 Gy, with an average of approximately 20 Gy. The surface dose from 131I (130 mci) is 240 Gy, and diminishes to 20 Gy in .05 cm in the planar case, whereas a hemispherical tumor receives a dose of 90 Gy over a large fraction of the volume, with the distal portions receiving 40 Gy. The surface dose for an administration of 70 mci of 211 At is 450 Gy and decreases to 50% of this value in 30 microns. Both surface geometry and tumor size are important determinants in the heterogeneity of tumor dose, as are the dose administered, antibody uptake, biodistribution, and residence time factors. These initial studies suggest that the size of disease which may be effectively treated is much less than the range of the particle emitted by radiolabeled antibodies. Furthermore, therapy is ultimately limited by the degree to which the antibody/radionuclide complex can diffuse and permeate the tumor.

  3. Fractional Noether Theorem Based on Extended Exponentially Fractional Integral

    NASA Astrophysics Data System (ADS)

    Long, Zi-Xuan; Zhang, Yi

    2013-10-01

    Based on the new type of fractional integral definition, namely extended exponentially fractional integral introduced by EI-Nabulsi, we study the fractional Noether symmetries and conserved quantities for both holonomic system and nonholonomic system. First, the fractional variational problem under the sense of extended exponentially fractional integral is established, the fractional d'Alembert-Lagrange principle is deduced, then the fractional Euler-Lagrange equations of holonomic system and the fractional Routh equations of nonholonomic system are given; secondly, the invariance of fractional Hamilton action under infinitesimal transformations of group is also discussed, the corresponding definitions and criteria of fractional Noether symmetric transformations and quasi-symmetric transformations are established; finally, the fractional Noether theorems for both holonomic system and nonholonomic system are explored. What's more, the relationship between the fractional Noether symmetry and conserved quantity are revealed.

  4. Dose reconstruction technique using non-rigid registration to evaluate spatial correspondence between high-dose region and late radiation toxicity: a case of tracheobronchial stenosis after external beam radiotherapy combined with endotracheal brachytherapy for tracheal cancer

    PubMed Central

    Murakami, Naoya; Inaba, Koji; Wakita, Akihisa; Nakamura, Satoshi; Okamoto, Hiroyuki; Sato, Jun; Umezawa, Rei; Takahashi, Kana; Igaki, Hiroshi; Ito, Yoshinori; Shigematsu, Naoyuki; Itami, Jun

    2016-01-01

    Purpose Small organ subvolume irradiated by a high-dose has been emphasized to be associated with late complication after radiotherapy. Here, we demonstrate a potential use of surface-based, non-rigid registration to investigate how high-dose volume topographically correlates with the location of late radiation morbidity in a case of tracheobronchial radiation stenosis. Material and methods An algorithm of point set registration was implemented to handle non-rigid registration between contour points on the organ surfaces. The framework estimated the global correspondence between the dose distribution and the varying anatomical structure. We applied it to an 80-year-old man who developed tracheobronchial stenosis 2 years after high-dose-rate endobronchial brachytherapy (HDR-EBT) (24 Gy in 6 Gy fractions) and external beam radiotherapy (EBRT) (40 Gy in 2 Gy fractions) for early-stage tracheal cancer. Results and conclusions Based on the transformation function computed by the non-rigid registration, irradiated dose distribution was reconstructed on the surface of post-treatment tracheobronchial stenosis. For expressing the equivalent dose in a fractional dose of 2 Gy in HDR-EBT, α/β of linear quadratic model was assumed as 3 Gy for the tracheal bronchus. The tracheobronchial surface irradiated by more than 100 Gyαβ3 tended to develop severe stenosis, which attributed to a more than 50% decrease in the luminal area. The proposed dose reconstruction technique can be a powerful tool to predict late radiation toxicity with spatial consideration. PMID:27257421

  5. Radiation Dose-Volume Effects in the Spinal Cord

    SciTech Connect

    Kirkpatrick, John P.; Kogel, Albert J. van der; Schultheiss, Timothy E.

    2010-03-01

    Dose-volume data for myelopathy in humans treated with radiotherapy (RT) to the spine is reviewed, along with pertinent preclinical data. Using conventional fractionation of 1.8-2 Gy/fraction to the full-thickness cord, the estimated risk of myelopathy is <1% and <10% at 54 Gy and 61 Gy, respectively, with a calculated strong dependence on dose/fraction (alpha/beta = 0.87 Gy.) Reirradiation data in animals and humans suggest partial repair of RT-induced subclinical damage becoming evident about 6 months post-RT and increasing over the next 2 years. Reports of myelopathy from stereotactic radiosurgery to spinal lesions appear rare (<1%) when the maximum spinal cord dose is limited to the equivalent of 13 Gy in a single fraction or 20 Gy in three fractions. However, long-term data are insufficient to calculate a dose-volume relationship for myelopathy when the partial cord is treated with a hypofractionated regimen.

  6. Evaluation of wound healing properties of bioactive aqueous fraction from Moringa oleifera Lam on experimentally induced diabetic animal model.

    PubMed

    Muhammad, Abubakar Amali; Arulselvan, Palanisamy; Cheah, Pike See; Abas, Farida; Fakurazi, Sharida

    2016-01-01

    Diabetic foot ulcer is a serious complication of diabetes, which affects a significant percentage (15%) of diabetics and up to 15%-24% of those affected may require amputation. Therefore, the economic burden of diabetic foot ulcers is enormous and is associated with high cost of treatment and prolongs hospitalization. The present study was conducted to evaluate antibacterial and in vivo wound healing activities of an aqueous fraction of Moringa oleifera on a diabetic condition. Antibacterial activity testing was carried out using agar well and tube dilution techniques. The in vivo study was conducted using six groups of animals that comprise of one normal and diabetic control group each, three treatment groups of 0.5%, 1%, and 2% w/w aqueous fraction, and a positive control group (1% w/w silver sulfadiazine). Rats were induced with diabetes using a combination of streptozotocin 65 and 150 mg/kg nicotinamide daily for 2 days, and excision wounds were created and treated with various doses (0.5%, 1%, and 2% w/w aqueous fraction) daily for 21 days. Biophysical, histological, and biochemical parameters were investigated. The results of the study revealed that aqueous fraction possessed antibacterial activity through inhibition of growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli organisms. The topical application of aqueous fraction revealed enhancement of wound healing under sustained hyperglycemic condition for the duration of the experiment. This enhancement was achieved through decreased wound size, improved wound contraction, and tissue regeneration, as well as downregulation of inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2, and upregulation of an angiogenic marker vascular endothelial growth factor in wound tissue treated with various doses of aqueous fraction of M. oleifera. The findings suggest that aqueous fraction of M. oleifera

  7. Evaluation of wound healing properties of bioactive aqueous fraction from Moringa oleifera Lam on experimentally induced diabetic animal model.

    PubMed

    Muhammad, Abubakar Amali; Arulselvan, Palanisamy; Cheah, Pike See; Abas, Farida; Fakurazi, Sharida

    2016-01-01

    Diabetic foot ulcer is a serious complication of diabetes, which affects a significant percentage (15%) of diabetics and up to 15%-24% of those affected may require amputation. Therefore, the economic burden of diabetic foot ulcers is enormous and is associated with high cost of treatment and prolongs hospitalization. The present study was conducted to evaluate antibacterial and in vivo wound healing activities of an aqueous fraction of Moringa oleifera on a diabetic condition. Antibacterial activity testing was carried out using agar well and tube dilution techniques. The in vivo study was conducted using six groups of animals that comprise of one normal and diabetic control group each, three treatment groups of 0.5%, 1%, and 2% w/w aqueous fraction, and a positive control group (1% w/w silver sulfadiazine). Rats were induced with diabetes using a combination of streptozotocin 65 and 150 mg/kg nicotinamide daily for 2 days, and excision wounds were created and treated with various doses (0.5%, 1%, and 2% w/w aqueous fraction) daily for 21 days. Biophysical, histological, and biochemical parameters were investigated. The results of the study revealed that aqueous fraction possessed antibacterial activity through inhibition of growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli organisms. The topical application of aqueous fraction revealed enhancement of wound healing under sustained hyperglycemic condition for the duration of the experiment. This enhancement was achieved through decreased wound size, improved wound contraction, and tissue regeneration, as well as downregulation of inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2, and upregulation of an angiogenic marker vascular endothelial growth factor in wound tissue treated with various doses of aqueous fraction of M. oleifera. The findings suggest that aqueous fraction of M. oleifera

  8. Evaluation of wound healing properties of bioactive aqueous fraction from Moringa oleifera Lam on experimentally induced diabetic animal model

    PubMed Central

    Muhammad, Abubakar Amali; Arulselvan, Palanisamy; Cheah, Pike See; Abas, Farida; Fakurazi, Sharida

    2016-01-01

    Diabetic foot ulcer is a serious complication of diabetes, which affects a significant percentage (15%) of diabetics and up to 15%–24% of those affected may require amputation. Therefore, the economic burden of diabetic foot ulcers is enormous and is associated with high cost of treatment and prolongs hospitalization. The present study was conducted to evaluate antibacterial and in vivo wound healing activities of an aqueous fraction of Moringa oleifera on a diabetic condition. Antibacterial activity testing was carried out using agar well and tube dilution techniques. The in vivo study was conducted using six groups of animals that comprise of one normal and diabetic control group each, three treatment groups of 0.5%, 1%, and 2% w/w aqueous fraction, and a positive control group (1% w/w silver sulfadiazine). Rats were induced with diabetes using a combination of streptozotocin 65 and 150 mg/kg nicotinamide daily for 2 days, and excision wounds were created and treated with various doses (0.5%, 1%, and 2% w/w aqueous fraction) daily for 21 days. Biophysical, histological, and biochemical parameters were investigated. The results of the study revealed that aqueous fraction possessed antibacterial activity through inhibition of growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli organisms. The topical application of aqueous fraction revealed enhancement of wound healing under sustained hyperglycemic condition for the duration of the experiment. This enhancement was achieved through decreased wound size, improved wound contraction, and tissue regeneration, as well as downregulation of inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2, and upregulation of an angiogenic marker vascular endothelial growth factor in wound tissue treated with various doses of aqueous fraction of M. oleifera. The findings suggest that aqueous fraction of M. oleifera

  9. Houttuynia cordata Thunb fraction induces human leukemic Molt-4 cell apoptosis through the endoplasmic reticulum stress pathway.

    PubMed

    Prommaban, Adchara; Kodchakorn, Kanchanok; Kongtawelert, Prachya; Banjerdpongchai, Ratana

    2012-01-01

    Houttuynia cordata Thunb (HCT) is a native herb found in Southeast Asia which features various pharmacological activities against allergy, inflammation, viral and bacterial infection, and cancer. The aims of this study were to determine the cytotoxic effect of 6 fractions obtained from silica gel column chromatography of alcoholic HCT extract on human leukemic Molt-4 cells and demonstrate mechanisms of cell death. Six HCT fractions were cytotoxic to human lymphoblastic leukemic Molt-4 cells in a dose-dependent manner by MTT assay, fraction 4 exerting the greatest effects. Treatment with IC50 of HCT fraction 4 significantly induced Molt-4 apoptosis detected by annexinV-FITC/propidium iodide for externalization of phosphatidylserine to the outer layer of cell membrane. The mitochondrial transmembrane potential was reduced in HCT fraction 4-treated Molt-4 cells. Moreover, decreased expression of Bcl-xl and increased levels of Smac/Diablo, Bax and GRP78 proteins were noted on immunoblotting. In conclusion, HCT fraction 4 induces Molt-4 apoptosis cell through an endoplasmic reticulum stress pathway. PMID:22901157

  10. FRACTIONAL CRYSTALLIZATION FEED ENVELOPE

    SciTech Connect

    HERTING DL

    2008-03-19

    Laboratory work was completed on a set of evaporation tests designed to establish a feed envelope for the fractional crystallization process. The feed envelope defines chemical concentration limits within which the process can be operated successfully. All 38 runs in the half-factorial design matrix were completed successfully, based on the qualitative definition of success. There is no feed composition likely to be derived from saltcake dissolution that would cause the fractional crystallization process to not meet acceptable performance requirements. However, some compositions clearly would provide more successful operation than other compositions.

  11. Release Fraction Evaluation

    SciTech Connect

    Bamberger, Judith A.; Glissmeyer, John A.

    2004-01-01

    This document presents results of experiments conducted to measure release fractions during certain tank retrieval processes. The tests were performed in a 1/4 scale model of a waste storage tank. The retrieval processes simulated were: (1) Discharging liquid or slurry from the mouth of a vertically oriented two-in. Schedule 40 pipe. The discharging material was in free-fall from the mouth of the pipe near the top of the tank into a liquid or slurry pool at the bottom of the tank. (2) The jet from a 9/16-in.-diameter nozzle transferring liquid or slurry waste from one side of the tank to the other. The discharging liquid was aimed at the opposite side of the tank from the nozzle and either impacted the tank wall or fell into a liquid or slurry pool in the bottom of the tank. (3) A high pressure fan jet of liquid striking a steel plate or simulated waste from a stand-off distance of a few inches. For each process, a water-soluble fluorescent dye was added to the liquid fraction as a tracer. Kaolin clay was used to represent the solids. The tank was covered and there was no forced ventilation in the tank during the tests. Six air samples were collected during each test. The air samples were collected at fixed positions in the tank. The air sample filters were dried and weighed to determine the solids collection. The fluorescent dye was then leached from each filter and quantified with a fluorometer to determine the collection of liquid. Samples of the slurry and liquid simulants were also collected to determine the quantities of simulant used in each test. To calculate the release fraction, the quantity collected on each air sample was adjusted for the fraction of the tank volume sampled and divided by the quantity of material exposed in the simulation. The method was not as sensitive for the solids content as it was for the liquid content, but in those instances where a solids release fraction was determined, it was in relatively good agreement with that of the

  12. Radiation effects on the immiscible polymer blend of nylon1010 and high-impact polystyrene (HIPS) I: Gel/dose curves, mathematical expectation theorem and thermal behaviour

    NASA Astrophysics Data System (ADS)

    Dong, W.; Zhang, W.; Chen, G.; Liu, J.

    2000-01-01

    This paper studies the radiation properties of the immiscible blend of nylon1010 and HIPS. The gel fraction increased with increasing radiation dose. The network was found mostly in nylon1010, the networks were also found in both nylon1010 and HIPS when the dose reaches 0.85 MGy or more. We used the Charleby-Pinner equation and the modified Zhang-Sun-Qian equation to simulate the relationship with the dose and the sol fraction. The latter equation fits well with these polymer blends and the relationship used by it showed better linearity than the one by the Charleby-Pinner equation. We also studied the conditions of formation of the network by the mathematical expectation theorem for the binary system. Thermal properties of polymer blend were observed by DSC curves. The crystallization temperature decreases with increasing dose because the cross-linking reaction inhibited the crystallization procession and destroyed the crystals. The melting temperature also reduced with increasing radiation dose. The dual melting peak gradually shifted to single peak and the high melting peak disappeared at high radiation dose. However, the radiation-induced crystallization was observed by the heat of fusion increasing at low radiation dose. On the other hand, the crystal will be damaged by radiation. A similar conclusion may be drawn by the DSC traces when the polymer blends were crystallized. When the radiation dose increases, the heat of fusion reduces dramatically and so does the heat of crystallization.

