Bentzen, Søren M
2005-01-01
Clinically, there is growing interest in strategies for intensifying radiation therapy by escalating the dose per fraction. This paper considers the steepness of the dose-response curve in this case. The steepness of a radiation dose-response curve is most conveniently quantified by the normalized dose-response gradient, gamma. Under the assumption of a linear-quadratic dose-effect model, a simple analytical relationship is derived between the gamma-value for a dose-response curve generated by varying the total dose while keeping the number of fractions constant, i.e. escalating the dose per fraction, and the gamma-value for a dose-response curve generated by varying the total dose while keeping the dose per fraction constant. This formulation is compared with clinical dose-response data from the literature and shown to be in good agreement with the observations. Some implications of this formulation for non-uniform dose distributions delivered using 3D conformal radiotherapy or intensity modulated radiotherapy (IMRT) are briefly discussed.
[Diagnosis of uveitis with fractional doses of 32-P radionuclide].
Shambra, V V; Panfilova, G V
1989-01-01
For determination of the presence and activity of inflammation in the vascular coat of the eye as well as of the stopping of the disease, the authors propose to use radionuclide 32-P in a form of fractional doses in contradistinction to a single administration of a conventional dose. A common dose of the preparation is divided into four equal parts. At first, 1/4 of the dose is administered. One hour later, comparative external radiometry of the patient and the healthy eye is made. If there is seen no clear difference in intensity of accumulation, the second dose is administered. One hour later, repeated examination is made. After receiving clear data, further administration of the preparation is stopped. Administration of fractional doses suggests a decrease of ray load on the patient's organism, economy of the preparation without lowering the authenticity of examination.
Radiation effect in mouse skin: Dose fractionation and wound healing
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.
NASA Astrophysics Data System (ADS)
Tilly, David; Ahnesjö, Anders
2015-07-01
A fast algorithm is constructed to facilitate dose calculation for a large number of randomly sampled treatment scenarios, each representing a possible realisation of a full treatment with geometric, fraction specific displacements for an arbitrary number of fractions. The algorithm is applied to construct a dose volume coverage probability map (DVCM) based on dose calculated for several hundred treatment scenarios to enable the probabilistic evaluation of a treatment plan. For each treatment scenario, the algorithm calculates the total dose by perturbing a pre-calculated dose, separately for the primary and scatter dose components, for the nominal conditions. The ratio of the scenario specific accumulated fluence, and the average fluence for an infinite number of fractions is used to perturb the pre-calculated dose. Irregularities in the accumulated fluence may cause numerical instabilities in the ratio, which is mitigated by regularisation through convolution with a dose pencil kernel. Compared to full dose calculations the algorithm demonstrates a speedup factor of ~1000. The comparisons to full calculations show a 99% gamma index (2%/2 mm) pass rate for a single highly modulated beam in a virtual water phantom subject to setup errors during five fractions. The gamma comparison shows a 100% pass rate in a moving tumour irradiated by a single beam in a lung-like virtual phantom. DVCM iso-probability lines computed with the fast algorithm, and with full dose calculation for each of the fractions, for a hypo-fractionated prostate case treated with rotational arc therapy treatment were almost indistinguishable.
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.
Glioblastoma multiforme: treatment by large dose fraction irradiation and metronidazole
Kapp, D.S.; Wagner, F.C.; Lawrence, R.
1982-03-01
In an attempt to overcome the possible radioresistance of glioblastoma multiforme related to the large shoulder on the in vitro survival curves and to sensitize hypoxic tumor cells, a treatment protocol was instituted at Yale University Medical Center and affiliated hospitals, using large dose fraction irradiation therapy in conjunction with the hypoxic cell sensitizer metronidazole. Nineteen patients with biopsy-confirmed, previously untreated, cerebral grade IV glioblastoma multiforme were, following surgery, irradiated once a week at 600 rad per fraction, 3.5 to 4 hours after ingestion of metronidazole, 6 gm/m/sup 2/. A total of 7 treatments were employed, with all patients maintained on antiseizure medications and corticosteroids. Metronidazole levels were determined prior to each treatment and patients were followed closely clinically and with serial computerized tomography (CT) scans. The treatment was well tolerated, in general, with no untoward side effects related to the high dose fraction irradiation. The majority of the patients experienced varying degrees of gastrointestinal upset lasting up to several hours following metronidazole administration. Three patients died of pulmonary emboli. One patient experienced moderately severe ototoxicity. A median survival of 9.4 months was obtained for all 19 patients, suggestive of a prolongation of survival compared to historical controls treated with conventionally fractionated radiation or with unconventional radiation fractionation schemes and metronidazole or misonidazole.
Advantage of dose fractionation in monoclonal antibody-targeted radioimmunotherapy
Schlom, J.; Molinolo, A.; Simpson, J.F.; Siler, K.; Roselli, M.; Hinkle, G.; Houchens, D.P.; Colcher, D. )
1990-05-02
Monoclonal antibody (MAb) B72.3 IgG was radiolabeled with 131I and administered to female athymic NCr-nu mice bearing the LS-174T human colon adenocarcinoma xenograft to determine if fractionation of MAb dose had any advantage in tumor therapy. In the LS-174T xenograft, only approximately 30%-60% of tumor cells express the B72.3-reactive TAG-72 antigen. The LS-174T xenograft was used to reflect the heterogeneity of the TAG-72 antigen often seen in biopsy specimens from patients. In contrast to a single 600-muCi dose of 131I-B72.3 IgG where 60% of the animals died from toxic effects, two 300-muCi doses of 131I-B72.3 IgG reduced or eliminated tumor growth in 90% of mice, with only 10% of the animals dying from toxic effects. Dose fractionation even permitted escalation of the dose to three doses of 300 muCi of 131I-B72.3 IgG, resulting in even more extensive tumor reduction or elimination and minimal toxic effects. The use of an isotype-matched control MAb revealed a nonspecific component to tumor growth retardation, but the use of the specific B72.3 IgG demonstrated a much greater therapeutic effect. Tumors that had escaped MAb therapy were analyzed for expression of the B72.3-reactive TAG-72 antigen with the use of the immunoperoxidase method; they were shown to have the same antigenic phenotype as the untreated tumors. We verified tumor elimination by killing the test animals after a 7-week observation period and performing histologic examination of tumor sites. We also monitored toxic effects by histologic examination of numerous organs. These studies thus demonstrate the advantage of dose fractionation of a radiolabeled MAb for tumor therapy. We anticipate that the concept of dose fractionation can be practically applied in radioimmunotherapeutic clinical trials with the development and use of recombinant-chimeric MAbs and modified constructs.
Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma
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
Paul, Subhadip; Roy, Prasun Kumar
2016-02-01
Radiation therapy is one of the important treatment procedures of cancer. The day-to-day delivered dose to the tissue in radiation therapy often deviates from the planned fixed dose per fraction. This day-to-day variation of radiation dose is stochastic. Here, we have developed the mathematical formulation to represent the day-to-day stochastic dose variation effect in radiation therapy. Our analysis shows that that the fixed dose delivery approximation under-estimates the biological effective dose, even if the average delivered dose per fraction is equal to the planned dose per fraction. The magnitude of the under-estimation effect relies upon the day-to-day stochastic dose variation level, the dose fraction size and the values of the radiobiological parameters of the tissue. We have further explored the application of our mathematical formulation for adaptive dose calculation. Our analysis implies that, compared to the premise of the Linear Quadratic Linear (LQL) framework, the Linear Quadratic framework based analytical formulation under-estimates the required dose per fraction necessary to produce the same biological effective dose as originally planned. Our study provides analytical formulation to calculate iso-effect in adaptive radiation therapy considering day-to-day stochastic dose deviation from planned dose and also indicates the potential utility of LQL framework in this context.
Dose fractionation theorem in 3-D reconstruction (tomography)
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.
Murphy, Martin J.; Lin, Peck-Sun; Ozhasoglu, Cihat
2007-02-15
The sequence of incremental dose delivery during a radiotherapy fraction can potentially influence the radiobiological effect. This would be most noticeable during the long fractions characteristic of hypo-fractionated stereotactic radiotherapy and radiosurgery. We demonstrate here the spatio-temporal variation of dose delivery by the CyberKnife to a lung tumor and propose strategies to reduce and/or correct for any resultant dose-time cytotoxic effects.
Accelerated heavy particles and the lens. III. Cataract enhancement by dose fractionation
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.
Effect of radiation protraction on BED in the case of large fraction dose
Kuperman, V. Y.
2013-08-15
Purpose: To investigate the effect of radiation protraction on biologically effective dose (BED) in the case when dose per fraction is significantly greater than the standard dose of 2 Gy.Methods: By using the modified linear-quadratic model with monoexponential repair, the authors investigate the effect of long treatment times combined with dose escalation.Results: The dependences of the protraction factor and the corresponding BED on fraction time were determined for different doses per fraction typical for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). In the calculations, the authors consider changes in the BED to the normal tissue under the condition of fixed BED to the target.Conclusion: The obtained results demonstrate that simultaneous increase in fraction time and dose per fraction can be beneficial for SRS and SBRT because of the related decrease in BED to normal structures while BED to the target is fixed.
The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery.
Kirkpatrick, John P; Meyer, Jeffrey J; Marks, Lawrence B
2008-10-01
The linear-quadratic (LQ) model is widely used to model the effect of total dose and dose per fraction in conventionally fractionated radiotherapy. Much of the data used to generate the model are obtained in vitro at doses well below those used in radiosurgery. Clinically, the LQ model often underestimates tumor control observed at radiosurgical doses. The underlying mechanisms implied by the LQ model do not reflect the vascular and stromal damage produced at the high doses per fraction encountered in radiosurgery and ignore the impact of radioresistant subpopulations of cells. The appropriate modeling of both tumor control and normal tissue toxicity in radiosurgery requires the application of emerging understanding of molecular-, cellular-, and tissue-level effects of high-dose/fraction-ionizing radiation and the role of cancer stem cells.
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.
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.
ANALYSIS OF RESPIRATORY DESPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS
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...
Hill, R.P.
1982-03-01
The ability of five nitroimidazoles, metronidazole (MET), misonidazole (MISO), desmethymisonidazole (DMM), SR 2508 and SR 2555, to sensitize the KHT sarcoma to radiation treatment has been compared for drug doses in the range 0-1.5 g/Kg. Single radiation doses or two different daily fractionation schedules (4 fractions of 5 Gy each or 7 fraction of 3 Gy each) were used; the tumor cell survival was determined using either an in vivo or in vitro colony assay. Each radiation (100 kVp X rays at 11 Gy/min) treatment was given locally, 60-70 min (MET) or 30-40 min (other drugs) after either intraperitoneal (MET, MISO, DMM) or intraveous (SR 2508, SR 2555) injection of the drugs; these times have been shown to be optimum for this tumor. For the single doses and both fractionation schedules the tumor cell survival, following the irradiation treatment, declined as the drug dose increased in the range 0 to 0.75 g/Kg for all the drugs, but above this dose level a plateau was reached and the amount of sensitization remained essentially constant. In this plateau region the reduction in survival achieved was similar for single doses and 5 Gy fraction but was less for 3 Gy fractions, indicating that sensitization was smaller for the smaller dose fractions. For the 4 x 5 Gy fractionation schedule the plateau level of survival was lowest for MISO, DMM and SR 2508, slightly higher for SR 2555 and much higher for MET. For the 3 Gy fractions SR 2508 appeared slightly less effective than MISO and DMM.
High-dose fractionated radiation therapy for select patients with brain metastases
Pezner, R.D.; Lipsett, J.A.; Archambeau, J.O.; Fine, R.M.; Moss, W.T.
1981-08-01
Four patients with metastases to the brain were treated by high-dose fractionated radiation therapy. In all four cases, a complete response and prolonged disease-free survival could be documented. Unlike the standard therapy for such patients (i.e., craniotomy and postoperative irradiation), high-dose fractionated radiation therapy carries no operative risk and can encompass multiple brain metastases and metastases in deep or critical intracranial sites. The risk of radiotherapy side effects in the brain is discussed.
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.
Biological dose representation for carbon-ion radiotherapy of unconventional fractionation
NASA Astrophysics Data System (ADS)
Kanematsu, Nobuyuki; Inaniwa, Taku
2017-02-01
In carbon-ion radiotherapy, single-beam delivery each day in alternate directions has been common practice for efficient operation, taking advantage of the Bragg peak and the relative biological effectiveness (RBE) for uniform dose conformation to a tumor. Treatments are usually fractionated and treatment plans are evaluated with the total RBE-weighted dose; however, this is of limited relevance to the biological effect. In this study, we reformulate the biologically effective dose (BED) to normalize the dose-fractionation and cell-repopulation effects as well as the RBE of treating radiation, based on inactivation of a reference cell line by a reference carbon-ion radiation. The BED distribution virtually represents the biological effect of a treatment regardless of radiation modality or fractionation scheme. We applied the BED formulation to simplistic model treatments and to a preclinical survey for hypofractionation based on an actual prostate cancer treatment with carbon ions. The proposed formulation was demonstrated to be practical and to give theoretical implications. For a prostate cancer treatment in 12 fractions, the distributions of BED and of RBE-weighted dose were very similar. With hypofractionation, while the RBE-weighted dose distribution varied significantly, the BED distribution was nearly invariant, implying that carbon-ion radiotherapy would be effectively insensitive to fractionation. However, treatment evaluation with such a simplistic biological dose is intrinsically limited and must be complemented in practice by clinical experience and biological experiments.
Analysis of dose fractionation in the palliation of metastases from malignant melanoma
Konefal, J.B.; Emami, B.; Pilepich, M.V.
1988-01-15
Sixty-five visceral metastases from malignant melanoma were treated with radiation therapy. A variety of total doses and dose fractions were used. Significant palliation was achieved in 40 of 65 (62%) symptomatic lesions. There was no correlation between total dose or dose fraction size and significant palliation. Brain and bone metastases were separately analyzed. Nineteen of 28 (68%) bone metastases were palliated. Appendicular bony metastases were more likely to be palliated than axial bony metastases (88% versus 60%). The palliation of bone metastases did not depend on total dose given or fraction size. Nine of 23 (39%) symptomatic brain metastases were palliated. There was no difference in the rate of palliation between solitary and multiple brain metastases. Palliation of brain lesions was not dependent on fraction size, although there was a trend to better palliation with higher total doses. These findings suggest that unlike treating cutaneous or nodal melanoma lesions for local control, there is no advantage in large fraction size when treating with palliative intent visceral melanoma lesions.
Target point correction optimized based on the dose distribution of each fraction in daily IGRT
NASA Astrophysics Data System (ADS)
Stoll, Markus; Giske, Kristina; Stoiber, Eva M.; Schwarz, Michael; Bendl, Rolf
2014-03-01
Purpose: To use daily re-calculated dose distributions for optimization of target point corrections (TPCs) in image guided radiation therapy (IGRT). This aims to adapt fractioned intensity modulated radiation therapy (IMRT) to changes in the dose distribution induced by anatomical changes. Methods: Daily control images from an in-room on-rail spiral CT-Scanner of three head-and-neck cancer patients were analyzed. The dose distribution was re-calculated on each control CT after an initial TPC, found by a rigid image registration method. The clinical target volumes (CTVs) were transformed from the planning CT to the rigidly aligned control CTs using a deformable image registration method. If at least 95% of each transformed CTV was covered by the initially planned D95 value, the TPC was considered acceptable. Otherwise the TPC was iteratively altered to maximize the dose coverage of the CTVs. Results: In 14 (out of 59) fractions the criterion was already fulfilled after the initial TPC. In 10 fractions the TPC can be optimized to fulfill the coverage criterion. In 31 fractions the coverage can be increased but the criterion is not fulfilled. In another 4 fractions the coverage cannot be increased by the TPC optimization. Conclusions: The dose coverage criterion allows selection of patients who would benefit from replanning. Using the criterion to include daily re-calculated dose distributions in the TPC reduces the replanning rate in the analysed three patients from 76% to 59% compared to the rigid image registration TPC.
SU-E-T-511: Do Presage 3D Dosimeters Show Dose Fractionation Sensitivity?
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
Fractionated doses of radioiodine for ablation of postsurgical thyroid tissue remnants
Arad, E.; Flannery, K.; Wilson, G.A.; O'Mara, R.E. )
1990-10-01
Patients who have differentiated thyroid carcinoma and have undergone total thyroidectomy are treated with radioiodine for ablation of functional thyroid remnants. Administration of a single therapeutic dose in excess of 30 mCi of l-131 requires hospitalization. In an attempt to obviate the necessity for hospitalization, the prospective ablative dose was divided into two or three fractions given at weekly intervals on an ambulatory basis. To assess the effectiveness of this approach, this group of patients was compared to a cohort of hospitalized patients treated with a single dose. Ablation was achieved in 9 out of 12 patients treated in a fractionated manner (a 75% success rate), whereas in 16 out of 20 patients given a single dose the thyroid remnants were completely eradicated (an 80% success rate). That the use of split, smaller doses administered at weekly intervals on an ambulatory basis presents a reasonable alternative for ablation of postsurgical, residual-functioning thyroid tissue.
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
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.
Recalculation of dose for each fraction of treatment on TomoTherapy
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
Huo, Michael; Sahgal, Arjun; Pryor, David; Redmond, Kristin; Lo, Simon; Foote, Matthew
2017-01-01
Background: Stereotactic body radiotherapy (SBRT) is an emerging treatment option for spinal metastases with demonstrated efficacy in the upfront, postoperative, and re-treatment settings, as well as for tumor histologies considered radioresistant. Uncertainty exists regarding the optimal dose and fractionation schedule, with single and multifraction regimens commonly utilized. Methods: A literature search of the PubMed and Medline databases was conducted to identify papers specific to spine SBRT and the effect of varying dose/fractionation regimens on outcomes. Bibliographies of relevant papers were searched for further references, and international spine SBRT experts were consulted. Results: Local control rates generally exceed 80% at 1 year, while high rates of pain control have been attained. There is insufficient evidence to suggest superiority of either single or multiple fraction regimens with respect to local control and pain control. Low rates of toxicity have been reported, assuming strict dose constraints are respected. Radiation myelopathy may be the most morbid toxicity, although the rates are low. The risk of vertebral compression fracture appears to be associated with higher doses per fraction such as those used in single-fraction regimens. The Spinal Instability Neoplastic Score should be considered when evaluating patients for spine SBRT, and prophylactic stabilisation may be warranted. Pain flare is a relatively common toxicity which may be mediated with prophylactic dexamethasone. Because of the treatment complexity and potentially serious toxicities, strict quality assurance should occur at the organizational, planning, dosimetric, and treatment delivery levels. Conclusion: Both single and multifraction regimens are safe and efficacious in spine SBRT for spinal metastases. There may be advantages to hypofractionated treatment over single-fraction regimens with respect to toxicity. Ongoing investigation is underway to define optimal dose and
Escalation of radiation dose beyond 30 Gy in 10 fractions for metastatic spinal cord compression
Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Karstens, Johann H.; Hoskin, Peter J.; Rudat, Volker; Veninga, Theo; Schild, Steven E.; Dunst, Juergen
2007-02-01
Purpose: In many centers worldwide, radiotherapy for metastatic spinal cord compression (MSCC) is performed with 30 Gy in 10 fractions. This study investigated the potential benefit of dose escalation. Methods and Materials: Data from 922 patients with carcinomas causing MSCC were retrospectively evaluated. The outcome of 345 patients treated with 10 fractions of 3 Gy in 2 weeks was compared with the outcomes of 577 patients treated with 37.5 Gy in 15 fractions within 3 weeks or 40 Gy in 20 fractions within 4 weeks. Additionally, 10 potential prognostic factors were investigated: age, gender, performance status, tumor type, interval between cancer diagnosis and MSCC, number of involved vertebrae, other bone and visceral metastases, ambulatory status, and the interval to the development of motor deficits before radiotherapy. Results: Motor function improved in 19% of patients after 30 Gy in 10 fractions and in 22% after greater doses (p = 0.31). The local control (p = 0.28) and survival (p = 0.85) rates were not significantly different with doses >30 Gy. Better functional outcome was associated with the absence of visceral metastases, an interval between tumor diagnosis and MSCC of >12 months, ambulatory status, and an interval to the development of motor deficits of >7 days. Improved local control was significantly associated with no visceral metastases, improved survival with favorable histologic features (breast or prostate cancer), no visceral metastases, ambulatory status, an interval between cancer diagnosis and MSCC of >12 months, and an interval to the development of motor deficits of >7days. Conclusion: Escalation of the radiation dose to >30 Gy in 10 fractions did not improve the outcomes in terms of motor function, local control, or survival but did increase the treatment time for these frequently debilitated patients. Therefore, doses >30 Gy in 10 fractions are not recommended.
Somnolence syndrome in leukemic children following reduced daily dose fractions of cranial radiation
Littman, P.; Rosenstock, J.; Gale, G.; Krisch, R.E.; Meadows, A.; Sather, H.; Coccia, P.; DeCamagro, B.
1984-10-01
A group of children with acute lymphocytic leukemia was studied to investigate if a reduction in daily dose fraction of cranial radiation would reduce the incidence of somnolence syndrome. Thirty-one evaluable patients received 100 rad x 18 cranial radiation therapy. Sixty-six similar evaluable patients were given 180 rad x 10. Both groups received the same chemotherapy including intrathecal methotrexate. Clinically detectable somnolence appeared in 58% of each group without significant differences in the overall frequency or severity of somnolence. This study failed to substantiate a radiation dose fraction size dependence for somnolence syndrome in children with acute lymphocytic leukemia.
Park, Clint; Papiez, Lech; Zhang Shichuan; Story, Michael; Timmerman, Robert D.
2008-03-01
Purpose: Overprediction of the potency and toxicity of high-dose ablative radiotherapy such as stereotactic body radiotherapy (SBRT) by the linear quadratic (LQ) model led to many clinicians' hesitating to adopt this efficacious and well-tolerated therapeutic option. The aim of this study was to offer an alternative method of analyzing the effect of SBRT by constructing a universal survival curve (USC) that provides superior approximation of the experimentally measured survival curves in the ablative, high-dose range without losing the strengths of the LQ model around the shoulder. Methods and Materials: The USC was constructed by hybridizing two classic radiobiologic models: the LQ model and the multitarget model. We have assumed that the LQ model gives a good description for conventionally fractionated radiotherapy (CFRT) for the dose to the shoulder. For ablative doses beyond the shoulder, the survival curve is better described as a straight line as predicted by the multitarget model. The USC smoothly interpolates from a parabola predicted by the LQ model to the terminal asymptote of the multitarget model in the high-dose region. From the USC, we derived two equivalence functions, the biologically effective dose and the single fraction equivalent dose for both CFRT and SBRT. Results: The validity of the USC was tested by using previously published parameters of the LQ and multitarget models for non-small-cell lung cancer cell lines. A comparison of the goodness-of-fit of the LQ and USC models was made to a high-dose survival curve of the H460 non-small-cell lung cancer cell line. Conclusion: The USC can be used to compare the dose fractionation schemes of both CFRT and SBRT. The USC provides an empirically and a clinically well-justified rationale for SBRT while preserving the strengths of the LQ model for CFRT.
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
Deeg, H.J.; Flournoy, N.; Sullivan, K.M.; Sheehan, K.; Buckner, C.D.; Sanders, J.E.; Storb, R.; Witherspoon, R.P.; Thomas, E.D.
1984-07-01
Two hundred seventy-seven patients, who have been followed for 1 to 12 years after marrow transplantation, have been examined for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing /sup 60/Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients). To date, 86 patients have developed cataracts. Kaplan-Meier product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only, suggesting a significant sparing effect with use of TBI dose fractionation.
Fractional poisson--a simple dose-response model for human norovirus.
Messner, Michael J; Berger, Philip; Nappier, Sharon P
2014-10-01
This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (<100), estimation error is small for the fractional Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures.
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.
Cerebral radionecrosis: incidence and risk in relation to dose, time, fractionation and volume
Marks, J.E.; Baglan, R.J.; Prassad, S.C.; Blank, W.F.
1981-02-01
The authors irradiated 152 patients with primary brain and pituitary tumors from 1974 to 1976. Seven of 139 patients (5%) who received 4500 rad or grater using 180 to 200 rad fractions, developed pathologically documented cerebral radioecrosis within a median time of 14 months after completion of irradiation. The necrosis was documented by autopsy in four patients, at reoperation in two and after needle biopsy in one. It was located in the brain, distant from the original tumor in three patients, adjacent to tumor in two, and within the tumor bed in two. The latter two were classified as radionecrosis because one patient died with only minimal tumor remaining and the other patient deteriorated neurologically and stabilized after removal of the necrotic mass. On clinical grounds, we suspect that two additional patients had radiation damage to the brain, because they deteriorated neurologically without neuroradiologic evidence of tumor. Study of computerized tomography (CT) scans and superimposed dose distributions showed that necrosis was not always within the zone of highest dose (3 patients). Risk of radionecrosis was greatest in the upper regions of dose but could not be associated with shorter time, larger fractions, or larger field size. Pathologically documented radionecrosis of brain did not develop below doses that were biologically equivalent to 5400 rad in 30 fractions over 42 days.
Kim, M; Ghate, A; Phillips, M H
2009-07-21
The current state of the art in cancer treatment by radiation optimizes beam intensity spatially such that tumors receive high dose radiation whereas damage to nearby healthy tissues is minimized. It is common practice to deliver the radiation over several weeks, where the daily dose is a small constant fraction of the total planned. Such a 'fractionation schedule' is based on traditional models of radiobiological response where normal tissue cells possess the ability to repair sublethal damage done by radiation. This capability is significantly less prominent in tumors. Recent advances in quantitative functional imaging and biological markers are providing new opportunities to measure patient response to radiation over the treatment course. This opens the door for designing fractionation schedules that take into account the patient's cumulative response to radiation up to a particular treatment day in determining the fraction on that day. We propose a novel approach that, for the first time, mathematically explores the benefits of such fractionation schemes. This is achieved by building a stylistic Markov decision process (MDP) model, which incorporates some key features of the problem through intuitive choices of state and action spaces, as well as transition probability and reward functions. The structure of optimal policies for this MDP model is explored through several simple numerical examples.
Electron absorbed fractions and dose conversion factors for marrow and bone by skeletal regions
Eckerman, K.F.; Stabin, M.G.
2000-02-01
The possible inductions of bone cancer and leukemia are the two health effects of primary concern in the irradiation of the skeleton. The relevant target tissues to consider in the dosimetric evaluation have been the cells on or near endosteal surfaces of bone, from which osteosarcomas are thought to arise, and hematopoietic bone marrow, which is associated with leukemia. The complex geometry of the soft tissue-bone intermixture makes calculations of absorbed doses to these target regions a difficult problem. In the case of photon or neutron radiations, charged particle equilibrium may not exist in the vicinity of a soft tissue-bone mineral interface. In this paper, absorbed fraction data are developed for calculations of the dose in the target tissues from electron emitters deposited within the volume or on the surfaces of trabecular bone. The skeletal average absorbed fractions presented are consistent with usage of this quantity in the contemporary dosimetric formulations of the International Commission on Radiological Protection (ICRP). Implementation of the new bone and marrow model is then developed within the context of the calculational schema of the Medical Internal Radiation Dose (MIRD) Committee. Model parameters relevant to the calculation of dose conversion factors (S values) for different regions of the skeleton of individuals of various age are described, and an example calculation is performed for a monoclonal antibody which localizes in the marrow. The utility of these calculations for radiation dose calculations in nuclear medicine is discussed.
Melamed, J.S.; Chen, M.G.; Brown, J.W.; Katagiri, C.A.
1980-02-01
Using a dose fractionation scheme patterned after the current regimen for treatment of disseminated non-Hodgkin lymphoma, the authors studied the effects of irradation on progenitor and effector cells for hematopoiesis in five-month-old BC3F/sub 1/ mice. Fractions of 20 or 50 rad (0.2 or 0.5 Gy) total body irradation were given twice weekly to a final total dose of 200 or 500 rad (2 or 5 Gy), respectively. Weekly assays revealed a marked, sustained depression of stem cell activity, measured as numbers of spleen colony-forming units (CFU-S) and in vitro colony-forming cells (CFU-C), without corresponding depression of effector cells (red and white cells, and platelets). The lack of correlation between numbers of stem cells and peripheral elements is relevant to clinical assessment of marrow reserve.
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.
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
Lee, Seung Heon; Lee, Kyu Chan; Choi, Jinho; Ahn, So Hyun; Lee, Seok Ho; Sung, Ki Hoon; Kil, Se Hee
2015-01-01
Background. The aim of the study was to investigate whether biologically effective dose (BED) based on linear-quadratic model can be used to estimate spinal cord tolerance dose in spine stereotactic body radiation therapy (SBRT) delivered in 4 or more fractions. Patients and methods. Sixty-three metastatic spinal lesions in 47 patients were retrospectively evaluated. The most frequently prescribed dose was 36 Gy in 4 fractions. In planning, we tried to limit the maximum dose to the spinal cord or cauda equina less than 50% of prescription or 45 Gy2/2. BED was calculated using maximum point dose of spinal cord. Results. Maximum spinal cord dose per fraction ranged from 2.6 to 6.0 Gy (median 4.3 Gy). Except 4 patients with 52.7, 56.4, 62.4, and 67.9 Gy2/2, equivalent total dose in 2-Gy fraction of the patients was not more than 50 Gy2/2 (12.1–67.9, median 32.0). The ratio of maximum spinal cord dose to prescription dose increased up to 82.2% of prescription dose as epidural spinal cord compression grade increased. No patient developed grade 2 or higher radiation-induced spinal cord toxicity during follow-up period of 0.5 to 53.9 months. Conclusions. In fractionated spine SBRT, BED can be used to estimate spinal cord tolerance dose, provided that the dose per fraction to the spinal cord is moderate, e.g. < 6.0 Gy. It appears that a maximum dose of up to 45–50 Gy2/2 to the spinal cord is tolerable in 4 or more fractionation regimen. PMID:26029031
Fractionated low doses of abdominal irradiation alters jejunal uptake of nutrients
Thomson, A.B.; Keelan, M.; Cheeseman, C.I.; Walker, K.
1986-06-01
Abdominal radiation is associated with changes in intestinal uptake of nutrients that begins within three days and persist for over 33 weeks. Clinically, fractionated doses of radiation (FDR) are used in an attempt to minimize the complications of this therapy, but the effects of fractionated doses of radiation on intestinal transport have not been defined. An in vitro technique was used to assess the jejunal and ileal uptake of varying concentrations of glucose and leucine, as well as the uptake of single concentrations of fatty acids and decanol in rats exposed 3, 7, and 14 days previously to a course of 200 cGy given on each of five consecutive days. FDR was associated with an increase in the uptake of decanol, and therefore a decrease in the effective resistance of the unstirred water layer. FDR had a variable effect on the uptake of glucose and leucine, with a decline in the value of the Michaelis constant (Km) and the passive permeability coefficient for glucose (Pd), whereas the Km for leucine was unchanged and the Pd for leucine was variably affected by FDR. The maximal transport rate (Jdm) for leucine progressively rose following FDR, whereas the Jdm for glucose initially rose, then fell. The uptake of galactose and medium chain-length fatty acids was unchanged by FDR, whereas the jejunal uptake of myristic acid rose, and the uptake of cholic acid declined, then returned to normal. FDR was associated with greater body weight gain and jejunal and ileal weight. The changes in nutrient uptake following FDR differed from the absorption changes occurring after a single dose of radiation. Thus, fractionated doses of abdominal radiation produce complex changes in the intestinal uptake of actively and passively transported nutrients, and these variable changes are influenced by the time following radiation exposure and by the solute studied.
Effects of fractionated doses of ionizing radiation on small intestinal motor activity
Otterson, M.F.; Sarna, S.K.; Moulder, J.E.
1988-11-01
The small intestinal motor effects of fractionated doses of ionizing radiation were studied in 6 conscious dogs. Eight strain-gauge transducers were implanted on the small intestine and a single gauge on the ascending colon, of each dog. After control recordings, an abdominal dose of 250 cGy was administered three times a week on alternate days for 3 successive weeks (total dose, 2250 cGy). Recordings were then made for 4 wk of follow-up. Giant migrating contractions occurred 11 times in 520 h of control recordings in the fasted and fed state, with a mean distance of origin of 55 +/- 16 cm from the ileocolonic junction. Abdominal field irradiation significantly increased the incidence and distance of origin of these giant contractions to 438 in 745 recording hours and 158 +/- 7 cm from the ileocolonic junction, respectively. The incidence of giant migrating contractions peaked after the second dose of radiation. The amplitude ratio of radiation-induced giant migrating contractions to phase III contractions, and their duration and velocity of migration, were similar to the control state. The dogs developed diarrhea and vomiting as early as the first fraction of radiation. Irradiation also increased the incidence of retrograde giant contractions from 8 in 520 h of control recording to 42 in 745 h of recording during the radiation schedule. The radiation-induced retrograde giant contractions peaked in incidence on the day of the first fraction of radiation and were more likely to be associated with a vomiting episode than those occurring in the control period. Migrating motor complex cycling persisted during radiation and its cycle length was not different from the control or postradiation values.
Otsuka, Shinya; Shibamoto, Yuta; Iwata, Hiromitsu; Murata, Rumi; Sugie, Chikao; Ito, Masato; Ogino, Hiroyuki
2011-12-01
Purpose: To evaluate the compliance of linear-quadratic (LQ) model calculations in the high-dose range as used in stereotactic irradiation in a murine tumor model. Methods and Materials: Female 10-week-old Balb/c mice bearing 1-cm-diameter EMT6 tumors in the hind legs were used. Single doses of 10-25 Gy were compared with 2-5 fractions of 4-13 Gy given at 4-hour intervals. Cell survival after irradiation was determined by an in vivo-in vitro assay. Using an {alpha}/{beta} ratio determined for in vitro EMT6 cells and the LQ formalism, equivalent single doses for the hypofractionated doses were calculated. They were then compared with actually measured equivalent single doses for the hypofractionated doses. These fractionation schedules were also compared simultaneously to investigate the concordance/divergence of dose-survival curves plotted against actual radiation doses and biologically effective doses (BED). Results: Equivalent single doses for hypofractionated doses calculated from LQ formalism were lower than actually measured doses by 21%-31% in the 2- or 3-fraction experiments and by 27%-42% in the 4- or 5-fraction experiments. The differences were all significant. When a higher {alpha}/{beta} ratio was assumed, the discrepancy became smaller. In direct comparison of the 2- to 5-fraction schedules, respective dose-response curves almost overlapped when cell survival was plotted against actual radiation doses. However, the curves tended to shift downward by increasing the fraction number when cell survival was plotted against BED calculated using an {alpha}/{beta} ratio of 3.5 Gy for in vitro EMT6 cells. Conclusion: Conversion of hypofractionated radiation doses to single doses using the LQ formalism underestimated the in vivo effect of hypofractionated radiation by approximately 20%-40%. The discrepancy appeared to be larger than that seen in the previous in vitro study and tended to increase with the fraction number. BED appeared to be an unreliable measure
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.
A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images
Liu, Yixun; Liu, Songtao; Nacif, Marcelo S.; Sibley, Christopher T.; Bluemke, David A.; Summers, Ronald M.; Yao, Jianhua
2013-01-01
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. PMID:24089934
Deeg, H.J.; Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.
1982-04-01
Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given eigher as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to 4 x 10(8) cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis. In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after i vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.
Deeg, H.J.; Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.
1982-04-01
Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given either as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to to 4 X 10/sup 8/ cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single-dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis.In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after in vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.
Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery
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
Badheka, Jigisha Prahaladray; Oza, Vrinda Pravinbhai; Vyas, Ashutosh; Baria, Deepika; Nehra, Poonam; Babu, Thomas
2017-01-01
Background and Aims: Spinal anaesthesia (SA) with bolus dose has rapid onset but may precipitate hypotension. When we inject local anaesthetic in fractions with a time gap, it provides a dense block with haemodynamic stability and also prolongs the duration of analgesia. We aimed to compare fractionated dose with bolus dose in SA for haemodynamic stability and duration of analgesia in patients undergoing elective lower segment caesarean section (LSCS). Methods: After clearance from the Institutional Ethics Committee, the study was carried out in sixty patients undergoing elective LSCS. Patients were divided into two groups. Group B patients received single bolus SA with injection bupivacaine heavy (0.5%) and Group F patients fractionated dose with two-third of the total dose of injection bupivacaine heavy (0.5%) given initially followed by one-third dose after 90 s. Time of onset and regression of sensory and motor blockage, intraoperative haemodynamics and duration of analgesia were recorded and analysed with Student's unpaired t-test. Result: All the patients were haemodynamically stable in Group F as compared to Group B. Five patients in Group F and fourteen patients in Group B required vasopressor. Duration of sensory and motor block and duration of analgesia were longer in Group F (273.83 ± 20.62 min) compared to Group B (231.5 ± 31.87 min) P < 0.05. Conclusion: Fractionated dose of SA provides greater haemodynamic stability and longer duration of analgesia compared to bolus dose. PMID:28216705
Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy
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
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.
Spatial fractionation of the dose using neon and heavier ions: A Monte Carlo study
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
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.
Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery
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
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.
Tiwari, M; Sahu, S K; Bhangare, R C; Pandit, G G
2016-10-01
In this study, size fractionated mass and (210)Po activity concentrations in mainstream cigarette smoke (MCS) were monitored for three popular cigarette brands. Size segregated collection of MCS was carried out using a cascade type impactor, while mass and (210)Po activity concentration were analyzed gravimetrically and alpha spectrometry (following the radiochemical separation) respectively. Multiple-Path Particle Dosimetry (MPPD V2.11) model is used for prediction of deposition fraction calculations for the MCS deposition in different compartment of human respiratory tract. The activity concentration of (210)Po is founds 10.56 ± 2.46 mBq per cigarette for the tested cigarette brands. (210)Po size distribution indicates most of this associates with fine fraction (Dp < 2.23 μm) of cigarette smoke. The committed annual effective dose to smokers (smoking on an average 20 cigarette a day), considering the (210)Po and (210)Pb concentrations (assuming it is in secular equilibrium with (210)Po) in MCS, was estimated between 0.22 and 0.40 mSv, with mean value of 0.30 mSv for tested cigarette brands. Considering the risk factor of fatal cancer due to radiation exposure of lung (exposure time of 30 years); the average collective estimated fatal cancer risk is estimated as 1.5 × 10(-4) due to (210)Po and (210)Pb exposure to smokers.
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.