  13. Treatment Outcome of Medium-Dose-Rate Intracavitary Brachytherapy for Carcinoma of the Uterine Cervix: Comparison With Low-Dose-Rate Intracavitary Brachytherapy

    SciTech Connect

    Kaneyasu, Yuko; Kita, Midori; Okawa, Tomohiko; Maebayashi, Katsuya; Kohno, Mari; Sonoda, Tatsuo; Hirabayashi, Hisae; Nagata, Yasushi; Mitsuhashi, Norio

    2012-09-01

    Purpose: To evaluate and compare the efficacy of medium-dose-rate (MDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for uterine cervical cancer. Methods and Materials: We evaluated 419 patients with squamous cell carcinoma of the cervix who were treated by radical radiotherapy with curative intent at Tokyo Women's Medical University from 1969 to 1999. LDR was used from 1969 to 1986, and MDR has been used since July 1987. When compared with LDR, fraction dose was decreased and fraction size was increased (1 or 2 fractions) for MDR to make the total dose of MDR equal to that of LDR. In general, the patients received a total dose of 60 to 70 Gy at Point A with external beam radiotherapy combined with brachytherapy according to the International Federation of Gynecology and Obstetrics stage. In the LDR group, 32 patients had Stage I disease, 81 had Stage II, 182 had Stage III, and 29 had Stage IVA; in the MDR group, 9 patients had Stage I disease, 19 had Stage II, 55 had Stage III, and 12 had Stage IVA. Results: The 5-year overall survival rates for Stages I, II, III, and IVA in the LDR group were 78%, 72%, 55%, and 34%, respectively. In the MDR group, the 5-year overall survival rates were 100%, 68%, 52%, and 42%, respectively. No significant statistical differences were seen between the two groups. The actuarial rates of late complications Grade 2 or greater at 5 years for the rectum, bladder, and small intestine in the LDR group were 11.1%, 5.8%, and 2.0%, respectively. The rates for the MDR group were 11.7%, 4.2%, and 2.6%, respectively, all of which were without statistical differences. Conclusion: These data suggest that MDR ICBT is effective, useful, and equally as good as LDR ICBT in daytime (about 5 hours) treatments of patients with cervical cancer.

  14. Neuroprotective effect of rough aster butanol fraction against oxidative stress in the brain of mice challenged with kainic acid.

    PubMed

    Sok, Dai-Eun; Oh, Sang Hee; Kim, Yun-Bae; Kim, Mee Ree

    2003-07-30

    The neuroprotective effect of the butanol fraction from the methanol extract of Aster scaber Thunb. (rough aster butanol fraction) on oxidative damage in the brain of mice challenged with kainic acid was examined using behavioral signs and biochemical parameters of oxidative stress. The rough aster butanol fraction (0.4-1.0 g/kg) was administered to ICR male mice, 6-8 weeks, through a gavage for 4 days consecutively, and on the third day, kainic acid (50 mg/kg) was ip administered. When compared to the vehicle-treated control, no significant changes in body and brain weight were observed in mice administered the rough aster butanol fraction. Administration of kainic acid only, causing a lethality of approximately 54%, resulted in a significant decrease of total glutathione level and an increase of the thiobarbituric acid-reactive substances (TBARS) value in brain tissue. When the rough aster butanol fraction was examined for neuroprotective action, the rough aster butanol fraction (0.4 g/kg) alleviated the lethality (25%) of kainic acid and the behavioral sign of its neurotoxicity. Moreover, administration of the rough aster butanol fraction at a dose of 0.4 g/kg restored the glutathione level in the cytosolic portion of brain homogenate to approximately 80% (p < 0.05). Also, the rough aster butanol fraction (0.4 g/kg) led to a significant reduction of kainic acid-induced increase of TBARS value. In addition, the glutathione peroxidase activity was restored significantly (p < 0.05) in the cytosolic portion of brain homogenate, whereas glutathione reductase activity was not. On the basis of these results, the rough aster butanol fraction is suggested to contain a functional agent to prevent oxidative stress in the brain of mice.

  15. Antimicrobial activity of the solvent fractions from Bulbine natalensis Tuber.

    PubMed

    Yakubu, M T; Mostafa, M; Ashafa, A O T; Afolayan, A J

    2012-01-01

    Bulbine natalensis Baker has been acclaimed to be used as an antimicrobial agent in the folklore medicine of South Africa without scientific evidence to substantiate or refute this claim. In view of this, the in vitro antimicrobial activity of solvent fractions (ethanol, ethyl acetate, n-butanol and water) from Bulbine natalensis Tuber against 4 Gram positive and 12 Gram negative bacteria as well as 3 fungal species were investigated using agar dilution. The ethanolic extract, n-butanol and ethyl acetate fractions inhibited 75, 87.5 and 100% respectively of the bacterial species in this study. The ethanolic, n-butanol and ethyl acetate fractions produced growth inhibition at MIC range of 1-10, 3-10 as well as 1 and 5 mg/ml respectively whereas the water fraction did not inhibit the growth of any of the bacterial species. Again, it was only the ethyl acetate fraction that inhibited the growth of Shigelli flexneri, Staphyloccus aureus and Escherichia coli. The ethanolic, ethyl acetate and n-butanolic fractions dose dependently inhibited the growth of Aspergillus niger and A. flavus whereas the water fraction produced 100% growth inhibition of the Aspergillus species at all the doses investigated. In contrast, no growth inhibition was produced on Candida albicans. The growth inhibition produced by the solvent fractions of B. natalensis Tuber in this study thus justifies the acclaimed use of the plant as an antimicrobial agent. The ethyl acetate fraction was the most potent. PMID:23983381

  16. In vitro studies on the adjuvanticity of Brucella fractions.

    PubMed Central

    Serre, A; Vendrell, J P; Huguet, M F; Cannat, A

    1982-01-01

    Two Brucella fractions, the murein-linked fraction PI and the murein-free fraction SF, behave as in vitro adjuvants for primary anti-sheep erythrocyte responses: added to Mishell and Dutton-type cultures of spleen cells from B6/DB F1 mice they significantly enhance the number of direct anti-sheep erythrocyte PFC observed on day 5. They exert both nonspecific, polyclonal activating effects and antigen-dependent specific adjuvanticity. These two functions, however, differ in their dose responses and in their cellular requirements and can therefore be dissociated. Thus, polyclonal activation requires high doses of the "adjuvant fraction," is enhanced by adherent-cell depletion, and is not impaired by T-cell depletion. Specific adjuvanticity, on the other hand, requires lower doses of the adjuvant fractions (very high doses are in fact suppressive) and is T-cell and adherent-cell dependent. Moreover, adjuvanticity can be transferred to unstimulated spleen cells (or restored in adherent-cell-depleted populations) by PI- or SF-stimulated adherent cells or by the filtered supernatants of such cultures; adjuvant-soluble factors are therefore involved in the phenomena of adherent, T- and B-cell cooperation required for the adjuvanticity of Brucella fractions. PMID:6982864

  17. Intensity-Modulated Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Dose-Escalation Planning Study

    SciTech Connect

    Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

    2011-05-01

    Purpose: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods and Materials: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). Results: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p {<=}.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. Conclusion: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

  18. Fractional Brownian motion and motion governed by the fractional Langevin equation in confined geometries.

    PubMed

    Jeon, Jae-Hyung; Metzler, Ralf

    2010-02-01

    Motivated by subdiffusive motion of biomolecules observed in living cells, we study the stochastic properties of a non-Brownian particle whose motion is governed by either fractional Brownian motion or the fractional Langevin equation and restricted to a finite domain. We investigate by analytic calculations and simulations how time-averaged observables (e.g., the time-averaged mean-squared displacement and displacement correlation) are affected by spatial confinement and dimensionality. In particular, we study the degree of weak ergodicity breaking and scatter between different single trajectories for this confined motion in the subdiffusive domain. The general trend is that deviations from ergodicity are decreased with decreasing size of the movement volume and with increasing dimensionality. We define the displacement correlation function and find that this quantity shows distinct features for fractional Brownian motion, fractional Langevin equation, and continuous time subdiffusion, such that it appears an efficient measure to distinguish these different processes based on single-particle trajectory data.

  19. Momentum fractionation on superstrata

    DOE PAGES

    Bena, Iosif; Martinec, Emil; Turton, David; Warner, Nicholas P.

    2016-05-11

    Superstrata are bound states in string theory that carry D1, D5, and momentum charges, and whose supergravity descriptions are parameterized by arbitrary functions of (at least) two variables. In the D1-D5 CFT, typical three-charge states reside in highdegree twisted sectors, and their momentum charge is carried by modes that individually have fractional momentum. Understanding this momentum fractionation holographically is crucial for understanding typical black-hole microstates in this system. We use solution-generating techniques to add momentum to a multi-wound supertube and thereby construct the first examples of asymptotically-flat superstrata. The resulting supergravity solutions are horizonless and smooth up to well-understood orbifoldmore » singularities. Upon taking the AdS3 decoupling limit, our solutions are dual to CFT states with momentum fractionation. We give a precise proposal for these dual CFT states. Lastly, our construction establishes the very nontrivial fact that large classes of CFT states with momentum fractionation can be realized in the bulk as smooth horizonless supergravity solutions.« less

  20. Understanding Fraction Multiplication.

    ERIC Educational Resources Information Center

    Bezuk, Nadine S.; Armstrong, Barbara E.

    1992-01-01

    Presents five activities to help students construct meaning for multiplying fractions through real-world problem contexts, physical or pictorial models, the recognition of patterns, and the use of calculators. In the context of a garden plot, worksheets examine various aspects of parts of plots, patterns in plots, and a maximization problem.…

  1. Fractions through Fruit Salad.

    ERIC Educational Resources Information Center

    Lincoln, Lisa

    1987-01-01

    The mathematics concept of fractions was taught to a group of learning disabled, dyslexic, and multiply handicapped students (15-20 years old) by preparing a fruit salad. Enthusiastic student participation and enhanced knowledge illustrated the effectiveness of employing several sensory modes in learning activities. (CB)

  2. Field-Flow Fractionation.

    ERIC Educational Resources Information Center

    Caldwell, Karin D.

    1988-01-01

    Describes a technique for separating samples that range over 15 orders of magnitude in molecular weight. Discusses theory, apparatus, and sample preparation techniques. Lists several types of field-flow fractionation (FFF) and their uses: sedimentation FFF, thermal FFF, flow FFF, electrical FFF, and steric FFF. (ML)

  3. Avoidance of Fractions.

    ERIC Educational Resources Information Center

    Hart, Kathleen; Kerslake, Daphne

    The Concepts in Secondary Mathematics and Science (CSMS) and Strategies and Errors in Secondary Mathematics (SESM) research projects based at Chelsa College, England, have shown the marked reluctance of secondary school students to use fractions when solving mathematical problems, even though they have been taught the topic for a number of years.…

  4. Sweet Work with Fractions

    ERIC Educational Resources Information Center

    Vinogradova, Natalya; Blaine, Larry

    2013-01-01

    Almost everyone loves chocolate. However, the same cannot be said about fractions, which are loved by markedly fewer. Middle school students tend to view them with wary respect, but little affection. The authors attempt to sweeten the subject by describing a type of game involving division of chocolate bars. The activity they describe provides a…

  5. Videodisc Instruction in Fractions.

    ERIC Educational Resources Information Center

    Carnine, Douglas; And Others

    1987-01-01

    How laser videodisc technology can be used to improve mathematics instruction is described, with note of the development of a videodisc curriculum on mastering fractions. Relevant research is reviewed, as well as how teachers can use the technology. The instructional design is described, and field-testing and revision reported. (MNS)

  6. Momentum fractionation on superstrata

    NASA Astrophysics Data System (ADS)

    Bena, Iosif; Martinec, Emil; Turton, David; Warner, Nicholas P.

    2016-05-01

    Superstrata are bound states in string theory that carry D1, D5, and momentum charges, and whose supergravity descriptions are parameterized by arbitrary functions of (at least) two variables. In the D1-D5 CFT, typical three-charge states reside in high-degree twisted sectors, and their momentum charge is carried by modes that individually have fractional momentum. Understanding this momentum fractionation holographically is crucial for understanding typical black-hole microstates in this system. We use solution-generating techniques to add momentum to a multi-wound supertube and thereby construct the first examples of asymptotically-flat superstrata. The resulting supergravity solutions are horizonless and smooth up to well-understood orbifold singularities. Upon taking the AdS3 decoupling limit, our solutions are dual to CFT states with momentum fractionation. We give a precise proposal for these dual CFT states. Our construction establishes the very nontrivial fact that large classes of CFT states with momentum fractionation can be realized in the bulk as smooth horizonless supergravity solutions.

  7. Relationship between Individual External Doses, Ambient Dose Rates and Individuals' Activity-Patterns in Affected Areas in Fukushima following the Fukushima Daiichi Nuclear Power Plant Accident.

    PubMed

    Naito, Wataru; Uesaka, Motoki; Yamada, Chie; Kurosawa, Tadahiro; Yasutaka, Tetsuo; Ishii, Hideki

    2016-01-01

    The accident at Fukushima Daiichi Nuclear Power Plant on March 11, 2011, released radioactive material into the atmosphere and contaminated the land in Fukushima and several neighboring prefectures. Five years after the nuclear disaster, the radiation levels have greatly decreased due to physical decay, weathering, and decontamination operations in Fukushima. The populations of 12 communities were forced to evacuate after the accident; as of March 2016, the evacuation order has been lifted in only a limited area, and permanent habitation is still prohibited in most of the areas. In order for the government to lift the evacuation order and for individuals to return to their original residential areas, it is important to assess current and future realistic individual external doses. Here, we used personal dosimeters along with the Global Positioning System and Geographic Information System to understand realistic individual external doses and to relate individual external doses, ambient doses, and activity-patterns of individuals in the affected areas in Fukushima. The results showed that the additional individual external doses were well correlated to the additional ambient doses based on the airborne monitoring survey. The results of linear regression analysis suggested that the additional individual external doses were on average about one-fifth that of the additional ambient doses. The reduction factors, which are defined as the ratios of the additional individual external doses to the additional ambient doses, were calculated to be on average 0.14 and 0.32 for time spent at home and outdoors, respectively. Analysis of the contribution of various activity patterns to the total individual external dose demonstrated good agreement with the average fraction of time spent daily in each activity, but the contribution due to being outdoors varied widely. These results are a valuable contribution to understanding realistic individual external doses and the corresponding

  8. Relationship between Individual External Doses, Ambient Dose Rates and Individuals' Activity-Patterns in Affected Areas in Fukushima following the Fukushima Daiichi Nuclear Power Plant Accident.