Saran, A; Pazzaglia, S; Pariset, L; Rebessi, S; Broerse, J J; Zoetelief, J; Di Majo, V; Coppola, M; Covelli, V
1994-05-01
As most occupational and environmental exposures to ionizing radiation are at low dose rates or in small dose fractions, risk estimation requires that the effects of the temporal distribution of dose are taken into account. Previous in vitro studies of oncogenic transformation, as well as in vivo studies of carcinogenesis induced by high-LET radiation, yielded controversial results concerning the presence of an inverse dose-rate effect. The present study tested the influence of one scheme of dose fractionation of monoenergetic neutrons on neoplastic transformation of C3H 10T1/2 cells. Neutrons of 0.5, 1.0 and 6.0 MeV were used. Cells were exposed to doses of 0.25 and 0.5 Gy, given acutely or in five fractions at 2-h intervals. The acute and fractionated irradiations with each energy were done on the same day. No significant difference between the two irradiation modes was found for both cell inactivation and neoplastic transformation at all energies. These results are in agreement with our data for fractionated fission-spectrum neutrons from the RSV-TAPIRO reactor.
Katsoulakis, Evangelia; Laufer, Ilya; Bilsky, Mark; Agaram, Narasimhan P; Lovelock, Michael; Yamada, Yoshiya
2017-01-01
OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator-based single-fraction (18-24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36-80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant
Impact of Fractionation and Dose in a Multivariate Model for Radiation-Induced Chest Wall Pain
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.
Lin, P.-S. . E-mail: plin@vcu.edu; Wu, Andrew
2005-10-01
Purpose: To test whether or not the commonly prescribed daily dose of 2 Gy (whole fraction), when delivered as various partial fraction (PF) dose sequences simulating clinical treatment fields, produces equal biologic effects. Methods and Materials: Eleven actively proliferating cell lines derived from human and animal tissues were used in this study. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and clonogenic assays were used to determine the radiation effects on cell proliferation and survival, respectively. The 2 Gy dose was divided into 2 or more PFs for delivery to simulate the delivery of clinical treatment fields. Most irradiation sequences contained two parts consisting of at least 1 small PF, denoted by S which was 0.5 Gy or less, and a large PF, denoted by L which was 1 Gy or more. Irradiation schemes were designed to include the following conditions: (a) the 2 Gy dose divided into combinations of an L-dose and one or more S-doses; (b) the L-dose given either before or after the S-doses; and (c) delivery of all partial fractions within a fixed total time. Results: Significant differences in biologic effect were observed between sequences in which the L-dose was given before or after the S-doses in both the MTT and clonogenic assays. Nearly all the latter schemes, that is S-L, produced greater cytotoxic effects than the L-S schemes. Conclusions: These data demonstrate that the biologic effects of 2 Gy may differ in different clinical settings depending on the size and sequence of the partial fractions. The variation between cytotoxic effects is likely a result of the combination of low-dose hyper-radiosensitivity (HRS) and higher-dose increased radioresistance (IRR) effects established recently. We suggest that to ensure the optimal biologic effect of a prescribed dose of 2 Gy clinically, it is critical to consider the sequence in which the treatment fields are delivered when partial fractions of different sizes are used.
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.
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
NASA Astrophysics Data System (ADS)
Bewes, J. M.; Suchowerska, N.; Jackson, M.; Zhang, M.; McKenzie, D. R.
2008-07-01
Intensity-modulated radiation therapy (IMRT) achieves optimal dose conformity to the tumor through the use of spatially and temporally modulated radiation fields. In particular, average dose rate and instantaneous dose rate (pulse amplitude) are highly variable within a single IMRT fraction. In this study we isolate these variables and determine their impact on cell survival. Survival was assessed using a clonogenic assay. Two cell lines of differing radiosensitivity were examined: melanoma (MM576) and non-small cell lung cancer (NCI-H460). The survival fraction was observed to be independent of instantaneous dose rate. A statistically significant trend to increased survival was observed as the average dose rate was decreased, for a constant total dose. The results are relevant to IMRT practice, where average treatment times can be significantly extended to allow for movement of the multi-leaf collimator (MLC). Our in vitro study adds to the pool of theoretical evidence for the consequences of protracted treatments. We find that extended delivery times can substantially increase the cell survival. This also suggests that regional variation in the dose-rate history across a tumor, which is inherent to IMRT, will affect radiation dose efficacy.
Sorbe, Bengt . E-mail: bengt.sorbe@orebroll.se; Straumits, Andris; Karlsson, Leif
2005-08-01
Purpose To compare two different fractionation schedules for postoperative vaginal high-dose-rate (HDR) irradiation in endometrial carcinomas. Methods and Materials In a complete geographic series of 290 low-risk endometrial carcinomas, the efficacy and side effects of two different fractionation schedules for postoperative vaginal irradiation were evaluated. The patients were treated during the years 1989-2003. The tumors were in International Federation of Gynecology and Obstetrics Stages IA-IB and Grades 1-2. The HDR MicroSelectron afterloading equipment (iridium-192) was used. Perspex vaginal applicators with diameters of 20-30 mm were used, and the dose was specified at 5 mm from the surface of the applicator. Six fractions were given, and the overall treatment time was 8 days. The size of the dose per fraction was randomly set to 2.5 Gy (total dose of 15.0 Gy) or 5.0 Gy (total dose of 30.0 Gy). One hundred forty-four patients were treated with the 2.5-Gy fraction and 146 patients with the 5.0-Gy fraction. Results The overall locoregional recurrence rate of the complete series was 1.4% and the rate of vaginal recurrences 0.7%. There was no difference between the two randomized groups. The vaginal shortening measured by colpometry was not significant (p = 0.159) in the 2.5-Gy group (mean, 0.3 cm) but was highly significant (p < 0.000001) in the 5.0-Gy group (mean 2.1 cm) after 5 years. Mucosal atrophy and bleedings were significantly more frequent in the 5.0-Gy group. Symptoms noted in the 2.5-Gy group were not different from what could be expected in a normal group of postmenopausal women. Conclusion The fractionation schedule recommended for postoperative vaginal irradiation in low-risk endometrial carcinoma is six fractions of 2.5 Gy when the HDR technique is used.
Hiniker, Susan M; Modlin, Leslie A; Choi, Clara Y; Atalar, Banu; Seiger, Kira; Binkley, Michael S; Harris, Jeremy P; Liao, Yaping Joyce; Fischbein, Nancy; Wang, Lei; Ho, Anthony; Lo, Anthony; Chang, Steven D; Harsh, Griffith R; Gibbs, Iris C; Hancock, Steven L; Li, Gordon; Adler, John R; Soltys, Scott G
2016-04-01
Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures
Maruyama, Y.; Wierzbicki, J. )
1990-12-01
Time-dose fractionation factors (TDF) were calculated for 252Cf (Cf) neutron therapy versus 137Cs for intracavitary use in the preoperative treatment of bulky/barrel-shaped Stage IB cervix cancers. The endpoint assessed was gross and microscopic tumor eradication from the hysterectomy specimen. We reviewed the data obtained in clinical trials between 1976-1987 at the University of Kentucky Medical Center. Preoperative photon therapy was approximately 45 Gy of whole pelvis irradiation in 5 weeks for both 137Cs and Cf treated patients. 137Cs implant was done after pelvic irradiation x1 to a mean dose of 2104 +/- 36 cGy at point A at a dose rate of 50.5 cGy/h. There were 37.5% positive specimens. Using Cf intracavitary implants, dose varied from 109 to 459 neutron cGy in 1-2 sessions. Specimens were more frequently cleared of tumor (up to 100% at appropriate dose) and showed a dose-response relationship, both by nominal dose and by TDF adjusted analysis of dose, dose-rate, number of sessions, and overall time. Limited understanding of relative biological effectiveness, schedule, effect of implants, and dose rate all made it difficult to use TDF to study neutron effects. Relative biological effectiveness (RBE) was estimated and showed that for Cf, RBE was a complex function of treatment variables. In the pilot clinical studies, a value of 6.0 had been assumed. The present findings of RBE for tumor destruction are larger than those assumed. Cf was effective for cervix tumor therapy and produced control without significant side effects due to the brachytherapy method used. The TDF model was of limited value in the present analysis and more information is still needed for RBE, dose-rate, and fractionation effects for Cf neutrons to develop a more sophisticated and relevant model.
SU-E-T-94: Daily Fraction Dose Recalculation Based On Rigid Registration Using Cone Beam CT
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.
Li, Xueming; Zheng, Shawn; Agard, David A; Cheng, Yifan
2015-11-01
Newly developed direct electron detection cameras have a high image output frame rate that enables recording dose fractionated image stacks of frozen hydrated biological samples by electron cryomicroscopy (cryoEM). Such novel image acquisition schemes provide opportunities to analyze cryoEM data in ways that were previously impossible. The file size of a dose fractionated image stack is 20-60 times larger than that of a single image. Thus, efficient data acquisition and on-the-fly analysis of a large number of dose-fractionated image stacks become a serious challenge to any cryoEM data acquisition system. We have developed a computer-assisted system, named UCSFImage4, for semi-automated cryo-EM image acquisition that implements an asynchronous data acquisition scheme. This facilitates efficient acquisition, on-the-fly motion correction, and CTF analysis of dose fractionated image stacks with a total time of ∼60s/exposure. Here we report the technical details and configuration of this system.
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.
Song, C.W.; Kim, T.H.; Khan, F.M.; Kersey, J.H.; Levitt, S.H.
1981-12-01
Total body irradiation (TBI) followed by bone marrow transplantation is being used in the treatment of malignant or non-malignant hemopoietic disorders. It has been believed that the ability of hemopoietic cells to repair sublethal radiation damage is negligible. Therefore, several schools of investigators suggested that TBI in a single exposure at extremely low dose rate (5 rad/min) over several hours, or in several fractions in 2-3 days, should yield a higher therapeutic gain, as compared with a single exposure at a high dose rate (25 rad/min). We reviewed the existing data in the literature, in particular, the response of hemopoietic cells to fractionated doses of irradiation and found that the repair capacity of both malignant and non-malignant hemopoietic cells might be greater than has been thought. It is concluded that we should not underestimate the ability of hemopoietic cells to repair sublethal radiation damage in using TBI.
Song, C.W.; Kim, T.H.; Khan, F.M.; Kersey, J.H.; Levitt, S.H.
1981-12-01
Total body irradiation (TBI) followed by bone marrow transplantation is being used in the treatment of malignant or non-malignant hemopoietic disorders. It has been believed that the ability of hemopoietic cells to repair sublethal radiation damage is negligible. Therefore, several schools of investigators suggested that TBI in a single exposure at extremely low dose rate (5 rad/min) over several hours, or in several fractions in 2-3 days, should yield a higher therapeutic gain, as compared with a single exposure at a high dose rate (26 rad/min). We reviewed the existing data in the literature, in particular, the response of hemopoietic cells to fractionated doses of irradiation and found that the repair capacity of both malignant and non-malignant hemopoietic cells might be greater than has been thought. It is concluded that we should not underestimate the ability of hemopoietic cells to repair sublethal radiation damage in using TBI.
Streitparth, Florian; Pech, Maciej; Boehmig, Michael; Ruehl, Ricarda; Peters, Nils; Wieners, Gero; Steinberg, Johannes; Lopez-Haenninen, Enrique; Felix, Roland; Wust, Peter; Ricke, Jens . E-mail: jens.ricke@medizin.uni-magdeburg.de
2006-08-01
Purpose: The aim of this study was to assess the tolerance dose of gastric mucosa for single-fraction computed tomography (CT)-guided, high-dose-rate (HDR) brachytherapy of liver malignancies. Methods and Materials: A total of 33 patients treated by CT-guided HDR brachytherapy of liver malignancies in segments II and/or III were included. Dose planning was performed upon a three-dimensional CT data set acquired after percutaneous applicator positioning. All patients received gastric protection post-treatment. For further analysis, the contours of the gastric wall were defined in every CT slice using Brachyvision Software. Dose-volume histograms were calculated for each treatment and correlated with clinical data derived from questionnaires assessing Common Toxicity Criteria (CTC). All patients presenting symptoms of upper GI toxicity were examined endoscopically. Results: Summarizing all patients the minimum dose applied to 1 ml of the gastric wall (D{sub 1ml}) ranged from 6.3 to 34.2 Gy; median, 14.3 Gy. Toxicity was present in 18 patients (55%). We found nausea in 16 (69%), emesis in 9 (27%), cramping in 13 (39%), weight loss in 12 (36%), gastritis in 4 (12%), and ulceration in 5 patients (15%). We found a threshold dose D{sub 1ml} of 11 Gy for general gastric toxicity and 15.5 Gy for gastric ulceration verified by an univariate analysis (p = 0.01). Conclusions: For a single fraction, small volume irradiation we found in the upper abdomen a threshold dose D{sub 1ml} of 15.5 Gy for the clinical endpoint ulceration of the gastric mucosa. This in vivo assessment is in accordance with previously published tolerance data.
Salivary secretion in children after fractionated or single-dose TBI.
Garming Legert, K; Remberger, M; Ringdèn, O; Heimdahl, A; Dahllöf, G
2012-03-01
The incidence of long-term oral complications after hematopoietic SCT (HSCT) varies between 60 and 100%. The aim of this study was to compare the salivary secretion rate and the contribution of known risk factors for a low salivary secretion rate 1 year after HSCT in children conditioned with fractionated TBI (fTBI) and in children conditioned with single-dose TBI (sTBI). The study involved 44 patients, 27 conditioned with sTBI and 17 conditioned with fTBI. The unstimulated and stimulated salivary secretion rates (USSRs and SSSRs) were estimated before HSCT and at 1-year follow-up. Risk factors that may have influenced the salivary secretion rate were recorded. An SSSR of ≤0.5 mL/min and a USSR of ≤0.1 mL/min were chosen as cut-off points for salivary dysfunction. The median reduction in stimulated salivary flow 1 year after HSCT was 56% in the sTBI group and 12% in the fTBI group (P=0.003). The median reduction in unstimulated salivary flow 1 year after HSCT was 74% in the sTBI group and 33% in the fTBI group (P=0.003). In the multivariate model, a significant correlation between both sTBI (odds ratio (OR)=6.49, 95% confidence interval (CI)=1.40-30, P=0.014) and seropositivity of the recipient for 3-4 herpesviruses (OR=6.57, 95% CI=1.26-34, P=0.021) and a low stimulated salivary secretion rate (<0.5 mL/min) was found 1 year after HSCT.
Ocean, Allyson J.; Pennington, Kenneth L.; Guarino, Michael J.; Sheikh, Arif; Bekaii-Saab, Tanios; Serafini, Aldo N.; Lee, Daniel; Sung, Max W.; Gulec, Seza A.; Goldsmith, Stanley J.; Manzone, Timothy; Holt, Michael; O’Neil, Bert H.; Hall, Nathan; Montero, Alberto J.; Kauh, John; Gold, David V.; Horne, Heather; Wegener, William A.; Goldenberg, David M.
2014-01-01
BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at
Lovelock, D. Michael; Zhang, Zhigang; Jackson, Andrew; Keam, Jennifer; Bekelman, Justin; Bilsky, Mark; Lis, Eric; Yamada, Yoshiya
2011-01-01
Purpose In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. Methods and Materials The minimum doses received by the hottest 100%, 98%, and 95% (Dmin, D98, and D95) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18–24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12–14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. Results With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV Dmin, D98, and D95 for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for Dmin, D98, and D95 were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. Conclusions The results indicate that Dmin, D98, and D95 may be important risk factors for local failure. No local failures in any histology were observed when Dmin was >15 Gy, suggesting that this metric may be an important predictor of local control. PMID:20350795
Yamada, Yoshiya Bilsky, Mark H.; Lovelock, D. Michael; Venkatraman, Ennapadam S.; Toner, Sean; Johnson, Jared; Zatcky, Joan N.P.; Zelefsky, Michael J.; Fuks, Zvi
2008-06-01
Purpose: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. Methods and Materials: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. Results: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. Conclusion: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.
Jagetia, Ganesh Chandra; Rajanikant, Golgod Krishnamurthy
2012-02-01
Fractionated irradiation (IR) before or after surgery of malignant tumours causes a high frequency of wound healing complications. Our aim was to investigate the effect of curcumin (CUM) on the healing of deep excision wound of mice exposed to fractionated IR by mimicking clinical conditions. A full-thickness dermal excision wound was created on the shaved dorsum of mice that were orally administered or not with 100 mg of CUM per kilogram body weight before partial body exposure to 10, 20 or 40 Gy given as 2 Gy/day for 5, 10 or 20 days. The wound contraction was determined periodically by capturing video images of the wound from day 1 until complete healing of wounds. Fractionated IR caused a dose-dependent delay in the wound contraction and prolonged wound healing time, whereas CUM administration before fractionated IR caused a significant elevation in the wound contraction and reduced mean wound healing time. Fractionated IR reduced the synthesis of collagen, deoxyribonucleic acid (DNA) and nitric oxide (NO) at different post-IR times and treatment of mice with CUM before IR elevated the synthesis of collagen, DNA and NO significantly. Histological examination showed a reduction in the collagen deposition, fibroblast and vascular densities after fractionated IR, whereas CUM pre-treatment inhibited this decline significantly. Our study shows that CUM pre-treatment accelerated healing of irradiated wound and could be a substantial therapeutic strategy in the management of irradiated wounds.
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
Nakamura, Jean L; Phong, Connie; Pinarbasi, Emile; Kogan, Scott C; Vandenberg, Scott; Horvai, Andrew E; Faddegon, Bruce A; Fiedler, Dorothea; Shokat, Kevan; Houseman, Benjamin T; Chao, Richard; Pieper, Russell O; Shannon, Kevin
2010-01-01
Secondary malignant neoplasms (SMNs) are increasingly common complications of cancer therapy that have proven difficult to model in mice. Clinical observations suggest that the development of SMN correlates with radiation dose; however, this relationship has not been investigated systematically. We developed a novel procedure for administering fractionated cranial irradiation (CI) and investigated the incidence and spectrum of cancer in control and heterozygous Nf1 mutant mice irradiated to a moderate (15 Gy) or high dose (30 Gy). Heterozygous Nf1 inactivation cooperated with CI to induce solid tumors and myeloid malignancies, with mice developing many of the most common SMNs found in human patients. CI-induced malignancies segregated according to radiation dose as Nf1+/− mice developed predominately hematologic abnormalities after 15 Gy, while solid tumors predominated at 30 Gy, suggesting that radiation dose thresholds exist for hematologic and non-hematologic cancers. Genetic and biochemical studies revealed discrete patterns of somatic Nf1 and Trp53 inactivation and we observed hyperactive Ras signaling in many radiation-induced solid tumors. This technique for administering focal fractionated irradiation will facilitate mechanistic and translational studies of SMNs. PMID:21199799
Kim, Yongbok; Hsu, I-Chow J; Pouliot, Jean
2007-09-17
The objective of this work is to measure the cranio-caudal displacement of catheters occurring between consecutive fractions of transrectal ultrasound (TRUS) guided high dose rate (HDR) prostate brachytherapy. Ten consecutive patients were treated with 2 fractions of 9.5 Gy TRUS guided HDR brachytherapy using dental putty for the fixation of catheters. For each patient, a CT scan with 3 mm slice thickness was acquired before each of the two fractions. Two different references were employed to measure the catheter displacement between fractions: the ischial bone as a bony marker (BM) and the center of two gold markers (COGM) implanted in the prostate. The catheter displacement was calculated by multiplying the thickness of CT slice with the difference in number of CT slices between the reference slice and the slice containing the tip of a catheter. The average (range) magnitude of caudal catheter displacement was 2.7 mm (-6.0 to 13.5 mm) for BM method and 5.4 mm (-3.75 to 18.0 mm) for COGM method, respectively. The measurement data obtained from BM and COGM methods verified that both prostate movement and catheter displacement occurred independently between fractions. The most anterior and medial two catheters (catheter position 8 and 12) had the greatest tendency to be displaced in the caudal direction because they were located at the most distant position from the fulcrum, susceptible to the rotation of the dental putty in lateral plane due to the movement of patient legs between fractions. In conclusion, the use of both BM and COGM methods can demonstrate the prostate and catheter movement relative to the BM between fractions. We found a pattern of catheter displacement using our technique. Based on our finding further improvement of our results may be possible by modification of our current technique.
Hijazi, Hussam; Chevallier, Daniel; Gal, Jocelyn; Chand, Marie-Eve; Gautier, Mathieu; Hannoun-Levi, Jean-Michel
2013-01-01
Purpose To analyse early toxicity of high-dose-rate brachytherapy (HDRB) boost for prostate cancer using 3 fractionation schemes. Material and methods From February 2009 to May 2012, after the first course of external beam radiation therapy (EBRT 46 Gy/23 f), 124 patients underwent HDRB boost for low (7%), intermediate (19%), and high-risk (73%) prostate cancers. From February to December 2009, Group 1 (G1) = 18 Gy/3 f/2 d (24%); from January 2010 to April 2011, Group 2 (G2) = 18 Gy/2 f/2 d (42%), and from May to September 2011, Group 3 (G3) = 14 Gy/1 f/1 d (34%). Planning and CT-scan was performed before each fraction. Dose constraints for G1/G2 were V100 rectum = 0 and V125 urethra = 0, while for G3 V90 rectum = 0 and V115 urethra = 0. Genito-urinary (GU) and Gastro-intestinal (GI) acute toxicities were assessed at 1 month (for the 3 fractionation schemes) and 6 months (for 18 Gy/3 f and 18 Gy/2 f) after the boost (CTCv3.0). Results Median follow-up was 25 months (8-46.9), median age was 71 years (50-82), and median CTV was 31 cc (16-71). The grades of acute GI and GU toxicities at 1 and 6 months after HDRB were mainly Grade 1 with few Grade 2 (GU: 5% at 1 month; GI: 1% at 6 months). One patient developed G4 sepsis toxicity 2 days after HDRB and recovered without after-effects. No significant differences were observed at 1 and 6 months after the HDRB between treatment groups. Conclusions The right fractionation remains under discussion, but prostate cancer HDRB boost using a single fraction (providing similar results in terms of acute toxicity) is more comfortable for the patient, and less time consuming for the medical staff. PMID:24474968
Landuyt, W.; Ang, K. K.; van der Schueren, E.
1986-01-01
Tolerance of the lip mucosa of NMRI mice to single and fractionated irradiation combined with cis-diamminedichloroplatinum (II) (cis-DDP) was investigated. For the various combination schedules total drug doses varying from 6 mg kg-1 to 13 mg kg-1 were injected i.p. It was found that cis-DDP did not alter the radiation sensitivity of this tissue at any of the time intervals tested (ranging from 24 h before to 72 h after single dose irradiations). When 5 daily drug injections were given concomitantly with 5 daily radiation treatments, a slight reduction of the lip mucosal reactions occurred, possibly due to partial synchronisation during treatment. No effect was seen when a single injection of cis-DDP preceded two irradiations given with increasing intervals up to 4 h. Both these combined fractionated treatment data suggest no inhibitory effect on repair of sublethal radiation damage. When repeated daily injections of cis-DDP were given in between 2 radiation doses separated by 10 days, no interference with repopulation could be detected. The present study also demonstrated an increase in systemic drug toxicity when cis-DDP was combined with irradiation, compared with that seen with either agent alone. PMID:3778802
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.
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.
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.
Liu, J.C.; Bacza, E.T.; Findley, D.O.; Forell, B.W.
1983-09-01
Eighty-five patients with acute myelogenous or acute lymphoblastic leukemia were treated at the Cit of Hope National Medicine Center with chemotherapy, total body irradiation, and bone marrow transplant. The average mid-line dose to these patients was 1002 rad with a uniformity of 8%.
Simon, Raphael; Wang, Jin Y.; Boyd, Mary A.; Tulapurkar, Mohan E.; Ramachandran, Girish; Tennant, Sharon M.; Pasetti, Marcela; Galen, James E.; Levine, Myron M.
2013-01-01
Non-typhoidal Salmonella (NTS) serovars S. Enteritidis and S. Typhimurium are a major cause of invasive bacterial disease (e.g., bacteremia, meningitis) in infants and young children in sub-Saharan Africa and also occasionally cause invasive disease in highly susceptible hosts (young infants, the elderly, and immunocompromised subjects) in industrialized countries. No licensed vaccines exist against human NTS infections. NTS core and O polysaccharide (COPS) and FliC (Phase 1 flagellin subunits) each constitute protective antigens in murine models. S. Enteritidis COPS conjugated to FliC represents a promising vaccine approach that elicits binding and opsonophagocytic antibodies and protects mice against lethal challenge with virulent S. Enteritidis. We examined the protective efficacy of fractional dosages of S. Enteritidis COPS:FliC conjugate vaccines in mice, and also established that protection can be passively transferred to naïve mice by administering sera from mice immunized with conjugate. Mice were immunized with three doses of either 10 µg, 2.5 µg (full dose), 0.25 µg, or 0.025 µg S. Enteritidis COPS:FliC conjugate at 28 day intervals. Antibody titers to COPS and FliC measured by ELISA fell consonant with progressively smaller vaccine dosage levels; anti-FliC IgG responses remained robust at fractional dosages for which anti-COPS serum IgG titers were decreased. Nevertheless, >90% protection against intraperitoneal challenge was observed in mice immunized with fractional dosages of conjugate that elicited diminished titers to both FliC and COPS. Passive transfer of immune sera from mice immunized with the highest dose of COPS:FliC to naïve mice was also protective, demonstrating the role of antibodies in mediating protection. These results provide important insights regarding the potency of Salmonella glycoconjugate vaccines that use flagellin as a carrier protein. PMID:23741368
Little, Mark P; Gola, Anna; Tzoulaki, Ioanna
2009-10-01
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 radiation 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 cancer 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 extrapolation would be appropriate for this endpoint.
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.
Provisional Reference Dose for the Aromatic Fraction of Jet Fuel: Insight into Complex Mixtures
2005-04-01
Petroleum Hydrocarbon Criteria Working Group UF uncertainty factor UV ultraviolet light wt% weight percent vi PROVISIONAL REFERENCE DOSE FOR THE AROMATIC...week) included. RBC = red blood cell. UF = total uncertainty factor , including modifying factors when applied. aU.S. EPA (2004). bThis unpublished...approach applied uncertainty factors to NOAELs or LOAELs from the critical 11 studies. The TPHCWG primarily accepted default values of 10 for
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.
Tucker, Susan L.; Michalski, Jeff M.; Bosch, Walter R.; Mohan, Radhe; Dong, Lei; Winter, Kathryn; Purdy, James A.; Cox, James D.
2012-01-01
Background and Purpose For toxicities occurring during the course of radiotherapy, it is conceptually inaccurate to perform normal-tissue complication probability analyses using the complete dose-volume histogram. The goal of this study was to analyze acute rectal toxicity using a novel approach in which the fit of the Lyman-Kutcher-Burman (LKB) model is based on the fractional rectal dose-volume histogram (DVH). Materials and Methods Grade ≥2 acute rectal toxicity was analyzed in 509 patients treated on Radiation Therapy Oncology Group (RTOG) protocol 94-06. These patients had no field reductions or treatment-plan revisions during therapy, allowing the fractional rectal DVH to be estimated from the complete rectal DVH based on the total number of dose fractions delivered. Results The majority of patients experiencing Grade ≥2 acute rectal toxicity did so before completion of radiotherapy (70/80=88%). Acute rectal toxicity depends on fractional mean rectal dose, with no significant improvement in the LKB model fit when the volume parameter differs from n=1. The incidence of toxicity was significantly lower for patients who received hormone therapy (P=0.024). Conclusions Variations in fractional mean dose explain the differences in incidence of acute rectal toxicity, with no detectable effect seen here for differences in numbers of dose fractions delivered. PMID:22673726
High-dose-rate brachytherapy delivered in two fractions as monotherapy for low-risk prostate cancer
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
Stubblefield, Michael D; Ibanez, Katarzyna; Riedel, Elyn R; Barzilai, Ori; Laufer, Ilya; Lis, Eric; Yamada, Yoshiya; Bilsky, Mark H
2017-03-01
OBJECTIVE The object of this study was to determine the percentage of high-dose (1800-2600 cGy) single-fraction stereotactic radiosurgery (SF-SRS) treatments to the spine that result in peripheral nervous system (PNS) injury. METHODS All patients treated with SF-SRS for primary or metastatic spine tumors between January 2004 and May 2013 and referred to the Rehabilitation Medicine Service for evaluation and treatment of neuromuscular, musculoskeletal, or functional impairments or pain were retrospectively identified. RESULTS Five hundred fifty-seven SF-SRS treatments in 447 patients resulted in 14 PNS injuries in 13 patients. All injures resulted from SF-SRS delivered to the cervical or lumbosacral spine at 2400 cGy. The overall percentage of SF-SRS treatments resulting in PNS injury was 2.5%, increasing to 4.5% when the thoracic spine was excluded from analysis. The median time to symptom onset following SF-SRS was 10 months (range 4-32 months). The plexus (cervical, brachial, and/or lumbosacral) was affected clinically and/or electrophysiologically in 12 (86%) of 14 cases, the nerve root in 2 (14%) of 14, and both in 6 (43%) of 14 cases. All patients experienced pain and most (93%) developed weakness. Peripheral nervous system injuries were CTCAE Grade 1 in 14% of cases, 2 in 64%, and 3 in 21%. No dose relationship between SF-SRS dose and PNS injury was detected. CONCLUSIONS Single-fraction SRS to the spine can result in PNS injury with major implications for function and quality of life.
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.
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
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.
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.
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%.
Favor, J; Neuhäuser-Klaus, A; Ehling, U H; Wulff, A; van Zeeland, A A
1997-03-21
Our earlier analyses have suggested an apparent threshold dose-response for ethylnitrosourea-induced specific-locus mutations in treated spermatogonia of the mouse to be due to a saturable repair process. In the current study a series of fractionated-treatment experiments was carried out in which male (102 x C3H)F1 mice were exposed to 4 x 10, 2 x 40. 4 x 20 or 4 x 40 mg ethylnitrosourea per kg body weight with 24 h between applications; 4 x 40 mg ethylnitrosourea per kg body weight with 72 h between dose applications; and 2 x 40, 4 x 20 and 4 x 40 mg ethylnitrosourea per kg body weight with 168 h between dose applications. For all experiments with 24-h intervals between dose applications, there was no effect due to dose fractionation on the observed mutation rates, indicating the time interval between dose applications to be shorter than the recovery time of the repair processes acting on ethylnitrosourea-induced DNA adducts. In contrast, a fractionation interval of 168 h was associated with a significant reduction in the observed mutation rate due to recovery of the repair process. However, although reduced, the observed mutation rates for fractionation intervals of 168 h were higher than the spontaneous specific-locus mutation rate. These observations contradict the expectation for a true threshold dose response. We interpret this discrepancy to be due to the differences in the predictions of a mathematical abstraction of experimental data and the complexities of the biological system being studied. Biologically plausible explanations of the discrepancy are presented.
Kiratli, Pinar Ozgen; Salanci, Bilge Volkan
2003-06-01
Since its release for routine clinical use, (99m)Tc-mercaptoacetyltriglycine (MAG3) has become an important alternative to (131)I-labeled orthoiodohippuran. The cold kit for MAG3 is expensive, especially in developing countries. Therefore, unique storage conditions should be provided for cost reduction. Cold fractioning is a well-known procedure but has special requirements, such as a nitrogen tank and a laminar flow hood. The aim of this study was to prolong the shelf life of (99m)Tc-labeled MAG3 by a hot fractioning method, which separates the patient doses after (99m)Tc labeling. The radiochemical purity of the (99m)Tc-labeled MAG3 kit was tested under different storage conditions. Hot fractioning of the (99m)Tc-labeled MAG3 kit was found to be a possible alternative to cold fractioning for routine clinical studies.
Tran, Kathy Ngoc; Zanjani, Salman; Smith, Wayne; Karpelowsky, Jonathan; Summerhayes, Katie; Estoesta, Edgar; Chard, Jennifer
2016-01-01
Purpose To report peri-operative fractionated high-dose-rate (HDR) brachytherapy with a 3D customized Freiburg flap applicator to treat locally recurrent Wilms’ tumor, followed by immediate hyperthermic intraperitoneal chemotherapy for a 16-year-old with a second recurrence of nephroblastoma (Wilms’ tumor). Material and methods The tumor was excised and surgical bed was treated with fractionated HDR brachytherapy using a Freiburg flap applicator. Hyperthermic intraperitoneal chemotherapy was performed immediately after the removal of brachytherapy applicator. Results The Freiburg flap was successfully reconstructed to enable delivery of conformable peri-operative HDR brachytherapy. The clinical target volume (CTV) D90 was 26 Gy in 5 fractions. Conclusions Peri-operative fractionated HDR brachytherapy with a customized Freiburg flap applicator was delivered successfully across a large multi-disciplinary team. PMID:27895685
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
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.
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.
K-Ras mutant fraction in A/J mouse lung increases as a function of benzo[a]pyrene dose
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...
Yoon, Sang Min; Huh, Seung Jae . E-mail: sjhuh@smc.samsung.co.kr; Park, Won; Lee, Jeung Eun; Park, Young Je; Nam, Hee Rim; Lim, Do Hoon; Ahn, Yong Chan
2006-08-01
Purpose: This study evaluated the treatment results of external beam radiotherapy administered in six fractions per week and high-dose-rate (HDR) brachytherapy for the treatment of cervical cancer. Methods and Materials: From July 2000 to July 2003, 43 patients were enrolled in this study. The patients received 45 Gy from a 10-MV photon beam using four-field box or anterior-posterior beams. Parametrial regions and the pelvic side walls were boosted with up to 50.4 Gy using a midline block. The daily fraction dose was 1.8 Gy administered in six-weekly fractions, from Monday to Saturday. HDR brachytherapy was also delivered at doses of 24 Gy to point A in six fractions twice a week. The median follow-up time was 37 months (range, 9-60 months). Results: The median overall treatment time was 51 days for all patients (range, 44-62 days). Thirty-four patients (79.1%) achieved complete remission and 8 (18.6%) achieved partial remission after radiotherapy. Locoregional recurrence occurred in 5 patients (11.6%), and a distant metastasis was encountered in 6 patients (13.9%). The 3-year overall survival, locoregional, and distant metastasis-free survival rates were 74.7%, 87.8%, and 84.7%, respectively. Grade 2 and 3 late rectal complications were encountered in 3 (6.5%) and 1 (2.2%), respectively. There were no Grade 3 late bladder complications. Conclusions: Six fractions per week of external beam radiotherapy and HDR brachytherapy is an effective treatment for patients with a carcinoma of the uterine cervix and can be used as a possible alternative to concomitant chemoradiotherapy in elderly patients or in patients with co-morbidity.
Favor, J; Neuhäuser-Klaus, A; Ehling, U H
1988-04-01
A combined dominant cataract-recessive specific locus mutation experiment for fractionated exposure to ethylnitrosourea (2 X 80 mg/kg, 24-h fractionation interval) was designed to determine if lower doses of ethylnitrosourea are more effective in inducing dominant cataract mutations as suggested by previous results. This observation was not confirmed by the present experiment. The extensive, statistically more reliable specific locus results indicate an additive effect of fractionated ethylnitrosourea treatment. A saturable repair system for ethylnitrosourea-induced DNA damage has been previously documented (Karran et al., 1979; Sega et al., 1986; Van Zeeland et al., 1985). Two parameters inherent to a saturable system, the minimal time required for the saturated system to recover and the minimal dose to saturate the system are important, and results of experiments employing a fractionation exposure protocol must be interpreted relative to these two parameters. Longer fractionation intervals or smaller doses result in a reduced mutagenic effect. Due to the inherently lower experimental variability of the specific locus mutation assay as compared to the dominant cataract assay, the specific locus assay is the test of choice to determine factors affecting the mammalian germ cell mutation rate. The dominant cataract test requires a larger investment of experimental resources to achieve a comparable degree of accuracy. The dominant cataract mutation test is important in assessing the mutation rate to dominant alleles in germ cells of mammals. Due to the immediate expression of the mutant phenotype in newly occurring dominant mutations, a dominant mutation assay screens a genetically relevant endpoint in an assessment of the mutagenic hazard for man in mouse experiments. A multi-endpoint design screening specific locus, dominant cataract, and biochemical mutational endpoints (Ehling et al., 1985) allows a systematic comparison of mutagenic results for different classes
Shimura, Tsutomu; Hamada, Nobuyuki; Sasatani, Megumi; Kamiya, Kenji; Kunugita, Naoki
2014-01-01
Cyclin D1 is a mitogenic sensor that responds to growth signals from the extracellular environment and regulates the G 1-to-S cell cycle transition. When cells are acutely irradiated with a single dose of 10 Gy, cyclin D1 is degraded, causing cell cycle arrest at the G 1/S checkpoint. In contrast, cyclin D1 accumulates in human tumor cells that are exposed to long-term fractionated radiation (0.5 Gy/fraction of X-rays). In this study we investigated the effect of fractionated low-dose radiation exposure on cyclin D1 localization in 3 strains of normal human fibroblasts. To specifically examine the nuclear accumulation of cyclin D1, cells were treated with a hypotonic buffer containing detergent to remove cytoplasmic cyclin D1. Proliferating cell nuclear antigen (PCNA) immunofluorescence was used to identify cells in S phase. With this approach, we observed S-phase nuclear retention of cyclin D1 following low-dose fractionated exposures, and found that cyclin D1 nuclear retention increased with exposure time. Cells that retained nuclear cyclin D1 were more likely to have micronuclei than non-retaining cells, indicating that the accumulation of nuclear cyclin D1 was associated with genomic instability. Moreover, inhibition of the v-akt murine thymoma viral oncogene homolog (AKT) pathway facilitated cyclin D1 degradation and eliminated cyclin D1 nuclear retention in cells exposed to fractionated radiation. Thus, cyclin D1 may represent a useful marker for monitoring long-term effects associated with exposure to low levels of radiation.
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.
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.
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.
Chen, Wei-Yu; Fang, Chia-Lang; Al-Suwayeh, Saleh A; Yang, Hung-Hsu; Li, Yi-Ching; Fang, Jia-You
2013-09-01
The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO2 laser, using fluences of 4-10 mJ with spot densities of 100-400 spots/cm(2). In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm(2)/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70-1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2-3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing.