    PubMed

    Naito, Wataru; Uesaka, Motoki; Yamada, Chie; Kurosawa, Tadahiro; Yasutaka, Tetsuo; Ishii, Hideki

    2016-01-01

    The accident at Fukushima Daiichi Nuclear Power Plant on March 11, 2011, released radioactive material into the atmosphere and contaminated the land in Fukushima and several neighboring prefectures. Five years after the nuclear disaster, the radiation levels have greatly decreased due to physical decay, weathering, and decontamination operations in Fukushima. The populations of 12 communities were forced to evacuate after the accident; as of March 2016, the evacuation order has been lifted in only a limited area, and permanent habitation is still prohibited in most of the areas. In order for the government to lift the evacuation order and for individuals to return to their original residential areas, it is important to assess current and future realistic individual external doses. Here, we used personal dosimeters along with the Global Positioning System and Geographic Information System to understand realistic individual external doses and to relate individual external doses, ambient doses, and activity-patterns of individuals in the affected areas in Fukushima. The results showed that the additional individual external doses were well correlated to the additional ambient doses based on the airborne monitoring survey. The results of linear regression analysis suggested that the additional individual external doses were on average about one-fifth that of the additional ambient doses. The reduction factors, which are defined as the ratios of the additional individual external doses to the additional ambient doses, were calculated to be on average 0.14 and 0.32 for time spent at home and outdoors, respectively. Analysis of the contribution of various activity patterns to the total individual external dose demonstrated good agreement with the average fraction of time spent daily in each activity, but the contribution due to being outdoors varied widely. These results are a valuable contribution to understanding realistic individual external doses and the corresponding

  9. Relationship between Individual External Doses, Ambient Dose Rates and Individuals’ Activity-Patterns in Affected Areas in Fukushima following the Fukushima Daiichi Nuclear Power Plant Accident

    PubMed Central

    Kurosawa, Tadahiro; Yasutaka, Tetsuo; Ishii, Hideki

    2016-01-01

    The accident at Fukushima Daiichi Nuclear Power Plant on March 11, 2011, released radioactive material into the atmosphere and contaminated the land in Fukushima and several neighboring prefectures. Five years after the nuclear disaster, the radiation levels have greatly decreased due to physical decay, weathering, and decontamination operations in Fukushima. The populations of 12 communities were forced to evacuate after the accident; as of March 2016, the evacuation order has been lifted in only a limited area, and permanent habitation is still prohibited in most of the areas. In order for the government to lift the evacuation order and for individuals to return to their original residential areas, it is important to assess current and future realistic individual external doses. Here, we used personal dosimeters along with the Global Positioning System and Geographic Information System to understand realistic individual external doses and to relate individual external doses, ambient doses, and activity-patterns of individuals in the affected areas in Fukushima. The results showed that the additional individual external doses were well correlated to the additional ambient doses based on the airborne monitoring survey. The results of linear regression analysis suggested that the additional individual external doses were on average about one-fifth that of the additional ambient doses. The reduction factors, which are defined as the ratios of the additional individual external doses to the additional ambient doses, were calculated to be on average 0.14 and 0.32 for time spent at home and outdoors, respectively. Analysis of the contribution of various activity patterns to the total individual external dose demonstrated good agreement with the average fraction of time spent daily in each activity, but the contribution due to being outdoors varied widely. These results are a valuable contribution to understanding realistic individual external doses and the corresponding

  10. Estimation of Rectal Dose Using Daily Megavoltage Cone-Beam Computed Tomography and Deformable Image Registration

    SciTech Connect

    Akino, Yuichi; Yoshioka, Yasuo; Fukuda, Shoichi; Maruoka, Shintaroh; Takahashi, Yutaka; Yagi, Masashi; Mizuno, Hirokazu; Isohashi, Fumiaki; Ogawa, Kazuhiko

    2013-11-01

    Purpose: The actual dose delivered to critical organs will differ from the simulated dose because of interfractional organ motion and deformation. Here, we developed a method to estimate the rectal dose in prostate intensity modulated radiation therapy with consideration to interfractional organ motion using daily megavoltage cone-beam computed tomography (MVCBCT). Methods and Materials: Under exemption status from our institutional review board, we retrospectively reviewed 231 series of MVCBCT of 8 patients with prostate cancer. On both planning CT (pCT) and MVCBCT images, the rectal contours were delineated and the CT value within the contours was replaced by the mean CT value within the pelvis, with the addition of 100 Hounsfield units. MVCBCT images were rigidly registered to pCT and then nonrigidly registered using B-Spline deformable image registration (DIR) with Velocity AI software. The concordance between the rectal contours on MVCBCT and pCT was evaluated using the Dice similarity coefficient (DSC). The dose distributions normalized for 1 fraction were also deformed and summed to estimate the actual total dose. Results: The DSC of all treatment fractions of 8 patients was improved from 0.75±0.04 (mean ±SD) to 0.90 ±0.02 by DIR. Six patients showed a decrease of the generalized equivalent uniform dose (gEUD) from total dose compared with treatment plans. Although the rectal volume of each treatment fraction did not show any correlation with the change in gEUD (R{sup 2}=0.18±0.13), the displacement of the center of gravity of rectal contours in the anterior-posterior (AP) direction showed an intermediate relationship (R{sup 2}=0.61±0.16). Conclusion: We developed a method for evaluation of rectal dose using DIR and MVCBCT images and showed the necessity of DIR for the evaluation of total dose. Displacement of the rectum in the AP direction showed a greater effect on the change in rectal dose compared with the rectal volume.

  11. Optimal fractionation in radiotherapy with multiple normal tissues.

    PubMed

    Saberian, Fatemeh; Ghate, Archis; Kim, Minsun

    2016-06-01

    The goal in radiotherapy is to maximize the biological effect (BE) of radiation on the tumour while limiting its toxic effects on healthy anatomies. Treatment is administered over several sessions to give the normal tissue time to recover as it has better damage-repair capabilities than tumour cells. This is termed fractionation. A key problem in radiotherapy involves finding an optimal number of treatment sessions (fractions) and the corresponding dosing schedule. A major limitation of existing mathematically rigorous work on this problem is that it includes only a single normal tissue. Since essentially no anatomical region of interest includes only one normal tissue, these models may incorrectly identify the optimal number of fractions and the corresponding dosing schedule. We present a formulation of the optimal fractionation problem that includes multiple normal tissues. Our model can tackle any combination of maximum dose, mean dose and dose-volume type constraints for serial and parallel normal tissues as this is characteristic of most treatment protocols. We also allow for a spatially heterogeneous dose distribution within each normal tissue. Furthermore, we do not a priori assume that the doses are invariant across fractions. Finally, our model uses a spatially optimized treatment plan as input and hence can be seamlessly combined with any treatment planning system. Our formulation is a mixed-integer, non-convex, quadratically constrained quadratic programming problem. In order to simplify this computationally challenging problem without loss of optimality, we establish sufficient conditions under which equal-dosage or single-dosage fractionation is optimal. Based on the prevalent estimates of tumour and normal tissue model parameters, these conditions are expected to hold in many types of commonly studied tumours, such as those similar to head-and-neck and prostate cancers. This motivates a simple reformulation of our problem that leads to a closed

  12. Optimal fractionation in radiotherapy with multiple normal tissues.

    PubMed

    Saberian, Fatemeh; Ghate, Archis; Kim, Minsun

    2016-06-01

    The goal in radiotherapy is to maximize the biological effect (BE) of radiation on the tumour while limiting its toxic effects on healthy anatomies. Treatment is administered over several sessions to give the normal tissue time to recover as it has better damage-repair capabilities than tumour cells. This is termed fractionation. A key problem in radiotherapy involves finding an optimal number of treatment sessions (fractions) and the corresponding dosing schedule. A major limitation of existing mathematically rigorous work on this problem is that it includes only a single normal tissue. Since essentially no anatomical region of interest includes only one normal tissue, these models may incorrectly identify the optimal number of fractions and the corresponding dosing schedule. We present a formulation of the optimal fractionation problem that includes multiple normal tissues. Our model can tackle any combination of maximum dose, mean dose and dose-volume type constraints for serial and parallel normal tissues as this is characteristic of most treatment protocols. We also allow for a spatially heterogeneous dose distribution within each normal tissue. Furthermore, we do not a priori assume that the doses are invariant across fractions. Finally, our model uses a spatially optimized treatment plan as input and hence can be seamlessly combined with any treatment planning system. Our formulation is a mixed-integer, non-convex, quadratically constrained quadratic programming problem. In order to simplify this computationally challenging problem without loss of optimality, we establish sufficient conditions under which equal-dosage or single-dosage fractionation is optimal. Based on the prevalent estimates of tumour and normal tissue model parameters, these conditions are expected to hold in many types of commonly studied tumours, such as those similar to head-and-neck and prostate cancers. This motivates a simple reformulation of our problem that leads to a closed

  13. Hypolipidemic and antioxidant properties of tocotrienol rich fraction isolated from rice bran oil in experimentally induced hyperlipidemic rats.

    PubMed

    Minhajuddin, Mohammad; Beg, Zafarul H; Iqbal, Jahangir

    2005-05-01

    We investigated a dose-dependent hypolipidemic and antioxidant effect of tocotrienol rich fraction (TRF) isolated from rice bran oil on experimentally induced hyperlipidemic rats. Feeding of atherogenic diet (5% hydrogenated fat, 0.5% cholic acid and 1% cholesterol) for three weeks resulted in a significant increase in plasma triglyceride (3.3-fold) and total cholesterol (2.4-fold) levels. There was a 5-fold increase in the level of LDL cholesterol with only a small increase in HDL cholesterol. On the other hand, HMG-CoA reductase activity was significantly reduced in these animals. The formation of TBARS, thiobarbituric acid reactive substances, (86%) and conjugated dienes (78%) were also significantly higher in these rats compared to normals. After the induction of hyperlipidemia for three weeks, rats were supplemented with different doses of TRF for one week. TRF supplementation decreased the lipid parameters in a dose-dependent manner with an optimum effect at a dose of 8 mg TRF/kg/day. HMG-CoA reductase activity, which was increased after the withdrawal of atherogenic diet, remained significantly decreased during the TRF treatment. Feeding of TRF also decreased TBARS and conjugated dienes significantly. These results suggest that TRF supplementation has significant health benefits through the modulation of physiological functions that include various atherogenic lipid profiles and antioxidants in hypercholesterolemia.

  14. Exploring the dose response of radiochromic dosimeters

    NASA Astrophysics Data System (ADS)

    Skyt, P. S.; Wahlstedt, I.; Yates, E. S.; Muren, L. P.; Petersen, J. B. B.; Balling, P.

    2013-06-01

    The aim of this study was to explore the dose response of a newly developed radio-chromic hydrogel dosimeter based on leuco malachite green dye in a gelatine matrix. The original dosimeter composition was first investigated in terms of dose response and dose-rate dependence. In addition, the initiating compounds producing chlorine radicals were substituted with compounds producing fluorine radicals, oxygen-centered radicals, carbon-centered radicals and bromine radicals. Also the surfactant was substituted by other compounds of different molecular size and charge. The original composition gave a dose response of 3.5·10-3 Gy-1cm-1 at 6 Gy/min with a dose rate dependence giving a 27 % increase when decreasing the dose rate to 1 Gy/min. None of the substituted initiating components contributed to an increase in dose response while only one surfactant increased the dose response slightly.

  15. Delayed activation of human microglial cells by high dose ionizing radiation.

    PubMed

    Chen, Hongxin; Chong, Zhao Zhong; De Toledo, Sonia M; Azzam, Edouard I; Elkabes, Stella; Souayah, Nizar

    2016-09-01

    Recent studies have shown that microglia affects the fate of neural stem cells in response to ionizing radiation, which suggests a role for microglia in radiation-induced degenerative outcomes. We therefore investigated the effects of γ-irradiation on cell survival, proliferation, and activation of microglia and explored associated mechanisms. Specifically, we evaluated cellular and molecular changes associated with exposure of human microglial cells (CHME5) to low and high doses of acute cesium-137 γ rays. Twenty-four hours after irradiation, cell cycle analyses revealed dose-dependent decreases in the fraction of cells in S and G2/M phase, which correlated with significant oxidative stress. By one week after irradiation, 20-30% of the cells exposed to high doses of γ rays underwent apoptosis, which correlated with significant concomitant decrease in metabolic activity as assessed by the MTT assay, and microglial activation as judged by both morphological changes and increased expression of Glut-5 and CR43. These changes were associated with increases in the mRNA levels for IL-1α, IL-10 and TNFα. Together, the results show that human CHME5 microglia are relatively resistant to low and moderate doses of γ rays, but are sensitive to acute high doses, and that CHME5 cells are a useful tool for in vitro study of human microglia. PMID:27265419

  16. An Introduction to Continued Fractions.

    ERIC Educational Resources Information Center

    Moore, Charles G.

    Provided is an introduction to the properties of continued fractions for the intellectually curious high school student. Among the topics included are (1) Expansion of Rational Numbers into Simple Continued Fractions, (2) Convergents, (3) Continued Fractions and Linear Diophantine Equations of the Type am + bn = c, (4) Continued Fractions and…

  17. Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors

    SciTech Connect

    Richter, Daniel; Saito, Nami; Chaudhri, Naved; Härtig, Martin; Ellerbrock, Malte; Jäkel, Oliver; Combs, Stephanie E.; Habermehl, Daniel; Herfarth, Klaus; Durante, Marco; Bert, Christoph

    2014-05-01

    Purpose: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. Methods and Materials: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporal correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V{sub 95}) and 107% (V{sub 107}) of the planned doses. Results: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V{sub 95} and V{sub 107} values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V{sub 95} > 87%, SD < 3%) and overdose (mean V{sub 107} < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. Conclusions: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.

  18. Lung dose analysis in loco-regional hypofractionated radiotherapy of breast cancer

    PubMed Central

    Attar, Mohammad A.; Bahadur, Yasir A.; Constantinescu, Camelia T.; Eltaher, Maha M.

    2016-01-01

    Objectives: To report the ipsilateral lung dosimetry data of breast cancer (BC) patients treated with loco-regional hypofractionated radiotherapy (HFRT). Methods: Treatment plans of 150 patients treated in the Radiotherapy Unit, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia between January 2012 and March 2015 by HFRT for BC were retrospectively reviewed. All patients received 42.4 Gy in 16 fractions by tangential and supra-clavicular fields with 6 MV, 18 MV, or mixed energies. Ipsilateral lung dosimetric data V20Gy and mean lung dose (MLD) were recorded. Correlations between lung dose, patient characteristics, and treatment delivery parameters were assessed by a logistic regression test. Results: The mean ipsilateral lung V20Gy was 24.6% and mean MLD was 11.9 Gy. A weak, but statistically significant correlation was found between lung dose and lung volume (p=0.043). The lung dose was significantly decreasing with patient separation and depth of axillary lymph node (ALN) and supra-claviculary lymph nodes (SCLN) (p<0.0001), and increasing with ALN (p=0.001) and SCLN (p=0.003) dose coverage. Lung dose significantly decreased with beam energy (p<0.0001): mean V20Gy was 27.8%, 25.4% for 6 MV, mixed energy, and 21.2% for 18 MV. The use of a low breast-board angle correlates with low lung dose. Conclusion: Our data suggest that the use of high energy photon beams and low breast-board angulation can reduce the lung dose. PMID:27279508

  19. Daucus carota Pentane-Based Fractions Suppress Proliferation and Induce Apoptosis in Human Colon Adenocarcinoma HT-29 Cells by Inhibiting the MAPK and PI3K Pathways.

    PubMed

    Shebaby, Wassim N; Bodman-Smith, K B; Mansour, Anthony; Mroueh, Mohamad; Taleb, Robin I; El-Sibai, Mirvat; Daher, Costantine F

    2015-07-01

    Daucus carota L. ssp. carota (Apiacea, wild carrot, Queen Anne's lace) has been used in folk medicine throughout the world and recently was shown to possess anticancer and antioxidant activities. This study aims to determine the anticancer activity of the pentane fraction (F1) and the 1:1 pentane:diethyl ether fraction (F2) of the Daucus Carota oil extract (DCOE) against human colon adenocarcinoma cell lines (HT-29 and Caco-2). Treatment of cells with various concentrations of F1 or F2 fractions produced a dose-dependent inhibition of cell proliferation. Flow cytometric analysis indicated that both fractions induced sub-G1 phase accumulation and increased apoptotic cell death. Western blot revealed the activation of caspase-3, PARP cleavage, and a considerable increase in Bax and p53 levels, and a decrease in Bcl-2 level. Treatment of HT-29 cells with either fraction markedly decreased the levels of both phosphorylated Erk and Akt. Furthermore, the combined treatment of F1 or F2 with wortmannin showed no added inhibition of cell survival suggesting an effect of F1 or F2 through the phosphatidyl inositol 3-kinase (PI3K) pathway. This study proposes that DCOE fractions (F1 and F2) inhibit cell proliferation by inducing cell cycle arrest and apoptosis in HT-29 cells through the suppression of mitogen-activated protein kinase (MAPK)/Erk and PI3K/Akt pathways.

  20. Antidermatophytic and Toxicological Evaluations of Dichloromethane-Methanol Extract, Fractions and Compounds Isolated from Coula edulis

    PubMed Central

    Tamokou, Jean De Dieu; Kuiate, Jules Roger; Gatsing, Donatien; Efouet, Alango Pépin Nken; Njouendou, Abdel Jélil

    2011-01-01

    Background: Coula edulis Bail (Olacaceae), is an evergreen tree growing to a height of 25. This study aimed at evaluating the antidermatophytic and toxicological properties of the stem bark of C. edulis extract as well as fractions and compounds isolated from it. Methods: The plant extract was prepared by maceration in CH2Cl2-MeOH (1:1 v/v). The fractionation of this extract was done by silica gel column chromatography. Antidermatophytic activities were assayed using agar dilution method. The acute and sub-acute toxicities of oral administrations of the extract were studied in rodents. Results: The crude extract of C. edulis displayed antidermatophytic activity against the tested microorganisms with highest activity against Microsporum audouinii and Trichophyton mentagrophytes. The fractionation enhanced the antidermatophytic activity in fraction F3 (MIC=0.62-1.25 mg/ml) compared to the crude extract (MIC=1.25-5 mg/ml). Further fractionation and purification of the fractions F2 and F3 gave respectively 3-O-β-D-glucopyranoside of sitosterol (MIC=0.20-0.40 mg/ml) and a mixture of β-sitosterol, stigmasterol and n-hexadecanoid acid (MIC=0.80 mg/ml). The median lethal doses (LD50) of the crude extract were 16.8 and 19.6 g/kg body weight (BW) in male and female mice, respectively. At 200 mg/kg BW, there was a decrease in body weight gain, food and water consumptions. Gross anatomical analysis revealed white vesicles on the liver of the rats treated with the extract at 200 mg/kg BW. This dose also induced significant (P<0.05) changes on hematological and biochemical parameters in rats after 28 days of treatment. Conclusion: These data suggest that the CH2Cl2-MeOH (1:1 v/v) extract of C. edulis stem bark possesses antidermatophytic properties. They also show that at high doses (≥ 200 mg/kg BW), the extract has significant hepatotoxic and nephrotoxic activities. PMID:23357938

  1. The emergence of nonuniform spatiotemporal fractionation schemes within the standard BED model

    SciTech Connect

    Unkelbach, Jan Papp, Dávid

    2015-05-15

    Purpose: Nonuniform spatiotemporal radiotherapy fractionation schemes, i.e., delivering distinct dose distributions in different fractions can potentially improve the therapeutic ratio. This is possible if the dose distributions are designed such that similar doses are delivered to normal tissues (exploit the fractionation effect) while hypofractionating subregions of the tumor. In this paper, the authors develop methodology for treatment planning with nonuniform fractions and demonstrate this concept in the context of intensity-modulated proton therapy (IMPT). Methods: Treatment planning is performed by simultaneously optimizing (possibly distinct) IMPT dose distributions for multiple fractions. This is achieved using objective and constraint functions evaluated for the cumulative biologically equivalent dose (BED) delivered at the end of treatment. BED based treatment planning formulations lead to nonconvex optimization problems, such that local gradient based algorithms require adequate starting positions to find good local optima. To that end, the authors develop a combinatorial algorithm to initialize the pencil beam intensities. Results: The concept of nonuniform spatiotemporal fractionation schemes is demonstrated for a spinal metastasis patient treated in two fractions using stereotactic body radiation therapy. The patient is treated with posterior oblique beams with the kidneys being located in the entrance region of the beam. It is shown that a nonuniform fractionation scheme that hypofractionates the central part of the tumor allows for a skin and kidney BED reduction of approximately 10%–20%. Conclusions: Nonuniform spatiotemporal fractionation schemes represent a novel approach to exploit fractionation effects that deserves further exploration for selected disease sites.

  2. Testing fractional action cosmology

    NASA Astrophysics Data System (ADS)

    Shchigolev, V. K.

    2016-08-01

    The present work deals with a combined test of the so-called Fractional Action Cosmology (FAC) on the example of a specific model obtained by the author earlier. In this model, the effective cosmological term is proportional to the Hubble parameter squared through the so-called kinematic induction. The reason of studying this cosmological model could be explained by its ability to describe two periods of accelerated expansion, that is in agreement with the recent observations and the cosmological inflation paradigm. First of all, we put our model through the theoretical tests, which gives a general conception of the influence of the model parameters on its behavior. Then, we obtain some restrictions on the principal parameters of the model, including the fractional index, by means of the observational data. Finally, the cosmography parameters and the observational data compared to the theoretical predictions are presented both analytically and graphically.

  3. New Dry Fractionation Methods

    NASA Technical Reports Server (NTRS)

    McKay, David S.; Cooper, Bonnie L.

    2010-01-01

    This slide presentation describes new fractionation methods that are used to create dust that is respirable for testing the effects of inhalation of lunar dust in preparation for future manned lunar exploration. Because lunar dust is a very limited commodity, a method that does not result in loss of the material had to be developed. The dust separation system that is described incorporates some traditional methods, while preventing the dust from being contaminated or changed in reactivity properties while also limiting losses.

  4. Fractional Galilean symmetries

    NASA Astrophysics Data System (ADS)

    Hosseiny, Ali; Rouhani, Shahin

    2016-09-01

    We generalize the differential representation of the operators of the Galilean algebras to include fractional derivatives. As a result a whole new class of scale invariant Galilean algebras are obtained. The first member of this class has dynamical index z = 2 similar to the Schrödinger algebra. The second member of the class has dynamical index z = 3 / 2, which happens to be the dynamical index Kardar-Parisi-Zhang equation.

  5. Effect of Drying on Heavy Metal Fraction Distribution in Rice Paddy Soil

    PubMed Central

    Qi, Yanbing; Huang, Biao; Darilek, Jeremy Landon

    2014-01-01

    An understanding of how redox conditions affect soil heavy metal fractions in rice paddies is important due to its implications for heavy metal mobility and plant uptake. Rice paddy soil samples routinely undergo oxidation prior to heavy metal analysis. Fraction distribution of Cu, Pb, Ni, and Cd from paddy soil with a wide pH range was investigated. Samples were both dried according to standard protocols and also preserved under anaerobic conditions through the sampling and analysis process and heavy metals were then sequentially extracted for the exchangeable and carbonate bound fraction (acid soluble fraction), iron and manganese oxide bound fraction (reducible fraction), organic bound fraction (oxidizable fraction), and residual fraction. Fractions were affected by redox conditions across all pH ranges. Drying decreased reducible fraction of all heavy metals. Curesidual fraction, Pboxidizable fraction, Cdresidual fraction, and Niresidual fraction increased by 25%, 33%, 35%, and >60%, respectively. Pbresidual fraction, Niacid soluble fraction, and Cdoxidizable fraction decreased 33%, 25%, and 15%, respectively. Drying paddy soil prior to heavy metal analysis overestimated Pb and underestimated Cu, Ni, and Cd. In future studies, samples should be stored after injecting N2 gas to maintain the redox potential of soil prior to heavy metal analysis, and investigate the correlation between heavy metal fraction distribution under field conditions and air-dried samples. PMID:24823670

  6. Inhibiting the Aurora B Kinase Potently Suppresses Repopulation During Fractionated Irradiation of Human Lung Cancer Cell Lines

    SciTech Connect

    Sak, Ali; Stuschke, Martin; Groneberg, Michael; Kuebler, Dennis; Poettgen, Christoph; Eberhardt, Wilfried E.E.

    2012-10-01

    Purpose: The use of molecular-targeted agents during radiotherapy of non-small-cell lung cancer (NSCLC) is a promising strategy to inhibit repopulation, thereby improving therapeutic outcome. We assessed the combined effectiveness of inhibiting Aurora B kinase and irradiation on human NSCLC cell lines in vitro. Methods and Materials: NSCLC cell lines were exposed to concentrations of AZD1152-hydroxyquinazoline pyrazol anilide (AZD1152-HQPA) inhibiting colony formation by 50% (IC50{sub clone}) in combination with single dose irradiation or different fractionation schedules using multiple 2-Gy fractions per day up to total doses of 4-40 Gy. The total irradiation dose required to control growth of 50% of the plaque monolayers (TCD50) was determined. Apoptosis, G2/M progression, and polyploidization were also analyzed. Results: TCD50 values after single dose irradiation were similar for the H460 and H661 cell lines with 11.4 {+-} 0.2 Gy and 10.7 {+-} 0.3 Gy, respectively. Fractionated irradiation using 3 Multiplication-Sign 2 Gy/day, 2 Multiplication-Sign 2 Gy/day, and 1 Multiplication-Sign 2 Gy/day schedules significantly increased TCD50 values for both cell lines grown as plaque monolayers with increasing radiation treatment time. This could be explained by a repopulation effect per day that counteracts 75 {+-} 8% and 27 {+-} 6% of the effect of a 2-Gy fraction in H460 and H661 cells, respectively. AZD1152-HQPA treatment concomitant to radiotherapy significantly decreased the daily repopulation effect (H460: 28 {+-} 5%, H661: 10 {+-} 4% of a 2-Gy fraction per day). Treatment with IC50{sub clone} AZD1152-HPQA did not induce apoptosis, prolong radiation-induced G2 arrest, or delay cell cycle progression before the spindle check point. However, polyploidization was detected, especially in cell lines without functional p53. Conclusions: Inhibition of Aurora B kinase with low AZD1152-HQPA concentrations during irradiation of NSCLC cell lines affects repopulation during

  7. Model Fractional Chern Insulators.

    PubMed

    Behrmann, Jörg; Liu, Zhao; Bergholtz, Emil J

    2016-05-27

    We devise local lattice models whose ground states are model fractional Chern insulators-Abelian and non-Abelian topologically ordered states characterized by exact ground state degeneracies at any finite size and infinite entanglement gaps. Most saliently, we construct exact parent Hamiltonians for two distinct families of bosonic lattice generalizations of the Z_{k} parafermion quantum Hall states: (i) color-entangled fractional Chern insulators at band filling fractions ν=k/(C+1) and (ii) nematic states at ν=k/2, where C is the Chern number of the lowest band. In spite of a fluctuating Berry curvature, our construction is partially frustration free: the ground states reside entirely within the lowest band and exactly minimize a local (k+1) body repulsion term by term. In addition to providing the first known models hosting intriguing states such as higher Chern number generalizations of the Fibonacci anyon quantum Hall states, the remarkable stability and finite-size properties make our models particularly well suited for the study of novel phenomena involving, e.g., twist defects and proximity induced superconductivity, as well as being a guide for designing experiments.

  8. Model Fractional Chern Insulators

    NASA Astrophysics Data System (ADS)

    Behrmann, Jörg; Liu, Zhao; Bergholtz, Emil J.

    2016-05-01

    We devise local lattice models whose ground states are model fractional Chern insulators—Abelian and non-Abelian topologically ordered states characterized by exact ground state degeneracies at any finite size and infinite entanglement gaps. Most saliently, we construct exact parent Hamiltonians for two distinct families of bosonic lattice generalizations of the Zk parafermion quantum Hall states: (i) color-entangled fractional Chern insulators at band filling fractions ν =k /(C +1 ) and (ii) nematic states at ν =k /2 , where C is the Chern number of the lowest band. In spite of a fluctuating Berry curvature, our construction is partially frustration free: the ground states reside entirely within the lowest band and exactly minimize a local (k +1 ) body repulsion term by term. In addition to providing the first known models hosting intriguing states such as higher Chern number generalizations of the Fibonacci anyon quantum Hall states, the remarkable stability and finite-size properties make our models particularly well suited for the study of novel phenomena involving, e.g., twist defects and proximity induced superconductivity, as well as being a guide for designing experiments.

  9. Model Fractional Chern Insulators.

    PubMed

    Behrmann, Jörg; Liu, Zhao; Bergholtz, Emil J

    2016-05-27

    We devise local lattice models whose ground states are model fractional Chern insulators-Abelian and non-Abelian topologically ordered states characterized by exact ground state degeneracies at any finite size and infinite entanglement gaps. Most saliently, we construct exact parent Hamiltonians for two distinct families of bosonic lattice generalizations of the Z_{k} parafermion quantum Hall states: (i) color-entangled fractional Chern insulators at band filling fractions ν=k/(C+1) and (ii) nematic states at ν=k/2, where C is the Chern number of the lowest band. In spite of a fluctuating Berry curvature, our construction is partially frustration free: the ground states reside entirely within the lowest band and exactly minimize a local (k+1) body repulsion term by term. In addition to providing the first known models hosting intriguing states such as higher Chern number generalizations of the Fibonacci anyon quantum Hall states, the remarkable stability and finite-size properties make our models particularly well suited for the study of novel phenomena involving, e.g., twist defects and proximity induced superconductivity, as well as being a guide for designing experiments. PMID:27284668

  10. Contraceptive studies of isolated fractions of Cuminum cyminum in male albino rats.

    PubMed

    Saxena, Poonam; Gupta, Rajnish; Gupta, R S

    2015-01-01

    The contraceptive efficacy of Cuminum cyminum isolated fractions (CcFr) in male albino rats was investigated. Oral dose of CcFr at 50 mg/rat/day for 60 days revealed no significant changes in body weight, while marked abnormalities in spermatogenesis were observed with decreased counts (P ≤ 0.001) in round spermatids, preleptotene spermatocytes and secondary spermatocytes. Cross sectional surface area of Sertoli cells as well as number of mature Leydig cell were decreased significantly (P ≤ 0.001). Testicular as well as accessory sex organ biochemical parameters were significantly changed (P ≤ 0.001). Sperm motility, density and morphology were resulted in 100% negative fertility. Testosterone levels were declined significantly. In conclusion, Cuminum cyminum inhibited spermatogenesis in rats, indicating the possibility of developing an herbal male contraceptive.