Destée, Alain; Rérat, Karin; Bourdeix, Isabelle
2009-01-01
Two strategies to manage symptom re-emergence due to wearing-off with conventional levodopa/dopa-decarboxylase inhibitor (DDCI) therapy were compared in patients with Parkinson's disease (PD) in this randomized, open-label trial. PD patients receiving 3 daily doses of levodopa/DDCI were randomized to either levodopa/DDCI and entacapone or an increased dose frequency of levodopa/DDCI with or without an increased total daily dose (dose fractionation). After 1 month of treatment, patients were followed up for 1 year. A greater proportion of levodopa/DDCI and entacapone-treated patients had treatment success compared with dose-fractionated patients, according to investigator Clinical Global Impression of Change scores at 1 month (68 vs. 59%, respectively) and 1 year (60 vs. 51%, respectively). Mean 'off' time (time with symptoms) was improved in both groups at 1 month and 1 year, despite a reduction in the mean daily levodopa dose in the levodopa/DDCI and entacapone group at 1 month. The mean daily levodopa dose was increased in the dose fractionation group. At 1 month, there was a 4% reduction in patients experiencing dyskinesia with levodopa/DDCI and entacapone and a 3% increase with dose fractionation. These data suggest that levodopa/DDCI and entacapone reduces time with symptoms, the rate of motor complications and the daily levodopa dose compared with dose fractionation. However, as the observed differences were not statistically significant, further studies are required to confirm these results.
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.
López-Palop, Ramón; Carrillo, Pilar; Frutos, Araceli; Cordero, Alberto; Agudo, Pilar; Mashlab, Samer; Bertomeu-Martínez, Vicente
2013-05-01
Intravenous adenosine is considered the drug of choice to obtain maximum hyperemia in the measurement of the fractional flow reserve (FFR). However, comparative studies performed between intravenous and intracoronary administration have not used high doses of intracoronary adenosine. The present study compared the efficacy and safety of high doses of intracoronary adenosine to intravenous administration when calculating the FFR. Intracoronary bolus doses of 60, 180, 300, and 600 μg adenosine were compared to an intravenous administration of 140 μg/kg/min, 200 μg/kg/min, and 140 μg/kg/min plus an intracoronary bolus of 120 μg. All the cases were performed using the radial approach. FFR was assessed in 102 patients with 108 intermediate lesions by an intracoronary pressure wire. The intracoronary dose of 60 μg was associated with a significantly greater FFR compared to the intravenous infusion (0.02 ± 0.03, p = 0.001). The intracoronary doses of 300 (-0.01 ± 0.00; p = 0.006) and 600 μg (-0.02 ± 0.00; p <0.0005) were significantly associated with a smaller FFR compared to the intravenous infusion. An intracoronary dose of 600 μg revealed a significantly greater percentage of lesions with an FFR <0.80 compared to intravenous infusion at 140 μg/kg/min (37.6 vs 31.5%; p <0.05) and 200 μg/kg/min (37.6 vs 32.4%; p <0.05) and compared to intracoronary doses of 60 (26.9%) and 180 μg (31.5%). In conclusion, an intracoronary bolus dose >300 μg can be equal to or more effective than an intravenous infusion of adenosine in achieving maximum hyperemia when calculating the FFR. Its use could simplify these procedures without having an effect on safety.
Yoshioka, Yasuo; Konishi, Koji; Sumida, Iori; Takahashi, Yutaka; Isohashi, Fumiaki; Ogata, Toshiyuki; Koizumi, Masahiko; Yamazaki, Hideya; Nonomura, Norio; Okuyama, Akihiko; Inoue, Takehiro
2011-06-01
Purpose: To evaluate an extreme hypofractionation regimen with 54 Gy in nine fractions provided by high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer by reporting 5-year clinical results. Methods and Materials: Between 1996 and 2005, 112 patients with localized prostate cancer were treated with HDR brachytherapy without external beam radiotherapy. Of the 112 patients, 15 were considered low risk, 29 intermediate risk, and 68 as high risk. The prescribed dose was uniformly 54 Gy in nine fractions within 5 days. Of the 112 patients, 94 also received hormonal therapy. The median follow-up time was 5.4 years. Results: All the patients safely completed the treatment regimen. The 5-year prostate-specific antigen (PSA) failure-free, local control, disease-free survival, and overall survival rate was 83%, 97%, 87%, and 96%, respectively. The 5-year PSA failure-free rate for low-, intermediate-, and high-risk patients was 85% (95% confidence interval, 66-100%), 93% (95% confidence interval, 83-100%), and 79% (95% confidence interval, 69-89%), respectively. The significant prognostic factors for PSA failure were the initial PSA level (p = .029) and younger age (p = .019). The maximal toxicities observed were Grade 3 using the Common Terminology Criteria for Adverse Events, version 3.0, for both acute and late toxicity (6 and 3 patients had acute and late Grade 3 toxicity, respectively). Late Grade 2 toxicity was observed in 13 patients. Conclusion: Monotherapeutic HDR brachytherapy with an extreme hypofractionation regimen of 54 Gy in nine fractions associated with hormonal therapy was feasible, and its toxicity was acceptable. The interim tumor control rate at a median 5.4 years was promising, even for patients with locally advanced disease. This dose-fractionation scheme might be referred to by other terms, such as stereotactic body radiotherapy. Studies with longer follow-up periods and from multiple institutions are needed to confirm the efficacy of
Dewan, M. Zahidunnabi; Galloway, Ashley E.; Kawashima, Noriko; Dewyngaert, J. Keith; Babb, James S.; Formenti, Silvia C.; Demaria, Sandra
2009-01-01
Purpose This study tested the hypothesis that the type of dose-fractionation regimen determines the ability of radiotherapy to synergize with anti-CTLA-4 antibody. Experimental design TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice at two separate sites, defined as a “primary” site that was irradiated, and a “secondary” site outside the radiotherapy field. When both tumors were palpable mice were randomly assigned to 8 groups receiving no radiotherapy or 3 distinct regimens of radiotherapy (20 Gy × 1, 8 Gy × 3 or 6 Gy × 5 fractions in consecutive days) in combination or not with 9H10 mAb against CTLA-4. Mice were followed for tumors growth/regression. Similar experiments were conducted in the MCA38 mouse colon carcinoma model. Results In either of the 2 models tested treatment with 9H10 alone had no detectable effect. Each of the radiotherapy regimens caused comparable growth delay of the primary tumors, but had no effect on the secondary tumors, outside the radiation field. Conversely, the combination of 9H10 and either fractionated radiotherapy regimens achieved enhanced tumor response at the primary site (p<0.0001). Moreover, an abscopal effect, defined as a significant growth inhibition of the tumor outside the field occurred only in mice treated with the combination of 9H10 and fractionated radiotherapy (p<0.01). Frequency of CD8+ T cells showing tumor-specific IFNγ production was proportional to the inhibition of the secondary tumor. Conclusions Fractionated, but not single dose radiotherapy, induces an abscopal effect when in combination with anti-CTLA-4 antibody, in two preclinical carcinoma models. PMID:19706802
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.
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.
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.
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.
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
Desai, Sejal; Kumar, Amit; Laskar, S; Pandey, B N
2013-01-01
Cytokines are known to play pivotal roles in cancer initiation, progression and pathogenesis. Accumulating evidences suggest differences in basal and stress-induced cytokine profiles of cancers with diverse origin. However, a comprehensive investigation characterising the cytokine profile of various tumor types after acute and fractionated doses of gamma-irradiation, and its effect on survival of bystander cells is not well known in literature. In the present study, we have evaluated the cytokine secretion profile of human tumor cell lines (HT1080, U373MG, HT29, A549 and MCF-7) either before (basal) or after acute (2, 6 Gy) and fractionated doses (3×2 Gy) of gamma-irradiation in culture medium obtained from these cells by multiplex bead array/ELISA. Moreover, clonogenic assays were performed to evaluate the effect of conditioned medium (CM) on the survival and growth of respective cells. Based on the screening of 28 analytes, our results showed that the basal profiles of these cell lines varied considerably in terms of the number and magnitude of secreted factors, which was minimum in MCF-7. Interestingly, TNF-α, IL-1β, PDGF-AA, TGF-β1, fractalkine, IL-8, VEGF and GCSF were found in CM of all the cell lines. However, secretion of certain cytokines was cell line-specific. Moreover, CM caused increase in clonogenic survival of respective tumor cells (in the order HT1080>U373MG>HT29>A549>MCF-7), which was correlated with the levels of IL-1β, IL-6, IL-8, GMCSF and VEGF in their CM. After irradiation, the levels of most of the cytokines increased markedly in a dose dependent manner. The fold change in cytokine levels was lower in irradiated conditioned medium (ICM) of tumor cells collected after fractionated than respective acute dose, except in MCF-7. Interestingly, amongst these cell lines, the radiation-induced fold increase in cytokine levels was maximum in ICM of A549 cells. Moreover, bystander A549 cells treated with respective ICM showed dose dependent
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.
Paubelle, Etienne; Ducastelle-Leprêtre, Sophie; Labussière-Wallet, Hélène; Nicolini, Franck Emmanuel; Barraco, Fiorenza; Plesa, Adriana; Salles, Gilles; Wattel, Eric; Thomas, Xavier
2017-03-01
Outcome of patients with primary refractory/relapsed (R/R) acute myeloid leukemia (AML) remains dismal. Herein, we present a retrospective monocentric study of 24 very high-risk AML patients who received a combination of fractionated gemtuzumab ozogamicin (GO) with intermediate-dose cytarabine and daunorubicin as salvage therapy. Median age was 55.3 years. Diagnostic was secondary AML for 33% of them. Seven patients had favorable risk, 8 had intermediate-1 or intermediate-2, and 6 had unfavorable risk of AML according to the European LeukemiaNet prognostic index. Complete remission was achieved in 50% of cases (46% in refractory and 55% in relapsed AML) without excessive toxicity. Thirteen patients could be referred for transplant. Only allogeneic hematopoietic stem cell transplantation provided a benefit in this patient cohort with a 1-year overall survival of 50.7 versus 18.1% in the absence of transplantation. Patients treated with reduced intensity conditioning (RIC) showed a longer survival as compared to those undergoing myeloablative conditioning regimen mainly because of decreased toxicity.Our data suggest that salvage therapy with fractionated GO combined with intermediate-dose cytarabine and daunorubicin in very high-risk patients may serve as a potential bridge therapy to RIC transplant.
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
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.
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.
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.
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
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
van de Glind, Gerline; Rebel, Heggert; van Kempen, Marika; Tensen, Kees; de Gruijl, Frank
2016-01-01
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 ≥4mm/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
Stanojlović, Miloš; Zlatković, Jelena; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša; Zarić, Marina; Horvat, Anica; Drakulić, Dunja
2015-01-01
Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17β-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 µg/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Bax and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes.
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
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.
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.
James, S.J.; Enger, S.M.; Peterson, W.J.; Makinodan, T. )
1990-06-01
Very low doses of ionizing radiation can enhance immune responsiveness and extend life span in normal mice. Total lymphoid irradiation at relatively high doses of radiation can retard autoimmune disease in genetically susceptible mice, but may impair immune function. In order to determine whether fractionated low dose exposure would enhance immune response and retard lymphadenopathy in autoimmune-prone mice, groups of C57B1/6 lpr/lpr mice were sham irradiated, exposed 5 days/week for 4 weeks to 0.04 Gy/day, or to 0.1 Gy/day. After the radiation protocol, the mice were evaluated for splenic T cell proliferative capacity, T cell subset distribution, and total spleen cell numbers. The independent and additive effect of caloric restriction was additionally assessed since this intervention has been shown to increase immune responsiveness and retard disease progression in autoimmune-prone mice. The congenic C57B1/6 +/+ immunologically normal strain was evaluated in parallel as congenic control. The results indicated that mitogen-stimulated proliferation was up-regulated in both strains of mice after exposure to 0.04 Gy/day. The proliferative capacity was additively enhanced when radiation at this dose level was combined with caloric restriction. Exposure to 0.1 Gy/day resulted in further augmentation of proliferative response in the lpr/lpr mice, but was depressive in the +/+ mice. Although the proportions of the various T cell subpopulations were altered in both strains after exposure to LDR, the specific subset alterations were different within each strain. Additional experiments were subsequently performed to assess whether the thymus is required for LDR-induced immune potentiation. Thymectomy completely abrogated the LDR effect in the +/+ mice, suggesting that thymic processing and/or trafficking is adaptively altered with LDR in this strain.
Burigo, Lucas; Pshenichnov, Igor; Mishustin, Igor; Bleicher, Marcus
2015-04-21
Depth and radial dose profiles for therapeutic (1)H, (4)He, (12)C and (16)O beams are calculated using the Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT). (4)He and (16)O ions are presented as alternative options to (1)H and (12)C 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 (12)C and (16)O 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 (1)H and (4)He ions. In general, (4)He beam is found to be a good candidate for therapy. It better spares healthy tissues in all considered cases compared to (1)H. Besides, the dose conformation is improved for deep-seated tumors compared to (1)H, 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 (16)O with respect to (12)C ions are found in this study.
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.
Sakaguchi, N.; Sakaguchi, S. Scripps Research Institute, La Jolla, CA PRESTO, JRDC, Institute of Phical and Chemical Research, Tsukuba, Ibaraki ); Miyai, K. )
1992-11-01
Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.
Pumford, N R; Roberts, D W; Benson, R W; Hinson, J A
1990-08-01
The hepatotoxicity of acetaminophen correlates with the formation of 3-(cystein-S-yl)acetaminophen protein adducts. Using a sensitive and specific immunochemical assay, we quantitated the formation of these protein adducts in liver fractions and serum after administration of a hepatotoxic dose of acetaminophen (400 mg/kg) to B6C3F1 mice. Adducts in the cytosolic fraction increased to 3.6 nmol/mg protein at 2 hr and then decreased to 1.1 nmol/mg protein by 8 hr. Concomitant with the decrease in adducts in the cytosol, 3-(cystein-S-yl)acetaminophen protein adducts appeared in serum and their levels paralleled increases in serum alanine aminotransferase. Microsomal protein adducts peaked at 1 hr (0.7 nmol/mg protein) and subsequently decreased to 0.2 nmol/mg at 8 hr. The 4000 g pellet (nuclei, plasma membranes, and cell debris) had the highest level of adducts (3.5 nmol/mg protein), which remained constant from 1 to 8 hr. Evaluation of fractions purified from a 960 g pellet indicated that the highest concentration of 3-(cystein-S-yl)acetaminophen protein adducts was located in plasma membranes and mitochondria; peak levels were 10.3 and 5.1 nmol/mg respectively. 3-(Cystein-S-yl)acetaminophen protein adducts were detected in nuclei only after enzymatic hydrolysis of the proteins. The localization of high levels of 3-(cystein-S-yl)acetaminophen protein adducts in plasma membranes and mitochondria may play a critical role in acetaminophen toxicity.
Jamal, Syed M; Bouma, Annemarie; van den Broek, Jan; Stegeman, Arjan; Chénard, Gilles; Dekker, Aldo
2008-11-25
The aim of this study was to determine a relationship between vaccine potency (amount of PD50 per dose) and fraction of clinically protected cattle following homologous challenge with infectious foot-and-mouth disease (FMD) virus, and to determine the effect of method of fractionation, serotype, type of adjuvant, valency and type of virus culture on the dose-response curve. Data from 297 potency tests of FMD vaccines, comprising 4004 vaccinated cattle, performed at the FMD vaccine production facility in the Netherlands, were used for the present study. A generalised linear mixed effect model was used to analyse the results. Our study showed that the relation between FMD vaccine potency and fraction protected was also affected by the serotype and type of adjuvant. No common level of protection could be assigned to all FMD vaccines with the same amount of PD50 per dose, this information is essential when designing a new standard FMD vaccines control.
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.
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
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%.
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
Sau, Sourav; Sau, Saikat; Dutta, Premnath; Gayen, Ganesh Chandra; Banerjee, Sanatan; Basu, Avijit
2014-01-01
Introduction: To investigate the effect of different hypo fractionated thoracic radiotherapy schedules in relation to thoracic pain relief, overall survival and post radiotherapy HRQOL in metastatic NSCLC. Material and methods: Stage IV NSCLC and had intra-thoracic symptoms, included in the study. Patients were randomly assigned to three treatments arms. (i) 17 Gy in 2 fractions in one week (ii) 20 Gy in five fractions in one week. (iii) 30 Gy in 10 fractions in two weeks. BPI module was used to assess pain score before and after the thoracic radiotherapy. Functional assessment of cancer therapy-G (FACT-G) used to investigate changes in HRQOL. Clinicians’ assessment of symptom improvement were recorded at 2nd, 6th and 12th weeks after completion of TRT. Results: Pain relief, HRQOL and OS were equivalent in all the three arms. The median OS were 6 months, 5 months, 6 months in arm A, B and arm C, respectively. Conclusion: Protracted palliative thoracic radiotherapy renders no added advantage of relief of symptoms, HRQOL and overall survival compared to short course palliative TRT in metastatic NSCLC. PMID:25378842
Moreno-Cantú, J J; Thompson, C J; Zatorre, R J
1998-12-01
We evaluated the performance of the ECAT EXACT HR+ 3-D whole-body positron emission tomography (PET) scanner when employed to measure brain function using H2(15)O bolus activation protocols that are completed in single same-day data acquisition sessions. Using vibrotactile and auditory stimuli as independent activation tasks, we studied the scanner performance under different imaging conditions in five healthy volunteers. Cerebral blood flow images were acquired from each volunteer using H2(15)O bolus injections of activity varying from 5-20 mCi. One-session dose-fractionation strategies were analyzed for rCBF, standard activity-concentration, switched, and cold-bolus/switched protocols. Performance characteristics. The scanner dead time grew linearly with injected dose from 10% to 25%. Random events varied from 30% to 50% of the detected events. Random and scattered events were corrected adequately at all doses. Estimated noise-effective-count curves plateau at about 10 mCi. One-session 12-injection bolus PET activation protocols. Using an acquisition protocol that accounts for the scanner performance and the practical aspects of imaging volunteers and neurological patients in a single same-day session, we assessed the correlation between the significance of activation foci and the dose/injection used. The one-session protocol employs 12 bolus injections/subject. We present evidence suggesting that when an rCBF protocol is used, image noise is reduced significantly when the activity injected increases from 5 to 10 mCi. Increasing the dose from 10 to 15 or 20 mCi yielded further but smaller reductions. Our observations also suggest that image noise will be strongly reduced if a 20-mCi dose/injection is used when data are collected using protocols that employ long acquisition times such as a switched or a cold-bolus/switched protocol.
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
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.
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.
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.
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
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.
Understanding Multiplication of Fractions.
ERIC Educational Resources Information Center
Sweetland, Robert D.
1984-01-01
Discussed the use of Cuisenaire rods in teaching the multiplication of fractions. Considers whole number times proper fraction, proper fraction multiplied by proper fraction, mixed number times proper fraction, and mixed fraction multiplied by mixed fractions. (JN)
ERIC Educational Resources Information Center
Bhattacharyya, Sonalee; Namakshi, Nama; Zunker, Christina; Warshauer, Hiroko K.; Warshauer, Max
2016-01-01
Making math more engaging for students is a challenge that every teacher faces on a daily basis. These authors write that they are constantly searching for rich problem-solving tasks that cover the necessary content, develop critical-thinking skills, and engage student interest. The Mystery Fraction activity provided here focuses on a key number…
1981-12-15
13 3. Solvent Fractionation Experiments .................................... 15 4. Fourier Transform Infrared Spectra for A240 Petrolem Pitch AG 12...34 and Mesophase Pitch AG 164B ............................... 21 5. Fourier Transform Infrared Spectra ................................... 23 6...compared by Fourier transform infrared (FTIR) analysis using a Digilab Model FTS 14 spectrophotometer (Rockwell International, Anaheim, California
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.
NASA Astrophysics Data System (ADS)
Bell, Peter M.
A rash of new controversy has emerged around the subject of mass-independent isotope fractionation effects, particularly in the case of the oxygen isotopes. To be sure, the controversy has been around for awhile, but it has been given new impetus by the results of a recent study by Mark H. Thiemens and John E. Heidenreich III of the University of California, San Diego (Science, March 4, 1983).Gustav Arrhenius has been trying to convince the planetary science community that chemical effects in isotope fractionation processes could explain observations in meteorites that appear to be outside of the traditionally understood mass-dependent fractionations (G. Arrhenius, J . L. McCrumb, and N. F. Friedman, Astrophys. Space Sci, 65, 297, 1974). Robert Clayton had made the basic observations of oxygen in carbonaceous chondrites that the slope of the δ17 versus δ18 line was 1 instead of the slope of ½ characteristic of terrestrial rocks and lunar samples (Ann. Rev. Nucl. Part. Sci., 28, 501, 1978). The mass-independent effects were ascribed to the apparent contribution of an ancient presolar system component of O16.
Maximizing Tumor Immunity With Fractionated Radiation
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.
A dynamic programming approach to adaptive fractionation
NASA Astrophysics Data System (ADS)
Ramakrishnan, Jagdish; Craft, David; Bortfeld, Thomas; Tsitsiklis, John N.
2012-03-01
We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are as follows: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a ‘favorable’ anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5-85%) depending on the amount of motion in the anatomy, the number of fractions and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting) and (iii) we allow large daily fraction size deviations.
Calculation of effective dose.
McCollough, C H; Schueler, B A
2000-05-01
The concept of "effective dose" was introduced in 1975 to provide a mechanism for assessing the radiation detriment from partial body irradiations in terms of data derived from whole body irradiations. The effective dose is the mean absorbed dose from a uniform whole-body irradiation that results in the same total radiation detriment as from the nonuniform, partial-body irradiation in question. The effective dose is calculated as the weighted average of the mean absorbed dose to the various body organs and tissues, where the weighting factor is the radiation detriment for a given organ (from a whole-body irradiation) as a fraction of the total radiation detriment. In this review, effective dose equivalent and effective dose, as established by the International Commission on Radiological Protection in 1977 and 1990, respectively, are defined and various methods of calculating these quantities are presented for radionuclides, radiography, fluoroscopy, computed tomography and mammography. In order to calculate either quantity, it is first necessary to estimate the radiation dose to individual organs. One common method of determining organ doses is through Monte Carlo simulations of photon interactions within a simplified mathematical model of the human body. Several groups have performed these calculations and published their results in the form of data tables of organ dose per unit activity or exposure. These data tables are specified according to particular examination parameters, such as radiopharmaceutical, x-ray projection, x-ray beam energy spectra or patient size. Sources of these organ dose conversion coefficients are presented and differences between them are examined. The estimates of effective dose equivalent or effective dose calculated using these data, although not intended to describe the dose to an individual, can be used as a relative measure of stochastic radiation detriment. The calculated values, in units of sievert (or rem), indicate the amount of
Multiple anatomy optimization of accumulated dose
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.
Fractional vector calculus and fractional Maxwell's equations
Tarasov, Vasily E.
2008-11-15
The theory of derivatives and integrals of non-integer order goes back to Leibniz, Liouville, Grunwald, Letnikov and Riemann. The history of fractional vector calculus (FVC) has only 10 years. The main approaches to formulate a FVC, which are used in the physics during the past few years, will be briefly described in this paper. We solve some problems of consistent formulations of FVC by using a fractional generalization of the Fundamental Theorem of Calculus. We define the differential and integral vector operations. The fractional Green's, Stokes' and Gauss's theorems are formulated. The proofs of these theorems are realized for simplest regions. A fractional generalization of exterior differential calculus of differential forms is discussed. Fractional nonlocal Maxwell's equations and the corresponding fractional wave equations are considered.
Functional fractionation of platelets.
Haver, V M; Gear, A R
1981-02-01
Studies of platelet populations suggest that they are heterogeneous in size, age, and metabolic parameters. In an attempt to correlate these parameters with efficiency of aggregation, a new technique, functional fractionation, was developed. Platelet populations are separated by their differential reactivity to aggregating agents. For example, low doses of ADP (0.1 to 0.7 microM) are added to stirred PRP, after which gentle centrifugation is used to remove aggregates from single unreacted platelets. The loose aggregates can be readily dispersed for comparison of the physical or biochemical properties of the reacted versus unreacted platelets. It was found that reactive platelets were larger (6.5 micrometer3) than unreacted platelets (5.51 micrometer3). No significant difference in density existed between the two populations, and no release of [14C]serotonin from prelabeled platelets occurred during functional fractionation. Scanning and transmission electron microscopy confirmed the size difference and revealed that in both populations platelets were structurally intact with a normal discoid shape and no significant difference in organelle content. Human platelets most reactive to ADP were also enriched in glycogen (3.6-fold), ATP (1.6-fold), and ADP (twofold), compared with less reactive cells. These "reactive" cells took up more 51[Cr] and contained 1.9 times more surface sialic acid. In an in vivo aging experiment, rats were injected with 75[Se]methionine. Shortly after labeling (1 day), the most reactive platelets possessed the highest amount of 75[Se]. These results reveal that functionally active platelets, which are also larger, are more active metabolically than less reactive platelets, possess a higher negative surface charge, and may be a younger population.
Fractional kinetics in multi-compartmental systems.
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.
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.
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.
Radiation dose estimates for radiopharmaceuticals
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.
Fraction Sense: Foundational Understandings.
Fennell, Francis Skip; Karp, Karen
2016-08-09
The intent of this commentary is to identify elements of fraction sense and note how the research studies provided in this special issue, in related but somewhat different ways, validate the importance of such understandings. Proficiency with fractions serves as a prerequisite for student success in higher level mathematics, as well as serving as a gateway to many occupations and varied contexts beyond the mathematics classroom. Fraction sense is developed through instructional opportunities involving fraction equivalence and magnitude, comparing and ordering fractions, using fraction benchmarks, and computational estimation. Such foundations are then extended to operations involving fractions and decimals and applications involving proportional reasoning. These components of fraction sense are all addressed in the studies provided in this issue, with particular consideration devoted to the significant importance of the use of the number line as a central representational tool for conceptually understanding fraction magnitude.
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
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.
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.
ERIC Educational Resources Information Center
Graham, Alan; Graham, Louise
2003-01-01
Describes a very successful attempt to teach fractions to year 5 pupils based on pupils making their own fraction pack. Children decided for themselves how to make the fractional slices used in the activity using colored cardboard sheets and templates of a paper circle consisting of 24 equal slices. (Author/NB)
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.
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.
Pitch fractionation. Technical report
Weinberg, V.L.; White, J.L.
1981-12-15
Petroleum pitch (Ashland A240) has been subjected to thermal treatment and solvent fractionation to produce refined pitches to be evaluated as impregnants for carbon-carbon composites. The solvent fractions were obtained by sequential Soxhlet extraction with solvents such as hexane, cyclohexane, toluene, and pyridine. The most severe thermal treatment produced a mesophase pitch (approximately 50% mesophase); an appreciable portion of the mesophase was soluble in strong solvents. There were substantial differences in chemical composition and in pyrolysis behavior of the fractions. As the depth of fraction increased, the pyrolysis yield and bloating increased, and the microstructure of the coke became finer until glassy microconstituents were formed in the deepest fractions.
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…
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
FRACTIONAL PEARSON DIFFUSIONS.
Leonenko, Nikolai N; Meerschaert, Mark M; Sikorskii, Alla
2013-07-15
Pearson diffusions are governed by diffusion equations with polynomial coefficients. Fractional Pearson diffusions are governed by the corresponding time-fractional diffusion equation. They are useful for modeling sub-diffusive phenomena, caused by particle sticking and trapping. This paper provides explicit strong solutions for fractional Pearson diffusions, using spectral methods. It also presents stochastic solutions, using a non-Markovian inverse stable time change.
Leonenko, Nikolai N.; Meerschaert, Mark M.
2013-01-01
Pearson diffusions are governed by diffusion equations with polynomial coefficients. Fractional Pearson diffusions are governed by the corresponding time-fractional diffusion equation. They are useful for modeling sub-diffusive phenomena, caused by particle sticking and trapping. This paper provides explicit strong solutions for fractional Pearson diffusions, using spectral methods. It also presents stochastic solutions, using a non-Markovian inverse stable time change. PMID:23626377
Helical tomotherapy superficial dose measurements
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
Can Kindergartners Do Fractions?
ERIC Educational Resources Information Center
Cwikla, Julie
2014-01-01
Mathematics professor Julie Cwikla decided that she needed to investigate young children's understandings and see what precurricular partitioning notions young minds bring to the fraction table. Cwikla realized that only a handful of studies have examined how preschool-age and early elementary school-age students solve fraction problems (Empson…
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…
Bajona-Xandri, C.; Martinez-Legaz, J.E.
1994-12-31
This paper studies the minimax fractional programming problem, assuming quasiconvexity of the objective function, under the lower subdifferentiability viewpoint. Necessary and sufficient optimality conditions and dual properties are found. We present applications of this theory to find the Pareto efficient solutions of a multiobjective fractional problem and to solve several economic models.
(Carbon isotope fractionation inplants)
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.
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.
Dose rate mapping of VMAT treatments.
Podesta, Mark; Popescu, I Antoniu; Verhaegen, Frank
2016-06-07
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.
Fractional dissipative standard map.
Tarasov, Vasily E; Edelman, M
2010-06-01
Using kicked differential equations of motion with derivatives of noninteger orders, we obtain generalizations of the dissipative standard map. The main property of these generalized maps, which are called fractional maps, is long-term memory. The memory effect in the fractional maps means that their present state of evolution depends on all past states with special forms of weights. Already a small deviation of the order of derivative from the integer value corresponding to the regular dissipative standard map (small memory effects) leads to the qualitatively new behavior of the corresponding attractors. The fractional dissipative standard maps are used to demonstrate a new type of fractional attractors in the wide range of the fractional orders of derivatives.
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.
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 36.25Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30Gy in 3 fractions of HDR brachytherapy regimen. The D5% of the target in the CyberKnife hypofractionation was 41.57 ± 2.41Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86Gy. The mean HDR fractionation equivalent dose, D98%, was 27.93 ± 0.84Gy. The V100% of the prostate target was 95.57% ± 3.47%. The V100% of the bladder and the rectum were 717.16 and 79.6mm(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 (D98% to D80%) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D10% and D5%. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife.
Fractional calculus in bioengineering.
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
Radiation Dose-Volume Effects in the Spinal Cord
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.
NASA Astrophysics Data System (ADS)
Laskin, Nick
2000-12-01
A new extension of a fractality concept in financial mathematics has been developed. We have introduced a new fractional Langevin-type stochastic differential equation that differs from the standard Langevin equation: (i) by replacing the first-order derivative with respect to time by the fractional derivative of order μ; and (ii) by replacing “white noise” Gaussian stochastic force by the generalized “shot noise”, each pulse of which has a random amplitude with the α-stable Lévy distribution. As an application of the developed fractional non-Gaussian dynamical approach the expression for the probability distribution function (pdf) of the returns has been established. It is shown that the obtained fractional pdf fits well the central part and the tails of the empirical distribution of S&P 500 returns.
Catalytic reforming of naphtha fractions
Bishop, K.C.; Vorhis, F.H.
1980-09-16
Production of motor gasoline and a btx-enriched reformate by fractionating a naphtha feedstock into a mid-boiling btxprecursor fraction, a relatively high-boiling fraction and a relatively low-boiling fraction; catalytically reforming the btxprecursor fraction in a first reforming zone; combining the relatively high-boiling and low-boiling fractions and catalytically reforming the combined fractions in a second reforming zone.
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.
Thermodynamics in Fractional Calculus
NASA Astrophysics Data System (ADS)
Meilanov, R. P.; Magomedov, R. A.
2014-11-01
A generalization of thermodynamics in the formalism of fractional-order derivatives is given. Results of the traditional thermodynamics of Carnot, Clausius, and Helmholtz are obtained in the particular case where the exponent of a fractional-order derivative is equal to unity. A one-parametric "fractal" equation of state is obtained with account of the second virial coefficient. The application of the resulting equation of state in the case of the gas argon is considered.
Panprasitwech, Oranit; Laohakosol, Vichian; Chaichana, Tuangrat
2010-11-11
Explicit formulae for continued fractions with symmetric patterns in their partial quotients are constructed in the field of formal power series. Similar to the work of Cohn in 1996, which generalized the so-called folding lemma to {kappa}-fold symmetry, the notion of {kappa}-duplicating symmetric continued fractions is investigated using a modification of the 1995 technique due to Clemens, Merrill and Roeder.
Chromatographic methods of fractionation.
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.
Fractional laser skin resurfacing.
Alexiades-Armenakas, Macrene R; Dover, Jeffrey S; Arndt, Kenneth A
2012-11-01
Laser skin resurfacing (LSR) has evolved over the past 2 decades from traditional ablative to fractional nonablative and fractional ablative resurfacing. Traditional ablative LSR was highly effective in reducing rhytides, photoaging, and acne scarring but was associated with significant side effects and complications. In contrast, nonablative LSR was very safe but failed to deliver consistent clinical improvement. Fractional LSR has achieved the middle ground; it combined the efficacy of traditional LSR with the safety of nonablative modalities. The first fractional laser was a nonablative erbium-doped yttrium aluminum garnet (Er:YAG) laser that produced microscopic columns of thermal injury in the epidermis and upper dermis. Heralding an entirely new concept of laser energy delivery, it delivered the laser beam in microarrays. It resulted in microscopic columns of treated tissue and intervening areas of untreated skin, which yielded rapid reepithelialization. Fractional delivery was quickly applied to ablative wavelengths such as carbon dioxide, Er:YAG, and yttrium scandium gallium garnet (2,790 nm), providing more significant clinical outcomes. Adjustable laser parameters, including power, pitch, dwell time, and spot density, allowed for precise determination of percent surface area, affected penetration depth, and clinical recovery time and efficacy. Fractional LSR has been a significant advance to the laser field, striking the balance between safety and efficacy.
Repair of skin damage during fractionated irradiation with gamma rays and low-LET carbon ions.
Ando, Koichi; Koike, Sachiko; Uzawa, Akiko; Takai, Nobuhiko; Fukawa, Takeshi; Furusawa, Yoshiya; Aoki, Mizuho; Hirayama, Ryoichi
2006-06-01
In clinical use of carbon-ion beams, a deep-seated tumor is irradiated with a Spread-Out Bragg peak (SOBP) with a high-LET feature, whereas surface skin is irradiated with an entrance plateau, the LET of which is lower than that of the peak. The repair kinetics of murine skin damage caused by an entrance plateau of carbon ions was compared with that caused by photons using a scheme of daily fractionated doses followed by a top-up dose. Right hind legs received local irradiations with either 20 keV/microm carbon ions or gamma rays. The skin reaction of the irradiated legs was scored every other day up to Day 35 using a scoring scale that consisted of 10 steps, ranging from 0.5 to 5.0. An isoeffect dose to produce a skin reaction score of 3.0 was used to obtain a total dose and a top-up dose for each fractionation. Dependence on a preceding dose and on the time interval of a top-up dose was examined using gamma rays. For fractionated gamma rays, the total dose linearly increased while the top-up dose linearly decreased with an increase in the number of fractions. The magnitude of damage repair depended on the size of dose per fraction, and was larger for 5.2 Gy than 12.5 Gy. The total dose of carbon ions with 5.2 Gy per fraction did not change till 2 fractions, but abruptly increased at the 3rd fraction. Factors such as rapid repopulation, induced repair and cell cycle synchronization are possible explanations for the abrupt increase. As an abrupt increase/decrease of normal tissue damage could be caused by changing the number of fractions in carbon-ion radiotherapy, we conclude that, unlike photon therapy, skin damage should be carefully studied when the number of fractions is changed in new clinical trials.
Stewart, F.A.; Oussoren, Y.; Luts, A.; Begg, A.C.; Dewit, L.; Lebesque, J.; Bartelink, H.
1987-05-01
Functional kidney damage in mice was measured after a series of fractionated X-irradiations. Doses per fraction of 0.75-12.5 Gy were given as 2, 5, 10, 30, 40, 60, or 80 equal doses in a total treatment time of 4 weeks. Renal function (measured by clearance of /sup 51/CrEDTA or hematocrit levels) deteriorated progressively, in a dose related manner, from 20 to 46 weeks after the start of treatment. The changes in renal function versus time were fitted by a polynomial regression through all data and interpolated values for /sup 51/CrEDTA clearance were then calculated at 30 and 40 weeks after treatment. Steep dose response curves were obtained and these were used to calculate isoeffective doses for the different fractionation schedules. There was a marked increase in total isoeffective doses from 2-30 fractions and these data were well described by a linear quadratic (L.Q.) expression for damage with an alpha/beta ratio of 2.3 +/- 0.2 Gy. There was only a slight increase in the total isoeffect dose as the size of the dose per fraction was decreased below 2 Gy and the measured isoeffect doses after 40 to 80 fractions were lower than predicted on the basis of an L.Q. model assuming complete repair between successive irradiations. The flexure dose for mouse kidneys irradiated 3 times per day was, effectively, 1 to 2 Gy and hyperfractionation using lower doses per fraction did not lead to significant, additional repair.
Identifying Fractions on Number Lines.
ERIC Educational Resources Information Center
Bright, George W.; And Others
1988-01-01
This study investigated the ways students represented fractions on number lines and the effects of instruction on those representations. The instruction primarily concerned representing fractions and ordering fractions on number lines. (Author/PK)
Antimicrobial activity of the solvent fractions from Bulbine natalensis Tuber.
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.
In vitro studies on the adjuvanticity of Brucella fractions.
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
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
FRACTIONAL CRYSTALLIZATION FEED ENVELOPE
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.
Jaikuna, Tanwiwat; Khadsiri, Phatchareewan; Chawapun, Nisa; Saekho, Suwit
2017-01-01
Purpose To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model. Material and methods The Isobio software was developed using MATLAB version 2014b to calculate and generate the biological dose distribution and biological dose volume histograms. The physical dose from each voxel in treatment planning was extracted through Computational Environment for Radiotherapy Research (CERR), and the accuracy was verified by the differentiation between the dose volume histogram from CERR and the treatment planning system. An equivalent dose in 2 Gy fraction (EQD2) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD2 verification with pair t-test statistical analysis using IBM SPSS Statistics version 22 (64-bit). Results Two and three-dimensional biological dose distribution and biological dose volume histogram were displayed correctly by the Isobio software. Different physical doses were found between CERR and treatment planning system (TPS) in Oncentra, with 3.33% in high-risk clinical target volume (HR-CTV) determined by D90%, 0.56% in the bladder, 1.74% in the rectum when determined by D2cc, and less than 1% in Pinnacle. The difference in the EQD2 between the software calculation and the manual calculation was not significantly different with 0.00% at p-values 0.820, 0.095, and 0.593 for external beam radiation therapy (EBRT) and 0.240, 0.320, and 0.849 for brachytherapy (BT) in HR-CTV, bladder, and rectum, respectively. Conclusions The Isobio software is a feasible tool to generate the biological dose distribution and biological dose volume histogram for treatment plan evaluation in both EBRT and BT. PMID:28344603
Momentum fractionation on superstrata
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 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. 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.