  11. Water dynamics in different biochar fractions.

    PubMed

    Conte, Pellegrino; Nestle, Nikolaus

    2015-09-01

    Biochar is a carbonaceous porous material deliberately applied to soil to improve its fertility. The mechanisms through which biochar acts on fertility are still poorly understood. The effect of biochar texture size on water dynamics was investigated here in order to provide information to address future research on nutrient mobility towards plant roots as biochar is applied as soil amendment. A poplar biochar has been stainless steel fractionated in three different textured fractions (1.0-2.0 mm, 0.3-1.0 mm and <0.3 mm, respectively). Water-saturated fractions were analyzed by fast field cycling (FFC) NMR relaxometry. Results proved that 3D exchange between bound and bulk water predominantly occurred in the coarsest fraction. However, as porosity decreased, water motion was mainly associated to a restricted 2D diffusion among the surface-site pores and the bulk-site ones. The X-ray μ-CT imaging analyses on the dry fractions revealed the lowest surface/volume ratio for the coarsest fraction, thereby corroborating the 3D water exchange mechanism hypothesized by FFC NMR relaxometry. However, multi-micrometer porosity was evidenced in all the samples. The latter finding suggested that the 3D exchange mechanism cannot even be neglected in the finest fraction as previously excluded only on the basis of NMR relaxometry results. X-ray μ-CT imaging showed heterogeneous distribution of inorganic materials inside all the fractions. The mineral components may contribute to the water relaxation mechanisms by FFC NMR relaxometry. Further studies are needed to understand the role of the inorganic particles on water dynamics. PMID:25594163

  12. Assessment of the antidiarrhoeal properties of the aqueous extract and its soluble fractions of Chebulae Fructus (Terminalia chebula fruits).

    PubMed

    Sheng, Zunlai; Yan, Xin; Zhang, Ruili; Ni, Huilin; Cui, Yuanxu; Ge, Junwei; Shan, Anshan

    2016-09-01

    Context Chebulae Fructus is used as an herbal remedy for diarrhoea in traditional Chinese medicine. However, there is no scientific evidence to support its antidiarrhoeal activity. Objective This study evaluates the antidiarrhoeal properties of Chebulae Fructus aqueous extract (CFAE) and determines the active fraction. Materials and methods The antidiarrhoeal effect of CFAE (200-800 mg/kg) was investigated by determining the wet dropping, intestinal transit in BALB/c mice and enteropooling in Wister rats. The protective effects of the CFAE on the intestinal and liver were tested by histopathological analyses. The antidiarrhoeal fraction was determined by castor oil-induced diarrhoea and its main constituents were identified by HPLC-ESI-MS. Results The extract at doses of 200, 400 and 800 mg/kg reduced the diarrhoea by 9.1, 40.0 and 58.2% and inhibited intestinal transit by 18.3, 24.1 and 35.7%, respectively. Additionally, the CFAE (200, 400 and 800 mg/kg) decreased the volume of enteropooling by 47.1, 58.8 and 64.7%, respectively. Mice treated with castor oil presented morphological alterations in the small intestine and the liver. However, the lesions of mice treated with CFAE were alleviated. Moreover, the ethyl acetate fraction was the active fraction of CFAE, the fraction (41.7, 83.4 and 166.8 mg/kg) reduced the diarrhoea by 9.1, 38.2 and 54.5%, respectively. The major components of the ethyl acetate fraction were tannins, including gallic acid, 3, 4, 6-tri-O-galloyl-β-d-Glc, corilagin and ellagic acid according to the HPLC-ESI-MS analysis. Conclusion The CFAE possessed antidiarrhoeal property and the ethyl acetate fraction was its main active fraction.

  13. Assessment of the antidiarrhoeal properties of the aqueous extract and its soluble fractions of Chebulae Fructus (Terminalia chebula fruits).

    PubMed

    Sheng, Zunlai; Yan, Xin; Zhang, Ruili; Ni, Huilin; Cui, Yuanxu; Ge, Junwei; Shan, Anshan

    2016-09-01

    Context Chebulae Fructus is used as an herbal remedy for diarrhoea in traditional Chinese medicine. However, there is no scientific evidence to support its antidiarrhoeal activity. Objective This study evaluates the antidiarrhoeal properties of Chebulae Fructus aqueous extract (CFAE) and determines the active fraction. Materials and methods The antidiarrhoeal effect of CFAE (200-800 mg/kg) was investigated by determining the wet dropping, intestinal transit in BALB/c mice and enteropooling in Wister rats. The protective effects of the CFAE on the intestinal and liver were tested by histopathological analyses. The antidiarrhoeal fraction was determined by castor oil-induced diarrhoea and its main constituents were identified by HPLC-ESI-MS. Results The extract at doses of 200, 400 and 800 mg/kg reduced the diarrhoea by 9.1, 40.0 and 58.2% and inhibited intestinal transit by 18.3, 24.1 and 35.7%, respectively. Additionally, the CFAE (200, 400 and 800 mg/kg) decreased the volume of enteropooling by 47.1, 58.8 and 64.7%, respectively. Mice treated with castor oil presented morphological alterations in the small intestine and the liver. However, the lesions of mice treated with CFAE were alleviated. Moreover, the ethyl acetate fraction was the active fraction of CFAE, the fraction (41.7, 83.4 and 166.8 mg/kg) reduced the diarrhoea by 9.1, 38.2 and 54.5%, respectively. The major components of the ethyl acetate fraction were tannins, including gallic acid, 3, 4, 6-tri-O-galloyl-β-d-Glc, corilagin and ellagic acid according to the HPLC-ESI-MS analysis. Conclusion The CFAE possessed antidiarrhoeal property and the ethyl acetate fraction was its main active fraction. PMID:26916441

  14. A Comprehensive Analysis of Cardiac Dose in Balloon-Based High-Dose-Rate Brachytherapy for Left-Sided Breast Cancer

    SciTech Connect

    Valakh, Vladimir; Kim, Yongbok; Werts, E. Day; Trombetta, Mark G.

    2012-04-01

    Purpose: To investigate radiation dose to the heart in 60 patients with left-sided breast cancer who were treated with balloon-based high-dose-rate brachytherapy using MammoSite or Contura applicators. Methods and Materials: We studied 60 consecutive women with breast cancer who were treated with 34 Gy in 10 twice-daily fractions using MammoSite (n = 37) or Contura (n = 23) applicators. The whole heart and the left and right ventricles were retrospectively delineated, and dose-volume histograms were analyzed. Multiple dosimetrics were reported, such as mean dose (D{sub mean}); relative volume receiving 1.7, 5, 10, and 20 Gy (V1.7, V5, V10, and V20, respectively); dose to 1 cc (D{sub 1cc}); and maximum point dose (D{sub max}). Biologic metrics, biologically effective dose and generalized equivalent uniform dose were computed. The impact of lumpectomy cavity location on cardiac dose was investigated. Results: The average {+-} standard deviation of D{sub mean} was 2.45 {+-} 0.94 Gy (range, 0.56-4.68) and 3.29 {+-} 1.28 Gy (range, 0.77-6.35) for the heart and the ventricles, respectively. The average whole heart V5 and V10 values were 10.2% and 1.3%, respectively, and the heart D{sub max} was >20 Gy in 7 of 60 (11.7%) patients and >25 Gy in 3 of 60 (5%) patients. No cardiac tissue received {>=}30 Gy. The V1.7, V5, V10, V20, and D{sub mean} values were all higher for the ventricles than for the whole heart. For balloons located in the upper inner quadrant of the breast, the average whole heart D{sub mean} was highest. The D{sub mean}, biologically effective dose, and generalized equivalent uniform dose values for heart and ventricles decreased with increasing minimal distance from the surface of the balloon. Conclusions: On the basis of these comprehensive cardiac dosimetric data, we recommend that cardiac dose be routinely reported and kept as low as possible in balloon-based high-dose-rate brachytherapy treatment planning for patients with left-sided breast cancer so

  15. Statistical iterative reconstruction using adaptive fractional order regularization

    PubMed Central

    Zhang, Yi; Wang, Yan; Zhang, Weihua; Lin, Feng; Pu, Yifei; Zhou, Jiliu

    2016-01-01

    In order to reduce the radiation dose of the X-ray computed tomography (CT), low-dose CT has drawn much attention in both clinical and industrial fields. A fractional order model based on statistical iterative reconstruction framework was proposed in this study. To further enhance the performance of the proposed model, an adaptive order selection strategy, determining the fractional order pixel-by-pixel, was given. Experiments, including numerical and clinical cases, illustrated better results than several existing methods, especially, in structure and texture preservation. PMID:27231604

  16. Dynamically accumulated dose and 4D accumulated dose for moving tumors

    SciTech Connect

    Li Heng; Li Yupeng; Zhang Xiaodong; Li Xiaoqiang; Liu Wei; Gillin, Michael T.; Zhu, X. Ronald

    2012-12-15

    Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove the principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference

  17. Incorporating heterogeneity correction and 4DCT in lung stereotactic body radiation therapy (SBRT): The effect on target coverage, organ-at-risk doses, and dose conformity.

    PubMed

    Franks, Kevin N; Purdie, Thomas G; Dawson, Laura A; Bezjak, Andrea; Jaffray, David A; Bissonnette, Jean-Pierre

    2010-01-01

    This study evaluates the dosimetric impact of 4-dimensional computed tomography (4DCT) target volumes and heterogeneity correction (HC) on target coverage, organ-at-risk (OAR) doses, and dose conformity in lung stereotactic body radiation therapy (SBRT). Twelve patients with lung cancer, scanned using both helical CT and 4DCT, were treated with SBRT (60 Gy in 3 fractions). The clinical plans were calculated without HC and based on targets from the free-breathing helical CT scan (PTV(HEL)). Retrospectively, the clinical plans were recalculated with HC and were evaluated based on targets from 4DCT datasets (PTV(4D)) accounting for patient-specific target motion. The PTV(4D) was greater than PTV(HEL) when tumor motion exceeded 7.5 mm (vector). There were significant decreases in target coverage (V100) for the recalculated vs. clinical plans (0.84 vs. 0.94, p < 0.02) for the same monitor units. When the recalculated plans were optimized for equivalent V100 of the clinical plans, there were significant increases in the 60-Gy dose spillage (1.27 vs. 1.13, p < 0.001) and 30-Gy dose spillage (5.20 vs. 3.73, p < 0.001) vs. the clinical plans. There was a significant increase (p < 0.04) in the mean OAR doses between the optimized re-calculated and the clinical plan. Tumor motion is an important consideration for target volumes defined using helical CT. Lower prescription doses may be required when prospectively planning with HC to achieve a similar level of toxicity and dose spillage as expected when planning based on homogeneous dose calculations.

  18. Incorporating Heterogeneity Correction and 4DCT in Lung Stereotactic Body Radiation Therapy (SBRT): The Effect on Target Coverage, Organ-At-Risk Doses, and Dose Conformity

    SciTech Connect

    Franks, Kevin N.; Purdie, Thomas G. Dawson, Laura A.; Bezjak, Andrea; Jaffray, David A.; Bissonnette, Jean-Pierre

    2010-07-01

    This study evaluates the dosimetric impact of 4-dimensional computed tomography (4DCT) target volumes and heterogeneity correction (HC) on target coverage, organ-at-risk (OAR) doses, and dose conformity in lung stereotactic body radiation therapy (SBRT). Twelve patients with lung cancer, scanned using both helical CT and 4DCT, were treated with SBRT (60 Gy in 3 fractions). The clinical plans were calculated without HC and based on targets from the free-breathing helical CT scan (PTV{sub HEL}). Retrospectively, the clinical plans were recalculated with HC and were evaluated based on targets from 4DCT datasets (PTV{sub 4D}) accounting for patient-specific target motion. The PTV{sub 4D} was greater than PTV{sub HEL} when tumor motion exceeded 7.5 mm (vector). There were significant decreases in target coverage (V100) for the recalculated vs. clinical plans (0.84 vs. 0.94, p < 0.02) for the same monitor units. When the recalculated plans were optimized for equivalent V100 of the clinical plans, there were significant increases in the 60-Gy dose spillage (1.27 vs. 1.13, p < 0.001) and 30-Gy dose spillage (5.20 vs. 3.73, p < 0.001) vs. the clinical plans. There was a significant increase (p < 0.04) in the mean OAR doses between the optimized re-calculated and the clinical plan. Tumor motion is an important consideration for target volumes defined using helical CT. Lower prescription doses may be required when prospectively planning with HC to achieve a similar level of toxicity and dose spillage as expected when planning based on homogeneous dose calculations.

  19. Acute and fractionated exposure to high-LET (56)Fe HZE-particle radiation both result in similar long-term deficits in adult hippocampal neurogenesis.

    PubMed

    Rivera, Phillip D; Shih, Hung-Ying; Leblanc, Junie A; Cole, Mara G; Amaral, Wellington Z; Mukherjee, Shibani; Zhang, Shichuan; Lucero, Melanie J; Decarolis, Nathan A; Chen, Benjamin P C; Eisch, Amelia J

    2013-12-01

    Astronauts on multi-year interplanetary missions will be exposed to a low, chronic dose of high-energy, high-charge particles. Studies in rodents show acute, nonfractionated exposure to these particles causes brain changes such as fewer adult-generated hippocampal neurons and stem cells that may be detrimental to cognition and mood regulation and thus compromise mission success. However, the influence of a low, chronic dose of these particles on neurogenesis and stem cells is unknown. To examine the influence of galactic cosmic radiation on neurogenesis, adult-generated stem and progenitor cells in Nestin-CreER(T2)/R26R-YFP transgenic mice were inducibly labeled to allow fate tracking. Mice were then sham exposed or given one acute 100 cGy (56)Fe-particle exposure or five fractionated 20 cGy (56)Fe-particle exposures. Adult-generated hippocampal neurons and stem cells were quantified 24 h or 3 months later. Both acute and fractionated exposure decreased the amount of proliferating cells and immature neurons relative to sham exposure. Unexpectedly, neither acute nor fractionated exposure decreased the number of adult neural stem cells relative to sham expsoure. Our findings show that single and fractionated exposures of (56)Fe-particle irradiation are similarly detrimental to adult-generated neurons. Implications for future missions and ground-based studies in space radiation are discussed. PMID:24320054

  20. Acute and Fractionated Exposure to High-LET 56Fe HZE-Particle Radiation Both Result in Similar Long-Term Deficits in Adult Hippocampal Neurogenesis

    PubMed Central

    Rivera, Phillip D.; Shih, Hung-Ying; LeBlanc, Junie A.; Cole, Mara G.; Amaral, Wellington Z.; Mukherjee, Shibani; Zhang, Shichuan; Lucero, Melanie J.; DeCarolis, Nathan A.; Chen, Benjamin P. C.; Eisch, Amelia J.