Momentum fractionation on superstrata
Bena, Iosif; Martinec, Emil; Turton, David; ...
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
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…
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)
Fraction collector for electrophoresis
NASA Technical Reports Server (NTRS)
Bier, M.
1977-01-01
Rotating-tube electrophoresis apparatus employs rotating jet of eluting buffer to reduce effects of convection during separation. Designed for separation of microorganisms and biological species, system combines gravity/gradient compensating of lumen with buffer flush at fraction outlet to increase separation efficiency.
Dynamically accumulated dose and 4D accumulated dose for moving tumors
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
Acoustic dose and acoustic dose-rate.
Duck, Francis
2009-10-01
Acoustic dose is defined as the energy deposited by absorption of an acoustic wave per unit mass of the medium supporting the wave. Expressions for acoustic dose and acoustic dose-rate are given for plane-wave conditions, including temporal and frequency dependencies of energy deposition. The relationship between the acoustic dose-rate and the resulting temperature increase is explored, as is the relationship between acoustic dose-rate and radiation force. Energy transfer from the wave to the medium by means of acoustic cavitation is considered, and an approach is proposed in principle that could allow cavitation to be included within the proposed definitions of acoustic dose and acoustic dose-rate.
The emergence of nonuniform spatiotemporal fractionation schemes within the standard BED model
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.
Young Children's Notations for Fractions
ERIC Educational Resources Information Center
Brizuela, Barbara M.
2006-01-01
This paper focuses on the kinds of notations young children make for fractional numbers. The extant literature in the area of fractional numbers acknowledges children's difficulties in conceptualizing fractional numbers. Some of the research suggests possibly delaying an introduction to conventional notations for algorithms and fractions until…
Creating, Naming, and Justifying Fractions
ERIC Educational Resources Information Center
Siebert, Daniel; Gaskin, Nicole
2006-01-01
For students to develop meaningful conceptions of fractions and fraction operations, they need to think of fractions in terms other than as just whole-number combinations. In this article, we suggest two powerful images for thinking about fractions that move beyond whole-number reasoning. (Contains 5 figures.)
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.
Akine, Y.; Tokita, N.; Ogino, T.; Kajiura, Y.; Tsukiyama, I.; Egawa, S. )
1990-12-01
By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low-dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low-dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy.
Arbitrage with fractional Gaussian processes
NASA Astrophysics Data System (ADS)
Zhang, Xili; Xiao, Weilin
2017-04-01
While the arbitrage opportunity in the Black-Scholes model driven by fractional Brownian motion has a long history, the arbitrage strategy in the Black-Scholes model driven by general fractional Gaussian processes is in its infancy. The development of stochastic calculus with respect to fractional Gaussian processes allowed us to study such models. In this paper, following the idea of Shiryaev (1998), an arbitrage strategy is constructed for the Black-Scholes model driven by fractional Gaussian processes, when the stochastic integral is interpreted in the Riemann-Stieltjes sense. Arbitrage opportunities in some fractional Gaussian processes, including fractional Brownian motion, sub-fractional Brownian motion, bi-fractional Brownian motion, weighted-fractional Brownian motion and tempered fractional Brownian motion, are also investigated.
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.
Fractional lattice charge transport
Flach, Sergej; Khomeriki, Ramaz
2017-01-01
We consider the dynamics of noninteracting quantum particles on a square lattice in the presence of a magnetic flux α and a dc electric field E oriented along the lattice diagonal. In general, the adiabatic dynamics will be characterized by Bloch oscillations in the electrical field direction and dispersive ballistic transport in the perpendicular direction. For rational values of α and a corresponding discrete set of values of E(α) vanishing gaps in the spectrum induce a fractionalization of the charge in the perpendicular direction - while left movers are still performing dispersive ballistic transport, the complementary fraction of right movers is propagating in a dispersionless relativistic manner in the opposite direction. Generalizations and the possible probing of the effect with atomic Bose-Einstein condensates and photonic networks are discussed. Zak phase of respective band associated with gap closing regime has been computed and it is found converging to π/2 value. PMID:28102302
Floquet Fractional Chern Insulators
NASA Astrophysics Data System (ADS)
Grushin, Adolfo G.; Gómez-León, Álvaro; Neupert, Titus
2014-04-01
We show theoretically that periodically driven systems with short range Hubbard interactions offer a feasible platform to experimentally realize fractional Chern insulator states. We exemplify the procedure for both the driven honeycomb and the square lattice, where we derive the effective steady state band structure of the driven system by using the Floquet theory and subsequently study the interacting system with exact numerical diagonalization. The fractional Chern insulator state equivalent to the 1/3 Laughlin state appears at 7/12 total filling (1/6 filling of the upper band). The state also features spontaneous ferromagnetism and is thus an example of the spontaneous breaking of a continuous symmetry along with a topological phase transition. We discuss light-driven graphene and shaken optical lattices as possible experimental systems that can realize such a state.
Fractional Trajectories: Decorrelation Versus Friction
2013-07-27
from the integration of fractional differential equations in time. In Section 2 we provide a general demonstration of the new perspective on fractional ...section we demonstrate the equivalence between a fractional trajectory that is the solution of a Caputo fractional differential equation , and the... fractional differential equation dα dtα V(t) = OV(t), (1) where 0 < α < 1 and O is an operator, either linear or nonlinear, acting on the vector V(t
Gottlieb, A; Schleibinger, H; Ketseridis, G; Wullenweber, M; Rüden, H
1983-01-01
Suspended particulate matter (PM) with a Dae less than 0.4 micron was collected from July 1981 till January 1982. The ether/benzene soluble extract (EEOM) and the acidic, basic and neutral fractions were determined and investigated for their mutagenic activities in the Ames bioassay. In addition particles (Dae) less than 10.2 micron derived in January were investigated. Five compounds of the basic fraction were determined by gaschromatography. The following results were obtained: Suspended particulate matter (Dae less than 0.4 micron) and the ether/benzene extract increase from July to January. The lowest rates occur in July (PM: 16.9 micron/m3) and August (EEOM: 3.0 micrograms/m3), the highest in January (PM: 48.9 micrograms/m3, EEOM: 10.5 micrograms/m3). The ether/benzene soluble portion of the suspended particulate matter increases from the average rate of 16.3% (July-September) to 22.7% (November-January). The neutral fraction amounts to 44.9%, the acidic fraction to 27.3% and the basic fraction to 3.5% of the organic matter (on an average). In experiments with metabolic activation 99% of the total mutagenicity during the period of July till September can be demonstrated by summing up the mutagenicity of the three fractions on the other hand only 59.7% from November till January. The EEOMs derived from winter exhibit without metabolic activation (250 micrograms/plate) distinctively higher numbers of revertants than the single fractions. Dose-response curves of extracts derived from back-up filters (Dae less than 0.4 micron) in January show that the acidic fraction has a slightly higher mutagenic activity than the neutral fraction (mean values of tests with and without S9-mix). The basic fraction shows no mutagenicity without S9-mix, with activation the mutagenic activity is lower than that of the other fractions. Mutagenicity expressed as rev./m3 air shows, that the neutral fraction is most efficient. The number of revertants per plate reveals-in relation to
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.
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.
Spatially fractionated radiotherapy (GRID) using helical tomotherapy.
Zhang, Xin; Penagaricano, Jose; Yan, Yulong; Liang, Xiaoying; Morrill, Steven; Griffin, Robert J; Corry, Peter; Ratanatharathorn, Vaneerat
2016-01-08
Spatially fractionated radiotherapy (GRID) was designed to treat large tumors while sparing skin, and it is usually delivered with a linear accelerator using a commercially available block or multileaf collimator (LINAC-GRID). For deep-seated (skin to tumor distance (> 8 cm)) tumors, it is always a challenge to achieve adequate tumor dose coverage. A novel method to perform GRID treatment using helical tomotherapy (HT-GRID) was developed at our institution. Our approach allows treating patients by generating a patient-specific virtual GRID block (software-generated) and using IMRT technique to optimize the treatment plan. Here, we report our initial clinical experience using HT-GRID, and dosimetric comparison results between HT-GRID and LINAC-GRID. This study evaluates 10 previously treated patients who had deep-seated bulky tumors with complex geometries. Five of these patients were treated with HT-GRID and replanned with LINAC-GRID for comparison. Similarly, five other patients were treated with LINAC-GRID and replanned with HT-GRID for comparison. The prescription was set such that the maximum dose to the GTV is 20 Gy in a single fraction. Dosimetric parameters compared included: mean GTV dose (DGTV mean), GTV dose inhomogeneity (valley-to-peak dose ratio (VPR)), normal tissue doses (DNmean), and other organs-at-risk (OARs) doses. In addition, equivalent uniform doses (EUD) for both GTV and normal tissue were evaluated. In summary, HT-GRID technique is patient-specific, and allows adjustment of the GRID pattern to match different tumor sizes and shapes when they are deep-seated and cannot be adequately treated with LINAC-GRID. HT-GRID delivers a higher DGTV mean, EUD, and VPR compared to LINAC-GRID. HT-GRID delivers a higher DNmean and lower EUD for normal tissue compared to LINAC-GRID. HT-GRID plans also have more options for tumors with complex anatomical relationships between the GTV and the avoidance OARs (abutment or close proximity).
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.
Statistical iterative reconstruction using adaptive fractional order regularization
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
Use of radiation protraction to escalate biologically effective dose to the treatment target
Kuperman, V. Y.; Spradlin, G. S.
2011-12-15
Purpose: The aim of this study is to evaluate how simultaneously increasing fraction time and dose per fraction affect biologically effective dose for the target (BED{sub tar}) while biologically effective dose for the normal tissue (BED{sub nt}) is fixed. Methods: In this investigation, BED{sub tar} and BED{sub nt} were studied by assuming mono-exponential repair of sublethal damage with tissue dependent repair half-time. Results: Our results demonstrate that under certain conditions simultaneously increasing fraction time and dose per fraction result in increased BED{sub tar} while BED{sub nt} is fixed. The dependence of biologically effective dose on fraction time is influenced by the dose rate. In this investigation we analytically determined time-varying dose rate R-tilde which minimizes BED. Changes in BED with fraction time were compared for constant dose rate and for R-tilde. Conclusions: A number of recent experimental and theoretical studies have demonstrated that slow delivery of radiation (known as radiation protraction) leads to reduced therapeutic effect because of increased repair of sublethal damage. In contrast, our analysis shows that under certain conditions simultaneously increasing fraction time and dose per fraction are radiobiologically advantageous.
Fractionated radiotherapy and radiosurgery of intracranial meningiomas.
Biau, J; Khalil, T; Verrelle, P; Lemaire, J-J
2015-06-19
This review focuses on the role of radiosurgery and fractionated radiotherapy in the management of intracranial meningiomas, which are the most common benign intracranial tumors. Whenever feasible, surgery remains a cornerstone of treatment in effective health care treatment where modern radiotherapy plays an important role. Irradiation can be proposed as first-line treatment, as adjuvant treatment, or as a second-line treatment after recurrence. Stereotactic radiosurgery consists of delivering, a high-dose of radiation with high precision, to the tumor in a single-fraction with a minimal exposure of surrounding healthy tissue. Stereotactic radiosurgery, especially with the gamma knife technique, has reached a high level of success for the treatment of intracranial meningiomas with excellent local control and low morbidity. However, stereotactic radiosurgery is limited by tumor size,<3-4cm, and location, i.e. reasonable distance from the organs at risk. Fractionated radiation therapy is an interesting alternative (5 to 6weeks treatment time) for large inoperable tumors. The results of fractionated radiation therapy seem encouraging as regards both local control and morbidity although long-term prospective studies are still needed.
Fractionated total body irradiation for metastatic neuroblastoma
Kun, L.E.; Casper, J.T.; Kline, R.W.; Piaskowski, V.D.
1981-11-01
Twelve patients over one year old with neuroblastoma (NBL) metastatic to bone and bone marrow entered a study of adjuvant low-dose, fractionated total body irradiation (TBI). Six children who achieved a ''complete clinical response'' following chemotherapy (cyclophosphamide and adriamycin) and surgical resection of the abdominal primary received TBI (10 rad/fraction to totals of 100-120 rad/10-12 fx/12-25 days). Two children received concurrent local irradiation for residual abdominal tumor. The intervals from cessation of chemotherapy to documented progression ranged from 2-16 months, not substatially different from patients receiving similar chemotherapy and surgery without TBI. Three additional children with progressive NBL received similar TBI (80-120 rad/8-12 fx) without objective response.
Radiation Dose-Volume Effects in the Lung
Marks, Lawrence B.; Bentzen, Soren M. D.Sc.; Deasy, Joseph O.; Kong, F.-M.; Bradley, Jeffrey D.; Vogelius, Ivan S.; El Naqa, Issam; Hubbs, Jessica L. M.S.; Lebesque, Joos V.; Timmerman, Robert D.; Martel, Mary K.; Jackson, Andrew
2010-03-01
The three-dimensional dose, volume, and outcome data for lung are reviewed in detail. The rate of symptomatic pneumonitis is related to many dosimetric parameters, and there are no evident threshold 'tolerance dose-volume' levels. There are strong volume and fractionation effects.
[Ablative and fractional lasers].
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.
Low dose neutron late effects: Cataractogenesis
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.
Peripheral doses from pediatric IMRT
Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David
2006-07-15
from 0.47-0.94) doses {approx}[0.4-1.8 cGy]/[0.9-2.9 cGy]/fraction, respectively. Prior phantom reports are for fields 10 cm or greater, while pediatric central nervous system fields range from 4 to 7 cm, and effectively much smaller for IMRT (2-6 cm). Peripheral dose in close proximity (<10 cm from the field edge) is dominated by internal scatter; therefore, field-size differences overwhelm phantom size affects and increased MU. Distant peripheral dose, dominated by head leakage, was higher than predicted, even when accounting for MUs ({approx}factor of 3) likely due to the pediatric phantom size. The ratio of the testes dose ranged from 3.3-5.3 for IMRT/conventional. PD to OAR for pediatric IMRT cannot be predicted from large-field full phantom studies. For regional OAR, doses are likely lower than predicted by existing ''large field'' data, while the distant PD is higher.
Fractional channel multichannel analyzer
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.
Fractional channel multichannel analyzer
Brackenbush, L.W.; Anderson, G.A.
1994-08-23
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 asynchronous 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. 9 figs.
Solvent Fractionation of Lignin
Chatterjee, Sabornie; Saito, Tomonori
2014-01-01
Lignin is a highly abundant source of renewable carbon that can be considered as a valuable sustainable source of biobased materials. The major issues for the commercial production of value added high performance lignin products are lignin s physical and chemical heterogenities. To overcome these problems, a variety of procedures have been developed to produce pure lignin suitable for high performace applications such as lignin-derived carbon materials. However, most of the isolation procedures affect lignin s properties and structure. In this chapter, a short review of the effect of solvent fractionation on lignin s properties and structure is presented.
Body Fractions: A Physical Approach to Fraction Learning
ERIC Educational Resources Information Center
Mills, Judith
2011-01-01
Many students experience great difficulty understanding the meaning of fractions. For many students who have spent their early mathematics lessons focusing on counting (whole) numbers, recognising that there are many numbers between those whole numbers called fractional numbers, is quite revolutionary. The foundation of understanding fractions is…
Ejection Fraction Heart Failure Measurement
... Thromboembolism Aortic Aneurysm More Ejection Fraction Heart Failure Measurement Updated:Feb 15,2017 The ejection fraction (EF) is an important measurement in determining how well your heart is pumping ...
Fractional Hopfield Neural Networks: Fractional Dynamic Associative Recurrent Neural Networks.
Pu, Yi-Fei; Yi, Zhang; Zhou, Ji-Liu
2016-07-14
This paper mainly discusses a novel conceptual framework: fractional Hopfield neural networks (FHNN). As is commonly known, fractional calculus has been incorporated into artificial neural networks, mainly because of its long-term memory and nonlocality. Some researchers have made interesting attempts at fractional neural networks and gained competitive advantages over integer-order neural networks. Therefore, it is naturally makes one ponder how to generalize the first-order Hopfield neural networks to the fractional-order ones, and how to implement FHNN by means of fractional calculus. We propose to introduce a novel mathematical method: fractional calculus to implement FHNN. First, we implement fractor in the form of an analog circuit. Second, we implement FHNN by utilizing fractor and the fractional steepest descent approach, construct its Lyapunov function, and further analyze its attractors. Third, we perform experiments to analyze the stability and convergence of FHNN, and further discuss its applications to the defense against chip cloning attacks for anticounterfeiting. The main contribution of our work is to propose FHNN in the form of an analog circuit by utilizing a fractor and the fractional steepest descent approach, construct its Lyapunov function, prove its Lyapunov stability, analyze its attractors, and apply FHNN to the defense against chip cloning attacks for anticounterfeiting. A significant advantage of FHNN is that its attractors essentially relate to the neuron's fractional order. FHNN possesses the fractional-order-stability and fractional-order-sensitivity characteristics.
How Weird Are Weird Fractions?
ERIC Educational Resources Information Center
Stuffelbeam, Ryan
2013-01-01
A positive rational is a weird fraction if its value is unchanged by an illegitimate, digit-based reduction. In this article, we prove that each weird fraction is uniquely weird and initiate a discussion of the prevalence of weird fractions.
The random continued fraction transformation
NASA Astrophysics Data System (ADS)
Kalle, Charlene; Kempton, Tom; Verbitskiy, Evgeny
2017-03-01
We introduce a random dynamical system related to continued fraction expansions. It uses random combinations of the Gauss map and the Rényi (or backwards) continued fraction map. We explore the continued fraction expansions that this system produces, as well as the dynamical properties of the system.
Fractional diffusion on bounded domains
Defterli, Ozlem; D'Elia, Marta; Du, Qiang; ...
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.
Numerical approaches to fractional calculus and fractional ordinary differential equation
NASA Astrophysics Data System (ADS)
Li, Changpin; Chen, An; Ye, Junjie
2011-05-01
Nowadays, fractional calculus are used to model various different phenomena in nature, but due to the non-local property of the fractional derivative, it still remains a lot of improvements in the present numerical approaches. In this paper, some new numerical approaches based on piecewise interpolation for fractional calculus, and some new improved approaches based on the Simpson method for the fractional differential equations are proposed. We use higher order piecewise interpolation polynomial to approximate the fractional integral and fractional derivatives, and use the Simpson method to design a higher order algorithm for the fractional differential equations. Error analyses and stability analyses are also given, and the numerical results show that these constructed numerical approaches are efficient.
Tolerance doses for treatment planning
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.
Effect of Fractionation in Stereotactic Body Radiation Therapy Using the Linear Quadratic Model
Yang, Jun; Lamond, John; Fowler, Jack; Lanciano, Rachelle; Feng, Jing; Brady, Luther
2013-05-01
Purpose: To examine the fractionation effect of stereotactic body radiation therapy with a heterogeneous dose distribution. Methods: Derived from the linear quadratic formula with measurements from a hypothetical 2-cm radiosurgical tumor, the threshold percentage was defined as (α/β{sub tissue}/α/β{sub tumor}), the balance α/β ratio was defined as (prescription dose/tissue tolerance*α/β{sub tumor}), and the balance dose was defined as (tissue tolerance/threshold percentage). Results: With increasing fractions and equivalent peripheral dose to the target, the biological equivalent dose of “hot spots” in a target decreases. The relative biological equivalent doses of serial organs decrease only when the relative percentage of its dose to the prescription dose is above the threshold percentage. The volume of parallel organs at risk decreases only when the tumor's α/β ratio is above the balance α/β ratio and the prescription dose is lower than balance dose. Conclusions: The potential benefits of fractionation in stereotactic body radiation therapy depend on the complex interplay between the total dose, α/β ratios, and dose differences between the target and the surrounding normal tissues.
NASA Astrophysics Data System (ADS)
Amir, Ornit; Braunstein, David; Altman, Ami
2003-05-01
A dose optimization tool for CT scanners is presented using patient raw data to calculate noise. The tool uses a single patient image which is modified for various lower doses. Dose optimization is carried out without extra measurements by interactively visualizing the dose-induced changes in this image. This tool can be used either off line, on existing image(s) or, as a pre - requisite for dose optimization for the specific patient, during the patient clinical study. The algorithm of low-dose simulation consists of reconstruction of two images from a single measurement and uses those images to create the various lower dose images. This algorithm enables fast simulation of various low dose (mAs) images on a real patient image.
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.
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.
Fractional chemotaxis diffusion equations.
Langlands, T A M; Henry, B I
2010-05-01
We introduce mesoscopic and macroscopic model equations of chemotaxis with anomalous subdiffusion for modeling chemically directed transport of biological organisms in changing chemical environments with diffusion hindered by traps or macromolecular crowding. The mesoscopic models are formulated using continuous time random walk equations and the macroscopic models are formulated with fractional order differential equations. Different models are proposed depending on the timing of the chemotactic forcing. Generalizations of the models to include linear reaction dynamics are also derived. Finally a Monte Carlo method for simulating anomalous subdiffusion with chemotaxis is introduced and simulation results are compared with numerical solutions of the model equations. The model equations developed here could be used to replace Keller-Segel type equations in biological systems with transport hindered by traps, macromolecular crowding or other obstacles.
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.
Variability of Marker-Based Rectal Dose Evaluation in HDR Cervical Brachytherapy
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.
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.
Absorbed fractions for electrons in ellipsoidal volumes.
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.
The radiobiology of prostate cancer including new aspects of fractionated radiotherapy.
Fowler, Jack F
2005-01-01
Total radiation dose is not a reliable measure of biological effect when dose-per-fraction or dose-rate is changed. Large differences in biological effectiveness (per gray) are seen between the 2 Gy doses of external beam radiotherapy and the large boost doses given at high dose-rate from afterloading sources. The effects are profoundly different in rapidly or slowly proliferating tissues, that is for most tumors versus late complications. These differences work the opposite way round for prostate tumors versus late complications compared with most other types of tumor. Using the Linear-Quadratic formula it is aimed to explain these differences, especially for treatments of prostate cancer. The unusually slow growth rate of prostate cancers is associated with their high sensitivity to increased fraction size, so a large number of small fractions, such as 35 or 40 "daily" doses of 2 Gy, is not an optimum treatment. Theoretical modeling shows a stronger enhancement of tumor effect than of late complications for larger (and fewer) fractions, in prostate tumors uniquely. Biologically Effective Doses and Normalized Total Doses (in 2 Gy fraction equivalents) are given for prostate tumor, late rectal reactions, and--a new development--acute rectal mucosa. Tables showing the change of fraction-size sensitivity (the alpha/beta ratio) with proliferation rates of tissues lead to the association of slow cell doubling times in prostate tumors with small alpha/beta ratios. Clinical evidence to confirm this biological expectation is reviewed. The alpha/beta ratios of prostate tumors appear to be as low as 1.5 Gy (95% confidence interval 1.3-1.8 Gy), in contrast with the value of about 10 Gy for most other types of tumor. The important point is that alpha/beta =1.5 Gy appears to be significantly less than the alpha/beta =3 Gy for late complications in rectal tissues. Such differences are also emerging from recent clinical results. From this important difference stems the superior
Fraction Reduction in Membrane Systems
Zhang, Hong
2014-01-01
Fraction reduction is a basic computation for rational numbers. P system is a new computing model, while the current methods for fraction reductions are not available in these systems. In this paper, we propose a method of fraction reduction and discuss how to carry it out in cell-like P systems with the membrane structure and the rules with priority designed. During the application of fraction reduction rules, synchronization is guaranteed by arranging some special objects in these rules. Our work contributes to performing the rational computation in P systems since the rational operands can be given in the form of fraction. PMID:24772037
NASA Astrophysics Data System (ADS)
Hanin, Leonid; Zaider, Marco
2014-08-01
We revisit a long-standing problem of optimization of fractionated radiotherapy and solve it in considerable generality under the following three assumptions only: (1) repopulation of clonogenic cancer cells between radiation exposures follows linear birth-and-death Markov process; (2) clonogenic cancer cells do not interact with each other; and (3) the dose response function s(D) is decreasing and logarithmically concave. Optimal schedules of fractionated radiation identified in this work can be described by the following ‘greedy’ principle: give the maximum possible dose as soon as possible. This means that upper bounds on the total dose and the dose per fraction reflecting limitations on the damage to normal tissue, along with a lower bound on the time between successive fractions of radiation, determine the optimal radiation schedules completely. Results of this work lead to a new paradigm of dose delivery which we term optimal biologically-based adaptive boosting (OBBAB). It amounts to (a) subdividing the target into regions that are homogeneous with respect to the maximum total dose and maximum dose per fraction allowed by the anatomy and biological properties of the normal tissue within (or adjacent to) the region in question and (b) treating each region with an individual optimal schedule determined by these constraints. The fact that different regions may be treated to different total dose and dose per fraction mean that the number of fractions may also vary between regions. Numerical evidence suggests that OBBAB produces significantly larger tumor control probability than the corresponding conventional treatments.
Low dose neutron late effects: Cataractogenesis
Worgul, B.V.
1991-04-01
The work is formulated to resolve the uncertainty regarding the relative biological effectiveness. The endpoint which is being utilized is cataractogenesis. The advantages conferred by this system stems primarily from the non-invasive longitudinal analysis which it allows. It also exploits a well defined system and one which has demonstrated sensitivity to the inverse dose rate effect observed with heavy ions. Four week old rats were divided into 8 dose groups which received single or fractionated total doses of .2, 1.0, 5.0 and 25 cGy of monoenergetic 435 keV neutrons. Special restraining jigs were devised to insure that the eye at the midpoint of the lens received the appropriate energy and dose with a relative error of {plus minus} 5%. The fractionated regimen consisted of four exposures, each administered at 3 hour intervals. The reference radiations, 250 kVp X-rays, were administered in the same fashion but in doses ranging from .5 to 6.0 Gy. The animals are examined on a bi-weekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit-lamp Imaging System. The follow-ups will continue throughout the lifespan of the animals. When opacification begins full documentation will involve the Zeiss imaging system and Oxford retroillumination photography. The processing routinely employs the Merriam/Focht scoring system for cross-referencing with previous cataract studies and establish cataractogenecity using a proven scoring method.
Effect-independent measures of tissue responses to fractionated irradiation.
Thames, H D
1984-01-01
Tissue repair factors measure the sparing that can be achieved from dose fractionation in the absence of proliferation. Four repair factors are analysed in these terms: FR, Frec, the ratio of linear-quadratic survival model parameters beta/alpha, and the half-time T1/2 for intracellular repair processes. A desirable feature of any repair factor is that it be independent of the level of injury induced in the tissue (or its single-dose equivalent, D1), since the comparison of tissues on the basis of the factor would not be meaningful, if they were characterized by differing D1S. Theoretically, FR and Frec are increasing functions of D1, and thus depend on level of effect. This is confirmed by analysis of skin reactions after multifractionated radiation. By contrast, beta/alpha is effect-independent as a measure of repair capacity in skin, gut, and bone marrow, tissues for which it is reasonable to assume that survival of identifiable target cells is the primary determinant of the endpoint. For a functional endpoint not clearly connected with the depletion of a specific target-cell population (late fibrotic reactions in the kidney), there was an increase in beta/alpha with increased levels of injury, but this was statistically insignificant. Effect-independence is defined for T1/2 as independence from size of dose per fraction. T1/2 is independent of fraction size in skin, gut, and spinal cord, and is longer (1.5 hours) in the late-reacting tissues (lung and spinal cord) than in those that react acutely (T1/2 less than 1 hour), with skin as the exception (T1/2 approximately 1.3 hours). Therefore, early and late-responding normal tissues may be distinguished in terms of both repair capacity and repair kinetics: repair is slower in late-responding tissues, which are also more sensitive to changes in dose fractionation. If generally true, these results imply that the potential for a therapeutic gain from hyperfractionation to spare late effects differentially would be
Cell-oriented alternatives to dose, quality factor, and dose equivalent for low-level radiation
Sondhaus, C.A.; Bond, V.P.; Feinendegen, L.E. )
1990-07-01
Randomly occurring energy deposition events produced by low levels of ionizing radiation interacting with tissue deliver variable amounts of energy to sensitive target volumes within a small fraction of the tissue cell population. A model is described in which an experimentally derived function relating event size to cell response probability operates mathematically on the microdosimetric event size distribution characterizing a given irradiation and thus determines the total fractional number of responding cells; this fraction measures the effectiveness of the given radiation. Applying this cell response or hit size effectiveness function (HSEF) to different radiations and normalizing to equal numbers of responses produced by each radiation should define its radiation quality, or relative effectiveness, on a more nearly absolute basis than do the absorbed dose and dose equivalent, both of which are confounded when applied to low-level irradiations. Similar cell response probability functions calculated from different experimental data are presented.
Alternatives to dose, quality factor and dose equivalent for low level irradiation
Sondhaus, C.A.; Bond, V.P.; Feinendegen, L.E.
1988-01-01
Randomly occurring energy deposition events produced by low levels of ionizing radiation interacting with tissue deliver variable amounts of energy to the sensitive target volumes within a small fraction of the cell population. A model is described in which an experimentally derived function relating event size to cell response probability operates mathematically on the microdosimetric event size distribution characterizing a given irradiation and thus determines the total fractional number of responding cells; this fraction measures the effectiveness of the given radiation. Normalizing to equal numbers of events produced by different radiations and applying this cell response or hit size effectiveness function (HSEF) should define radiation quality, or relative effectiveness, on a more nearly absolute basis than do the absorbed dose and dose evaluation, which are confounded when applied to low level irradiations. Examples using both calculation and experimental data are presented. 15 refs., 18 figs.
Cell-oriented alternatives to dose, quality factor, and dose equivalent for low-level radiation.
Sondhaus, C A; Bond, V P; Feinendegen, L E
1990-07-01
Randomly occurring energy deposition events produced by low levels of ionizing radiation interacting with tissue deliver variable amounts of energy to sensitive target volumes within a small fraction of the tissue cell population. A model is described in which an experimentally derived function relating event size to cell response probability operates mathematically on the microdosimetric event size distribution characterizing a given irradiation and thus determines the total fractional number of responding cells; this fraction measures the effectiveness of the given radiation. Applying this cell response or hit size effectiveness function (HSEF) to different radiations and normalizing to equal numbers of responses produced by each radiation should define its radiation quality, or relative effectiveness, on a more nearly absolute basis than do the absorbed dose and dose equivalent, both of which are confounded when applied to low-level irradiations. Similar cell response probability functions calculated from different experimental data are presented.
Sudahar, H; Kurup, P G G; Murali, V; Mahadev, P; Velmurugan, J
2012-04-01
As the α/β value of prostate is very small and lower than the surrounding critical organs, hypofractionated radiotherapy became a vital mode of treatment of prostate cancer. Cyberknife (Accuray Inc., Sunnyvale, CA, USA) treatment for localized prostate cancer is performed in hypofractionated dose regimen alone. Effective dose escalation in the hypofractionated regimen can be estimated if the corresponding conventional 2 Gy per fraction equivalent normalized total dose (NTD) distribution is known. The present study aims to analyze the hypofractionated dose distribution of localized prostate cancer in terms of equivalent NTD. Randomly selected 12 localized prostate cases treated in cyberknife with a dose regimen of 36.25 Gy in 5 fractions were considered. The 2 Gy per fraction equivalent NTDs were calculated using the formula derived from the linear quadratic (LQ) model. Dose distributions were analyzed with the corresponding NTDs. The conformity index for the prescribed target dose of 36.25 Gy equivalent to the NTD dose of 90.63 Gy (α/β = 1.5) or 74.31 Gy (α/β = 3) was ranging between 1.15 and 1.73 with a mean value of 1.32 ± 0.15. The D5% of the target was 111.41 ± 8.66 Gy for α/β = 1.5 and 90.15 ± 6.57 Gy for α/β = 3. Similarly, the D95% was 91.98 ± 3.77 Gy for α/β = 1.5 and 75.35 ± 2.88 Gy for α/β = 3. The mean values of bladder and rectal volume receiving the prescribed dose of 36.25 Gy were 0.83 cm3 and 0.086 cm3, respectively. NTD dose analysis shows an escalated dose distribution within the target for low α/β (1.5 Gy) with reasonable sparing of organs at risk. However, the higher α/β of prostate (3 Gy) is not encouraging the fact of dose escalation in cyberknife hypofractionated dose regimen of localized prostate cancer.
Fractionally charged skyrmions in fractional quantum Hall effect.
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.
Fractionally charged skyrmions in fractional quantum Hall effect
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.
The Dose Response Relationship for Radiation Carcinogenesis
NASA Astrophysics Data System (ADS)
Hall, Eric
2008-03-01
Recent surveys show that the collective population radiation dose from medical procedures in the U.S. has increased by 750% in the past two decades. It would be impossible to imagine the practice of medicine today without diagnostic and therapeutic radiology, but nevertheless the widespread and rapidly increasing use of a modality which is a known human carcinogen is a cause for concern. To assess the magnitude of the problem it is necessary to establish the shape of the dose response relationship for radiation carcinogenesis. Information on radiation carcinogenesis comes from the A-bomb survivors, from occupationally exposed individuals and from radiotherapy patients. The A-bomb survivor data indicates a linear relationship between dose and the risk of solid cancers up to a dose of about 2.5 Sv. The lowest dose at which there is a significant excess cancer risk is debatable, but it would appear to be between 40 and 100 mSv. Data from the occupation exposure of nuclear workers shows an excess cancer risk at an average dose of 19.4 mSv. At the other end of the dose scale, data on second cancers in radiotherapy patients indicates that cancer risk does not continue to rise as a linear function of dose, but tends towards a plateau of 40 to 60 Gy, delivered in a fractionated regime. These data can be used to estimate the impact of diagnostic radiology at the low dose end of the dose response relationship, and the impact of new radiotherapy modalities at the high end of the dose response relationship. In the case of diagnostic radiology about 90% of the collective population dose comes from procedures (principally CT scans) which involve doses at which there is credible evidence of an excess cancer incidence. While the risk to the individual is small and justified in a symptomatic patient, the same is not true of some screening procedures is asymptomatic individuals, and in any case the huge number of procedures must add up to a potential public health problem. In the
Constantinescu, Camelia; Hassouna, Ashraf H.; Eltaher, Maha M.; Ghassal, Noor M.; Awad, Nesreen A.
2014-01-01
Purpose To retrospectively compare the potential dosimetric advantages of a multichannel vaginal applicator vs. a single channel one in intracavitary vaginal high-dose-rate (HDR) brachytherapy after hysterectomy, and evaluate the dosimetric advantage of fractional re-planning. Material and methods We randomly selected 12 patients with endometrial carcinoma, who received adjuvant vaginal cuff HDR brachytherapy using a multichannel applicator. For each brachytherapy fraction, two inverse treatment plans (for central channel and multichannel loadings) were performed and compared. The advantage of fractional re-planning was also investigated. Results Dose-volume-histogram (DVH) analysis showed limited, but statistically significant difference (p = 0.007) regarding clinical-target-volume dose coverage between single and multichannel approaches. For the organs-at-risk rectum and bladder, the use of multichannel applicator demonstrated a noticeable dose reduction, when compared to single channel, but statistically significant for rectum only (p = 0.0001). For D2cc of rectum, an average fractional dose of 6.1 ± 0.7 Gy resulted for single channel vs. 5.1 ± 0.6 Gy for multichannel. For D2cc of bladder, an average fractional dose of 5 ± 0.9 Gy occurred for single channel vs. 4.9 ± 0.8 Gy for multichannel. The dosimetric benefit of fractional re-planning was demonstrated: DVH analysis showed large, but not statistically significant differences between first fraction plan and fractional re-planning, due to large inter-fraction variations for rectum and bladder positioning and filling. Conclusions Vaginal HDR brachytherapy using a multichannel vaginal applicator and inverse planning provides dosimetric advantages over single channel cylinder, by reducing the dose to organs at risk without compromising the target volume coverage, but at the expense of an increased vaginal mucosa dose. Due to large inter-fraction dose variations, we recommend individual fraction treatment plan
Yang, Haihua; Tu, Yu; Wang, Wei; Hu, Wei; Ding, Weijun; Yu, Changhui; Zhou, Chao
2013-11-04
The purpose of this study was to compare anatomical and dosimetric variations in first 15 fractions, and between fractions 16 and 25, during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Twenty-three NPC patients who received IMRT in 33 fractions were enrolled. Each patient had two repeat computed tomography (CT) scans before the 16th and 25th fraction. Hybrid IMRT plans were generated to evaluate the dosimetric changes. There was a significant decrease of the transverse diameter of nasopharyngeal and neck as well as gross tumor volume (GTV) in the primary nasopharyngeal carcinoma (GTVnx) and involved lymph nodes (GTVnd) during the first 15 fractions, and between fraction 16 and 25 (p < 0.05). Consequently, there was a significant reduction of the percentage of the volume receiving the prescribed dose (V100) of CTV1 and GTVnd, which was more prominent after the first 15 fractions treatment compared to that between fraction 16 and 25 (p < 0.05). Additionally, there was a significant increase in the mean dose (Dmean) and percentage of volume receiving ≥ 30 Gy (V30) to the bilateral parotid in the first 15 fractions (p < 0.05), but not between fraction 16 and 25. While the maximum dose to the spinal cord was significantly increased both in the first 15 fractions, and between fraction 16 and 25 (p < 0.05), the increase of the percent of spinal cord volume receiving ≥ 40 Gy (V40) was significantly higher in the first 15 fractions compared to that between fraction 16 and 25 (p < 0.05). Based on the dose constraint criterion in the RTOG0225 protocol, a total 39.1% (9/23) of phantom plan 1 (generated by applying the beam configurations of the original IMRT treatment plan to the anatomy of the second CT scan) and 17.4% (4/23) of phantom 2 (generated by applying the beam configurations of the replan 1 to the anatomy of the third CT scan) were out of limit for the dose to the normal critical structures. In conclusion, our data indicated that
Levin-Plotnik, D; Hamilton, R J
2004-02-07
We find the dose distribution that maximizes the tumour control probability (TCP) for a fixed mean tumour dose per fraction. We consider a heterogeneous tumour volume having a radiation response characterized by the linear quadratic model with heterogeneous radiosensitivity and repopulation rate that may vary in time. Using variational calculus methods a general solution is obtained. We demonstrate the spatial dependence of the optimal dose distribution by explicitly evaluating the solution for different functional forms of the tumour properties. For homogeneous radiosensitivity and growth rate, we find that the dose distribution that maximizes TCP is homogeneous when the clonogen cell density is homogeneous, while for a heterogeneous initial tumour density we find that the first dose fraction is inhomogeneous, which homogenizes the clonogen cell density, and subsequent dose fractions are homogeneous. When the tumour properties have explicit spatial dependence, we show that the spatial variation of the optimized dose distribution is insensitive to the functional form. However, the dose distribution and tumour clonogen density are sensitive to the value of the repopulation rate. The optimized dose distribution yields a higher TCP than a typical clinical dose distribution or a homogeneous dose distribution.
Fractional variational calculus in terms of Riesz fractional derivatives
NASA Astrophysics Data System (ADS)
Agrawal, O. P.
2007-06-01
This paper presents extensions of traditional calculus of variations for systems containing Riesz fractional derivatives (RFDs). Specifically, we present generalized Euler-Lagrange equations and the transversality conditions for fractional variational problems (FVPs) defined in terms of RFDs. We consider two problems, a simple FVP and an FVP of Lagrange. Results of the first problem are extended to problems containing multiple fractional derivatives, functions and parameters, and to unspecified boundary conditions. For the second problem, we present Lagrange-type multiplier rules. For both problems, we develop the Euler-Lagrange-type necessary conditions which must be satisfied for the given functional to be extremum. Problems are considered to demonstrate applications of the formulations. Explicitly, we introduce fractional momenta, fractional Hamiltonian, fractional Hamilton equations of motion, fractional field theory and fractional optimal control. The formulations presented and the resulting equations are similar to the formulations for FVPs given in Agrawal (2002 J. Math. Anal. Appl. 272 368, 2006 J. Phys. A: Math. Gen. 39 10375) and to those that appear in the field of classical calculus of variations. These formulations are simple and can be extended to other problems in the field of fractional calculus of variations.
Biological effects and equivalent doses in radiotherapy: A software solution
Voyant, Cyril; Julian, Daniel; Roustit, Rudy; Biffi, Katia; Lantieri, Céline
2013-01-01
Background The limits of TDF (time, dose, and fractionation) and linear quadratic models have been known for a long time. Medical physicists and physicians are required to provide fast and reliable interpretations regarding delivered doses or any future prescriptions relating to treatment changes. Aim We, therefore, propose a calculation interface under the GNU license to be used for equivalent doses, biological doses, and normal tumor complication probability (Lyman model). Materials and methods The methodology used draws from several sources: the linear-quadratic-linear model of Astrahan, the repopulation effects of Dale, and the prediction of multi-fractionated treatments of Thames. Results and conclusions The results are obtained from an algorithm that minimizes an ad-hoc cost function, and then compared to an equivalent dose computed using standard calculators in seven French radiotherapy centers. PMID:24936319
Radiation dose to the lens and cataract formation
Henk, J.M.; Whitelocke, R.A.F.; Warrington, A.P.; Bessell, E.M. )
1993-04-02
The purpose of this work was to determine the radiation tolerance of the lens of the eye and the incidence of radiation-induced lens changes in patients treated by fractionated supervoltage radiation therapy for orbital tumors. Forty patients treated for orbital lymphoma and pseudotumor with tumor doses of 20--40 Gy were studied. The lens was partly shielded using lead cylinders in most cases. The dose to the germinative zone of the lens was estimated by measurements in a tissue equivalent phantom using both film densitometry and thermoluminescent dosimetry. Opthalmological examination was performed at 6 monthly intervals after treatment. The lead shield was found to reduce the dose to the germinative zone of the lens to between 36--50% of the tumor dose for Cobalt beam therapy, and to between 11--18% for 5 MeV x-rays. Consequently, the lens doses were in the range 4.5--30 Gy in 10--20 fractions. Lens opacities first appeared from between 3 and 9 years after irradiation. Impairment of visual acuity ensued in 74% of the patients who developed lens opacities. The incidence of lens changes was strongly dose-related. None was seen after doses of 5 Gy or lower, whereas doses of 16.5 Gy or higher were all followed by lens opacities which impaired visual acuity. The largest number of patients received a maximum lens dose of 15 Gy; in this group the actuarial incidence of lens opacities at 8 years was 57% with visual impairment in 38%. The adult lens can tolerate a total dose of 5 Gy during a fractionated course of supervoltage radiation therapy without showing any changes. Doses of 16.5 Gy or higher will almost invariably lead to visual impairment. The dose which causes a 50% probability of visual impairment is approximately 15 Gy. 10 refs., 4 figs., 1 tab.
Accessible solitons of fractional dimension
Zhong, Wei-Ping; Belić, Milivoj; Zhang, Yiqi
2016-05-15
We demonstrate that accessible solitons described by an extended Schrödinger equation with the Laplacian of fractional dimension can exist in strongly nonlocal nonlinear media. The soliton solutions of the model are constructed by two special functions, the associated Legendre polynomials and the Laguerre polynomials in the fraction-dimensional space. Our results show that these fractional accessible solitons form a soliton family which includes crescent solitons, and asymmetric single-layer and multi-layer necklace solitons. -- Highlights: •Analytic solutions of a fractional Schrödinger equation are obtained. •The solutions are produced by means of self-similar method applied to the fractional Schrödinger equation with parabolic potential. •The fractional accessible solitons form crescent, asymmetric single-layer and multilayer necklace profiles. •The model applies to the propagation of optical pulses in strongly nonlocal nonlinear media.
Paul, Subhadip; Roy, Prasun Kumar
2016-09-01
The efficacy of radiation therapy, a primary modality of cancer treatment, depends in general upon the total radiation dose administered to the tumour during the course of therapy. Nevertheless, the delivered radiation also irradiates normal tissues and dose escalation procedure often increases the elimination of normal tissue as well. In this article, we have developed theoretical frameworks under the premise of linear-quadratic-linear (LQL) model using stochastic differential equation and Jensen's inequality for exploring the possibility of attending to the two therapeutic performance objectives in contraposition-increasing the elimination of prostate tumour cells and enhancing the relative sparing of normal tissue in fractionated radiation therapy, within a prescribed limit of total radiation dose. Our study predicts that stochastic temporal modulation in radiation dose-rate appreciably enhances prostate tumour cell elimination, without needing dose escalation in radiation therapy. However, constant higher dose-rate can also enhance the elimination of tumour cells. In this context, we have shown that the sparing of normal tissue with stochastic dose-rate is considerably more than the sparing of normal tissue with the equivalent constant higher dose-rate. Further, by contrasting the stochastic dose-rate effects under LQL and linear-quadratic (LQ) models, we have also shown that the LQ model over-estimates stochastic dose-rate effect in tumour and under-estimates the stochastic dose-rate effect in normal tissue. Our study indicates the possibility of utilizing stochastic modulation of radiation dose-rate for designing enhanced radiation therapy protocol for cancer.
Trigonometric Integrals via Partial Fractions
ERIC Educational Resources Information Center
Chen, H.; Fulford, M.
2005-01-01
Parametric differentiation is used to derive the partial fractions decompositions of certain rational functions. Those decompositions enable us to integrate some new combinations of trigonometric functions.
Fractional-time quantum dynamics.
Iomin, Alexander
2009-08-01
Application of the fractional calculus to quantum processes is presented. In particular, the quantum dynamics is considered in the framework of the fractional time Schrödinger equation (SE), which differs from the standard SE by the fractional time derivative: partial differential/partial differentialt --> partial differential(alpha)/partial differentialt(alpha). It is shown that for alpha=1/2 the fractional SE is isospectral to a comb model. An analytical expression for the Green's functions of the systems are obtained. The semiclassical limit is discussed.
Beam Attenuators and the Risk of Unrecognized Large-Fraction Irradiation of Critical Tissues
Luka, S.; Marks, J.E.
2015-01-15
The use of radiation beam attenuators led to radiation injury of the spinal cord in one patient and of the peripheral nerve in another due to unsuspected large-fraction irradiation. The anatomic distribution of radiation dose was reconstructed in the sagittal plane for the patient who developed radiation myelopathy and in the axial plane for the patient who developed peripheral neuropathy. The actual dose delivered to the injured structure in each patient was taken from the dose distribution and recorded along with the time, number of fractions, and dose per fraction. The patient who developed radiation myelopathy received a total of 46.5 Gy in twenty-three 2.1 Gy fractions in 31 days to the upper cervical spinal cord where the thickness of the neck was less than the central axis thickness due to cervical lordosis and absence of a posterior compensating filter. The patient who developed peripheral neuropathy received 55 Gy in twenty-five 2.2 Gy fractions in 50 days to the femoral nerve using bolus over the groins and an anterior one-half value layer Cerrobend pelvic block to bias the dose anteriorly. Compensating filters and other beam attenuators should be used with caution because they may result in unsuspected large-fraction irradiation and total doses of radiation that exceed the tolerance of critical structures.
Lee, Larissa J.; Sadow, Cheryl A.; Russell, Anthony; Viswanathan, Akila N.
2009-11-01
Purpose: To compare high dose rate (HDR) point B to pelvic lymph node dose using three-dimensional-planned brachytherapy for cervical cancer. Methods and Materials: Patients with FIGO Stage IB-IIIB cervical cancer received 70 tandem HDR applications using CT-based treatment planning. The obturator, external, and internal iliac lymph nodes (LN) were contoured. Per fraction (PF) and combined fraction (CF) right (R), left (L), and bilateral (Bil) nodal doses were analyzed. Point B dose was compared with LN dose-volume histogram (DVH) parameters by paired t test and Pearson correlation coefficients. Results: Mean PF and CF doses to point B were R 1.40 Gy +- 0.14 (CF: 7 Gy), L 1.43 +- 0.15 (CF: 7.15 Gy), and Bil 1.41 +- 0.15 (CF: 7.05 Gy). The correlation coefficients between point B and the D100, D90, D50, D2cc, D1cc, and D0.1cc LN were all less than 0.7. Only the D2cc to the obturator and the D0.1cc to the external iliac nodes were not significantly different from the point B dose. Significant differences between R and L nodal DVHs were seen, likely related to tandem deviation from irregular tumor anatomy. Conclusions: With HDR brachytherapy for cervical cancer, per fraction nodal dose approximates a dose equivalent to teletherapy. Point B is a poor surrogate for dose to specific nodal groups. Three-dimensional defined nodal contours during brachytherapy provide a more accurate reflection of delivered dose and should be part of comprehensive planning of the total dose to the pelvic nodes, particularly when there is evidence of pathologic involvement.
Ojima, Mitsuaki; Ito, Maki; Suzuki, Keiji; Kai, Michiaki
2015-01-01
We determined the frequencies of dicentric chromosomes per cell in non-dividing confluent normal human fibroblasts (MRC-5) irradiated with a single 1 Gy dose or a fractionated 1 Gy dose (10X0.1 Gy, 5X0.2 Gy, and 2X0.5 Gy). The interval between fractions was between 1 min to 1440 min. After the completion of X-irradiation, the cells were incubated for 24 hours before re-plating at a low density. Then, demecolcine was administrated at 6 hours, and the first mitotic cells were collected for 42 hours. Our study demonstrated that frequencies of dicentric chromosomes in cells irradiated with a 1 Gy dose at different fractions were significantly reduced if the fraction interval was increased from 1 min to 5 min (p<0.05, χ2-test). Further increasing the fraction interval from 5 up to 1440 min did not significantly affect the frequency of dicentric chromosomes. Since misrejoining of two independent chromosome breaks introduced in close proximity gives rise to dicentric chromosome, our results indicated that such circumstances might be quite infrequent in cells exposed to fractionated X-irradiation with prolonged fraction intervals. Our findings should contribute to improve current estimation of cancer risk from chronic low-dose-rate exposure, or intermittent exposure of low-dose radiation by medical exposure. PMID:25723489
Olsher, Richard H.; Hsu, Hsiao-Hua; Casson, William H.; Vasilik, Dennis G.; Kleck, Jeffrey H.; Beverding, Anthony
1996-01-01
A neutron dose equivalent detector for measuring neutron dose capable of accurately responding to neutron energies according to published fluence to dose curves. The neutron dose equivalent meter has an inner sphere of polyethylene, with a middle shell overlying the inner sphere, the middle shell comprising RTV.RTM. silicone (organosiloxane) loaded with boron. An outer shell overlies the middle shell and comprises polyethylene loaded with tungsten. The neutron dose equivalent meter defines a channel through the outer shell, the middle shell, and the inner sphere for accepting a neutron counter tube. The outer shell is loaded with tungsten to provide neutron generation, increasing the neutron dose equivalent meter's response sensitivity above 8 MeV.
DMLC tracking and gating can improve dose coverage for prostate VMAT
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
Fractional random walk lattice dynamics
NASA Astrophysics Data System (ADS)
Michelitsch, T. M.; Collet, B. A.; Riascos, A. P.; Nowakowski, A. F.; Nicolleau, F. C. G. A.
2017-02-01
We analyze time-discrete and time-continuous ‘fractional’ random walks on undirected regular networks with special focus on cubic periodic lattices in n = 1, 2, 3,.. dimensions. The fractional random walk dynamics is governed by a master equation involving fractional powers of Laplacian matrices {{L}\\fracα{2}}} where α =2 recovers the normal walk. First we demonstrate that the interval 0<α ≤slant 2 is admissible for the fractional random walk. We derive analytical expressions for the transition matrix of the fractional random walk and closely related the average return probabilities. We further obtain the fundamental matrix {{Z}(α )} , and the mean relaxation time (Kemeny constant) for the fractional random walk. The representation for the fundamental matrix {{Z}(α )} relates fractional random walks with normal random walks. We show that the matrix elements of the transition matrix of the fractional random walk exihibit for large cubic n-dimensional lattices a power law decay of an n-dimensional infinite space Riesz fractional derivative type indicating emergence of Lévy flights. As a further footprint of Lévy flights in the n-dimensional space, the transition matrix and return probabilities of the fractional random walk are dominated for large times t by slowly relaxing long-wave modes leading to a characteristic {{t}-\\frac{n{α}} -decay. It can be concluded that, due to long range moves of fractional random walk, a small world property is emerging increasing the efficiency to explore the lattice when instead of a normal random walk a fractional random walk is chosen.
Unwrapping Students' Ideas about Fractions
ERIC Educational Resources Information Center
Lewis, Rebecca M.; Gibbons, Lynsey K.; Kazemi, Elham; Lind, Teresa
2015-01-01
Supporting students to develop an understanding of the meaning of fractions is an important goal of elementary school mathematics. This involves developing partitioning strategies, creating representations, naming fractional quantities, and using symbolic notation. This article describes how teachers can use a formative assessment problem to…
Rational Exponentials and Continued Fractions
ERIC Educational Resources Information Center
Denny, J. K.
2012-01-01
Using continued fraction expansions, we can approximate constants, such as pi and e, using an appropriate integer n raised to the power x[superscript 1/x], x a suitable rational. We review continued fractions and give an algorithm for producing these approximations.
Understanding Magnitudes to Understand Fractions
ERIC Educational Resources Information Center
Gabriel, Florence
2016-01-01
Fractions are known to be difficult to learn and difficult to teach, yet they are vital for students to have access to further mathematical concepts. This article uses evidence to support teachers employing teaching methods that focus on the conceptual understanding of the magnitude of fractions.
Validation of the photon dose calculation model in the VARSKIN 4 skin dose computer code.
Sherbini, Sami; Decicco, Joseph; Struckmeyer, Richard; Saba, Mohammad; Bush-Goddard, Stephanie
2012-12-01
An updated version of the skin dose computer code VARSKIN, namely VARSKIN 4, was examined to determine the accuracy of the photon model in calculating dose rates with different combinations of source geometry and radionuclides. The reference data for this validation were obtained by means of Monte Carlo transport calculations using MCNP5. The geometries tested included the zero volume sources point and disc, as well as the volume sources sphere and cylinder. Three geometries were tested using source directly on the skin, source off the skin with an absorber material between source and skin, and source off the skin with only an air gap between source and skin. The results of these calculations showed that the non-volume sources produced dose rates that were in very good agreement with the Monte Carlo calculations, but the volume sources resulted in overestimates of the dose rates compared with the Monte Carlo results by factors that ranged up to about 2.5. The results for the air gap showed poor agreement with Monte Carlo for all source geometries, with the dose rates overestimated in all cases. The conclusion was that, for situations where the beta dose is dominant, these results are of little significance because the photon dose in such cases is generally a very small fraction of the total dose. For situations in which the photon dose is dominant, use of the point or disc geometries should be adequate in most cases except those in which the dose approaches or exceeds an applicable limit. Such situations will often require a more accurate dose assessment and may require the use of methods such as Monte Carlo transport calculations.
Radiating subdispersive fractional optical solitons
NASA Astrophysics Data System (ADS)
Fujioka, J.; Espinosa, A.; Rodríguez, R. F.; Malomed, B. A.
2014-09-01
It was recently found [Fujioka et al., Phys. Lett. A 374, 1126 (2010)] that the propagation of solitary waves can be described by a fractional extension of the nonlinear Schrödinger (NLS) equation which involves a temporal fractional derivative (TFD) of order α > 2. In the present paper, we show that there is also another fractional extension of the NLS equation which contains a TFD with α < 2, and in this case, the new equation describes the propagation of radiating solitons. We show that the emission of the radiation (when α < 2) is explained by resonances at various frequencies between the pulses and the linear modes of the system. It is found that the new fractional NLS equation can be derived from a suitable Lagrangian density, and a fractional Noether's theorem can be applied to it, thus predicting the conservation of the Hamiltonian, momentum and energy.
Radiating subdispersive fractional optical solitons
Fujioka, J. Espinosa, A.; Rodríguez, R. F.; Malomed, B. A.
2014-09-01
It was recently found [Fujioka et al., Phys. Lett. A 374, 1126 (2010)] that the propagation of solitary waves can be described by a fractional extension of the nonlinear Schrödinger (NLS) equation which involves a temporal fractional derivative (TFD) of order α > 2. In the present paper, we show that there is also another fractional extension of the NLS equation which contains a TFD with α < 2, and in this case, the new equation describes the propagation of radiating solitons. We show that the emission of the radiation (when α < 2) is explained by resonances at various frequencies between the pulses and the linear modes of the system. It is found that the new fractional NLS equation can be derived from a suitable Lagrangian density, and a fractional Noether's theorem can be applied to it, thus predicting the conservation of the Hamiltonian, momentum and energy.
A new fractional wavelet transform
NASA Astrophysics Data System (ADS)
Dai, Hongzhe; Zheng, Zhibao; Wang, Wei
2017-03-01
The fractional Fourier transform (FRFT) is a potent tool to analyze the time-varying signal. However, it fails in locating the fractional Fourier domain (FRFD)-frequency contents which is required in some applications. A novel fractional wavelet transform (FRWT) is proposed to solve this problem. It displays the time and FRFD-frequency information jointly in the time-FRFD-frequency plane. The definition, basic properties, inverse transform and reproducing kernel of the proposed FRWT are considered. It has been shown that an FRWT with proper order corresponds to the classical wavelet transform (WT). The multiresolution analysis (MRA) associated with the developed FRWT, together with the construction of the orthogonal fractional wavelets are also presented. Three applications are discussed: the analysis of signal with time-varying frequency content, the FRFD spectrum estimation of signals that involving noise, and the construction of fractional Harr wavelet. Simulations verify the validity of the proposed FRWT.
Fractional active disturbance rejection control.
Li, Dazi; Ding, Pan; Gao, Zhiqiang
2016-05-01
A fractional active disturbance rejection control (FADRC) scheme is proposed to improve the performance of commensurate linear fractional order systems (FOS) and the robust analysis shows that the controller is also applicable to incommensurate linear FOS control. In FADRC, the traditional extended states observer (ESO) is generalized to a fractional order extended states observer (FESO) by using the fractional calculus, and the tracking differentiator plus nonlinear state error feedback are replaced by a fractional proportional-derivative controller. To simplify controller tuning, the linear bandwidth-parameterization method has been adopted. The impacts of the observer bandwidth ωo and controller bandwidth ωc on system performance are then analyzed. Finally, the FADRC stability and frequency-domain characteristics for linear single-input single-output FOS are analyzed. Simulation results by FADRC and ADRC on typical FOS are compared to demonstrate the superiority and effectiveness of the proposed scheme.
Dose prescription in boron neutron capture therapy
Gupta, N.M.S.; Gahbauer, R.A. ); Blue, T.E. ); Wambersie, A. )
1994-03-30
The purpose of this paper is to address some aspects of the many considerations that need to go into a dose prescription in boron neutron capture therapy (BNCT) for brain tumors; and to describe some methods to incorporate knowledge from animal studies and other experiments into the process of dose prescription. Previously, an algorithm to estimate the normal tissue tolerance to mixed high and low linear energy transfer radiations in BNCT was proposed. The authors have developed mathematical formulations and computational methods to represent this algorithm. Generalized models to fit the central axis dose rate components for an epithermal neutron field were also developed. These formulations and beam fitting models were programmed into spreadsheets to simulate two treatment techniques which are expected to be used in BNCT: a two-field bilateral scheme and a single-field treatment scheme. Parameters in these spreadsheets can be varied to represent the fractionation scheme used, the [sup 10]B microdistribution in normal tissue, and the ratio of [sup 10]B in tumor to normal tissue. Most of these factors have to be determined for a given neutron field and [sup 10]B compound combination from large animal studies. The spreadsheets have been programmed to integrate all of the treatment-related information and calculate the location along the central axis where the normal tissue tolerance is exceeded first. This information is then used to compute the maximum treatment time allowable and the maximum tumor dose that may be delivered for a given BNCT treatment. The effect of different treatment variables on the treatment time and tumor dose has been shown to be very significant. It has also been shown that the location of D[sub max] shifts significantly, depending on some of the treatment variables-mainly the fractionation scheme used. These results further emphasize the fact that dose prescription in BNCT is very complicated and nonintuitive. 11 refs., 6 figs., 3 tabs.
Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei
2013-05-15
Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor
Lang, Stefan Kirisits, Christian; Dimopoulos, Johannes; Georg, Dietmar; Poetter, Richard
2007-10-01
Purpose: To develop a method for treatment planning and optimization of magnetic resonance imaging (MRI)-assisted gynecologic brachytherapy that includes biologically weighted total dose constraints. Methods and Materials: The applied algorithm is based on the linear-quadratic model and includes dose, dose rate, and fractionation of the whole radiotherapy setting, consisting of external beam therapy plus high-dose-rate (HDR), low-dose-rate (LDR) or pulsed-dose rate (PDR) brachytherapy. Biologically effective doses (BED) are converted to more familiar isoeffective (equivalent) doses in 2-Gy fractions. For individual treatment planning of each brachytherapy fraction, the algorithm calculates the physical dose per brachytherapy fraction that corresponds to a predefined isoeffective total dose constraint. Achieved target dose and sparing of organs at risk of already delivered brachytherapy fractions are incorporated. Results: Since implementation for use in clinical routine in 2001, MRI assisted treatment plans of 216 gynecologic patients (161 HDR, 55 PDR brachytherapy) were prospectively optimized taking into account isoeffective dose-volume histogram-based total dose constraints for high-risk clinical target volume (HR CTV) and organs at risk (bladder, rectum, sigmoid). The algorithm is implemented in a spreadsheet and the procedure is fast and efficient. An uncertainty analysis of the isoeffective total doses based on variations of tissue parameters shows that confidence intervals are larger for PDR compared with HDR brachytherapy. For common treatment schedules, overall uncertainties of high-risk clinical target volume and organs at risk are within 8 Gy, except for the bladder when using the PDR technique. Conclusion: The presented method to respect total dose constraints is reliable and efficient and an essential tool when aiming to increase local control and minimize side effects.
Chavan, Machindra J; Wakte, Pravin S; Shinde, Devanand B
2012-01-01
The sesquiterpene fraction of Annona reticulata bark was studied by GC/MS. Three major components were identified: copaene (35.40%), patchoulane (13.49%) and 1H-cycloprop(e)azulene (22.77%). The fraction was also screened for its analgesic and anti-inflammatory activities. The sesquiterpene fraction at doses 12.5 and 25 mg kg⁻¹ and the unsaponified petroleum ether extract at a dose of 50 mg kg⁻¹ exhibited significant central as well as peripheral analgesic and anti-inflammatory activities. These activities were comparable with the standard drugs used in the respective experiments.
Radiation Dose-Volume Effects in the Brain
Lawrence, Yaacov Richard; Li, X. Allen; El Naqa, Issam; Hahn, Carol A.; Marks, Lawrence B.; Merchant, Thomas E.; Dicker, Adam P.
2010-03-01
We have reviewed the published data regarding radiotherapy (RT)-induced brain injury. Radiation necrosis appears a median of 1-2 years after RT; however, cognitive decline develops over many years. The incidence and severity is dose and volume dependent and can also be increased by chemotherapy, age, diabetes, and spatial factors. For fractionated RT with a fraction size of <2.5 Gy, an incidence of radiation necrosis of 5% and 10% is predicted to occur at a biologically effective dose of 120 Gy (range, 100-140) and 150 Gy (range, 140-170), respectively. For twice-daily fractionation, a steep increase in toxicity appears to occur when the biologically effective dose is >80 Gy. For large fraction sizes (>=2.5 Gy), the incidence and severity of toxicity is unpredictable. For single fraction radiosurgery, a clear correlation has been demonstrated between the target size and the risk of adverse events. Substantial variation among different centers' reported outcomes have prevented us from making toxicity-risk predictions. Cognitive dysfunction in children is largely seen for whole brain doses of >=18 Gy. No substantial evidence has shown that RT induces irreversible cognitive decline in adults within 4 years of RT.
Fractionally charged skyrmions in fractional quantum Hall effect
Balram, Ajit C.; Wurstbauer, U.; Wójs, A.; ...
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 Zeemanmore » 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.« less
Recalcitrant dissolved organic carbon fractions.
Hansell, Dennis A
2013-01-01
Marine dissolved organic carbon (DOC) exhibits a spectrum of reactivity, from very fast turnover of the most bioavailable forms in the surface ocean to long-lived materials circulating within the ocean abyss. These disparate reactivities group DOC by fractions with distinctive functions in the cycling of carbon, ranging from support of the microbial loop to involvement in the biological pump to a hypothesized major source/sink of atmospheric CO(2) driving paleoclimate variability. Here, the major fractions constituting the global ocean's recalcitrant DOC pool are quantitatively and qualitatively characterized with reference to their roles in carbon biogeochemistry. A nomenclature for the fractions is proposed based on those roles.
Papp, D; Unkelbach, J
2014-06-01
Purpose: Non-uniform fractionation, i.e. delivering distinct dose distributions in two subsequent fractions, can potentially improve outcomes by increasing biological dose to the target without increasing dose to healthy tissues. This is possible if both fractions deliver a similar dose to normal tissues (exploit the fractionation effect) but high single fraction doses to subvolumes of the target (hypofractionation). Optimization of such treatment plans can be formulated using biological equivalent dose (BED), but leads to intractable nonconvex optimization problems. We introduce a novel optimization approach to address this challenge. Methods: We first optimize a reference IMPT plan using standard techniques that delivers a homogeneous target dose in both fractions. The method then divides the pencil beams into two sets, which are assigned to either fraction one or fraction two. The total intensity of each pencil beam, and therefore the physical dose, remains unchanged compared to the reference plan. The objectives are to maximize the mean BED in the target and to minimize the mean BED in normal tissues, which is a quadratic function of the pencil beam weights. The optimal reassignment of pencil beams to one of the two fractions is formulated as a binary quadratic optimization problem. A near-optimal solution to this problem can be obtained by convex relaxation and randomized rounding. Results: The method is demonstrated for a large arteriovenous malformation (AVM) case treated in two fractions. The algorithm yields a treatment plan, which delivers a high dose to parts of the AVM in one of the fractions, but similar doses in both fractions to the normal brain tissue adjacent to the AVM. Using the approach, the mean BED in the target was increased by approximately 10% compared to what would have been possible with a uniform reference plan for the same normal tissue mean BED.
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.
Fractionation of radioactivity in the milk of goats administered UC-aflatoxin B1
Goto, T.; Hsieh, D.P.
1985-05-01
A detailed fractionation of radioactivity in the milk of goats administered UC-aflatoxin B1 at low doses was performed. The milk collected in the first 24 h following dosing contained radioactivity equivalent to 0.45-1.1% of the dose given. The radioactivity in each sample was partitioned into 4 fractions: ether, protein, dichloromethane, and water-alcohol. Over 80% of the radioactivity was detected in the dichloromethane fraction, of which over 95% was attributable to aflatoxin M1. No aflatoxin B1 or other known aflatoxin metabolites were detected in any fraction. The results indicate that the major metabolite of aflatoxin B1 in goat milk is aflatoxin M1 and that other metabolites, including conjugates, are of minor significance.
Fractionated Stereotactic Radiotherapy for Facial Nerve Schwannomas
Shi, Wenyin; Jain, Varsha; Kim, Hyun; Champ, Colin; Jain, Gaurav; Farrell, Christopher; Andrews, David W.; Judy, Kevin; Liu, Haisong; Artz, Gregory; Werner-Wasik, Maria; Evans, James J.
2015-01-01
Purpose Data on the clinical course of irradiated facial nerve schwannomas (FNS) are lacking. We evaluated fractionated stereotactic radiotherapy (FSRT) for FNS. Methods Eight consecutive patients with FNS treated at our institution between 1998 and 2011 were included. Patients were treated with FSRT to a median dose of 50.4 Gy (range: 46.8–54 Gy) in 1.8 or 2.0 Gy fractions. We report the radiographic response, symptom control, and toxicity associated with FSRT for FNS. Results The median follow-up time was 43 months (range: 10–75 months). All patients presented with symptoms including pain, tinnitus, facial asymmetry, diplopia, and hearing loss. The median tumor volume was 1.57 cc. On the most recent follow-up imaging, five patients were noted to have stable tumor size; three patients had a net reduction in tumor volume. Additionally, six patients had improvement in clinical symptoms, one patient had stable clinical findings, and one patient had worsened House-Brackmann grade due to cystic degeneration. Conclusion FSRT treatment of FNS results in excellent control of growth and symptoms with a small rate of radiation toxicity. Given the importance of maintaining facial nerve function, FSRT could be considered as a primary management modality for enlarging or symptomatic FNS. PMID:26949592
Mandegary, Ali; Pournamdari, Mostafa; Sharififar, Fariba; Pournourmohammadi, Shirin; Fardiar, Reza; Shooli, Sedigheh
2012-07-01
The seeds of fenugreek (Trigonella foenum-graecum L.) have medicinal uses as hypoglycemic, antinociceptive and anti-inflammatory agents. We aimed to evaluate the antinociceptive and anti-inflammatory effects of the major fractions of fenugreek seeds. The methanolic extract of the plant seeds was partitioned using a liquid-liquid extraction procedure to give six major fractions. Following phytochemical screening of isolated fractions, the total extract and each fraction were evaluated for their antinociception and anti-inflammatory effects using formalin and carrageenan-induced paw edema tests respectively. The methanolic extract exhibited both antinociceptive and anti-inflammatory effects at a dose of 100mg/kg. Among the tested fractions, alkaline chloroform fraction (AKC), which was alkaloid positive in screening tests, showed the most anti-nociceptive effect in a dose-dependent manner. AKC fraction was as effective as morphine (5mg/kg) in this regard. Both aqueous and acidified chloroform fractions (ACC) could significantly inhibit paw edema at a different dose. The latter fraction dose-dependently inhibited carrageenan-induced paw edema. The results of phytochemical screening tests confirmed the presence of flavonoids in both ACC and aqueous fractions. It can be concluded that the alkaloid and flavonoid content of fenugreek seeds can be responsible for antinociception and anti-inflammatory effects of the plant respectively.
Haney, J
2015-02-01
The mouse dose at the lowest water concentration used in the National Toxicology Program hexavalent chromium (CrVI) drinking water study (NTP, 2008) is about 74,500 times higher than the approximate human dose corresponding to the 35-city geometric mean reported in EWG (2010) and over 1000 times higher than that based on the highest reported tap water concentration. With experimental and environmental doses differing greatly, it is a regulatory challenge to extrapolate high-dose results to environmental doses orders of magnitude lower in a meaningful and toxicologically predictive manner. This seems particularly true for the low-dose extrapolation of results for oral CrVI-induced carcinogenesis since dose-dependent differences in the dose fraction absorbed by mouse target tissues are apparent (Kirman et al., 2012). These data can be used for a straightforward adjustment of the USEPA (2010) draft oral slope factor (SFo) to be more predictive of risk at environmentally-relevant doses. More specifically, the evaluation of observed and modeled differences in the fraction of dose absorbed by target tissues at the point-of-departure for the draft SFo calculation versus lower doses suggests that the draft SFo be divided by a dose-specific adjustment factor of at least an order of magnitude to be less over-predictive of risk at more environmentally-relevant doses.
Australia's Next Top Fraction Model
ERIC Educational Resources Information Center
Gould, Peter
2013-01-01
Peter Gould suggests Australia's next top fraction model should be a linear model rather than an area model. He provides a convincing argument and gives examples of ways to introduce a linear model in primary classrooms.
Sampath, C; Holbik, M; Krenn, L; Butterweck, V
2011-06-01
The purpose of this study was to characterize the putative anxiolytic-like activity of fractions prepared from a hydroethanol extract of Passiflora incarnata L. using the elevated plus-maze (EPM) in mice. The fractions were prepared as published recently, yielding a butanol, petroleum ether and chloroform fraction. From the tested fractions, the butanol fraction showed significant increases in the number of open arm entries in the EPM in concentrations of 2.1 mg/kg and 4.2 mg/kg corresponding to 150 and 300 mg/kg of the original extract. The highest activity was found for the chloroform fraction in doses of 0.17 mg/kg (10.0 ± 1.9, p < 0.001) and 0.34 mg/kg (6.6 ± 0.86; p < 0.05) which corresponds to a total extract dose of 150 and 300 mg/kg, respectively. Interestingly, the petroleum ether fraction did not show any effects in the elevated plus maze. A sedative or stimulatory effect of each of the fractions could be excluded, since none of the compounds had an influence on the total distance that the animals covered during the observation period. The results suggest that the active principle of passion flower seems to be in the chloroform fraction and to a lower extent in the butanol fraction.
Mavroidis, P; Lind, B K; Brahme, A
2001-10-01
Developments in radiation therapy planning have improved the information about the three-dimensional dose distribution in the patient. Isodose graphs, dose volume histograms and most recently radiobiological models can be used to evaluate the dose distribution delivered to the irradiated organs and volumes of interest. The concept of a biologically effective uniform dose (D) assumes that any two dose distributions are equivalent if they cause the same probability for tumour control or normal tissue complication. In the present paper the D concept both for tumours and normal tissues is presented, making use of the fact that probabilities averaged over both dose distribution and organ radiosensitivity are more relevant to the clinical outcome than the expected number of surviving clonogens or functional subunits. D can be calculated in complex target volumes or organs at risk either from the 3D dose matrix or from the corresponding dose volume histograms of the dose plan. The value of the D concept is demonstrated by applying it to two treatment plans of a cervix cancer. Comparison is made of the D concept with the effective dose (Deff ) and equivalent uniform dose (EUD) that have been suggested in the past. The value of the concept for complex targets and fractionation schedules is also pointed out.
Xenon fractionation in porous planetesimals
NASA Technical Reports Server (NTRS)
Zahnle, Kevin; Pollack, James B.; Kasting, James F.
1990-01-01
The distinctively fractionated Xe on Mars and earth may have its root in a common source from which both planets accreted. Beginning with Ozima and Nakazawa's (1980) hypothesis that terrestrial Xe fractionation was caused by gravitational separation of adsorbed solar nebular gases inside large porous planetesimals, it is pointed out that Xe would have been trapped as the planetesimal grew and pores were squeezed shut by lithostatic pressure. It is shown that enough fractionated Xe to supply the earth could have been trapped this way. The degree of fractionation is controlled by the lithostatic pressure at the pore-closing front and so would have been roughly the same for all large planetesimals. The predicted degree of fractionation agrees well with that preserved in terrestrial and Martian Xe. Relative to Xe, this source is strongly depleted in other noble gases. In contrast to the original Ozima and Nakazawa hypothesis, the present hypothesis predicts the observed fractionation, and it allows planetary accretion to occur after the dissipation of the solar nebula.
Xenon fractionation in porous planetesimals.
Zahnle, K; Pollack, J B; Kasting, J F
1990-01-01
The distinctively fractionated Xe on Mars and Earth may have its root in a common source from which both planets accreted. We begin with Ozima and Nakazawa's hypothesis that terrestrial Xe fractionation was caused by gravitational separation of adsorbed solar nebular gases inside large porous planetesimals. We point out that Xe would have been trapped as the planetesimal grew and pores were squeezed shut by lithostatic pressure. We show that enough fractionated Xe to supply the Earth could have been trapped this way. The degree of fractionation is controlled by the lithostatic pressure at the pore-closing front and so would have been roughly the same for all large planetesimals. The predicted degree of fractionation agrees well with that preserved in terrestrial and martian Xe. Relative to Xe, this source is strongly depleted in other noble gases. In contrast to the original Ozima and Nakazawa hypothesis, our hypothesis predicts the observed fractionation, and it allows planetary accretion to occur after the dissipation of the solar nebula. The required planetesimals are large, representing a class of object now extinct in the solar system.
How to avoid unbounded drug accumulation with fractional pharmacokinetics.
Hennion, Maud; Hanert, Emmanuel
2013-12-01
A number of studies have shown that certain drugs follow an anomalous kinetics that can hardly be represented by classical models. Instead, fractional-order pharmacokinetics models have proved to be better suited to represent the time course of these drugs in the body. Unlike classical models, fractional models can represent memory effects and a power-law terminal phase. They give rise to a more complex kinetics that better reflects the complexity of the human body. By doing so, they also spotlight potential issues that were ignored by classical models. Among those issues is the accumulation of drug that carries on indefinitely when the infusion rate is constant and the elimination flux is fractional. Such an unbounded accumulation could have important clinical implications and thus requires a solution to reach a steady state. We have considered a fractional one-compartment model with a continuous intravenous infusion and studied how the infusion rate influences the total amount of drug in the compartment. By taking an infusion rate that decays like a power law, we have been able to stabilize the amount of drug in the compartment. In the case of multiple dosing administration, we propose recurrence relations for the doses and the dosing times that also prevent drug accumulation. By introducing a numerical discretization of the model equations, we have been able to consider a more realistic two-compartment model with both continuous infusion and multiple dosing administration. That numerical model has been applied to amiodarone, a drug known to have an anomalous kinetics. Numerical results suggest that unbounded drug accumulation can again be prevented by using a drug input function that decays as a power law.