    2014-01-01

    Astronauts on multi-year interplanetary missions will be exposed to a low, chronic dose of high-energy, high-charge particles. Studies in rodents show acute, nonfractionated exposure to these particles causes brain changes such as fewer adult-generated hippocampal neurons and stem cells that may be detrimental to cognition and mood regulation and thus compromise mission success. However, the influence of a low, chronic dose of these particles on neurogenesis and stem cells is unknown. To examine the influence of galactic cosmic radiation on neurogenesis, adult-generated stem and progenitor cells in Nestin-CreERT2/R26R-YFP transgenic mice were inducibly labeled to allow fate tracking. Mice were then sham exposed or given one acute 100 cGy 56Fe-particle exposure or five fractionated 20 cGy 56Fe-particle exposures. Adult-generated hippocampal neurons and stem cells were quantified 24 h or 3 months later. Both acute and fractionated exposure decreased the amount of proliferating cells and immature neurons relative to sham exposure. Unexpectedly, neither acute nor fractionated exposure decreased the number of adult neural stem cells relative to sham expsoure. Our findings show that single and fractionated exposures of 56Fe-particle irradiation are similarly detrimental to adult-generated neurons. Implications for future missions and ground-based studies in space radiation are discussed. PMID:24320054

  1. Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

    SciTech Connect

    Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj; Dhawan, Jasbeer; Beheshti, Afshin; Manickam, Krishnan; Thapar, Upasna; Pena, Louis; Natarajan, Mohan; Hlatky, Lynn; Demple, Bruce; Naidu, Mamta

    2015-07-24

    Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells ’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction of Apurinic Endonucle- ase-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of pro- tons cause latent damage to spinal cord architecture while fractionation of HZE (28Si) induce increase in APE1 with single dose, which then decreased with fractionation. In conclusion, the oligoden- drocyte progenitor cells differentiation was skewed with increase in immature oligodendro- cytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects

  2. Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

    DOE PAGES

    Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj; Dhawan, Jasbeer; Beheshti, Afshin; Manickam, Krishnan; Thapar, Upasna; Pena, Louis; Natarajan, Mohan; Hlatky, Lynn; et al

    2015-07-24

    Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells ’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction ofmore » Apurinic Endonucle- ase-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of pro- tons cause latent damage to spinal cord architecture while fractionation of HZE (28Si) induce increase in APE1 with single dose, which then decreased with fractionation. In conclusion, the oligoden- drocyte progenitor cells differentiation was skewed with increase in immature oligodendro- cytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects« less

  3. Dose to lung from inhaled tritiated particles.

    PubMed

    Richardson, R B; Hong, A

    2001-09-01

    Tritiated particulate materials are of potential hazard in fission, fusion, and other tritium handling facilities. The absorbed fractions (fraction of energy emitted that is absorbed by the target region) are calculated for tritiated particles deposited in the alveolar-interstitial (AI) region of the respiratory tract. The energy absorbed by radiologically sensitive tissue irradiated by tritiated particles, in regions of the lung other than in the AI region, is negligible. The ICRP Publication 71 assumes the absorbed fraction is unity for tritium deposited in the AI region. We employed Monte Carlo methods in a model to evaluate the energy deposition in the wall of the alveolar sac from particles of tritiated beryllium, tritiated graphite, titanium tritide, tritiated iron hydroxide and zirconium tritide. For the five materials examined, the absorbed fraction in alveolar tissue ranged from 0.31 to 0.61 for particles of 1 microm physical diameter and 0.07 to 0.21 for 5 microm diameter particles. The dose to alveolar tissue, for an acute inhalation of tritiated particles by an adult male worker, was calculated based on the ICRP 66 lung model and the particle dissolution model of Mercer (1967). For particles of 5 microm activity median aerodynamic diameter (AMAD), the committed equivalent dose to alveolar tissue, calculated for the five materials, ranged from 32-42%, respectively, of the committed equivalent dose derived assuming the absorbed fractions were unity. PMID:11513464

  4. [Ablative and fractional lasers].

    PubMed

    Beylot, C; Grognard, C; Michaud, T

    2009-10-01

    The use of pulsed or scanning Carbon Dioxide, and pulsed Erbium-YAG lasers allows the programmable and reproducible photocoagulation of thin layers of the epidermis and superficial dermis. Thermal damage depends on the type of laser and is greater with CO(2) lasers. The degree of neocollagenesis is proportional to the thermal damage and is better with CO(2) lasers. Their main indication is the correction of photoaged facial skin but they can also be used for corrective dermatology, e.g. for scars and genodermatosis. Results are highly satisfactory but the technique is invasive and the patient experiences a social hindrance of around two weeks. Fractionated techniques treat 25% of the defective skin area at each session in noncontiguous microzones; four sessions are therefore necessary to treat the entire cutaneous surface. The treatment is given under topical anesthesia and is much less invasive, particularly with nonablative fractional laser treatment in which photothermolysis does not penetrate below the epidermis and/or the effects are slight, with no or very little social isolation. However, the results are much less satisfactory than the results of ablative laser and there is no firming effect. Other zones than the face can be treated. With the fractional CO(2) and Erbium ablative lasers, which have multiplied over the past 2 years, the much wider impacts cause perforation of the epidermis and there is a zone of ablation by laser photovaporization, with a zone of thermal damage below. The results are better in correcting photoaging of the face, without, however, achieving the efficacy of ablative lasers, which remain the reference technique. However, the effects are not insignificant, requiring at least 5 days of social isolation.

  5. Fractional channel multichannel analyzer

    DOEpatents

    Brackenbush, Larry W.; Anderson, Gordon A.

    1994-01-01

    A multichannel analyzer incorporating the features of the present invention obtains the effect of fractional channels thus greatly reducing the number of actual channels necessary to record complex line spectra. This is accomplished by using an analog-to-digital converter in the asynscronous mode, i.e., the gate pulse from the pulse height-to-pulse width converter is not synchronized with the signal from a clock oscillator. This saves power and reduces the number of components required on the board to achieve the effect of radically expanding the number of channels without changing the circuit board.

  6. High-dose MVCT image guidance for stereotactic body radiation therapy

    SciTech Connect

    Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.; Chao, Edward; Lucas, Dan; Flynn, Ryan T.; Miften, Moyed

    2012-08-15

    Purpose: Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Methods: Two nonstandard, high-dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. Results: MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp/mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. Conclusions: High-dose imaging modes are made possible on a

  7. Assessment of organ-specific neutron equivalent doses in proton therapy using computational whole-body age-dependent voxel phantoms

    NASA Astrophysics Data System (ADS)

    Zacharatou Jarlskog, Christina; Lee, Choonik; Bolch, Wesley E.; Xu, X. George; Paganetti, Harald

    2008-02-01

    field is smaller than the reported scattered photon doses in a typical intensity-modulated photon treatment. Most importantly, our study shows that neutron doses to specific organs depend considerably on the patient's age and body stature. The younger the patient, the higher the dose deposited due to neutrons. Given the fact that the risk also increases with decreasing patient age, this factor needs to be taken into account when treating pediatric patients of very young ages and/or of small body size. The neutron dose from a course of proton therapy treatment (assuming 70 Gy in 30 fractions) could potentially (depending on patient's age, organ, treatment site and area of CT scan) be equivalent to up to ~30 CT scans.

  8. Absorbed Dose and Dose Equivalent Calculations for Modeling Effective Dose

    NASA Technical Reports Server (NTRS)

    Welton, Andrew; Lee, Kerry

    2010-01-01

    While in orbit, Astronauts are exposed to a much higher dose of ionizing radiation than when on the ground. It is important to model how shielding designs on spacecraft reduce radiation effective dose pre-flight, and determine whether or not a danger to humans is presented. However, in order to calculate effective dose, dose equivalent calculations are needed. Dose equivalent takes into account an absorbed dose of radiation and the biological effectiveness of ionizing radiation. This is important in preventing long-term, stochastic radiation effects in humans spending time in space. Monte carlo simulations run with the particle transport code FLUKA, give absorbed and equivalent dose data for relevant shielding. The shielding geometry used in the dose calculations is a layered slab design, consisting of aluminum, polyethylene, and water. Water is used to simulate the soft tissues that compose the human body. The results obtained will provide information on how the shielding performs with many thicknesses of each material in the slab. This allows them to be directly applicable to modern spacecraft shielding geometries.

  9. Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

    SciTech Connect

    Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

    1981-03-15

    To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600 to 800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800 to 400 to 400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients.

  10. Impact of geometric uncertainties on dose calculations for intensity modulated radiation therapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Jiang, Runqing

    Intensity-modulated radiation therapy (IMRT) uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI) during treatment delivery, a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or "blurred" dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). A Gaussian probability density function (PDF) is reasonable for modeling geometric uncertainties as indicated by the 118 patients group. The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. In addition, individual SD should not be determined or predicted from small imaging samples because of random nature of the fluctuations. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. Cumulative PDF data can be used for re-planning to assess accuracy of delivered dose. Group data is useful for determining worst case discrepancy between planned and delivered dose. The margins for the PTV should ideally represent true geometric uncertainties. The measured geometric uncertainties were used in this thesis to assess PTV coverage, dose to OAR, equivalent

  11. Low dose reirradiation in combination with hyperthermia: a palliative treatment for patients with breast cancer recurring in previously irradiated areas.

    PubMed

    van der Zee, J; Treurniet-Donker, A D; The, S K; Helle, P A; Seldenrath, J J; Meerwaldt, J H; Wijnmaalen, A J; van den Berg, A P; van Rhoon, G C; Broekmeyer-Reurink, M P

    1988-12-01

    Ninety-seven patients with breast cancer recurring in a previously irradiated area (mean dose 44 Gy) were reirradiated in combination with hyperthermia and had evaluable tumor responses. In the reirradiation series, radiotherapy was given twice weekly in most patients, with a fraction size varying from 200 to 400 cGy, the total dose varying from 8 to 32 Gy. Hyperthermia was given following the radiotherapy fractions. The combined treatment resulted in 35% complete and 55% partial responses. Duration of response was median 4 months for partial response and 26 months for complete response, respectively. The median survival time for all patients was 12 months. Acute skin reaction was mild, with more than moderate erythema in only 14/97 patients. Thermal burns occurred in 44/97 patients, generally at sites where pain sensation was decreased, and therefore they did not cause much inconvenience. In the 19 patients who survived more than 2 years, no late radiation damage was observed. When patients who received a "high dose" (greater than 29 Gy and hyperthermia) were compared with those who received a "low dose" (less than 29 Gy and hyperthermia), a higher complete response rate was observed in the high dose group (58% vs. 24%), whereas no difference in acute toxicity was found. We conclude that reirradiation with 8 x 4 Gy in combination with hyperthermia twice weekly is a safe, effective and well tolerated method for palliative treatment of patients with breast cancer recurring in previously irradiated areas.

  12. Optimal dose-setting study of curcumin for improvement of left ventricular systolic function after myocardial infarction in rats.

    PubMed

    Sunagawa, Yoichi; Sono, Shogo; Katanasaka, Yasufumi; Funamoto, Masafumi; Hirano, Sae; Miyazaki, Yusuke; Hojo, Yuya; Suzuki, Hidetoshi; Morimoto, Eriko; Marui, Akira; Sakata, Ryuzo; Ueno, Morio; Kakeya, Hideaki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2014-01-01

    A natural p300-specific histone acetyltransferase inhibitor, curcumin, may have a therapeutic potential for heart failure. However, a study of curcumin to identify an appropriate dose for heart failure has yet to be performed. Rats were subjected to a left coronary artery ligation. One week later, rats with a moderate severity of myocardial infarction (MI) were randomly assigned to 4 groups receiving the following: a solvent as a control, a low dose of curcumin (0.5 mg∙kg(-1)∙day(-1)), a medium dose of curcumin (5 mg∙kg(-1)∙day(-1)), or a high dose of curcumin (50 mg∙kg(-1)∙day(-1)). Daily oral treatment was continued for 6 weeks. After treatment, left ventricular (LV) fractional shortening was dose-dependently improved in the high-dose (25.2% ± 1.6%, P < 0.001 vs. vehicle) and medium-dose (19.6% ± 2.4%) groups, but not in the low-dose group (15.5% ± 1.4%) compared with the vehicle group (15.1% ± 0.8%). The histological cardiomyocyte diameter and perivascular fibrosis as well as echocardiographic LV posterior wall thickness dose-dependently decreased in the groups receiving high and medium doses. The beneficial effects of oral curcumin on the post-MI LV systolic function are lower at 5 compared to 50 mg∙kg(-1)∙day(-1) and disappear at 0.5 mg∙kg(-1)∙day(-1). To clinically apply curcumin therapy for heart failure patients, a precise, optimal dose-setting study is required.

  13. What is a fractional derivative?

    NASA Astrophysics Data System (ADS)

    Ortigueira, Manuel D.; Tenreiro Machado, J. A.

    2015-07-01

    This paper discusses the concepts underlying the formulation of operators capable of being interpreted as fractional derivatives or fractional integrals. Two criteria for required by a fractional operator are formulated. The Grünwald-Letnikov, Riemann-Liouville and Caputo fractional derivatives and the Riesz potential are accessed in the light of the proposed criteria. A Leibniz rule is also obtained for the Riesz potential.

  14. Positive fractional linear electrical circuits

    NASA Astrophysics Data System (ADS)

    Kaczorek, Tadeusz

    2013-10-01

    The positive fractional linear systems and electrical circuits are addressed. New classes of fractional asymptotically stable and unstable electrical circuits are introduced. The Caputo and Riemann-Liouville definitions of fractional derivatives are used to analysis of the positive electrical circuits composed of resistors, capacitors, coils and voltage (current) sources. The positive fractional electrical and specially unstable different types electrical circuits are analyzed. Some open problems are formulated.

  15. Experimental observation of fractional echoes

    NASA Astrophysics Data System (ADS)

    Karras, G.; Hertz, E.; Billard, F.; Lavorel, B.; Siour, G.; Hartmann, J.-M.; Faucher, O.; Gershnabel, Erez; Prior, Yehiam; Averbukh, Ilya Sh.

    2016-09-01

    We report the observation of fractional echoes in a double-pulse excited nonlinear system. Unlike standard echoes, which appear periodically at delays which are integer multiples of the delay between the two exciting pulses, the fractional echoes appear at rational fractions of this delay. We discuss the mechanism leading to this phenomenon, and provide experimental demonstration of fractional echoes by measuring third harmonic generation in a thermal gas of CO2 molecules excited by a pair of femtosecond laser pulses.

  16. Antibacterial efficacy of ethyl acetate fraction of Psidium guajava leaf aqueous extract on experimental Escherichia coli (O78) infection in chickens

    PubMed Central

    Geidam, Y. A.; Ambali, A. G.; Onyeyili, P. A.; Tijjani, M. B.; Gambo, H. I.; Gulani, I. A.