Anti-fertility effects of different fractions of Anethum graveolens L. extracts on female rats.
Malihezaman, Monsefi; Mojaba, Masoudi; Elham, Hosseini; Farnaz, Gramifar; Ramin, Miri
2012-01-01
Our previous studies showed the effects of aqueous and ethanol extracts of Anethum graveolens L. (dill) on female infertility. In the present study we investigated whether different fractions of this herb extract can cause infertility in rats. Female rats were divided into the control groups, the groups receiving either a low (0.5 g/kg)) or a high dose (5g/kg) of water, N-butanol, chloroform and ether fractions of the aqueous plant extract, and the groups receiving either a low (0.045 g/kg) or a high dose (0.45 g/kg) of the same fractions of ethanol extract. The mentioned doses were gavaged in 1mL for 10 days. Vaginal smears were prepared daily. Estradiol and progesterone levels were measured. The left oviduct and ovary were removed, their tissue subsequently being prepared in form of histology slides and stained using haematoxylin-eosin and Masson's trichrome. Female rats assigned to each group were mated with males; after that, crown-rump lengths and weights of newborn rats were measured. Results showed that each fraction produced some changes such as hormonal level reduction (chloroform fraction), diestrus phase prolongation and infertility (water fraction), and increase in pregnancy duration (chloroform and ether fractions). We concluded that each fraction comprises only some of the mentioned components and therefore recommended the usage of crude extract, especially the aqueous one, in case infertility aims to be induced.
Electron beam dose calculations.
Hogstrom, K R; Mills, M D; Almond, P R
1981-05-01
Electron beam dose distributions in the presence of inhomogeneous tissue are calculated by an algorithm that sums the dose distribution of individual pencil beams. The off-axis dependence of the pencil beam dose distribution is described by the Fermi-Eyges theory of thick-target multiple Coulomb scattering. Measured square-field depth-dose data serve as input for the calculations. Air gap corrections are incorporated and use data from'in-air' measurements in the penumbra of the beam. The effective depth, used to evaluate depth-dose, and the sigma of the off-axis Gaussian spread against depth are calculated by recursion relations from a CT data matrix for the material underlying individual pencil beams. The correlation of CT number with relative linear stopping power and relative linear scattering power for various tissues is shown. The results of calculations are verified by comparison with measurements in a 17 MeV electron beam from the Therac 20 linear accelerator. Calculated isodose lines agree nominally to within 2 mm of measurements in a water phantom. Similar agreement is observed in cork slabs simulating lung. Calculations beneath a bone substitute illustrate a weakness in the calculation. Finally a case of carcinoma in the maxillary antrum is studied. The theory suggests an alternative method for the calculation of depth-dose of rectangular fields.
Fractional characteristic times and dissipated energy in fractional linear viscoelasticity
NASA Astrophysics Data System (ADS)
Colinas-Armijo, Natalia; Di Paola, Mario; Pinnola, Francesco P.
2016-08-01
In fractional viscoelasticity the stress-strain relation is a differential equation with non-integer operators (derivative or integral). Such constitutive law is able to describe the mechanical behavior of several materials, but when fractional operators appear, the elastic and the viscous contribution are inseparable and the characteristic times (relaxation and retardation time) cannot be defined. This paper aims to provide an approach to separate the elastic and the viscous phase in the fractional stress-strain relation with the aid of an equivalent classical model (Kelvin-Voigt or Maxwell). For such equivalent model the parameters are selected by an optimization procedure. Once the parameters of the equivalent model are defined, characteristic times of fractional viscoelasticity are readily defined as ratio between viscosity and stiffness. In the numerical applications, three kinds of different excitations are considered, that is, harmonic, periodic, and pseudo-stochastic. It is shown that, for any periodic excitation, the equivalent models have some important features: (i) the dissipated energy per cycle at steady-state coincides with the Staverman-Schwarzl formulation of the fractional model, (ii) the elastic and the viscous coefficients of the equivalent model are strictly related to the storage and the loss modulus, respectively.
Patel, Firuza D.; Patil, Vijay M.; Oinam, Arun S.; Sharma, Suresh C.
2014-01-01
Background. Quantifying the interfraction dose variations in the organs at risk (OAR) in HDR intracavitary brachytherapy (HDR ICBT). Methods. Rectum and bladder were contoured in 44 patients of cervical carcinoma on CT after each fraction of HDR ICBT (9 Gy/2 fractions). Interfraction dose variations (VARact) were calculated. Rigid image registration of consecutive fraction images allowed quantification of the hypothetical variation in dose (VARhypo) arising exclusively due to changes in applicator placement and geometry. VARhypo was regressed against the VARact to find out to what extent the applicator variation could explain the VARact in the OAR. The rest of the variation was assumed to be due to organ deformation. Results. The VARact in the dose to 2 cc of bladder and rectum were 1.46 and 1.16 Gy, respectively. Increased dose was seen in 16 and 23 patients in the subsequent fraction for bladder and rectum, respectively. Doses to OAR would have exceeded constraints in 16% patients if second fraction was not imaged. VARhypo explained 19% and 47% of the VARact observed for the bladder and rectum respectively. Conclusions. Significant interfraction variations in OAR doses can occur in HDR ICBT. Organ deformations are mostly responsible for this variation. PMID:24693451
Radiotherapy of advanced laryngeal cancer using three small fractions daily
Bradley, P.J.; Morgan, D.A. )
1991-06-01
Since 1983, the authors have treated advanced (UICC stages 3 and 4) squamous carcinomas of the larynx by primary radiotherapy, using three small fractions a day, 3-4 h interfraction interval, 5 days per week. The early patients received doses per fraction of 1.5 Gy, and a total dose of approximately 70 Gy, given as a split-course over 6 to 7 weeks. While overall tumor control and laryngeal preservation was good, a number of severe late radiation reactions were seen. The schedule was then modified, with a reduction in the fraction size to 1.1 Gy, the total dose to 60 Gy, and the overall time to 4 weeks, with omission of the mid-treatment split. Since 1986, we have treated 26 patients in this way. Acute reactions are brisk, but rapidly healing. Loco-regional control was achieved in 22 patients, only one of whom has relapsed to date, in a solitary node, salvaged by radical neck dissection. Four have died of uncontrolled loco-regional malignancy, and three of intercurrent disease while in clinical remission. No serious late morbidity has been observed in surviving patients, and vocal quality is good in the majority. These results suggest that this hyperfractionated and accelerated radiotherapy schedule may offer an acceptable nonsurgical, voice-preserving treatment for advanced laryngeal carcinoma; it can be used in a normally working radiotherapy department.
Fractionated Stereotactic Radiotherapy of Vestibular Schwannomas Accelerates Hearing Loss
Rasmussen, Rune; Claesson, Magnus; Stangerup, Sven-Eric; Roed, Henrik; Christensen, Ib Jarle; Caye-Thomasen, Per; Juhler, Marianne
2012-08-01
Objective: To evaluate long-term tumor control and hearing preservation rates in patients with vestibular schwannoma treated with fractionated stereotactic radiotherapy (FSRT), comparing hearing preservation rates to an untreated control group. The relationship between radiation dose to the cochlea and hearing preservation was also investigated. Methods and Materials: Forty-two patients receiving FSRT between 1997 and 2008 with a minimum follow-up of 2 years were included. All patients received 54 Gy in 27-30 fractions during 5.5-6.0 weeks. Clinical and audiometry data were collected prospectively. From a 'wait-and-scan' group, 409 patients were selected as control subjects, matched by initial audiometric parameters. Radiation dose to the cochlea was measured using the original treatment plan and then related to changes in acoustic parameters. Results: Actuarial 2-, 4-, and 10-year tumor control rates were 100%, 91.5%, and 85.0%, respectively. Twenty-one patients had serviceable hearing before FSRT, 8 of whom (38%) retained serviceable hearing at 2 years after FSRT. No patients retained serviceable hearing after 10 years. At 2 years, hearing preservation rates in the control group were 1.8 times higher compared with the group receiving FSRT (P=.007). Radiation dose to the cochlea was significantly correlated to deterioration of the speech reception threshold (P=.03) but not to discrimination loss. Conclusion: FSRT accelerates the naturally occurring hearing loss in patients with vestibular schwannoma. Our findings, using fractionation of radiotherapy, parallel results using single-dose radiation. The radiation dose to the cochlea is correlated to hearing loss measured as the speech reception threshold.
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
Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma
Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.; La Quaglia, Michael P.; Happersett, Laura; Wolden, Suzanne L.
2012-11-01
Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.
Adaptive Dose Painting by Numbers for Head-and-Neck Cancer
Duprez, Frederic; De Neve, Wilfried; De Gersem, Werner; Coghe, Marc; Madani, Indira
2011-07-15
Purpose: To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. Methods and Materials: Each patient's treatment used three separate treatment plans: fractions 1-10 used a DPBN ([{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography [{sup 18}F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment {sup 18}F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a {sup 18}F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gy to the high-dose clinical target volume (CTV{sub highdose}) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. Results: All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second {sup 18}F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV{sub highdose} (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV{sub highdose} and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. Conclusion: To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.
Lung tumor induction in mice: neutron RBE at low doses. [0-50 rad range
Ullrich, R.L.
1982-01-01
Experimental studies have demonstrated that neutrons are more tumorigenic on a dose for dose basis than are gamma rays. However, recent studies examining dose-response relationships and dose rate or fractionation effects have served to emphasize inadequacies in our understanding of neutron carcinogenesis. These studies have demonstrated that the dose-response curves bend over at relatively low doses. This results in a dose response curve which has a convex upward form over the 20 to 240 rad dose range. Further, it has been demonstrated that the life shortening and tumorigenic response after fractionated or protracted neutron exposure is increased in this 20 to 240 rad dose range. Since the dose response is bending over in this dose range it is of importance to obtain information at lower doses. Experiments are being conducted on tumor induction with neutrons emphasizing the effects of neutrons in the 0 to 50 rad dose range on the induction of lung adenocarcinomas and mammary adenocarcinomas in BALB/c mice. Current data on the induction of lung adenocarcinomas after neutron or gamma ray irradiation and their implications for estimates of risk for neutron exposures at low doses are described. (ERB)
Delayed coker fractionator advanced control
Jaisinghani, R.; Minter, B. ); Tica, A.; Puglesi, A.; Ojeda, R. )
1993-08-01
In a delayed coking process, as coke drum switches are made, rapid changes occur in both the fractionator feed rate and composition. With conventional control, it is not unusual to see long transient behavior of large swings in both quality and flowrates of coker gas oils. This can extract a heavy economic toll, not only in coker operation, but in the operation of downstream units as the upset is propagated. An advanced process control application (APC) was recently implemented on the coker fractionator at the Yacimentos Petroliferos Fiscales (YPF), Lujan de Cuyo Refinery, in Mendoza, Argentina. This coker fractionator control design was unique as it handled two different operating objectives: control of product qualities via tower temperature profile during normal operation and control of gas oil product flow ratio during drum switch. This combination of control objectives in one multivariable predictive control program was achieved by including special logic to decouple the individual tuning requirements. Also, additional logic was included to unambiguously detect and identify drum switch and drum steam out as discrete events within 30 seconds of their actual occurrence. These discrete events were then used as disturbance variables to minimize fractionator transient behavior. As a performance measure, the overhead temperature was controlled within 2 C to 2.5 C of its target, gas oil flows were stabilized during drum switches and steam generation via pump around was maximized. Overall, implementing advanced control for the delayed coker fractionator resulted in substantial benefits from product quality control, product flow control and minimized energy consumption.
Benefits of online in vivo dosimetry for single-fraction total body irradiation
Eaton, David J.; Warry, Alison J.; Trimble, Rachel E.; Vilarino-Varela, Maria J.; Collis, Christopher H.
2014-01-01
Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.
Benefits of online in vivo dosimetry for single-fraction total body irradiation.
Eaton, David J; Warry, Alison J; Trimble, Rachel E; Vilarino-Varela, Maria J; Collis, Christopher H
2014-01-01
Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.
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.
Dominoes as Fractions: Misconceptions and Understandings.
ERIC Educational Resources Information Center
Ward, Robin A.
1999-01-01
Presents an activity in which students must arrange five fractions represented by dominoes in ascending order and justify their reasons for the ordering. Representing common fractions with dominoes helps identify students' misconceptions about fractions. (ASK)
REFractions: The Representing Equivalent Fractions Game
ERIC Educational Resources Information Center
Tucker, Stephen I.
2014-01-01
Stephen Tucker presents a fractions game that addresses a range of fraction concepts including equivalence and computation. The REFractions game also improves students' fluency with representing, comparing and adding fractions.
Antihepatoma activity of Artocarpus communis is higher in fractions with high artocarpin content.
Tzeng, Cheng-Wei; Yen, Feng-Lin; Lin, Liang-Tzung; Lee, Chiang-Wen; Yen, Ming-Hong; Tzeng, Wen-Sheng; Lin, Chun-Ching
2014-01-01
Extracts from natural plants have been used in traditional medicine for many centuries worldwide. Artocarpus communis is one such plant that has been used to treat liver cirrhosis, hypertension, and diabetes. To our knowledge, this study is the first to investigate the antihepatoma activity of A. communis toward HepG2 and PLC/PRF/5 cells and the first to explore the relationship between antihepatoma activity and the active compound artocarpin content in different fractions of A. communis. A. communis methanol extract and fractions induced dose-dependent reduction of tumor cell viability. DNA laddering analysis revealed that A. communis extract and fractions did not induce apoptosis in HepG2 and PLC/PRF/5 cells. Instead, acridine orange staining revealed that A. communis triggered autophagic cell death in a dose-dependent manner. The antihepatoma activity of A. communis is attributable to artocarpin. The fractions with the highest artocarpin content were also the fractions with the highest antihepatoma activity in the following order: dichloromethane fraction > methanol extract > ethyl acetate fraction > n-butanol fraction > n-hexane fraction. Taken together, A. communis showed antihepatoma activity through autophagic cell death. The effect was related to artocarpin content. Artocarpin could be considered an indicator of the anticancer potential of A. communis extract.
On the shape of neutron dose-effect curves for radiogenic cancers and life shortening in mice.
Storer, J B; Fry, R J
1995-03-01
Male and female hybrid BCF1 (C57BL/6 Bd x BALB/c Bd) were exposed to total neutron doses of 0.06, 0.12, 0.24, and 0.48 Gy in fractions over a period of 24 weeks. The fractionation regimens were: 24 weekly fractions of 0.0025 Gy, 12 fractions of 0.01 Gy every 2 weeks, 6 fractions of 0.04 Gy every 4 weeks, and 3 fractions of 0.16 Gy every 8 weeks. In order to detect any change in susceptibility with age over the period of exposures from 16 weeks to 40 weeks of age, mice were exposed to single doses of 0.025, 0.05, 0.10, and 0.2 Gy at 16 and 40 weeks of age. These experiments were designed to test whether the initial parts of the dose-response relationships for life shortening and cancer induction could be determined economically by using fractionated exposures and whether or not the initial slopes were linear. The conclusions were that for life shortening and most radiogenic cancers, the dose-effect curves are linear and that fractionation of the neutron dose has no effect on the magnitude of the response of equal total doses over the range of doses studied. The ratio of such initial slopes and comparable linear initial slopes for a reference radiation should provide maximum and constant relative biological effectiveness values.
On Fractional Model Reference Adaptive Control
Shi, Bao; Dong, Chao
2014-01-01
This paper extends the conventional Model Reference Adaptive Control systems to fractional ones based on the theory of fractional calculus. A control law and an incommensurate fractional adaptation law are designed for the fractional plant and the fractional reference model. The stability and tracking convergence are analyzed using the frequency distributed fractional integrator model and Lyapunov theory. Moreover, numerical simulations of both linear and nonlinear systems are performed to exhibit the viability and effectiveness of the proposed methodology. PMID:24574897
WAGGONER, L.O.
2000-05-16
As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program.
Tracking the dose distribution in radiation therapy by accounting for variable anatomy.
Schaly, B; Kempe, J A; Bauman, G S; Battista, J J; Van Dyk, J
2004-03-07
The goal of this research is to calculate the daily and cumulative dose distribution received by the radiotherapy patient while accounting for variable anatomy, by tracking the dose distribution delivered to tissue elements (voxels) that move within the patient. Non-linear image registration techniques (i.e., thin-plate splines) are used along with a conventional treatment planning system to combine the dose distributions computed for each 3D computed tomography (CT) study taken during treatment. For a clinical prostate case, we demonstrate that there are significant localized dose differences due to systematic voxel motion in a single fraction as well as in 15 cumulative fractions. The largest positive dose differences in rectum, bladder and seminal vesicles were 29%, 2% and 24%, respectively, after the first fraction of radiation treatment compared to the planned dose. After 15 cumulative fractions, the largest positive dose differences in rectum, bladder and seminal vesicles were 23%, 32% and 18%, respectively, compared to the planned dose. A sensitivity analysis of control point placement is also presented. This method provides an important understanding of actual delivered doses and has the potential to provide quantitative information to use as a guide for adaptive radiation treatments.
Fractional Schrödinger equation.
Laskin, Nick
2002-11-01
Some properties of the fractional Schrödinger equation are studied. We prove the Hermiticity of the fractional Hamilton operator and establish the parity conservation law for fractional quantum mechanics. As physical applications of the fractional Schrödinger equation we find the energy spectra of a hydrogenlike atom (fractional "Bohr atom") and of a fractional oscillator in the semiclassical approximation. An equation for the fractional probability current density is developed and discussed. We also discuss the relationships between the fractional and standard Schrödinger equations.
Simpkins, Ali
1997-06-10
VENTSAR XL is an EXCEL Spreadsheet that can be used to calculate downwind doses as a result of a hypothetical atmospheric release. Both building effects and plume rise may be considered. VENTSAR XL will run using any version of Microsoft EXCEL version 4.0 or later. Macros (the programming language of EXCEL) was used to automate the calculations. The user enters a minimal amount of input and the code calculates the resulting concentrations and doses at various downwind distances as specified by the user.
Single course IMRT plan to deliver 45 Gy to seminal vesicles and 81 Gy to prostate in 45 fractions.
Reddy, Nandanuri M S; Sood, Brij Mohan; Sampath, Seshadri; Mazur, Andrej; Osian, Adrian; Ravi, Akkamma; Poli, Jaganmohan; Nori, Dattatreyudu
2006-10-01
We treat prostate and seminal vesicles (SV) to 45 Gy in 25 fractions (course 1) and boost prostate to 81 Gy in 20 more fractions (course 2) with Intensity Modulated Radiation Therapy (IMRT). This two-course IMRT with 45 fractions delivered a non-uniform dose to SV and required two plans and two QA procedures. We used Linear Quadratic (LQ) model to develop a single course IMRT plan to treat SV to a uniform dose, which has the same biological effective dose (BED) as that of 45 Gy in 25 fractions and prostate to 81 Gy, in 45 fractions. Single course IMRT plans were compared with two-course IMRT plans, retrospectively for 14 patients. With two-course IMRT, prescription to prostate and SV was 45 Gy in 25 fractions and to prostate only was 36 Gy in 20 fractions, at 1.8 Gy/fraction. With 45-fraction single course IMRT plan, prescription to prostate was 81 Gy and to SV was 52 or 56 Gy for a alpha/beta of 1 and 3, respectively. 52 Gy delivered in 45 fractions has the same BED of 72 Gy3 as that of delivering 45 Gy in 25 fractions, and is called Matched Effective Dose (MED). LQ model was used to calculate the BED and MED to SV for alpha/beta values of 1-10. Comparison between two-course and single course IMRT plans was in terms of MUs, dose-max, and dose volume constraints (DVC). DVC were: 95% PTV to be covered by at least 95% of prescription dose; and 70, 50, and 30% of bladder and rectum should not receive more than 40, 60, and 70% of 81 Gy. SV Volumes ranged from 2.9-30 cc. With two-course IMRT plans, mean dose to SV was non-uniform and varied between patients by 48% (54 to 80 Gy). With single-course IMRT plan, mean dose to SV was more uniform and varied between patients by only 9.6% (58.2 to 63.8 Gy), to deliver MED of 56 Gy for alpha/beta - 1. Single course IMRT plan MUs were slightly larger than those for two-course IMRT plans, but within the range seen for two-course plans (549-959 MUs, n=51). Dose max for single-course plans were similar to two-course plans. Doses to
The Radiation Dose-Response of the Human Spinal Cord
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.
Nesvacil, Nicole; Tanderup, Kari; Hellebust, Taran P.; De Leeuw, Astrid; Lang, Stefan; Mohamed, Sandy; Jamema, Swamidas V.; Anderson, Clare; Pötter, Richard; Kirisits, Christian
2013-01-01
Background and purpose To compare the dosimetric impact of organ and target variations relative to the applicator for intracavitary brachytherapy by a multicentre analysis with different application techniques and fractionation schemes. Material and methods DVH data from 363 image/contour sets (120 patients, 6 institutions) were included for 1–6 fractions per patient, with imaging intervals ranging from several hours to ∼20 days. Variations between images acquired within one (intra-application) or between consecutive applicator insertions (inter-application) were evaluated. Dose plans based on a reference MR or CT image series were superimposed onto subsequent image sets and D2cm3 for the bladder, rectum and sigmoid and D90 for HR CTV were recorded. Results For the whole sample, the systematic dosimetric variations for all organs at risk, i.e. mean variations of D2cm3, were found to be minor (<5%), while random variations, i.e. standard deviations were found to be high due to large variations in individual cases. The D2cm3 variations (mean ± 1SD) were 0.6 ± 19.5%, 4.1 ± 21.7% and 1.6 ± 26.8%, for the bladder, rectum and sigmoid. For HR CTV, the variations of D90 were found to be −1.1 ± 13.1% for the whole sample. Grouping of the results by intra- and inter-application variations showed that random uncertainties for bladder and sigmoid were 3–7% larger when re-implanting the applicator for individual fractions. No statistically significant differences between the two groups were detected in dosimetric variations for the HR CTV. Using 20% uncertainty of physical dose for OAR and 10% for HR CTV, the effects on total treatment dose for a 4 fraction HDR schedule at clinically relevant dose levels were found to be 4–8 Gy EQD2 for OAR and 3 Gy EQD2 for HR CTV. Conclusions Substantial variations occur in fractionated cervix cancer BT with higher impact close to clinical threshold levels. The treatment approach has to balance uncertainties for
Tsang, Derek S; Yau, Vivian; Raziee, Hamid; Niglas, Mark; Soliman, Hany; Chow, Edward; Tsao, May
2015-10-01
There is controversy surrounding the optimal radiotherapy dose-fractionation for retreatment of painful bone metastases. Two commonly used regimens are 8 Gy in a single-fraction or 20 Gy in five or eight fractions. Randomized evidence, including the NCIC SC.20 randomized clinical trial, has failed to standardize clinical practice. Practitioners who use single-fraction regimens cite patient convenience, fewer acute adverse effects, and better cost-effectiveness. Practitioners who prefer multiple fractions raise questions about the interpretation of data that justifies single-fraction treatment, and the possibility that single-fraction treatment may provide inferior pain relief. Given this clinical controversy, should single-fraction irradiation be standard in retreatment of uncomplicated bone metastases? In this article, two teams debate both sides of the argument with commentary to summarize the relevant issues. The conclusion from the debate is that the "standard" treatment should be individualized to the patient with shared-decision making between the oncologist, patient and family members. In a cancer patient with poor performance status and short life expectancy, single-fraction repeat radiotherapy may be preferred; in a patient with a prolonged disease course, perhaps multiple fraction retreatments would be preferred. The choice between different fractionation schemes depends on an assessment of individual patient factors, tumour factors and unique patient circumstances.
NASA Technical Reports Server (NTRS)
Sparrow, A. H.; Underbrink, A. G.; Rossi, H. H.
1972-01-01
Dose-response curves for pink somatic mutations in Tradescantia stamen hairs were analyzed after neutron and X-ray irradiation with doses ranging from a fraction of a rad to the region of saturation. The dose-effect relation for neutrons indicates a linear dependence from 0.01 to 8 rads; between 0.25 and 5 rads, a linear dependence is indicated for X-rays also. As a consequence the relative biological effectiveness reaches a constant value (about 50) at low doses. The observations are in good agreement with the predictions of the theory of dual radiation action and support its interpretation of the effects of radiation on higher organisms. The doubling dose of X-rays was found to be nearly 1 rad.
Holloway, Lois Charlotte; Miller, Julie-Anne; Kumar, Shivani; Whelan, Brendan M.; Vinod, Shalini K.
2012-10-01
Treatment planning studies often require the calculation of a large number of dose and radiobiological metrics. To streamline these calculations, a computer program called Comp Plan was developed using MATLAB. Comp Plan calculates common metrics, including equivalent uniform dose, tumor control probability, and normal tissue complication probability from dose-volume histogram data. The dose and radiobiological metrics can be calculated for the original data or for an adjusted fraction size using the linear quadratic model. A homogeneous boost dose can be added to a given structure if desired. The final output is written to an Excel file in a format convenient for further statistical analysis. Comp Plan was verified by independent calculations. A lung treatment planning study comparing 45 plans for 7 structures using up to 6 metrics for each structure was successfully analyzed within approximately 5 minutes with Comp Plan. The code is freely available from the authors on request.
Mammography-oncogenecity at low doses.
Heyes, G J; Mill, A J; Charles, M W
2009-06-01
dose exposure, it is not a low dose rate examination, and protraction of dose should not be confused with fractionation. Although there is potential for a suppressive effect at low doses, recent epidemiological data, and several international radiation risk assessments, continue to promote the linear no-threshold (LNT) model. Finally, recent studies have shown that magnetic resonance imaging (MRI) is more sensitive than mammography in detecting invasive breast cancer in women with a genetic sensitivity. Since an increase in the risk associated with mammographic screening would blur the justification of exposure for this high risk subgroup, the use of other (non-ionising) screening modalities is preferable.
Understanding Partitive Division of Fractions.
ERIC Educational Resources Information Center
Ott, Jack M.; And Others
1991-01-01
Concrete experience should be a first step in the development of new abstract concepts and their symbolization. Presents concrete activities based on Hyde and Nelson's work with egg cartons and Steiner's work with money to develop students' understanding of partitive division when using fractions. (MDH)
Fractions, trees and unfinished business
NASA Astrophysics Data System (ADS)
Shraiman, Boris
In this talk, mourning the loss of a teacher and a dear friend, I would like to share some unfinished thoughts loosely connecting - via Farey fraction trees - Kadanoff's study of universality of quasi-periodic route to chaos with the effort to understand universal features of genealogical trees.
Optimization in fractional aircraft ownership
NASA Astrophysics Data System (ADS)
Septiani, R. D.; Pasaribu, H. M.; Soewono, E.; Fayalita, R. A.
2012-05-01
Fractional Aircraft Ownership is a new concept in flight ownership management system where each individual or corporation may own a fraction of an aircraft. In this system, the owners have privilege to schedule their flight according to their needs. Fractional management companies (FMC) manages all aspects of aircraft operations, including utilization of FMC's aircraft in combination of outsourced aircrafts. This gives the owners the right to enjoy the benefits of private aviations. However, FMC may have complicated business requirements that neither commercial airlines nor charter airlines faces. Here, optimization models are constructed to minimize the number of aircrafts in order to maximize the profit and to minimize the daily operating cost. In this paper, three kinds of demand scenarios are made to represent different flight operations from different types of fractional owners. The problems are formulated as an optimization of profit and a daily operational cost to find the optimum flight assignments satisfying the weekly and daily demand respectively from the owners. Numerical results are obtained by Genetic Algorithm method.
ERIC Educational Resources Information Center
Mokashi, Neelima A.
2009-01-01
This article depicts the rewarding experience of creating mathematical environments for kindergarten and elementary students by focusing on one of the most important and often difficult-to-grasp concepts (fractions) through play methods incorporated into a math fair. The basic concept of a math fair is threefold: (1) to create preplanned,…
Staircase and Fractional Part Functions
ERIC Educational Resources Information Center
Amram, Meirav; Dagan, Miriam; Ioshpe, Michael; Satianov, Pavel
2016-01-01
The staircase and fractional part functions are basic examples of real functions. They can be applied in several parts of mathematics, such as analysis, number theory, formulas for primes, and so on; in computer programming, the floor and ceiling functions are provided by a significant number of programming languages--they have some basic uses in…
Fractional quantum Hall effect revisited
NASA Astrophysics Data System (ADS)
Jacak, J.; Łydżba, P.; Jacak, L.
2015-10-01
The topology-based explanation of the fractional quantum Hall effect (FQHE) is summarized. The cyclotron braid subgroups crucial for this approach are introduced in order to identify the origin of the Laughlin correlations in 2D (two-dimensional) Hall systems. Flux-tubes and vortices for composite fermions in their standard constructions are explained in terms of cyclotron braids. The derivation of the hierarchy of the FQHE is proposed by mapping onto the integer effect within the topology-based approach. The experimental observations of the FQHE supporting the cyclotron braid picture are reviewed with a special attention paid to recent experiments with a suspended graphene. The triggering role of a carrier mobility for organization of the fractional state in Hall configuration is emphasized. The prerequisites for the FQHE are indicated including topological conditions substantially increasing the previously accepted set of physical necessities. The explanation of numerical studies by exact diagonalizations of the fractional Chern insulator states is formulated in terms of the topology condition applied to the Berry field flux quantization. Some new ideas withz regard to the synthetic fractional states in the optical lattices are also formulated.
Pythagorean Approximations and Continued Fractions
ERIC Educational Resources Information Center
Peralta, Javier
2008-01-01
In this article, we will show that the Pythagorean approximations of [the square root of] 2 coincide with those achieved in the 16th century by means of continued fractions. Assuming this fact and the known relation that connects the Fibonacci sequence with the golden section, we shall establish a procedure to obtain sequences of rational numbers…
Isotopic Fractionation in Interstellar Chemistry
NASA Technical Reports Server (NTRS)
Charnley, Steven
2009-01-01
Isotopically fractionated material is found in many solar system objects, including meteorites and comets. It is thought, in some cases, to trace interstellar material that was incorporated into the solar sys tem without undergoing significant processing. In this poster, we sho w the results of several models of the nitrogen, oxygen, and carbon f ractionation in proto-stellar cores.
Pimenta, Lúcia Pinheiro Santos; Garcia, Giani Martins; Gonçalves, Samuel Geraldo do Vale; Dionísio, Bárbara Lana; Braga, Erika Martins; Mosqueira, Vanessa Carla Furtado
2014-01-01
Annona crassiflora and Annonaceae plants are known to be used to treat malaria by traditional healers. In this work, the antimalarial efficacy of different fractions of A. crassiflora, particularly acetogenin, alkaloids and flavonoid-rich fractions, was determined in vivo using Plasmodium berghei-infected mice model and toxicity was accessed by brine shrimp assay. The A. crassiflora fractions were administered at doses of 12.5 mg/kg/day in a 4-day test protocol. The results showed that some fractions from woods were rich in acetogenins, alkaloids and terpenes, and other fractions from leaves were rich in alkaloids and flavonoids. The parasitaemia was significantly (p < 0.05, p < 0.001) reduced (57-75%) with flavonoid and alkaloid-rich leaf fractions, which also increased mean survival time of mice after treatment. Our results confirm the usage of this plant in folk medicine as an antimalarial remedy.
Fractional diffusion: recovering the distributed fractional derivative from overposed data
NASA Astrophysics Data System (ADS)
Rundell, W.; Zhang, Z.
2017-03-01
There has been considerable recent study in ‘subdiffusion’ models that replace the standard parabolic equation model by a one with a fractional derivative in the time variable. There are many ways to look at this newer approach and one such is to realize that the order of the fractional derivative is related to the time scales of the underlying diffusion process. This raises the question of what order α of derivative should be taken and if a single value actually suffices. This has led to models that combine a finite number of these derivatives each with a different fractional exponent {αk} and different weighting value c k to better model a greater possible range of time scales. Ultimately, one wants to look at a situation that combines derivatives in a continuous way—the so-called distributional model with parameter μ ≤ft(α \\right) . However all of this begs the question of how one determines this ‘order’ of differentiation. Recovering a single fractional value has been an active part of the process from the beginning of fractional diffusion modeling and if this is the only unknown then the markers left by the fractional order derivative are relatively straightforward to determine. In the case of a finite combination of derivatives this becomes much more complex due to the more limited analytic tools available for such equations, but recent progress in this direction has been made, (Li et al 2015 Appl. Math. Comput. 257 381–97, Li and Yamamoto 2015 Appl. Anal. 94 570–9). This paper considers the full distributional model where the order is viewed as a function μ ≤ft(α \\right) on the interval (0, 1]. We show existence, uniqueness and regularity for an initial-boundary value problem including an important representation theorem in the case of a single spatial variable. This is then used in the inverse problem of recovering the distributional coefficient μ ≤ft(α \\right) from a time trace of the solution and a uniqueness result is
Bond, V.P.
1991-01-01
Although an enormous amount of progress has been made in the fields of radiation protection and risk assessment, a number of significant problems remain. The one problem which transcends all the rest, and which has been subject to considerable misunderstanding, involves what has come to be known as the 'linear non-threshold hypothesis', or 'linear hypothesis'. Particularly troublesome has been the interpretation that any amount of radiation can cause an increase in the excess incidence of cancer. The linear hypothesis has dominated radiation protection philosophy for more than three decades, with enormous financial, societal and political impacts and has engendered an almost morbid fear of low-level exposure to ionizing radiation in large segments of the population. This document presents a different interpretation of the linear hypothesis. The basis for this view lies in the evolution of dose-response functions, particularly with respect to their use initially in the context of early acute effects, and then for the late effects, carcinogenesis and mutagenesis. 11 refs., 4 figs. (MHB)
A real time dose monitoring and dose reconstruction tool for patient specific VMAT QA and delivery
Tyagi, Neelam; Yang Kai; Gersten, David; Yan Di
2012-12-15
Purpose: To develop a real time dose monitoring and dose reconstruction tool to identify and quantify sources of errors during patient specific volumetric modulated arc therapy (VMAT) delivery and quality assurance. Methods: The authors develop a VMAT delivery monitor tool called linac data monitor that connects to the linac in clinical mode and records, displays, and compares real time machine parameters with the planned parameters. A new measure, called integral error, keeps a running total of leaf overshoot and undershoot errors in each leaf pair, multiplied by leaf width, and the amount of time during which the error exists in monitor unit delivery. Another tool reconstructs Pinnacle{sup 3} Trade-Mark-Sign format delivered plan based on the saved machine logfile and recalculates actual delivered dose in patient anatomy. Delivery characteristics of various standard fractionation and stereotactic body radiation therapy (SBRT) VMAT plans delivered on Elekta Axesse and Synergy linacs were quantified. Results: The MLC and gantry errors for all the treatment sites were 0.00 {+-} 0.59 mm and 0.05 {+-} 0.31 Degree-Sign , indicating a good MLC gain calibration. Standard fractionation plans had a larger gantry error than SBRT plans due to frequent dose rate changes. On average, the MLC errors were negligible but larger errors of up to 6 mm and 2.5 Degree-Sign were seen when dose rate varied frequently. Large gantry errors occurred during the acceleration and deceleration process, and correlated well with MLC errors (r= 0.858, p= 0.0004). PTV mean, minimum, and maximum dose discrepancies were 0.87 {+-} 0.21%, 0.99 {+-} 0.59%, and 1.18 {+-} 0.52%, respectively. The organs at risk (OAR) doses were within 2.5%, except some OARs that showed up to 5.6% discrepancy in maximum dose. Real time displayed normalized total positive integral error (normalized to the total monitor units) correlated linearly with MLC (r= 0.9279, p < 0.001) and gantry errors (r= 0.742, p= 0.005). There
Norpoth, K; Jacob, J; Grimmer, G; Mohtashamipur, E
1985-05-01
Automobile exhaust condensate of a passenger car (gasoline engine) was separated into fractions of 2-3 rings containing -, 4-7 rings containing polycyclic aromatic hydrocarbons (PAHs) and PAH-free fractions. All fractions were tested for mutagenicity by the Ames system. The highest dose-dependent increase in revertant colonies was found for the 4-7 ring PAH-fraction when tested with Salmonella typhimurium TA 98 and TA 100. These results are compatible with data obtained in in-vivo tests by previous investigations. The mutagenicity of these fractions in the absence of the oxygenase was negligible.
Low-Dose Carcinogenicity Studies
One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...
SU-E-T-70: A Radiobiological Model of Reoxygenation and Fractionation Effects
Guerrero, M; Carlson, DJ
2015-06-15
Purpose: To develop a simple reoxygenation model that fulfills the following goals:1-Quantify the reoxygenation effect in biologically effective dose (BED) and compare it to the repopulation effect.2-Model the hypoxic fraction in tumors as a function of the number of fractions.3-Develop a simple analytical expression for a reoxygenation term in BED calculations. Methods: The model considers tumor cells in two compartments: one normoxic population of cells and one hypoxic compartment including cells under a range of reduced oxygen concentrations. The surviving fraction is predicted using the linear-quadratic (LQ) model. A hypoxia reduction factor (HRF) is used to quantify reductions in radiosensitivity parameters α-A and β-A as cellular oxygen concentration decreases. The HRF is defined as the ratio of the dose at a specific level of hypoxia to the dose under fully aerobic conditions to achieve equal cell killing. The model assumes that a fraction of the hypoxic cells ( ) moves from the hypoxic to the aerobic compartment after each daily fraction. As an example, we consider standard fractionation for NSCLC (d=2Gy,n=33) versus a SBRT (n=5, d=10Gy) fractionation and compare the loss in reoxygenation biological effect with the gain in repopulation biological effect. Results: An analytic expression for the surviving fraction after n daily treatments is derived and the reoxygenation term in the biological effect is calculated. Reoxygenation and repopulation effects are the same order of magnitude for potential doubling time Td values of 2 to 5 days. The hypoxic fraction increases or decreases with n depending on the reoxygenation rate Δ. For certain combinations of parameters, the biological effect of reoxygenation goes as -(n-1)*ln(1-Δ) providing a simple expression that can be introduced in BED calculations. Conclusion: A novel radiobiological model was developed that can be used to evaluate the effect of reoxygenation in fractionated radiotherapy.