    2015-01-01

    Aim: This study was desingned to examine the efficacy of ethyl acetate fraction of aqueous extracted Psidium guajava leaves on chicks experimentally-infected with diarrheagenic strain of Escherichia coli O78. Methods: A total of 60 ISA brown male chicks were randomly divided into 6 Groups of ten chicks each in separate cages. Group A was not infected and not treated. Groups B, C and D were infected and treated with extracts at a dose of 25, 50 and 100 mg/kg respectively for 10 days. Group E was infected and treated with oxytetracycline while Group F was infected, but left untreated. Chicks from all groups were closely monitored for clinical signs, body weight change and fecal bacterial shedding load during the course of the experiment. Results: Diarrhea, vents pasted with feces, drop in feed intake accompanied by slow weight gain and decreased activity was observed in infected untreated groups. Groups treated with graded doses of the extract experienced a dose-dependent decreased in severity of the clinical signs shown compared to the infected untreated group. Bacterial shedding load was found to be lower in groups treated with the extract and oxytetracycline than those without intervention. Conclusion: Ethyl acetate soluble fraction of leaf extract of Psidium guajava effectively controlled diarrhea and decreased the severity of other clinical signs caused by experimental E. coli infections in chicks. PMID:27047097

  17. Fractional diffusion on bounded domains

    SciTech Connect

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; Gunzburger, Max Donald; Lehoucq, Richard B.; Meerschaert, Mark M.

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  18. Benchmark Dose Modeling

    EPA Science Inventory

    Finite doses are employed in experimental toxicology studies. Under the traditional methodology, the point of departure (POD) value for low dose extrapolation is identified as one of these doses. Dose spacing necessarily precludes a more accurate description of the POD value. ...

  19. Preventive Effect of Three Pomegranate (Punica granatum L.) Seeds Fractions on Cerulein-Induced Acute Pancreatitis in Mice

    PubMed Central

    Minaiyan, Mohsen; Zolfaghari, Behzd; Taheri, Diana; Gomarian, Mahdi

    2014-01-01

    Background: Acute pancreatitis (AP) refers to afflicted inflammation of pancreas with unfavorable adverse effects and developed multiple organ failures. Unfortunately, there is not a certain therapeutic method for this disease. Oxidative stress has a serious role in the pathogenesis of AP. Thus, decreasing of oxidative stress may prevent induction and progression of AP. Punica granatum L. has been extensively used in traditional medicine and possesses various active biological elements. Due to antioxidant and anti-inflammatory properties of pomegranate, it could be considered as a good candidate alternative medicine with beneficial effects on AP. In this study, we decided to study the protective effect of three fractions of pomegranate seeds on cerulein-induced AP. Methods: AP was induced in male Syrian mice by five intraperitoneal (i.p.) injection of cerulein (50 μg/kg) with 1 h intervals. Treatments with pomegranate freeze-dried powder (PFDP) and hydroalcoholic pomegranate seeds extract (PSE) at doses of 125, 250, 500 mg/kg (i.p.) were started 30 min before pancreatitis induction. Pomegranate seed oil fraction (PSOF) was orally administered (50, 100, 200 μL/kg) and continued for 10 days. Pancreatic tissue was evaluated for histopathological parameters and pancreatic myeloperoxidase (MPO) activity as well as lipase and amylase levels were measured in plasma. Results: The higher doses of three fractions (250 and 500 mg/kg for PFDP and PSE and doses of 100, 200 μL/kg for PSOF) significantly reduced amylase and lipase activity in serum (at least P < 0.01), pancreatic MPO activity (P < 0.001), edema, leukocyte infiltration and vacuolization in comparison to the control group (P < 0.05). Conclusions: These results propose that pomegranate seeds fractions can prevent and/or treat the AP. PMID:24829726

  20. Fractionation of Subcellular Organelles.

    PubMed

    Graham, John M

    2015-01-01

    This unit provides both a theoretical and a practical background to all the techniques associated with the application of differential and density gradient centrifugation for the analysis of subcellular membranes. The density gradient information focuses on the use of the modern gradient solute iodixanol, chosen for its ease of use, versatility, and compatibility with biological particles. Its use in both pre-formed discontinuous and continuous gradients and in self-generated gradients is discussed. Considerable emphasis is given to selection of the appropriate centrifuge rotors and tubes and their influence on the methods used for creation, fractionation, and analysis of density gradients. Without proper consideration of these critical ancillary procedures, the resolving power of the gradient can be easily compromised. PMID:26621372

  1. Fractionation of Subcellular Organelles.

    PubMed

    Graham, John M

    2015-12-01

    This unit provides both a theoretical and a practical background to all the techniques associated with the application of differential and density gradient centrifugation for the analysis of subcellular membranes. The density gradient information focuses on the use of the modern gradient solute iodixanol, chosen for its ease of use, versatility, and compatibility with biological particles. Its use in both pre-formed discontinuous and continuous gradients and in self-generated gradients is discussed. Considerable emphasis is given to selection of the appropriate centrifuge rotors and tubes and their influence on the methods used for creation, fractionation, and analysis of density gradients. Without proper consideration of these critical ancillary procedures, the resolving power of the gradient can be easily compromised.

  2. Soot Volume Fraction Imaging

    NASA Technical Reports Server (NTRS)

    Greenberg, Paul S.; Ku, Jerry C.

    1994-01-01

    A new technique is described for the full-field determination of soot volume fractions via laser extinction measurements. This technique differs from previously reported point-wise methods in that a two-dimensional array (i.e., image) of data is acquired simultaneously. In this fashion, the net data rate is increased, allowing the study of time-dependent phenomena and the investigation of spatial and temporal correlations. A telecentric imaging configuration is employed to provide depth-invariant magnification and to permit the specification of the collection angle for scattered light. To improve the threshold measurement sensitivity, a method is employed to suppress undesirable coherent imaging effects. A discussion of the tomographic inversion process is provided, including the results obtained from numerical simulation. Results obtained with this method from an ethylene diffusion flame are shown to be in close agreement with those previously obtained by sequential point-wise interrogation.

  3. Decrease of plasma and urinary oxidative metabolites of acetaminophen after consumption of watercress by human volunteers.

    PubMed

    Chen, L; Mohr, S N; Yang, C S

    1996-12-01

    To investigate the effect of the consumption of watercress (Nasturtium officinale R. Br.), a cruciferous vegetable, on acetaminophen metabolism, the pharmacokinetics of acetaminophen and its metabolites were studied in a crossover trial of human volunteers. A single oral dose of acetaminophen (1 gm) was given 10 hours after ingestion of watercress homogenates (50 gm). In comparison with acetaminophen only, the ingestion of watercress resulted in a significant reduction in the area under the plasma cysteine acetaminophen (Cys-acetaminophen) concentration-time curve and in the peak plasma Cys-acetaminophen concentration by 28% +/- 3% and by 21% +/- 4% (mean +/- SE; n = 7; p < 0.005), respectively. Correspondingly, the Cys-acetaminophen formation rate constant and Cys-acetaminophen formation fraction were decreased by 55% +/- 9% and 52% +/- 7% (p < 0.01), respectively. Consistent with the results obtained from the plasma, the total urinary excretion of Cys-acetaminophen in 24 hours was also reduced. A decrease of mercapturate acetaminophen, a Cys-acetaminophen metabolite, was also shown in the plasma and urine samples. However, the plasma pharmacokinetic processes and the urinary excretions of acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate were not altered significantly by the watercress treatment. These results suggest that the consumption of watercress causes a decrease in the levels of oxidative metabolites of acetaminophen, probably due to inhibition of oxidative metabolism of this drug.

  4. Calculation of dose conversion factors for thoron decay products.

    PubMed

    Ishikawa, Tetsuo; Tokonami, Shinji; Nemeth, Csaba

    2007-12-01

    The dose conversion factors for short-lived thoron decay products were calculated using a dosimetric approach. The calculations were based on a computer program LUDEP, which implements the ICRP 66 respiratory tract model. The dose per equilibrium equivalent concentration for thoron (EETC) was calculated with respect to (1) equivalent dose to each region of the lung tissues (bronchial, bronchiolar and alveolar), (2) weighted equivalent dose to organs other than lung, and (3) effective dose. The calculations indicated that (1) the most exposed region of the lung tissues was the bronchial for the unattached fraction and the bronchiolar for the attached fraction, (2) the effective dose is dominated by the contribution of lung dose, and (3) the effective dose per EETC was about four times larger than the effective dose per equilibrium equivalent concentration for radon (EERC). The calculated dose conversion factors were applied to the comparative dosimetry for some thoron-enhanced areas where the EERC and EETC have been measured. In the case of a spa in Japan, the dose from thoron decay products was larger than the dose from radon decay products.

  5. Absorbed fractions for electrons in ellipsoidal volumes.

    PubMed

    Amato, E; Lizio, D; Baldari, S

    2011-01-21

    We applied a Monte Carlo simulation in Geant4 in order to calculate the absorbed fractions for monoenergetic electrons in the energy interval between 10 keV and 2 MeV, uniformly distributed in ellipsoids made from soft tissue. For each volume, we simulated a spherical shape, four oblate and four prolate ellipsoids, and one scalene shape. For each energy and for every geometrical configuration, an analytical relationship between the absorbed fraction and a 'generalized radius' was found, and the dependence of the fit parameters from electron energy is discussed and fitted by proper parametric functions. With the proposed formulation, the absorbed fraction for electrons in the 10-2000 keV energy range can be calculated for all volumes and for every ellipsoidal shape of practical interest. This method can be directly applied to evaluation of the absorbed fraction from the radionuclide emission of monoenergetic electrons, such as Auger or conversion electrons. The average deposited energy per disintegration in the case of extended beta spectra can be evaluated through integration. Two examples of application to a pure beta emitter such as (90)Y and to (131)I, whose emission include monoenergetic and beta electrons plus gamma photons, are presented. This approach represent a generalization of our previous studies, allowing a comprehensive treatment of absorbed fractions from electron and photon sources uniformly distributed in ellipsoidal volumes of any ellipticity and volume, in the whole range of practical interest for internal dosimetry in nuclear medicine applications, as well as in radiological protection estimations of doses from an internal contamination.

  6. Absorbed fractions for electrons in ellipsoidal volumes

    NASA Astrophysics Data System (ADS)

    Amato, E.; Lizio, D.; Baldari, S.

    2011-01-01

    We applied a Monte Carlo simulation in Geant4 in order to calculate the absorbed fractions for monoenergetic electrons in the energy interval between 10 keV and 2 MeV, uniformly distributed in ellipsoids made from soft tissue. For each volume, we simulated a spherical shape, four oblate and four prolate ellipsoids, and one scalene shape. For each energy and for every geometrical configuration, an analytical relationship between the absorbed fraction and a 'generalized radius' was found, and the dependence of the fit parameters from electron energy is discussed and fitted by proper parametric functions. With the proposed formulation, the absorbed fraction for electrons in the 10-2000 keV energy range can be calculated for all volumes and for every ellipsoidal shape of practical interest. This method can be directly applied to evaluation of the absorbed fraction from the radionuclide emission of monoenergetic electrons, such as Auger or conversion electrons. The average deposited energy per disintegration in the case of extended beta spectra can be evaluated through integration. Two examples of application to a pure beta emitter such as 90Y and to 131I, whose emission include monoenergetic and beta electrons plus gamma photons, are presented. This approach represent a generalization of our previous studies, allowing a comprehensive treatment of absorbed fractions from electron and photon sources uniformly distributed in ellipsoidal volumes of any ellipticity and volume, in the whole range of practical interest for internal dosimetry in nuclear medicine applications, as well as in radiological protection estimations of doses from an internal contamination.

  7. Automated administration of intermittent intravenous doses.

    PubMed

    Lutomski, D M; Schwartz-Fulton, J; Rivera, J O

    1985-11-01

    The cost difference of administering cimetidine 300 mg via intravenous piggyback (IVPB) every six hours by a conventional separate container system versus using an automated intermittent i.v. administration system was evaluated. The study was conducted in two phases. Phase 1 documented the amount of drug waste with the two systems, and phase 2 examined the practical use of the IVAC Multi Dose System. Nurses who administered the medication using the multiple-dose system completed a questionnaire on its operation. A materials cost analysis was performed to compare the two methods. The two systems were found to have approximately equivalent amounts of drug waste over the 30-day evaluation period of phase 1. The mean percentage of doses wasted was 12.2% with the conventional single-dose minibag method and 12.7% with the automated multiple-dose method. The multiple-dose system had a lower cost per dose of cimetidine ($2.25 versus $3.47). These savings appear to outweigh the cost of the additional equipment necessary for the automated system. The majority of nurses preferred the multiple-dose system. Potential problems encountered in accurately delivering doses with the multiple-dose automated system were identified, and possible solutions are suggested. The use of an automated multiple-dose i.v. administration system can potentially decrease the materials cost portion of drug administration. The total impact on hospital costs needs to be evaluated, and other comparisons with alternative administration systems need to be performed.

  8. Low dose neutron late effects: Cataractogenesis

    SciTech Connect

    Worgul, B.V.

    1991-12-01

    The work is formulated to resolve the uncertainty regarding the relative biological effectiveness (RBE) of low dose neutron radiation. The study exploits the fact that cataractogenesis is sensitive to the inverse dose-rate effect as has been observed with heavy ions and was an endpoint considered in the follow-up of the A-bomb survivors. The neutron radiations were initiated at the Radiological Research Accelerator facility (RARAF) of the Nevis Laboratory of Columbia University. Four week old ({plus minus} 1 day) rats were divided into eight dose groups each receiving single or fractionated total doses of 0.2, 1.0, 5.0 and 25.0 cGy of monoenergetic 435 KeV neutrons. Special restraining jigs insured that the eye, at the midpoint of the lens, received the appropriate energy and dose with a relative error of {plus minus}5%. The fractionation regimen consisted of four exposures, each administered at three hour ({plus minus}) intervals. The neutron irradiated groups are being compared to rats irradiated with 250kVp X-rays in doses ranging from 0.5 to 7 Gy. The animals are being examined on a biweekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit Lamp Imaging System (Zeiss). The follows-ups, entering their second year, will continue throughout the life-span of the animals. This is essential inasmuch as given the extremely low doses which are being utilized clinically detectable opacities were not anticipated until a significant fraction of the life span has lapsed. Current data support this contention. At this juncture cataracts in the irradiated groups are beginning to exceed control levels.