Improving Children's Knowledge of Fraction Magnitudes
ERIC Educational Resources Information Center
Fazio, Lisa K.; Kennedy, Casey A.; Siegler, Robert S.
2016-01-01
We examined whether playing a computerized fraction game, based on the integrated theory of numerical development and on the Common Core State Standards' suggestions for teaching fractions, would improve children's fraction magnitude understanding. Fourth and fifth-graders were given brief instruction about unit fractions and played "Catch…
12 CFR 5.67 - Fractional shares.
Code of Federal Regulations, 2010 CFR
2010-01-01
... fair price upon the fraction not being issued through its sale, or the purchase of the additional fraction required for a full share, if there is an established and active market in the national bank's stock; (c) Remit the cash equivalent of the fraction not being issued to those to whom fractional...
A fractional Dirac equation and its solution
NASA Astrophysics Data System (ADS)
Muslih, Sami I.; Agrawal, Om P.; Baleanu, Dumitru
2010-02-01
This paper presents a fractional Dirac equation and its solution. The fractional Dirac equation may be obtained using a fractional variational principle and a fractional Klein-Gordon equation; both methods are considered here. We extend the variational formulations for fractional discrete systems to fractional field systems defined in terms of Caputo derivatives. By applying the variational principle to a fractional action S, we obtain the fractional Euler-Lagrange equations of motion. We present a Lagrangian and a Hamiltonian for the fractional Dirac equation of order α. We also use a fractional Klein-Gordon equation to obtain the fractional Dirac equation which is the same as that obtained using the fractional variational principle. Eigensolutions of this equation are presented which follow the same approach as that for the solution of the standard Dirac equation. We also provide expressions for the path integral quantization for the fractional Dirac field which, in the limit α → 1, approaches to the path integral for the regular Dirac field. It is hoped that the fractional Dirac equation and the path integral quantization of the fractional field will allow further development of fractional relativistic quantum mechanics.
Using Number Sense to Compare Fractions
ERIC Educational Resources Information Center
Bray, Wendy S.; Abreu-Sanchez, Laura
2010-01-01
One mathematical focus for third graders is to develop deep understanding of fractions and fraction equivalence, including comparing fractions through use of models and reasoning strategies. Before reading further, consider how you might solve the following problem: Which fraction is greater, 14/24 or 17/36? The initial impulse of many adults is…
Evaluating fractionated space systems - Status
NASA Astrophysics Data System (ADS)
Cornford, S.; Jenkins, S.; Wall, S.; Cole, B.; Bairstow, B.; Rouquette, N.; Dubos, G.; Ryan, T.; Zarifian, P.; Boutwell, J.
DARPA has funded a number of teams to further refine its Fractionated Spacecraft vision. Several teams, including this team led by JPL, have been tasked to develop a tool for the evaluation of the Business case for a fractionated system architecture. This evaluation is to understand under what conditions and constraints the fractionated architecture make more sense (in a cost/benefit sense) than the traditional monolithic paradigm. Our approach to this evaluation is to generate and evaluate a variety of trade space options. These options include various sets of stimuli, various degrees of fractionation and various subsystem element properties. The stimuli include many not normally modeled such as technology obsolescence, funding profile changes and changes in mission objectives during the mission itself. The degrees of fractionation enable various traditional subsystem elements to be distributed across different free flyers which then act in concert as needed. This will enable key technologies to be updated as need dictates and availability allows. We have described our approach in a previous IEEE Aerospace conference paper but will briefly summarize here. Our approach to generate the Business Case evaluation is to explicitly model both the implementation and operation phases for the life cycle of a fractionated constellation. A variety of models are integrated into the Phoenix ModelCenter framework and are used to generate various intermediate data which is aggregated into the Present Strategic Value (PSV). The PSV is essentially the value (including the value of the embedded real options) minus the cost. These PSVs are calculated for a variety of configurations and scenarios including variations of various stimuli or uncertainties (e.g. supply chain delays, launch vehicle failures and orbital debris events). There are various decision options (e.g. delay, accelerate, cancel) which can now be exercised for each stimulus. We can compute the PSV for the various comb
Antinociceptive and anti-inflammatory effects of a Geissospermum vellosii stem bark fraction.
Lima, Josélia A; Costa, Thiago W R; Silva, Leandro L; Miranda, Ana Luísa P; Pinto, Angelo C
2016-03-01
Geissospermum vellosii (Pao pereira) is a Brazilian tree whose stem barks are rich in indole alkaloids that present intense anticholinesterase activity. The present study evaluated the effects of a stem bark fraction (PPAC fraction) and ethanolic extract (EE) of Pao pereira in classic murine models of inflammation and pain. The EE and PPAC fraction, both at a dose of 30 mg/kg, significantly reduced mice abdominal constriction induced by acetic acid by 34.8% and 47.5%, respectively. In the formalin test, EE (30 mg/kg) and PPAC fraction (30 and 60 mg/kg) inhibited only the second phase, by 82.8%, 84.9% and 100%, respectively. Compared with indomethacin, similar doses of EE or PPAC fraction were approximately twice as effective in causing antinociception. PPAC fraction was not effective in the hot plate test but reduced the inflammatory response at the second (50.6%) and third (57.8%) hours of rat paw edema induced by carrageenan. Antihyperalgesic activity was observed within 30 min with a peak at 2 h (60.1%). These results demonstrate that compounds in PPAC fraction have anti-inflammatory and antinociceptive activity by a mechanism apparently unrelated to the opioid system. Regardless of similar responses to indomethacin, the effects of PPAC fraction are mainly attributed to acetylcholine actions.
Fractional variational calculus and the transversality conditions
NASA Astrophysics Data System (ADS)
Agrawal, O. P.
2006-08-01
This paper presents the Euler-Lagrange equations and the transversality conditions for fractional variational problems. The fractional derivatives are defined in the sense of Riemann-Liouville and Caputo. The connection between the transversality conditions and the natural boundary conditions necessary to solve a fractional differential equation is examined. It is demonstrated that fractional boundary conditions may be necessary even when the problem is defined in terms of the Caputo derivative. Furthermore, both fractional derivatives (the Riemann-Liouville and the Caputo) arise in the formulations, even when the fractional variational problem is defined in terms of one fractional derivative only. Examples are presented to demonstrate the applications of the formulations.
Altered fractionation schedules in radiotherapy of head and neck cancer. A review.
Fallai, C; Olmi, P
1992-10-31
The authors review the main contributions of international literature to show the current status in clinical trials on unconventional fractionations of the dose in radiotherapy of head and neck cancers. Several clinical (but only a few randomized) trials have been conducted over the last 15 years using hyperfractionated (HF), accelerated (AF) or mixed (HF-AF) schedules. HF schedules have obtained promising results in terms of local control in comparison with conventional fractionation (CF) of the dose. Improvement in survival was also obtained by the random trials of Pinto and Sanchiz, whereas in EORTC trial no. 22791, the improvement in survival rate was only marginal. A significant increase in local control and, less frequently, in survival has been claimed in several studies using HF-AF. Such data still need to be confirmed by a random study, since EORTC trial 22811 showed superimposable results in comparison with CF. Selection of the most suitable cases for altered fractionation schemes is also being studied in ongoing trials of the EORTC (22851) and RTOG (90-03). As regards acute reactions during and after altered fractionation, they are more severe than after CF. Only pure HF with a dose intensity approximately comparable to CF seems to produce similar acute reactions. Several factors have been found to influence the severity of acute mucosal reactions: interfraction interval, overall treatment time, total dose, and field size. As regards late damage, genuine HF schemes seem to cause roughly equivalent late damage in comparison to CF, whereas high-dose intensity schedules have a higher rate of complications. Interfraction interval, overall treatment time, total dose, fraction size and field size can influence the risk of late sequelae. Before altered fractionations can be considered standard therapy, more data are needed, which should be provided by multicentric randomized trials, some of which are already in progress.
Verification of Gamma Knife extend system based fractionated treatment planning using EBT2 film
Natanasabapathi, Gopishankar; Bisht, Raj Kishor
2013-12-15
Purpose: This paper presents EBT2 film verification of fractionated treatment planning with the Gamma Knife (GK) extend system, a relocatable frame system for multiple-fraction or serial multiple-session radiosurgery.Methods: A human head shaped phantom simulated the verification process for fractionated Gamma Knife treatment. Phantom preparation for Extend Frame based treatment planning involved creating a dental impression, fitting the phantom to the frame system, and acquiring a stereotactic computed tomography (CT) scan. A CT scan (Siemens, Emotion 6) of the phantom was obtained with following parameters: Tube voltage—110 kV, tube current—280 mA, pixel size—0.5 × 0.5 and 1 mm slice thickness. A treatment plan with two 8 mm collimator shots and three sectors blocking in each shot was made. Dose prescription of 4 Gy at 100% was delivered for the first fraction out of the two fractions planned. Gafchromic EBT2 film (ISP Wayne, NJ) was used as 2D verification dosimeter in this process. Films were cut and placed inside the film insert of the phantom for treatment dose delivery. Meanwhile a set of films from the same batch were exposed from 0 to 12 Gy doses for calibration purposes. An EPSON (Expression 10000 XL) scanner was used for scanning the exposed films in transparency mode. Scanned films were analyzed with inhouse written MATLAB codes.Results: Gamma index analysis of film measurement in comparison with TPS calculated dose resulted in high pass rates >90% for tolerance criteria of 1%/1 mm. The isodose overlay and linear dose profiles of film measured and computed dose distribution on sagittal and coronal plane were in close agreement.Conclusions: Through this study, the authors propose treatment verification QA method for Extend frame based fractionated Gamma Knife radiosurgery using EBT2 film.
Reporting small bowel dose in cervix cancer high-dose-rate brachytherapy.
Liao, Yixiang; Dandekar, Virag; Chu, James C H; Turian, Julius; Bernard, Damian; Kiel, Krystyna
2016-01-01
Small bowel (SB) is an organ at risk (OAR) that may potentially develop toxicity after radiotherapy for cervix cancer. However, its dose from brachytherapy (BT) is not systematically reported as in other OARs, even with image-guided brachytherapy (IGBT). This study aims to introduce consideration of quantified objectives for SB in BT plan optimization and to evaluate the feasibility of sparing SB while maintaining adequate target coverage. In all, 13 patients were included in this retrospective study. All patients were treated with external beam radiotherapy (EBRT) 45Gy in 25 fractions followed by high dose rate (HDR)-BT boost of 28Gy in 4 fractions using tandem/ring applicator. Magnetic resonance imaging (MRI) and computed tomographic (CT) images were obtained to define the gross tumor volume (GTV), high-risk clinical target volume (HR-CTV) and OARs (rectum, bladder, sigmoid colon, and SB). Treatment plans were generated for each patient using GEC-ESTRO recommendations based on the first CT/MRI. Treatment plans were revised to reduce SB dose when the [Formula: see text] dose to SB was > 5Gy, while maintaining other OAR constraints. For the 7 patients with 2 sets of CT and MRI studies, the interfraction variation of the most exposed SB was analyzed. Plan revisions were done in 6 of 13 cases owing to high [Formula: see text] of SB. An average reduction of 19% in [Formula: see text] was achieved. Meeting SB and other OAR constraints resulted in less than optimal target coverage in 2 patients (D90 of HR-CTV < 77Gyαβ10). The highest interfraction variation was observed for SB at 16 ± 59%, as opposed to 28 ± 27% for rectum and 21 ± 16% for bladder. Prospective reporting of SB dose could provide data required to establish a potential correlation with radiation-induced late complication for SB.
Effect of frequency of dosing of plant sterols on plasma cholesterol levels and synthesis rate
Technology Transfer Automated Retrieval System (TEKTRAN)
The objective was to compare the effects of plant sterols (PS) consumed as a single dose (single) at breakfast or as three doses consumed with breakfast, lunch and dinner (divided) on plasma lipoprotien levels and cholesterol endogenous fractional synthesis rate (FSR). A randomized, placebo-controll...
Stambaugh, Cassandra; Nelms, Benjamin E.; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir
2013-09-15
Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D{sub 99%}), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from
Complexity and the Fractional Calculus
2013-01-01
Paolo Grigolini,, Mauro Bologna,, Bruce West 611102 c. THIS PAGE The public reporting burden for this collection of information is estimated to...dx.doi.org/10.1155/2013/498789 Research Article Complexity and the Fractional Calculus Pensri Pramukkul,1 Adam Svenkeson,1 Paolo Grigolini,1 Mauro ...8. PERFORMING ORGANIZATION REPORT NUMBER 19a. NAME OF RESPONSIBLE PERSON 19b. TELEPHONE NUMBER Paolo Grigolini Pensri Pramukkul, Adam Svenkeson
FRACTIONAL DYNAMICS AT MULTIPLE TIMES
Meerschaert, Mark M.; Straka, Peter
2013-01-01
A continuous time random walk (CTRW) imposes a random waiting time between random particle jumps. CTRW limit densities solve a fractional Fokker-Planck equation, but since the CTRW limit is not Markovian, this is not sufficient to characterize the process. This paper applies continuum renewal theory to restore the Markov property on an expanded state space, and compute the joint CTRW limit density at multiple times. PMID:23378670
SU-E-J-105: Stromal-Epithelial Responses to Fractionated Radiotherapy
Qayyum, M
2014-06-01
Purpose: The stromal-epithelial-cell interactions that are responsible for directing normal breast-tissue development and maintenance play a central role in the progression of breast cancer. In the present study, we developed three-dimensional (3-D) cell co-cultures used to study cancerous mammary cell responses to fractionated radiotherapy. In particular, we focused on the role of the reactive stroma in determining the therapeutic ratio for postsurgical treatment. Methods: Cancerous human mammary epithelial cells were cultured in a 3-D collagen matrix with human fibroblasts stimulated by various concentrations of transforming growth factor beta 1 (TGF-β1). These culture samples were designed to model the post-lumpectomy mammary stroma in the presence of residual cancer cells. We tracked over time the changes in medium stiffness, fibroblast-cell activation (conversion to cancer activated fibroblasts (CAF)), and proliferation of both cell types under a variety of fractionated radiotherapy protocols. Samples were exposed to 6 MV X-rays from a linear accelerator in daily fraction sizes of 90, 180 and 360 cGy over five days in a manner consistent with irradiation exposure during radiotherapy. Results: We found in fractionation studies with fibroblasts and CAF that higher doses per fraction may be more effective early on in deactivating cancer-harboring cellular environments. Higher-dose fraction schemes inhibit contractility in CAF and prevent differentiation of fibroblasts, thereby metabolically uncoupling tumor cells from their surrounding stroma. Yet, over a longer time period, the higher dose fractions may slow wound healing and increase ECM stiffening that could stimulate proliferation of surviving cancer cells. Conclusion: The findings suggest that dose escalation to the region with residual disease can deactivate the reactive stroma, thus minimizing the cancer promoting features of the cellular environment. Large-fraction irradiation may be used to sterilize
Effect of aqueous fraction of Rosa damascena on ileum contractile response of guinea pigs
Dolati, Karim; Rakhshandeh, Hassan; Shafei, Mohammad Naser
2013-01-01
Objective: The use of drugs with herbal origin is increasing for treatment of gastrointestinal (GI) disorders. Rosa damascena (R. damascena) is a well-known plant suggested to have beneficial effect on GI system. In this study, the effect of aqueous fraction of R. damascena on the contractions of isolated guinea pig ileum was investigated. Materials and Methods: Aqueous fraction of plant was obtained from ethanolic extract after ethyl acetate and n-butanol fractions were discarded. To evaluate effect of this fraction on ileum contraction, guinea pig ileum was removed and mounted on organ bath and its contraction was recorded. Effect of various concentrations (0.66, 0.83, and 1.3 mg/ml) of aqueous fraction on ileum contraction in comparison with Ach in presence and absence of atropine, a muscarinic antagonist of cholinergic, was evaluated. The response of ileum to 1 µg/ml of acetylcholine was considered as 100% response. Results: Our results showed that aqueous fractions of R. damascena dose-dependently increased basal guinea pigs ileum contractions (p<0.05 to p<0.001). Maximal contraction of fraction (1.3 mg/ml) induced 23.4 % of maximal Ach response. The contraction of ileum to aqueous fraction was significant decreased in presence 0.001 µg/ml of atropine. Conclusion: It is concluded that aqueous fraction of R. damascena has mild excitatory effect on ileum contraction and this fraction may be beneficial as a mild laxative agent. PMID:25050281
Antioxidant potential of n-butanol fraction from extract of Jasminum mesnyi Hance leaves.
Borar, Sakshi; Punia, Priyanka; Kalia, A N
2011-01-01
Methanolic extract of Jasminum mesnyi Hance leaves having antidiabetic activity was subjected to fractionation to obtain antioxidant and antihyperglycemic rich fraction. Different concentrations of ethyl acetate and n-butanol fractions were subjected to antioxidant assay by DPPH method, nitric oxide scavenging activity and reducing power assay. The fractions showed dose dependent free radical scavenging property in all the models. IC50 values for ethyl acetate and n-butanol fractions were 153.45 +/- 6.65 and 6.22 +/- 0.25 microg/ml, respectively, as compared to L-ascorbic acid and rutin (as standards; IC50 values 6.54 +/- 0.24 and 5.43 +/- 0.21 microg/ml, respectively) in DPPH model. In nitric oxide scavenging activity, IC50 values were 141.54 +/- 9.95 microg/ml, 35.12 +/- 1.58 microg/ml, 21.06 +/- 0.95 microg/ml and 29.93 +/- 0.32 microg/ml for ethyl acetate, n-butanol fractions, L-ascorbic acid and rutin, respectively. n-Butanol fraction showed a good reducing potential and better free radical scavenging activity as compared to ethyl acetate fraction. Potent antioxidant n-butanol fraction showed better oral glucose tolerance test (antihyperglycemic) at par with metformin (standard drug), n-Butanol fraction contained secoiridoid glycosides which might be responsible for both antioxidant and antihyperglycemic activity.
Electrochemically controlled iron isotope fractionation
NASA Astrophysics Data System (ADS)
Black, Jay R.; Young, Edward D.; Kavner, Abby
2010-02-01
Variations in the stable isotope abundances of transition metals have been observed in the geologic record and trying to understand and reconstruct the physical/environmental conditions that produced these signatures is an area of active research. It is clear that changes in oxidation state lead to large fractionations of the stable isotopes of many transition metals such as iron, suggesting that transition metal stable isotope signatures could be used as a paleo-redox proxy. However, the factors contributing to these observed stable isotope variations are poorly understood. Here we investigate how the kinetics of iron redox electrochemistry generates isotope fractionation. Through a combination of electrodeposition experiments and modeling of electrochemical processes including mass-transport, we show that electron transfer reactions are the cause of a large isotope separation, while mass transport-limited supply of reactant to the electrode attenuates the observed isotopic fractionation. Furthermore, the stable isotope composition of electroplated transition metals can be tuned in the laboratory by controlling parameters such as solution chemistry, reaction overpotential, and solution convection. These methods are potentially useful for generating isotopically-marked metal surfaces for tracking and forensic purposes. In addition, our studies will help interpret stable isotope data in terms of identifying underlying electron transfer processes in laboratory and natural samples.
Fractional statistical potential in graphene
NASA Astrophysics Data System (ADS)
Ardenghi, J. S.
2017-03-01
In this work the fractional statistics is applied to an anyon gas in graphene to obtain the special features that the arbitrary phase interchange of the particle coordinates introduce in the thermodynamic properties. The electron gas is constituted by N anyons in the long wavelength approximation obeying fractional exclusion statistics and the partition function is analyzed in terms of a perturbation expansion up to first order in the dimensionless constant λ / L being L the length of the graphene sheet and λ = βℏvF the thermal wavelength. By considering the correct permutation expansion of the many-anyons wavefunction, taking into account that the phase changes with the number of inversions in each permutation, the statistical fermionic/bosonic potential is obtained and the intermediate statistical behavior is found. It is shown that "extra" fermonic and bosonic particles states appears and this "statistical particle" distribution depends on N. Entropy and specific heat is obtained up to first order in λ / L showing that the results obtained differs from those obtained in different approximation to the fractional exclusion statistics.
Estimation of the Dose and Dose Rate Effectiveness Factor
NASA Technical Reports Server (NTRS)
Chappell, L.; Cucinotta, F. A.
2013-01-01
Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.
Fractionated proton beam irradiation of pituitary adenomas
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.
Dose esclation in radioimmunotherapy based on projected whole body dose
Wahl, R.L.; Kaminski, M.S.; Regan, D.
1994-05-01
A variety of approaches have been utilized in conducting phase I radioimmunotherapy dose-escalation trials. Escalation of dose has been based on graded increases in administered mCi; mCi/kg; or mCi/m2. It is also possible to escalate dose based on tracer-projected marrow, blood or whole body radiation dose. We describe our results in performing a dose-escalation trial in patients with non-Hodgkin lymphoma based on escalating administered whole-body radiation dose. The mCi dose administered was based on a patient-individualized tracer projected whole-body dose. 25 patients were entered on the study. RIT with 131 I anti-B-1 was administered to 19 patients. The administered dose was prescribed based on the projected whole body dose, determined from patient-individualized tracer studies performed prior to RIT. Whole body dose estimates were based on the assumption that the patient was an ellipsoid, with 131 antibody kinetics determined using a whole-body probe device acquiring daily conjugate views of 1 minute duration/view. Dose escalation levels proceeded with 10 cGy increments from 25 cGy whole-body and continues, now at 75 cGy. The correlation among potential methods of dose escalation and toxicity was assessed. Whole body radiation dose by probe was strongly correlated with the blood radiation dose determined from sequential blood sampling during tracer studies (r=.87). Blood radiation dose was very weakly correlated with mCi dose (r=.4) and mCi/kg (r=.45). Whole body radiation dose appeared less well-correlated with injected dose in mCi (r=.6), or mCi/kg (r=.64). Toxicity has been infrequent in these patients, but appears related to increasing whole body dose. Non-invasive determination of whole-body radiation dose by gamma probe represents a non-invasive method of estimating blood radiation dose, and thus of estimating bone marrow radiation dose.
Study of antinociceptive effect of isolated fractions from Petiveria alliacea L. (tipi) in mice.
Gomes, Patrícia Bezerra; Oliveira, Maria Mirele da Silva; Nogueira, Carlos Renato Alves; Noronha, Emmanuelle Coelho; Carneiro, Lyvia Maria Vasconcelos; Bezerra, José Noberto Sousa; Neto, Manoel Andrade; Vasconcelos, Silvania Maria Mendes; Fonteles, Marta Maria França; Viana, Glauce Socorro Barros; de Sousa, Francisca Clea Florenço
2005-01-01
The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of Petiveria alliacea L. were evaluated for antinociceptive effect using the abdominal constriction induced by acetic acid, hot-plate, formalin tests. The open field and rota rod tests were used to evaluate psychomotor function and myorelaxant activity. The fractions were administered intraperitoneally in mice at doses of 100 and 200 mg/kg. Inhibitions of abdominal constrictions were observed with all doses of the fractions, as compared to control. FH and FHAppt, at both doses, reduced the nociception produced by formalin in the 1st (0-5 min) and 2nd (20-25 min) phases, however FHA (100, 200 mg/kg) and FA 200 mg/kg presented significant inhibition on the 1st and 2nd phases, respectively, of this test. A reduction of the locomotor activity was observed in the open field test with all the fractions. These fractions failed to affect the motor coordination in the rota rod test. Results showed that the different fractions of Petiveria alliacea L. have different antinociceptive potentials as demonstrated in the experimental models of nociception in mice, supporting folk medicine use of this plant.
Voxel-Based Dose Reconstruction for Total Body Irradiation With Helical TomoTherapy
Chao Ming; Penagaricano, Jose; Yan Yulong; Moros, Eduardo G.; Corry, Peter; Ratanatharathorn, Vaneerat
2012-04-01
Purpose: We have developed a megavoltage CT (MVCT)-based dose reconstruction strategy for total body irradiation (TBI) with helical TomoTherapy (HT) using a deformable registration model to account for the patient's interfraction changes. The proposed technique serves as an efficient tool for delivered dose verification and, potentially, plan adaptation. Methods and Materials: Four patients with acute myelogenous leukemia treated with TBI using HT were selected for this study. The prescription was 12 Gy, 2 Gy/fraction, twice per day, given at least 6 h apart. The original plan achieved coverage of 80% of the clinical target volume (CTV) by the 12 Gy isodose surface. MVCTs were acquired prior to each treatment. Regions of interest were contoured on each MVCT. The dose for each fraction was calculated based on the MVCT using the HT planned adaptive station. B-spline deformable registration was conducted to establish voxel-to-voxel correspondence between the MVCT and the planning CT. The resultant deformation vector was employed to map the reconstructed dose from each fraction to the same point as the plan dose, and a voxel-to-voxel summed dose from all six fractions was obtained. The reconstructed dose distribution and its dosimetric parameters were compared with those of the original treatment plan. Results: While changes in CTV contours occurred in all patients, the reconstructed dose distribution showed that the dose-volume histogram for CTV coverage was close (<1.5%) to that of the original plan. For sensitive structures, the differences between the reconstructed and the planned doses were less than 3.0%. Conclusion: Voxel-based dose reconstruction strategy that takes into account interfraction anatomical changes using MVCTs is a powerful tool for treatment verification of the delivered doses. This proposed technique can also be applied to adaptive TBI therapy using HT.
Photon dose rates from spent fuel assemblies with relation to self-protection (Rev. 1)
Pond, R.B.; Matos, J.E.
1996-02-01
Photon dose rates as a function of fission product decay times have been calculated for spent fuel assemblies typical of MTR-type research and test reactors. Based upon these dose rates, the length of time that a spent fuel assembly will be self-protecting (dose rate greater than 100 rem/h at 1 m in air) can be estimated knowing the mass of fuel burned, the fraction of fuel burned, and the fuel assembly specific power density.
Stromal-epithelial dynamics in response to fractionated radiotherapy
NASA Astrophysics Data System (ADS)
Qayyum, Muqeem Abdul
Radiotherapy is central to the management of a number of human cancers, either as an adjuvant or primary treatment modality. The principal objective in irradiating tumors is to permanently inhibit their proliferative ability. More than half of all malignancies are primarily treated with radiation, but the heterotypic nature of tumor cells greatly complicates their response to radiotherapy. The need for reliable parameters to predict tumor and normal tissue response to radiation is therefore a prime concern of clinical oncology. Post-operative radiotherapy has commonly been used for early stage breast cancer to treat residual disease. There is continued debate as to what might be the proper dose per fraction as well as the total dose of radiation that needs to be prescribed to prevent disease recurrence. Countries outside the US have adopted increased dose fractionation (i.e., hypofractionation) schemes for early stage breast cancer as a standard of practice; however there is a lack of confidence in these approaches in the United States. The tumor microenvironment plays a significant role in regulating the progression of carcinomas, although the mechanisms are not entirely clear. The primary objective of this work was to characterize, through mechanobiological and radiobiological modeling, a test bed for radiotherapy fractionation techniques assessment. Our goal is to understand how the tumor microenvironment responds to dose fractionation schemes for Breast Conserving Therapy (BCT). Although carcinomas are the major concern for oncology, in this project, the goal is to understand how the stromal microenvironment influences behavior of the cancer cell populations. By classifying 3-D cellular co-cultures as having a reactive or quiescent stroma using the mechanobiology profile (culture stiffness,cellular activation, differentiation, and proliferation) we aim to differentiate the effectiveness of various fractionation schemes. The benefits of understanding heterotypic
NASA Astrophysics Data System (ADS)
Blockhuys, S; Vanhoecke, B; Paelinck, L; Bracke, M; DeWagter, C
2009-03-01
We present different in vitro experimental models which allow us to evaluate the effect of spatially fractionated dose distributions on metabolic activity. We irradiated a monolayer of MCF-7/6 human breast cancer cells with a steep and a smooth 6 MV x-ray dose gradient. In the steep gradient model, we irradiated the cells with three separate small fields. We also developed two smooth gradient models. In the first model, the cells are cultured in a T25 flask and irradiated with a smooth dose gradient over the length of the flask, while in the second one, the cells are cultured in a 96-well plate and also irradiated over the length of the plate. In an attempt to correlate the spatially fractionated dose distributions with metabolic activity, the effect of irradiation was evaluated by means of the MTT assay. This assay is used to determine the metabolic activity by measuring the amount of formazan formed after the conversion of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) by cellular dehydrogenases. The results obtained with our different models suggest a dose-specific effect on metabolic activity, characterized by an increased formazan optical density occurring in the dose range 1.0-4.0 Gy in the steep dose gradient model and in the dose ranges 4.2-6.5 Gy and 2.3-5.1 Gy in the two smooth dose gradient models. The corresponding times for maximal formazan accumulation were 5-7 days in the steep dose gradient model and day 9-13 and day 9-11 in the smooth dose gradient models. Altogether, our results suggest that the MTT assay may be used as a biological dose-response meter to monitor the radiotherapeutic effectiveness.
Bubble-induced Color Doppler Feedback for Histotripsy Tissue Fractionation
Miller, Ryan M.; Zhang, Xi; Maxwell, Adam; Cain, Charles; Xu, Zhen
2016-01-01
Histotripsy therapy produces cavitating bubble clouds to increasingly fractionate and eventually liquefy tissue using high intensity ultrasound pulses. Following cavitation generated by each pulse, coherent motion of the cavitation residual nuclei can be detected using metrics formed from ultrasound color Doppler acquisitions. In this paper, three experiments were performed to investigate the characteristics of this motion as real-time feedback on histotripsy tissue fractionation. In the first experiment, bubble-induced color Doppler (BCD) and particle image velocimetry (PIV) analysis monitored the residual cavitation nuclei in the treatment region in an agarose tissue phantom treated with 2-cycle histotripsy pulses at > 30 MPa using a 500 kHz transducer. Both BCD and PIV results showed brief chaotic motion of the residual nuclei followed by coherent motion first moving away from the transducer and then rebounding back. Velocity measurements from both PIV and BCD agreed well, showing a monotonic increase in rebound time up to a saturation point for increased therapy dose. In a second experiment, a thin layer of red blood cells (RBC) was added to the phantom to allow quantification of the fractionation of the RBC layer to compare with BCD metrics. A strong linear correlation was observed between the fractionation level and the time to BCD peak rebound velocity over histotripsy treatment. Finally, the correlation between BCD feedback and histotripsy tissue fractionation was validated in ex vivo porcine liver evaluated histologically. BCD metrics showed strong linear correlation with fractionation progression, suggesting that BCD provides useful quantitative real-time feedback on histotripsy treatment progression. PMID:26863659
Improving Children's Knowledge of Fraction Magnitudes.
Fazio, Lisa K; Kennedy, Casey A; Siegler, Robert S
2016-01-01
We examined whether playing a computerized fraction game, based on the integrated theory of numerical development and on the Common Core State Standards' suggestions for teaching fractions, would improve children's fraction magnitude understanding. Fourth and fifth-graders were given brief instruction about unit fractions and played Catch the Monster with Fractions, a game in which they estimated fraction locations on a number line and received feedback on the accuracy of their estimates. The intervention lasted less than 15 minutes. In our initial study, children showed large gains from pretest to posttest in their fraction number line estimates, magnitude comparisons, and recall accuracy. In a more rigorous second study, the experimental group showed similarly large improvements, whereas a control group showed no improvement from practicing fraction number line estimates without feedback. The results provide evidence for the effectiveness of interventions emphasizing fraction magnitudes and indicate how psychological theories and research can be used to evaluate specific recommendations of the Common Core State Standards.
On fractional Langevin equation involving two fractional orders
NASA Astrophysics Data System (ADS)
Baghani, Omid
2017-01-01
In numerical analysis, it is frequently needed to examine how far a numerical solution is from the exact one. To investigate this issue quantitatively, we need a tool to measure the difference between them and obviously this task is accomplished by the aid of an appropriate norm on a certain space of functions. For example, Sobolev spaces are indispensable part of theoretical analysis of partial differential equations and boundary integral equations, as well as are necessary for the analysis of some numerical methods for the solving of such equations. But most of articles that appear in this field usually use ‖.‖∞ in the space of C[a, b] which is very restrictive. In this paper, we introduce a new norm that is convenient for the fractional and singular differential equations. Using this norm, the existence and uniqueness of initial value problems for nonlinear Langevin equation with two different fractional orders are studied. In fact, the obtained results could be used for the classical cases. Finally, by two examples we show that we cannot always speak about the existence and uniqueness of solutions just by using the previous methods.
Cryptosporidium Infection Risk: Results of New Dose-Response Modeling.
Messner, Michael J; Berger, Philip
2016-10-01
Cryptosporidium human dose-response data from seven species/isolates are used to investigate six models of varying complexity that estimate infection probability as a function of dose. Previous models attempt to explicitly account for virulence differences among C. parvum isolates, using three or six species/isolates. Four (two new) models assume species/isolate differences are insignificant and three of these (all but exponential) allow for variable human susceptibility. These three human-focused models (fractional Poisson, exponential with immunity and beta-Poisson) are relatively simple yet fit the data significantly better than the more complex isolate-focused models. Among these three, the one-parameter fractional Poisson model is the simplest but assumes that all Cryptosporidium oocysts used in the studies were capable of initiating infection. The exponential with immunity model does not require such an assumption and includes the fractional Poisson as a special case. The fractional Poisson model is an upper bound of the exponential with immunity model and applies when all oocysts are capable of initiating infection. The beta Poisson model does not allow an immune human subpopulation; thus infection probability approaches 100% as dose becomes huge. All three of these models predict significantly (>10x) greater risk at the low doses that consumers might receive if exposed through drinking water or other environmental exposure (e.g., 72% vs. 4% infection probability for a one oocyst dose) than previously predicted. This new insight into Cryptosporidium risk suggests additional inactivation and removal via treatment may be needed to meet any specified risk target, such as a suggested 10(-4) annual risk of Cryptosporidium infection.
Optimization of temporal dose modulation: Comparison of theory and experiment
Bewes, J. M.; Suchowerska, N.; Cartwright, L.; Ebert, M. A.; McKenzie, D. R.
2012-06-15
Purpose: To compare theoretical predictions and experimental measurements of cell survival after exposure to two different temporally modulated radiation dose patterns that deliver the same dose in the same overall time. Methods: The authors derived an analytic expression for the dose protraction factor G in the Lea-Catcheside formalism for cell survival for 'triangle' and 'V' temporal modulation of dose. These temporal dose patterns were used in experimental clonogenic studies of a melanoma cell line (MM576) and a nonsmall-cell lung cancer line (NCI-H460) that have different alpha, beta, and repair parameters. The overall treatment time and total dose were kept constant. Results: The analytic expressions for G for the two temporal modulations are presented as a function of a single variable, the product of the exposure time, and the repair constant, enabling G to be evaluated for any exposure time and for any cell line. G for the triangle delivery pattern is always the larger. For the MM576 cell line, following a large dose of 6 Gy, a larger survival fraction was found for the V delivery pattern. No difference in survival was observed for lower doses or for the NCI-H460 cell line at any dose. These results are predicted by our theory, using published values of alpha, beta, and repair time within the limits of experimental uncertainty. Conclusions: The study provides evidence to confirm that cell lines having large beta values exhibit a response that is sensitive to the pattern of dose delivery when the delivery time is comparable with the repair time. It is recommended that the dose delivery pattern be considered in hypofractionated treatments.
Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas
Neelis, Karen J. Schimmel, Erik C.; Vermeer, Maarten H.; Senff, Nancy J.; Willemze, Rein; Noordijk, Evert M.
2009-05-01
Purpose: To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). Methods and Materials: A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. Results: The complete response rate for CBCL lesions was 72%. Of the 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Conclusion: Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.
Assessment of dose during an SGTR
Adams, J.P.
1993-01-01
The Nuclear Regulatory Commission requires utilities to determine the response of a pressurized water reactor to a steam generator tube rupture (SGTR) as part of the safety analysis for the plant. The SGTR analysis includes assumptions regarding the iodine concentration in the reactor coolant system (RCS) due to iodine spikes, primary flashing and bypass fractions, and iodine partitioning in the secondary coolant system (SCS). Experimental and analytical investigations have recently been completed wherein these assumptions were tested to determine whether and to what degree they were conservative (that is, whether they result in a calculated iodine source term/dose that is at least as large or larger than that expected during an actual event). The current study has the objective to assess the overall effects of the results of these investigations on the calculated iodine dose to the environment during an SGTR. To assist in this study, a computer program, DOSE, was written. This program uses a simple, non-mechanistic model to calculate the iodine source term to the environment during an SGTR as a function of water mass inventories and flow rates and iodine concentrations in the RCS and SCS. The principal conclusion of this study is that the iodine concentration in the RCS is the dominant parameter, due to the dominance of primary flashing on the iodine source term.
A New Proton Dose Algorithm for Radiotherapy
NASA Astrophysics Data System (ADS)
Lee, Chungchi (Chris).
This algorithm recursively propagates the proton distribution in energy, angle and space at one level in an absorbing medium to another, at slightly greater depth, until all the protons are stopped. The angular transition density describing the proton trajectory is based on Moliere's multiple scattering theory and Vavilov's theory of energy loss along the proton's path increment. These multiple scattering and energy loss distributions are sampled using equal probability spacing to optimize computational speed while maintaining calculational accuracy. Nuclear interactions are accounted for by using a simple exponential expression to describe the loss of protons along a given path increment and the fraction of the original energy retained by the proton is deposited locally. Two levels of testing for the algorithm are provided: (1) Absolute dose comparisons with PTRAN Monte Carlo simulations in homogeneous water media. (2) Modeling of a fixed beam line including the scattering system and range modulator and comparisons with measured data in a homogeneous water phantom. The dose accuracy of this algorithm is shown to be within +/-5% throughout the range of a 200-MeV proton when compared to measurements except in the shoulder region of the lateral profile at the Bragg peak where a dose difference as large as 11% can be found. The numerical algorithm has an adequate spatial accuracy of 3 mm. Measured data as input is not required.
Studies on the immunomodulatory activity of flavonoidal fraction of Tephrosia purpurea.
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.
Conformable Fractional Nikiforov—Uvarov Method
NASA Astrophysics Data System (ADS)
Karayer, H.; Demirhan, D.; Büyükkılıç, F.