  9. Second Cancers After Fractionated Radiotherapy: Stochastic Population Dynamics Effects

    NASA Technical Reports Server (NTRS)

    Sachs, Rainer K.; Shuryak, Igor; Brenner, David; Fakir, Hatim; Hahnfeldt, Philip

    2007-01-01

    When ionizing radiation is used in cancer therapy it can induce second cancers in nearby organs. Mainly due to longer patient survival times, these second cancers have become of increasing concern. Estimating the risk of solid second cancers involves modeling: because of long latency times, available data is usually for older, obsolescent treatment regimens. Moreover, modeling second cancers gives unique insights into human carcinogenesis, since the therapy involves administering well characterized doses of a well studied carcinogen, followed by long-term monitoring. In addition to putative radiation initiation that produces pre-malignant cells, inactivation (i.e. cell killing), and subsequent cell repopulation by proliferation can be important at the doses relevant to second cancer situations. A recent initiation/inactivation/proliferation (IIP) model characterized quantitatively the observed occurrence of second breast and lung cancers, using a deterministic cell population dynamics approach. To analyze ifradiation-initiated pre-malignant clones become extinct before full repopulation can occur, we here give a stochastic version of this I I model. Combining Monte Carlo simulations with standard solutions for time-inhomogeneous birth-death equations, we show that repeated cycles of inactivation and repopulation, as occur during fractionated radiation therapy, can lead to distributions of pre-malignant cells per patient with variance >> mean, even when pre-malignant clones are Poisson-distributed. Thus fewer patients would be affected, but with a higher probability, than a deterministic model, tracking average pre-malignant cell numbers, would predict. Our results are applied to data on breast cancers after radiotherapy for Hodgkin disease. The stochastic IIP analysis, unlike the deterministic one, indicates: a) initiated, pre-malignant cells can have a growth advantage during repopulation, not just during the longer tumor latency period that follows; b) weekend

  10. From cellular doses to average lung dose.

    PubMed

    Hofmann, W; Winkler-Heil, R

    2015-11-01

    Sensitive basal and secretory cells receive a wide range of doses in human bronchial and bronchiolar airways. Variations of cellular doses arise from the location of target cells in the bronchial epithelium of a given airway and the asymmetry and variability of airway dimensions of the lung among airways in a given airway generation and among bronchial and bronchiolar airway generations. To derive a single value for the average lung dose which can be related to epidemiologically observed lung cancer risk, appropriate weighting scenarios have to be applied. Potential biological weighting parameters are the relative frequency of target cells, the number of progenitor cells, the contribution of dose enhancement at airway bifurcations, the promotional effect of cigarette smoking and, finally, the application of appropriate regional apportionment factors. Depending on the choice of weighting parameters, detriment-weighted average lung doses can vary by a factor of up to 4 for given radon progeny exposure conditions.

  11. 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).

  12. Fractionally charged skyrmions in fractional quantum Hall effect

    NASA Astrophysics Data System (ADS)

    Balram, Ajit C.; Wurstbauer, U.; Wójs, A.; Pinczuk, A.; Jain, J. K.

    2015-11-01

    The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region.

  13. Fractionally charged skyrmions in fractional quantum Hall effect.

    PubMed

    Balram, Ajit C; Wurstbauer, U; Wójs, A; Pinczuk, A; Jain, J K

    2015-01-01

    The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region. PMID:26608906

  14. Fractionally charged skyrmions in fractional quantum Hall effect

    PubMed Central

    Balram, Ajit C.; Wurstbauer, U.; Wójs, A.; Pinczuk, A.; Jain, J. K.

    2015-01-01

    The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region. PMID:26608906

  15. Fractionally charged skyrmions in fractional quantum Hall effect.

    PubMed

    Balram, Ajit C; Wurstbauer, U; Wójs, A; Pinczuk, A; Jain, J K

    2015-11-26

    The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region.

  16. Fractionally charged skyrmions in fractional quantum Hall effect

    SciTech Connect

    Balram, Ajit C.; Wurstbauer, U.; Wójs, A.; Pinczuk, A.; Jain, J. K.

    2015-11-26

    The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region.

  17. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs.

    PubMed

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-03-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH.

  18. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs

    PubMed Central

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-01-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH. PMID:23997262

  19. Simulated microgravity decreases apoptosis in fetal fibroblasts.

    PubMed

    Beck, Michaël; Tabury, Kevin; Moreels, Marjan; Jacquet, Paul; Van Oostveldt, Patrick; De Vos, Winnok H; Baatout, Sarah

    2012-08-01

    Space travel is a major challenge for human beings. Especially, the mechanisms through which space conditions might alter animal development have been questioned for a long time. The two major physical stress factors that are of relevance in this context are space radiation and weightlessness. While it has been extensively shown that high doses of ionizing radiation induce deleterious effects on embryonic development, so far, little is known about the potential harmful effects of radiation in combination with microgravity on the developing organism. In the present study, we investigated the effects of simulated microgravity on irradiated STO mouse fetal fibroblast cells using a random positioning machine (RPM). Radiation-induced cell cycle changes were not affected when cells were subjected to simulated microgravity for 24 h. Moreover, no morphological differences were observed in irradiated samples exposed to simulated microgravity compared to cells that were exclusively irradiated. However, microgravity simulation significantly decreased the level of apoptosis at all doses as measured by caspase-3 activity and it prevented cells from undergoing radiation-induced size increase up to 1 Gy.

  20. Dietary Squalene Increases High Density Lipoprotein-Cholesterol and Paraoxonase 1 and Decreases Oxidative Stress in Mice

    PubMed Central

    Gabás-Rivera, Clara; Barranquero, Cristina; Martínez-Beamonte, Roberto; Navarro, María A.; Surra, Joaquín C.; Osada, Jesús

    2014-01-01

    Background and Purpose Squalene, the main hydrocarbon in the unsaponifiable fraction of virgin olive oil, is involved in cholesterol synthesis and it has been reported to own antiatherosclerotic and antiesteatosic effects. However, the squalene's role on lipid plasma parameters and the influence of genotype on this effect need to be addressed. Experimental Approaches Three male mouse models (wild-type, Apoa1- and Apoe- deficient) were fed chow semisynthetic diets enriched in squalene to provide a dose of 1 g/kg during 11 weeks. After this period, their plasma parameters and lipoprotein profiles were analyzed. Key Results Squalene administration at a dose of 1 g/kg showed decreased reactive oxygen species in lipoprotein fractions independently of the animal background and caused an specific increase in high density lipoprotein (HDL)-cholesterol levels, accompanied by an increase in phosphatidylcholine and paraoxonase 1 and no changes in apolipoproteins A1 and A4 in wild-type mice. In these mice, the cholesterol increase was due to its esterified form and associated with an increased hepatic expression of Lcat. These effects were not observed in absence of apolipoprotein A1. The increases in HDL- paraoxonase 1 were translated into decreased plasma malondialdehyde levels depending on the presence of Apolipoprotein A1. Conclusions and Implications Dietary squalene promotes changes in HDL- cholesterol and paraoxonase 1 and decreases reactive oxygen species in lipoproteins and plasma malondialdehyde levels, providing new benefits of its intake that might contribute to explain the properties of virgin olive oil, although the phenotype related to apolipoproteins A1 and E may be particularly relevant. PMID:25117703

  1. Whole body protection against lethal ionizing radiation in mice by REC-2001: a semi-purified fraction of Podophyllum hexandrum.

    PubMed

    Lata, M; Prasad, J; Singh, S; Kumar, R; Singh, L; Chaudhary, P; Arora, R; Chawla, R; Tyagi, S; Soni, N L; Sagar, R K; Devi, M; Sharma, R K; Puri, S C; Tripathi, R P

    2009-01-01

    The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain 'A' mice exposed to 10 Gy whole-body gamma radiation. Animals were treated with 10 and 15 mg/kg b wt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of gamma-radiation (10 Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD(50) and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72 h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of gamma-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection. A single dose of REC-2001 (10 and 15 mg/kg b wt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75 mg/kg b wt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90 mg/kg b wt, resulted in 50% mortality (LD(50)), while the LD(100) was 115 mg/kg b wt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10 Gy radiation resulted in increased halo diameter (45+/-3 microm) in comparison to untreated controls (8+/-1 microm). REC-2001 administration (500 microg/ml) decreased the halo diameter to 15+/-2 microm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of gamma-radiation after further investigations in higher animal models.

  2. Fractional telegrapher's equation from fractional persistent random walks

    NASA Astrophysics Data System (ADS)

    Masoliver, Jaume

    2016-05-01

    We generalize the telegrapher's equation to allow for anomalous transport. We derive the space-time fractional telegrapher's equation using the formalism of the persistent random walk in continuous time. We also obtain the characteristic function of the space-time fractional process and study some particular cases and asymptotic approximations. Similarly to the ordinary telegrapher's equation, the time-fractional equation also presents distinct behaviors for different time scales. Specifically, transitions between different subdiffusive regimes or from superdiffusion to subdiffusion are shown by the fractional equation as time progresses.

  3. Fractional telegrapher's equation from fractional persistent random walks.

    PubMed

    Masoliver, Jaume

    2016-05-01

    We generalize the telegrapher's equation to allow for anomalous transport. We derive the space-time fractional telegrapher's equation using the formalism of the persistent random walk in continuous time. We also obtain the characteristic function of the space-time fractional process and study some particular cases and asymptotic approximations. Similarly to the ordinary telegrapher's equation, the time-fractional equation also presents distinct behaviors for different time scales. Specifically, transitions between different subdiffusive regimes or from superdiffusion to subdiffusion are shown by the fractional equation as time progresses. PMID:27300830

  4. Dose Effects of Ion Beam Exposure on Deinococcus Radiodurans: Survival and Dose Response

    NASA Astrophysics Data System (ADS)

    Song, Dao-jun; Wu, Li-fang; Wu, Li-jun; Yu, Zeng-liang

    2001-02-01

    To explore the survival and dose response of organism for different radiation sources is of great importance in the research of radiobiology. In this study, the survival-dose response of Deinococcus radiodurans (E.coli, as the control) for ultra-violet (UV), γ-rays radiation and ion beam exposure was investigated. The shoulder type of survival curves were found for both UV and γ-ray ionizing radiation, but the saddle type of survival curves were shown for H+, N+(20keV and 30keV) and Ar+ beam exposure. This dose effect of the survival initially decreased with the increase in dose and then increased in the high dose range and finally decreased again in the higher dose range. Our experimental results suggest that D. radiodurans, which is considerably radio-resistant to UV and x-ray and γ-ray ionizing radiation, do not resist ion beam exposure.

  5. UV-induced unscheduled DNA synthesis in human skin: dose response, correlation with erythema, time course and split dose exposure in vivo.

    PubMed

    Hönigsmann, H; Brenner, W; Tanew, A; Ortel, B

    1987-09-01

    Unscheduled DNA synthesis (UDS) has been shown to be saturated above a threshold dose of UV-C in human fibroblasts in vitro. We have investigated by autoradiography whether a similar saturation occurs in human skin in vivo with UV-B and whether this phenomenon correlates with the erythemal response. In addition, we determined the time course of UDS at 24 h after exposure and the effect of dual exposures separated by 24 h. The dose-response curve was established by exposure to 1/16, 1/8, 1/4, 1/2, 1, 2, 3, 4 and 6 MEDs UV-B. For the time-course study, areas exposed to 1/2 and 2 MEDs were biopsied after 1, 3, 6, 12 and 24 h. Autoradiography was performed in vitro. The dose-response curve showed a significant increase in UDS from 1/16 to 1 minimal erythema dose (MED), whereas no significant difference was observed between 1 MED and the higher UV-B doses tested. The 24 h time sequence revealed a gradual decrease in UDS activity. The 1/2 MED curve declined more rapidly and reached the zero-level between 12 h and 24 h, whereas about 50% of the initial UDS value was still retained 24 h after 2 MEDs. The dual-dose study revealed that a second hit of fractions of the MED resulted in lower levels of UDS than induced by these fractions alone in previously untreated areas. UDS increases with the erythemal dose between 1/16 and 1 MED. It reaches a plateau after 1 MED and cannot be increased by doses up to 6 MEDs, suggesting a saturation of excision repair in vivo. Time course studies support such a saturation phenomenon. The failure to increase significantly UDS by a second irradiation 24 h after the first exposure needs further clarification. Since persistence of DNA lesions may lead to an accumulation after repeated exposures, additional mechanisms other than excision repair may protect human skin by error-free removal of possibly mutagenic sites. Photoreactivation may be important in this respect.

  6. Variability of Marker-Based Rectal Dose Evaluation in HDR Cervical Brachytherapy

    SciTech Connect

    Wang Zhou; Jaggernauth, Wainwright; Malhotra, Harish K.; Podgorsak, Matthew B.

    2010-01-01

    In film-based intracavitary brachytherapy for cervical cancer, position of the rectal markers may not accurately represent the anterior rectal wall. This study was aimed at analyzing the variability of rectal dose estimation as a result of interfractional variation of marker placement. A cohort of five patients treated with multiple-fraction tandem and ovoid high-dose-rate (HDR) brachytherapy was studied. The cervical os point and the orientation of the applicators were matched among all fractional plans for each patient. Rectal points obtained from all fractions were then input into each clinical treated plan. New fractional rectal doses were obtained and a new cumulative rectal dose for each patient was calculated. The maximum interfractional variation of distances between rectal dose points and the closest source positions was 1.1 cm. The corresponding maximum variability of fractional rectal dose was 65.5%. The percentage difference in cumulative rectal dose estimation for each patient was 5.4%, 19.6%, 34.6%, 23.4%, and 13.9%, respectively. In conclusion, care should be taken when using rectal markers as reference points for estimating rectal dose in HDR cervical brachytherapy. The best estimate of true rectal dose for each fraction should be determined by the most anterior point among all fractions.

  7. HADOC: a computer code for calculation of external and inhalation doses from acute radionuclide releases

    SciTech Connect

    Strenge, D.L.; Peloquin, R.A.

    1981-04-01

    The computer code HADOC (Hanford Acute Dose Calculations) is described and instructions for its use are presented. The code calculates external dose from air submersion and inhalation doses following acute radionuclide releases. Atmospheric dispersion is calculated using the Hanford model with options to determine maximum conditions. Building wake effects and terrain variation may also be considered. Doses are calculated using dose conversion factor supplied in a data library. Doses are reported for one and fifty year dose commitment periods for the maximum individual and the regional population (within 50 miles). The fractional contribution to dose by radionuclide and exposure mode are also printed if requested.

  8. Analysis of high–dose rate brachytherapy dose distribution resemblance in CyberKnife hypofractionated treatment plans of localized prostate cancer

    SciTech Connect

    Sudahar, H.; Kurup, P.G.G.; Murali, V.; Mahadev, P.; Velmurugan, J.

    2013-01-01

    The present study is to analyze the CyberKnife hypofractionated dose distribution of localized prostate cancer in terms of high–dose rate (HDR) brachytherapy equivalent doses to assess the degree of HDR brachytherapy resemblance of CyberKnife dose distribution. Thirteen randomly selected localized prostate cancer cases treated using CyberKnife with a dose regimen of 36.25 Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30 Gy in 3 fractions of HDR brachytherapy regimen. The D{sub 5%} of the target in the CyberKnife hypofractionation was 41.57 ± 2.41 Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86 Gy. The mean HDR fractionation equivalent dose, D{sub 98%}, was 27.93 ± 0.84 Gy. The V{sub 100%} of the prostate target was 95.57% ± 3.47%. The V{sub 100%} of the bladder and the rectum were 717.16 and 79.6 mm{sup 3}, respectively. Analysis of the HDR equivalent dose of CyberKnife dose distribution indicates a comparable resemblance to HDR dose distribution in the peripheral target doses (D{sub 98%} to D{sub 80%}) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D{sub 10%} and D{sub 5%}. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife.

  9. Tolerance doses for treatment planning

    SciTech Connect

    Lyman, J.T.

    1985-10-01

    Data for the tolerance of normal tissues or organs to (low-LET) radiation has been compiled from a number of sources which are referenced at the end of this document. This tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD/sub 5/) or 50% (TD/sub 50/) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represents doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same endpoint. The data from some sources shows a tendancy to be quantized in 5 Gy increments. This reflects the size of possible round off errors. It is believed that all these data have been accumulated without the benefit of 3-D dose distributions and therefore the estimates of the size of the volume and/or the uniformity of the irradiation may be less accurate than is now possible. 19 refs., 4 figs.