2016-07-01
We introduce conformable fractional Nikiforov—Uvarov (NU) method by means of conformable fractional derivative which is the most natural definition in non-integer calculus. Since, NU method gives exact eigenstate solutions of Schrödinger equation (SE) for certain potentials in quantum mechanics, this method is carried into the domain of fractional calculus to obtain the solutions of fractional SE. In order to demonstrate the applicability of the conformable fractional NU method, we solve fractional SE for harmonic oscillator potential, Woods—Saxon potential, and Hulthen potential.
TU-AB-303-12: Towards Inter and Intra Fraction Plan Adaptation for the MR-Linac
Kontaxis, C; Bol, G; Lagendijk, J; Raaymakers, B
2015-06-15
Purpose: To develop a new sequencer for IMRT that during treatment can account for anatomy changes provided by online and real-time MRI. This sequencer employs a novel inter and intra fraction scheme that converges to the prescribed dose without a final segment weight optimization (SWO) and enables immediate optimization and delivery of radiation adapted to the deformed anatomy. Methods: The sequencer is initially supplied with a voxel-based dose prescription and during the optimization iteratively generates segments that provide this prescribed dose. Every iteration selects the best segment for the current anatomy state, calculates the dose it will deliver, warps it back to the reference prescription grid and subtracts it from the remaining prescribed dose. This process continues until a certain percentage of dose or a number of segments has been delivered. The anatomy changes that occur during treatment require that convergence is achieved without a final SWO. This is resolved by adding the difference between the prescribed and delivered dose up to this fraction to the prescription of the subsequent fraction. This process is repeated for all fractions of the treatment. Results: Two breast cases were selected to stress test the pipeline by producing artificial inter and intra fraction anatomy deformations using a combination of incrementally applied rigid transformations. The dose convergence of the adaptive scheme over the entire treatment, relative to the prescribed dose, was on average 8.6% higher than the static plans delivered to the respective deformed anatomies and only 1.6% less than the static segment weighted plans on the static anatomy. Conclusion: This new adaptive sequencing strategy enables dose convergence without the need of SWO while adapting the plan to intermediate anatomies, which is a prerequisite for online plan adaptation. We are now testing our pipeline on prostate cases using clinical anatomy deformation data from our department. This work
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.
Ng, J A; Booth, J; Poulsen, P; Kuncic, Z; Keall, P J
2013-01-01
Kilovoltage Intratreatment Monitoring (KIM) is a novel real-time localization modality where the tumor position is continuously measured during Intensity Modulated Radiation Therapy (IMRT) or Intensity Modulated Arc Therapy (IMAT) by a kilovoltage (kV) x-ray imager. Adding kV imaging during therapy adds radiation dose. The additional effective dose is quantified for prostate radiotherapy and compared to dose from other localization modalities. The software PCXMC 2.0 was used to calculate the effective dose delivered to a phantom as a function of imager angle and field size for a Varian On-Board Imager. The average angular effective dose was calculated for a field size of 6 cm × 6 cm. The average angular effective dose was used in calculations for different treatment scenarios. Treatment scenarios considered were treatment type and fractionation. For all treatment scenarios, (i.e. conventionally fractionated and SBRT; IMRT and IMAT), the total KIM dose at 1 Hz ranged from 2–10 mSv. This imaging dose is less than the Navotek radioactive implant dose (64 mSv) and a standard SBRT CBCT pretreatment scan dose (22 mSv) over an entire treatment regime. KIM delivers an acceptably low effective dose for daily use as a real-time image-guidance method for prostate radiotherapy. PMID:23938470
NASA Astrophysics Data System (ADS)
Ng, J. A.; Booth, J.; Poulsen, P.; Kuncic, Z.; Keall, P. J.
2013-09-01
Kilovoltage intratreatment monitoring (KIM) is a novel real-time localization modality where the tumor position is continuously measured during intensity modulated radiation therapy (IMRT) or intensity modulated arc therapy (IMAT) by a kilovoltage (kV) x-ray imager. Adding kV imaging during therapy adds radiation dose. The additional effective dose is quantified for prostate radiotherapy and compared to dose from other localization modalities. The software PCXMC 2.0 was used to calculate the effective dose delivered to a phantom as a function of imager angle and field size for a Varian On-Board Imager. The average angular effective dose was calculated for a field size of 6 cm × 6 cm. The average angular effective dose was used in calculations for different treatment scenarios. Treatment scenarios considered were treatment type and fractionation. For all treatment scenarios, (i.e. conventionally fractionated and stereotactic body radiotherapy (SBRT), IMRT and IMAT), the total KIM dose at 1 Hz ranged from 2-10 mSv. This imaging dose is less than the Navotek radioactive implant dose (64 mSv) and a standard SBRT cone beam computed tomography pretreatment scan dose (22 mSv) over an entire treatment regime. KIM delivers an acceptably low effective dose for daily use as a real-time image-guidance method for prostate radiotherapy.
FRACTIONATING COLUMN PRODUCT COLLECTOR CONTROL
Paxson, G.D. Jr.
1964-03-10
Means for detecting minute fluid products from a chemical separation column and for advancing a collector tube rack in order to automatically separate and collect successive fractionated products are described. A charge is imposed on the forming drops at the column orifice to create an electric field as the drop falls in the vicinity of a sensing plate. The field is detected by an electrometer tube coupled to the plate causing an output signal to actuate rotation of a collector turntable rack, thereby positioning new collectors under the orifice. The invention provides reliable automatic collection independent of drop size, rate of fall, or chemical composition. (AEC)
Trends in whey protein fractionation.
El-Sayed, Mayyada M H; Chase, Howard A
2011-08-01
Whey is a by-product of cheese manufacture that is normally treated as a waste. However, it contains a mixture of proteins with important nutritional and biological attributes. To extract these valuable proteins, whey fractionation has been developed using three main techniques; namely chromatographic (e.g., ion-exchange and hydrophobic adsorption), membrane (e.g., traditional pressure-driven and electro-separation)-, or combined methods. Recently, new promising techniques have been introduced such as aqueous two-phase separation (ATPS) and magnetic fishing. This article reviews the use of these techniques together with an evaluation of their performance regarding the yield and purity of two major proteins in whey.
Balik, M; Rybak, M; Strongosky, M; Blair, H; Obi, B; Vermont, C; Andrews, M
2015-06-15
Purpose: This study investigates whether replanning each fraction for vaginal cuff HDR therapy using a multichannel cylinder (MC) and brachytherapy inverse optimization (BIO) provides dosimetric benefits to organs-at-risk (OAR). The goal was to appropriately cover the target and limit dose to OAR, as well as evaluate dosimetric changes for each fraction, while doing this in a timely and cost effective manner. Methods: From an initial selection of 57 patients that were treated with 3 fractions using a MC and BIO, a subset of n=12 patients was selected based on the criterion that one plan was used for all 3 fractions. A simulation CT was acquired prior to each fraction. CT scans for fractions 2 and 3 were fused to the initial CT. Contours for the bladder and rectum were manually drawn on CTs for all 3 fractions, and the clinical treatment volume (PTVeval) was defined. Cylinders were reconstructed using applicator modeling library, influencing time and cost effectiveness. Planning objectives were at least 95% prescription dose to 95% (D95%) of target volume and limiting high dose to OAR. Dose to 2 cm{sup 3} (D2cc) for each OAR was analyzed using a t-test. Results: This study concentrated on comparing 2cm{sup 3} of highest dose to OAR (D2cc), for each fraction for the plans that were used to treat all 3 fraction. Based on statistical analysis, using the initial plan for fractions 2 and 3 resulted in approximately 6% change to the highest D2cc of the bladder (p=0.03). Conclusion: Performing CT fusion and contours of each OAR on each fraction allows objective plan evaluation and supports decision making on the necessity of replanning based on improved dose sparing for OAR. Future studies will investigate the effects of replanning on maximum dose (D0.1cc) using the same physician-drawn OAR contours to avoid subjectivity.
Hanford Environmental Dose Reconstruction Project
Finch, S.M.; McMakin, A.H.
1992-01-01
The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.
Hanford Environmental Dose Reconstruction Project
Finch, S.M.; McMakin, A.H.
1991-01-01
The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): Source terms; environmental transport environmental monitoring data; demographics, agriculture, food habits; environmental pathways and dose estimates.
Hanford Environmental Dose Reconstruction Project
Finch, S.M.; McMakin, A.H.
1992-02-01
The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demography, food consumption, and agriculture; environmental pathways and dose estimates.
Hanford Environmental Dose Reconstruction Project
Cannon, S.D.; Finch, S.M.
1992-10-01
The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.
Dose-effect relation of interstitial low-dose-rate radiation (Ir192) in an animal tumor model
Ruifrok, A.C.; Levendag, P.C.; Lakeman, R.F.; Deurloo, I.K.; Visser, A.G. )
1990-01-01
One way to deliver high doses of radiation to deep seated tumors without damaging the surrounding tissue is by interstitial techniques. This is commonly applied clinically; however, biological data of tumor response to interstitial low-dose-rate gamma irradiation are scarce. Therefore, we have studied the response of rhabdomyosarcoma R1 tumors implanted in the flanks of female Wag/Rij rats using an interstitial Ir192 afterloading system. A template was developed by which four catheters can be implanted in a square geometry with a fixed spacing. Subsequently four Ir192 wires of 2 cm length each are inserted. For dose prescription the highest isodose enveloping the tumor volume was chosen. Interstitial irradiation was performed using tumor volumes of 1500-2000 mm3. A range of minimum tumor doses of 20 up to 115 Gy were given at a mean dose-rate of 48 cGy/hr. Dose-effect relations were obtained from tumor growth curves and tumor cure data, and compared to data from external irradiation. The dose required for 50% cures with interstitial irradiation (TCD50) appears to be 95 +/- 9 Gy. The TCD50 for low-dose-rate interstitial gamma irradiation is 1.5 times the TCD50 for single dose external X ray irradiation at high dose rates, but is comparable to the TCD50 found after fractionated X ray irradiation at high dose rate. Sham treatment of the tumors had no effect on the time needed to reach twice the treatment volume. The growth rate of tumors regrowing after interstitial radiotherapy is not markedly different from the growth rate of untreated (control) tumors (volume doubting time 5.6 +/- 1 day), in contrast to the decreased growth rate after external X ray irradiation.
NASA Technical Reports Server (NTRS)
Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.
2011-01-01
The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.
Iwai, Hiroyuki; Matsuno, Etsuko ); Sasai, Keisuke; Abe, Mitsuyuki; Shibamoto, Yuta )
1994-06-15
In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions [times] three fractions/48 h or 5 Gy/fractions [times] five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab.
3D measurement of absolute radiation dose in grid therapy
NASA Astrophysics Data System (ADS)
Trapp, J. V.; Warrington, A. P.; Partridge, M.; Philps, A.; Leach, M. O.; Webb, S.
2004-01-01
Spatially fractionated radiotherapy through a grid is a concept which has a long history and was routinely used in orthovoltage radiation therapy in the middle of last century to minimize damage to the skin and subcutaneous tissue. With the advent of megavoltage radiotherapy and its skin sparing effects the use of grids in radiotherapy declined in the 1970s. However there has recently been a revival of the technique for use in palliative treatments with a single fraction of 10 to 20 Gy. In this work the absolute 3D dose distribution in a grid irradiation is measured for photons using a combination of film and gel dosimetry.
Immersed Boundary Fractional Step Method
NASA Astrophysics Data System (ADS)
Taira, Kunihiko
2005-11-01
We present a new formulation of the immersed boundary method for incompressible flow over moving rigid bodies. Like many existing techniques we introduce a set of interpolation points on the surface at which the no-slip boundary condition is satisfied by including a (regularized) force in the momentum equations. By introducing interpolation and regularization operators and grouping pressure and force unknowns together, the discretized Navier-Stokes equations with the immersed boundary method can be formulated with an identical structure to the traditional fractional step method, but with a modified Poisson equation whose unknowns are both the pressure and the boundary force. The method highlights the analogous roles of pressure and boundary forcing as Lagrange multipliers in order to satisfy the divergence free and no-slip constraints, respectively. The overall method is found to be a simple addition to an existing fractional step code and the extended Poisson equation is solved efficiently with the conjugate gradient method. We demonstrate convergence and present results for two-dimensional flows with a variety of moving rigid bodies.
Staircase and fractional part functions
NASA Astrophysics Data System (ADS)
Amram, Meirav; Dagan, Miriam; Ioshpe, Michael; Satianov, Pavel
2016-10-01
The staircase and fractional part functions are basic examples of real functions. They can be applied in several parts of mathematics, such as analysis, number theory, formulas for primes, and so on; in computer programming, the floor and ceiling functions are provided by a significant number of programming languages - they have some basic uses in various programming tasks. In this paper, we view the staircase and fractional part functions as a classical example of non-continuous real functions. We introduce some of their basic properties, present some interesting constructions concerning them, and explore some intriguing interpretations of such functions. Throughout the paper, we use these functions in order to explain basic concepts in a first calculus course, such as domain of definition, discontinuity, and oddness of functions. We also explain in detail how, after researching the properties of such functions, one can draw their graph; this is a crucial part in the process of understanding their nature. In the paper, we present some subjects that the first-year student in the exact sciences may not encounter. We try to clarify those subjects and show that such ideas are important in the understanding of non-continuous functions, as a part of studying analysis in general.
Dean flow fractionation of chromosomes
NASA Astrophysics Data System (ADS)
Hockin, Matt; Sant, Himanshu J.; Capecchi, Mario; Gale, Bruce K.
2016-03-01
Efforts to transfer intact mammalian chromosomes between cells have been attempted for more than 50 years with the consistent result being transfer of sub unit length pieces regardless of method. Inertial microfluidics is a new field that has shown much promise in addressing the fractionation of particles in the 2-20 μm size range (with unknown limits) and separations are based upon particles being carried by curving confined flows (within a spiral shaped, often rectangular flow chamber) and migrating to stable "equilibrium" positions of varying distance from a chamber wall depending on the balance of dean and lift forces. We fabricated spiral channels for inertial microfluidic separations using a standard soft lithography process. The concentration of chromosomes, small contaminant DNA and large cell debris in each outlets were evaluated using microscope (60X) and a flow cytometer. Using Dean Flow Fractionation, we were able to focus 4.5 times more chromosomes in outlet 2 compared to outlet 4 where most of the large debris is found. We recover 16% of the chromosomes in outlet #1- 50% in 2, 23% in 3 and 11% in 4. It should be noted that these estimates of recovery do not capture one piece of information- it actually may be that the chromosomes at each outlet are physically different and work needs to be done to verify this potential.
Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction
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
Ejection Fraction: What Does It Measure?
... does the term "ejection fraction" mean? What does it measure? Answers from Rekha Mankad, M.D. Ejection fraction ... percentage of blood leaving your heart each time it contracts. During each heartbeat pumping cycle, the heart ...
Fractional Topological Insulators in Three Dimensions
Maciejko, Joseph; Zhang Shoucheng; Qi Xiaoliang; Karch, Andreas
2010-12-10
Topological insulators can be generally defined by a topological field theory with an axion angle {theta} of 0 or {pi}. In this work, we introduce the concept of fractional topological insulator defined by a fractional axion angle and show that it can be consistent with time reversal T invariance if ground state degeneracies are present. The fractional axion angle can be measured experimentally by the quantized fractional bulk magnetoelectric polarization P{sub 3}, and a 'halved' fractional quantum Hall effect on the surface with Hall conductance of the form {sigma}{sub H}=(p/q)(e{sup 2}/2h) with p, q odd. In the simplest of these states the electron behaves as a bound state of three fractionally charged 'quarks' coupled to a deconfined non-Abelian SU(3) 'color' gauge field, where the fractional charge of the quarks changes the quantization condition of P{sub 3} and allows fractional values consistent with T invariance.
Calcium and titanium isotopic fractionations during evaporation
NASA Astrophysics Data System (ADS)
Zhang, Junjun; Huang, Shichun; Davis, Andrew M.; Dauphas, Nicolas; Hashimoto, Akihiko; Jacobsen, Stein B.
2014-09-01
Isotope fractionations associated with high temperature evaporation provide important constraints on the physicochemical processes that affected planetary materials at the birth of the solar system. Previous evaporation experiments have focused on isotopic fractionation of moderately to highly volatile elements. Here, we investigate the isotope fractionation behavior of two highly refractory elements, calcium and titanium, during evaporation of perovskite (CaTiO3) in a vacuum furnace. In our experiments, isotope fractionation during evaporation follows the Rayleigh law, but not the commonly used exponential law, with the dominant evaporating species being Ca(g) and TiO2(g). If isotope fractionations in early solar system materials did follow the Rayleigh law, the common practice of using an exponential fractionation law to correct for mass-dependent fractionation in the study of mass-independent fractionations may introduce significant artificial isotope anomalies.
Huang Engyen; Wang Chongjong; Lan Jenhong; Chen Huichun; Fang Fumin; Hsu, H.-C.; Huang Yujie; Wang Changyu; Wang Yuming
2010-02-01
Purpose: To evaluate the predictive factors for rectal dose of the first fraction of high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. Methods and Materials: From March 1993 through February 2008, 946 patients undergoing pelvic irradiation and HDR-ICBT were analyzed. Examination under anesthesia (EUA) at the first implantation of the applicator was usually performed in the early period. Rectal point was determined radiographically according to the 38th Report of the International Commission of Radiation Units and Measurements (ICRU). The ICRU rectal dose (PRD) as a percentage of point A dose was calculated; multiple linear regression models were used to predict PRD. Results: Factors influencing successful rectal dose calculation were EUA (p < 0.001) and absence of diabetes (p = 0.047). Age (p < 0.001), body weight (p = 0.002), diabetes (p = 0.020), and EUA (p < 0.001) were independent factors for the PRD. The predictive equation derived from the regression model was PRD (%) = 57.002 + 0.443 x age (years) - 0.257 x body weight (kg) + 6.028 x diabetes (no: 0; yes: 1) - 8.325 x EUA (no: 0; yes: 1) Conclusion: Rectal dose at the first fraction of HDR-ICBT is positively influenced by age and diabetes, and negatively correlated with EUA and body weight. A small fraction size at point A may be considered in patients with a potentially high rectal dose to reduce the biologically effective dose if the ICRU rectal dose has not been immediately obtained in the first fraction of HDR-ICBT.
Fractionation of Organosolv Lignin Using Acetone:Water and Properties of the Obtained Fractions
Sadeghifar, Hasan; Wells, Tyrone; Le, Rosemary Khuu; Sadeghifar, Fatemeh; Yuan, Joshua S.; Jonas Ragauskas, Arthur
2016-11-07
In this study, lignin fractions with different molecular weight were prepared using a simple and almost green method from switchgrass and pine organosolv lignin. Different proportions of acetone in water, ranging from 30 to 60%, were used for lignin fractionation. A higher concentration of acetone dissolved higher molecular weight fractions of the lignin. Fractionated organosolv lignin showed different molecular weight and functional groups. Higher molecular weight fractions exhibited more aliphatic and less phenolic OH than lower molecular weight fractions. Lower molecular weight fractions lead to more homogeneous structure compared to samples with a higher molecular weight. In conclusion, all fractions showed strong antioxidant activity.
Fast parareal iterations for fractional diffusion equations
NASA Astrophysics Data System (ADS)
Wu, Shu-Lin; Zhou, Tao
2017-01-01
Numerical methods for fractional PDEs is a hot topic recently. This work is concerned with the parareal algorithm for system of ODEs u‧ (t) + Au (t) = f that arising from semi-discretizations of time-dependent fractional diffusion equations with nonsymmetric Riemann-Liouville fractional derivatives. The spatial semi-discretization of this kind of fractional derivatives often results in a coefficient matrix A with spectrum σ (A)
An evaluation of human ADME and mass balance studies using regular or low doses of radiocarbon.
Roffel, A F; van Marle, S P; van Lier, J J; Hartstra, J; van Hoogdalem, E-J
2016-12-01
There has been increased interest in conducting human absorption, distribution, metabolism, and excretion (ADME) studies with low doses (up to 0.1 MBq) as opposed to regular doses (1.85-3.7 MBq) of radiocarbon ((14) C). This is due to the fact that low-dose human ADME studies may be conducted without dosimetry calculations and will lead to lower human radiation exposure. Here, we sought to compare the outcomes of low-dose versus regular-dose human ADME studies in healthy volunteers. Forty oral human ADME studies conducted at PRA were surveyed, among which 12 were low-dose studies. The fraction of drug material absorbed was 67% ± 7% in the regular-dose studies (data for 13 studies) versus 39% ± 16% in the low-dose studies (data for 5 studies). The average total recovery of (14) C in excreta was 93% ± 5% for regular-dose studies, and 21 of 28 such studies showed recoveries more than 90%. For low-dose studies, average total recovery was 89% ± 9%, and 6 of 12 studies showed recoveries more than 90%. Metabolite profiling was successful in all cases reported (13 regular-dose studies and 5 low-dose studies). There was no obvious relationship between the total recoveries of (14) C in excreta and the proportion of (14) C excreted in feces, or between the total recoveries and the plasma elimination half-lives for parent or total (14) C, neither in the low-dose nor the regular-dose studies. A significant correlation was found between the fraction absorbed and the recovery in feces in the low-dose but not in the regular-dose studies, and no correlation was found between the fractions absorbed and the total recoveries in both types of studies. Low-dose studies were more often conducted on drugs that had a plasma elimination half-life of parent drug more than 100 hours (5 of 12 studies) than regular-dose studies (1 of 26 studies). We conclude that both low-dose as well as regular-dose human ADME studies provide adequate data to support decision making for further
Automated segmentation and dose-volume analysis with DICOMautomaton
NASA Astrophysics Data System (ADS)
Clark, H.; Thomas, S.; Moiseenko, V.; Lee, R.; Gill, B.; Duzenli, C.; Wu, J.
2014-03-01
Purpose: Exploration of historical data for regional organ dose sensitivity is limited by the effort needed to (sub-)segment large numbers of contours. A system has been developed which can rapidly perform autonomous contour sub-segmentation and generic dose-volume computations, substantially reducing the effort required for exploratory analyses. Methods: A contour-centric approach is taken which enables lossless, reversible segmentation and dramatically reduces computation time compared with voxel-centric approaches. Segmentation can be specified on a per-contour, per-organ, or per-patient basis, and can be performed along either an embedded plane or in terms of the contour's bounds (e.g., split organ into fractional-volume/dose pieces along any 3D unit vector). More complex segmentation techniques are available. Anonymized data from 60 head-and-neck cancer patients were used to compare dose-volume computations with Varian's EclipseTM (Varian Medical Systems, Inc.). Results: Mean doses and Dose-volume-histograms computed agree strongly with Varian's EclipseTM. Contours which have been segmented can be injected back into patient data permanently and in a Digital Imaging and Communication in Medicine (DICOM)-conforming manner. Lossless segmentation persists across such injection, and remains fully reversible. Conclusions: DICOMautomaton allows researchers to rapidly, accurately, and autonomously segment large amounts of data into intricate structures suitable for analyses of regional organ dose sensitivity.
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.
Huq, M. Saiful; Houser, Chris; Beriwal, Sushil; Michalski, Dariusz
2014-01-01
Purpose For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recommendations for target doses and constraints are based on calculation of the equivalent dose in 2 Gy fractions (EQD2) from each phase. At present, the EBRT dose distribution is assumed to be uniform throughout the pelvis. We performed a preliminary study to determine whether deformable dose distribution mapping from the EBRT onto magnetic resonance (MR) images for the brachytherapy would yield differences in doses for organs at risk (OARs) and high-risk clinical target volume (HR-CTV). Material and methods Nine cervical cancer patients were treated to a total dose of 45 Gy in 25 fractions using intensity-modulated radiation therapy (IMRT), followed by MRI-based 3D high dose rate (HDR) brachytherapy. Retrospectively, the IMRT planning CT images were fused with the MR image for each fraction of brachytherapy using deformable image registration. The deformed IMRT dose onto MR images were converted to EQD2 and compared to the uniform dose assumption. Results For all patients, the EQD2 from the EBRT phase was significantly higher with deformable registration than with the conventional uniform dose distribution assumption. The mean EQD2 ± SD for HR-CTV D90 was 45.7 ± 0.7 Gy vs. 44.3 Gy for deformable vs. uniform dose distribution, respectively (p < 0.001). The dose to 2 cc of the bladder, rectum, and sigmoid was 46.4 ± 1.2 Gy, 46.2 ± 1.0 Gy, and 48.0 ± 2.5 Gy, respectively with deformable dose distribution, and was significantly higher than with uniform dose distribution (43.2 Gy for all OAR, p < 0.001). Conclusions This study reveals that deformed EBRT dose distribution to HR-CTV and OARs in MR images for brachytherapy is technically feasible, and achieves differences compared to a uniform dose distribution. Therefore, the assumption that EBRT contributes the same dose value may need to be carefully investigated further based on deformable image registration. PMID:25097559
Radiation retinopathy after external-beam irradiation: Analysis of time-dose factors
Parsons, J.T.; Bova, F.J.; Mendenhall, W.M.
1994-11-15
To investigate the risk of radiation-induced retinopathy according to total radiation dose and fraction size, based on both retorspective and prospectively collected data. Between October 1964 and May 1989, 68 retinae in 64 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 26 years; mean, 9 years; median, 8 years). Twenty-seven eyes in 26 patients developed radiation retinopathy resulting in visual acuity of 20/200 or worse. The mean and median times to the onset of symptoms attributable to retinal ischemia were 2.8 and 2.5 years, respectively. Fourteen of the injured eyes developed rubeosis iridis and/or neovascular glaucoma. Radiation retinopathy was not observed at doses below 45 Gy, but increased steadily in incidence at doses {ge}45Gy. In the range of doses between 45 and 55 Gy, there was an increased risk of injury among patients who received doses per fraction of {ge}1.9Gy (p - .09). There was also a trend toward increased risk of injury among patients who received chemotherapy (two of two vs. four of ten in the 45-51 Gy range; p - .23). The lowest dose associated with retinopathy was 45 Gy delivered to a diabetic patient by twice-a-day fractionation. The data did not suggest an increased risk of radiation retinopathy with increasing age. The current study suggests the importance of total dose as well as dose per fraction, and adds support to a small body of literature suggesting that patients with diabetes mellitus or who receive chemotherapy are at increased risk of injury. A sigmoid dose-response curve is constructed from our current data and data from the literature. 36 refs., 5 figs., 4 tabs.
3D Dose Verification Using Tomotherapy CT Detector Array
Sheng Ke; Jones, Ryan; Yang Wensha; Saraiya, Siddharth; Schneider, Bernard; Chen Quan; Sobering, Geoff; Olivera, Gustavo; Read, Paul
2012-02-01
Purpose: To evaluate a three-dimensional dose verification method based on the exit dose using the onboard detector of tomotherapy. Methods and Materials: The study included 347 treatment fractions from 24 patients, including 10 prostate, 5 head and neck (HN), and 9 spinal stereotactic body radiation therapy (SBRT) cases. Detector sonograms were retrieved and back-projected to calculate entrance fluence, which was then forward-projected on the CT images to calculate the verification dose, which was compared with ion chamber and film measurement in the QA plans and with the planning dose in patient plans. Results: Root mean square (RMS) errors of 2.0%, 2.2%, and 2.0% were observed comparing the dose verification (DV) and the ion chamber measured point dose in the phantom plans for HN, prostate, and spinal SBRT patients, respectively. When cumulative dose in the entire treatment is considered, for HN patients, the error of the mean dose to the planning target volume (PTV) varied from 1.47% to 5.62% with a RMS error of 3.55%. For prostate patients, the error of the mean dose to the prostate target volume varied from -5.11% to 3.29%, with a RMS error of 2.49%. The RMS error of maximum doses to the bladder and the rectum were 2.34% (-4.17% to 2.61%) and 2.64% (-4.54% to 3.94%), respectively. For the nine spinal SBRT patients, the RMS error of the minimum dose to the PTV was 2.43% (-5.39% to 2.48%). The RMS error of maximum dose to the spinal cord was 1.05% (-2.86% to 0.89%). Conclusions: An excellent agreement was observed between the measurement and the verification dose. In the patient treatments, the agreement in doses to the majority of PTVs and organs at risk is within 5% for the cumulative treatment course doses. The dosimetric error strongly depends on the error in multileaf collimator leaf opening time with a sensitivity correlating to the gantry rotation period.
Stretching Student Teachers' Understanding of Fractions
ERIC Educational Resources Information Center
Harvey, Roger
2012-01-01
The teaching of fractions in elementary school is known to be challenging. Literature indicates that teachers' and prospective teachers' lack of depth of fraction content knowledge and associated pedagogical knowledge is of concern. This study investigated the fraction content knowledge of prospective teachers and their ability to use that…
Mediants Make (Number) Sense of Fraction Foibles
ERIC Educational Resources Information Center
McDowell, Eric L.
2016-01-01
By the time they reach middle school, all students have been taught to add fractions. However, not all have "learned" to add fractions. The common mistake in adding fractions is to report that a/b + c/d is equal to (a + c)/(b + d). It is certainly necessary to correct this mistake when a student makes it. However, this occasion also…
Early Predictors of Middle School Fraction Knowledge
ERIC Educational Resources Information Center
Bailey, Drew H.; Siegler, Robert S.; Geary, David C.
2014-01-01
Recent findings that earlier fraction knowledge predicts later mathematics achievement raise the question of what predicts later fraction knowledge. Analyses of longitudinal data indicated that whole number magnitude knowledge in first grade predicted knowledge of fraction magnitudes in middle school, controlling for whole number arithmetic…
The Richness of Children's Fraction Strategies
ERIC Educational Resources Information Center
Kent, Laura B.; Empson, Susan B.; Nielsen, Lynne
2015-01-01
In this article, the authors discuss a special type of multiplication-and-division-of-fractions problem that elementary school teachers can use to promote children's understanding of fractional quantities and their relationships. These problems are accessible to students working at different levels of fraction understanding, and they can be solved…
Code of Federal Regulations, 2010 CFR
2010-01-01
... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Fractions. 500.17 Section 500.17 Commercial... LABELING ACT § 500.17 Fractions. (a) SI metric declarations of net quantity of contents of any consumer commodity may contain only decimal fractions. Other declarations of net quantity of contents may...
Locating Fractions on a Number Line
ERIC Educational Resources Information Center
Wong, Monica
2013-01-01
Understanding fractions remains problematic for many students. The use of the number line aids in this understanding, but requires students to recognise that a fraction represents the distance from zero to a dot or arrow marked on a number line which is a linear scale. This article continues the discussion from "Identifying Fractions on a…
Teaching Fractions. Educational Practices Series-22
ERIC Educational Resources Information Center
Fazio, Lisa; Siegler, Robert
2011-01-01
Students around the world have difficulties in learning about fractions. In many countries, the average student never gains a conceptual knowledge of fractions. This research guide provides suggestions for teachers and administrators looking to improve fraction instruction in their classrooms or schools. The recommendations are based on a…
Identifying Fractions on a Number Line
ERIC Educational Resources Information Center
Wong, Monica
2013-01-01
Fractions are generally introduced to students using the part--whole model. Yet the number line is another important representation which can be used to build fraction concepts (Australian Curriculum Assessment and Reporting Authority [ACARA], 2012). Number lines are recognised as key in students' number development not only of fractions, but…
An Alternative Starting Point for Fraction Instruction
ERIC Educational Resources Information Center
Cortina, José Luis; Višnovská, Jana; Zúñiga, Claudia
2015-01-01
We analyze the results of a study conducted for the purpose of assessing the viability of an alternative starting point for teaching fractions. The alternative is based on Freudenthal's insights about fraction as comparison. It involves portraying the entities that unit fractions quantify as always being apart from the reference unit, instead of…
Few Fractional Order Derivatives and Their Computations
ERIC Educational Resources Information Center
Bhatta, D. D.
2007-01-01
This work presents an introductory development of fractional order derivatives and their computations. Historical development of fractional calculus is discussed. This paper presents how to obtain computational results of fractional order derivatives for some elementary functions. Computational results are illustrated in tabular and graphical…
Preparing for Algebra by Building Fraction Sense
ERIC Educational Resources Information Center
Rodrigues, Jessica; Dyson, Nancy I.; Hansen, Nicole; Jordan, Nancy C.
2016-01-01
Fractions are troublesome for many children, especially students with learning difficulties and disabilities in mathematics. To address this serious educational concern, this article recommends the use of number lines to build fraction sense. Math activities that center on the number line build fraction concepts as early as third grade. A number…
Bachhav, R. S.; Sambathkumar, R.
2016-01-01
Trichopus zeylanicus Gaertn, (Trichopodaceae) is also known as “Arogyappacha” meaning the greener of health by tribal inhabitants (Kani tribes). This plant used as health tonic and rejuvenator. The whole plant material of Trichopus zeylanicus is defatted and successively extracted with methanol. The alkaloid fraction of Trichopus zeylanicus was obtained from methanol extract. Up to the dose of 2000 mg/kg b.w. per orally alkaloid fraction of Trichopus zeylanicus did not show any mortality or toxicity. Immunomodulatory activity of alkaloid fraction of Trichopus zeylanicus Gaertn was evaluated using various in vivo models including neutrophil adhesion test, delayed type hypersensitivity reaction, and effect on hematological parameter like, total white blood cell's, red blood cell's and hemoglobin and cyclophosphamide induce immunosupression. Sheep red blood cells were used to immunized the animals. The percentage of neutrophils adhesion to the nylon fiber was dose dependently increased in alkaloid fraction of Trichopus zeylanicus75, 150 and 300 mg/kg, p.o treated groups (50.57, 52.99 and 54.21%), respectively compared to control group. A dose dependent potentiating of delayed type hypersensitivity reaction induced by sheep red blood cells was also observed from the alkaloid fraction of Trichopus zeylanicus. On chronic administration of alkaloid fraction of Trichopus zeylanicus (75, 150 and 300 mg/kg. p.o.) caused significant (P<0.001) increased in hematological parameter like, total white blood cell's, red blood cell's and hemoglobin. Alkaloid fraction of Trichopus zeylanicus also prevented the myelosupression in mice treated cyclophosphamide (30 mg/kg, p.o.). The result of present investigation suggested that alkaloid fraction of Trichopus zeylanicus stimulate defense system by modulating several immunological parameters. PMID:27168696
Tsai, H. Y.; Tung, C. J.; Yu, C. C.; Tyan, Y. S.
2007-04-15
The IAEA and the ICRP recommended dose guidance levels for the most frequent computed tomography (CT) examinations to promote strategies for the optimization of radiation dose to CT patients. A national survey, including on-site measurements and questionnaires, was conducted in Taiwan in order to establish dose guidance levels and evaluate effective doses for CT. The beam quality and output and the phantom doses were measured for nine representative CT scanners. Questionnaire forms were completed by respondents from facilities of 146 CT scanners out of 285 total scanners. Information on patient, procedure, scanner, and technique for the head and body examinations was provided. The weighted computed tomography dose index (CTDI{sub w}), the dose length product (DLP), organ doses and effective dose were calculated using measured data, questionnaire information and Monte Carlo simulation results. A cost-effective analysis was applied to derive the dose guidance levels on CTDI{sub w} and DLP for several CT examinations. The mean effective dose{+-}standard deviation distributes from 1.6{+-}0.9 mSv for the routine head examination to 13{+-}11 mSv for the examination of liver, spleen, and pancreas. The surveyed results and the dose guidance levels were provided to the national authorities to develop quality control standards and protocols for CT examinations.
Collective dose-practical ways to estimate a dose matrix.
Simmonds, Jane; Sihra, Kamaljit; Bexon, Antony
2006-06-01
It has been suggested that collective doses should be presented in the form of a 'dose matrix' giving information on the breakdown of collective dose in space and time and by population group. This paper is an initial attempt to provide such a breakdown by geographic region and time, and to give an idea of associated individual doses for routine discharges to atmosphere. This is done through the use of representative per-caput individual doses but these need to be supplemented by information on the individual doses received by the critical group for a full radiological impact assessment. The results show that it is important to distinguish between the different population groups for up to a few hundred years following the discharge. However, beyond this time the main contribution is from global circulation and this distinction is less important. The majority of the collective dose was found to be delivered at low levels of individual doses; the estimated per-caput dose rates were significantly less than 10(-5) Sv y(-1), a level of dose felt to give rise to a trivial risk to the exposed individual.
Standardized radiological dose evaluations
Peterson, V.L.; Stahlnecker, E.
1996-05-01
Following the end of the Cold War, the mission of Rocky Flats Environmental Technology Site changed from production of nuclear weapons to cleanup. Authorization baseis documents for the facilities, primarily the Final Safety Analysis Reports, are being replaced with new ones in which accident scenarios are sorted into coarse bins of consequence and frequency, similar to the approach of DOE-STD-3011-94. Because this binning does not require high precision, a standardized approach for radiological dose evaluations is taken for all the facilities at the site. This is done through a standard calculation ``template`` for use by all safety analysts preparing the new documents. This report describes this template and its use.
Schneider, Uwe
2009-04-15
A simple mechanistic model for predicting cancer induction after fractionated radiotherapy is developed. The model is based upon the linear-quadratic model. The inductions of carcinomas and sarcomas are modeled separately. The linear-quadratic model of cell kill is applied to normal tissues which are unintentionally irradiated during a cancer treatment with radiotherapy. Tumor induction is modeled such that each transformation process results in a tumor cell. The microscopic transformation parameter was chosen such that in the limit of low dose and acute exposure, the parameters of the linear-no-threshold model for tumor induction were approached. The differential equations describing carcinoma and sarcoma inductions can be solved analytically. Cancer induction in this model is a function of treatment dose, the cell kill parameters ({alpha},{beta}), the tumor induction variable ({mu}), and the repopulation parameter ({xi}). Carcinoma induction shows a bell shaped behavior as long as cell repopulation is small. Assuming large cell repopulation rates, a plateaulike function is approached. In contrast, sarcoma induction is negligible for low doses and increases with increasing dose up to a constant value. The proposed model describes carcinoma and sarcoma inductions after fractionated radiotherapy as an analytical function of four parameters. In the limit of low dose and for an instant irradiation it reproduces the results of the linear-no-threshold model. The obtained dose-response curves for cancer induction can be implemented with other models such as the organ-equivalent dose model to predict second cancers after radiotherapy.
Nakagawa, Akiko; Ohno, Tatsuya; Noda, Shin-ei; Kubo, Nobuteru; Kuwako, Keiko; Saitoh, Jun-Ichi; Nakano, Takashi
2014-07-01
We investigated the rectal dose-sparing effect and tumor control of a point A dose-reduced plan in patients with Stage I-II cervical cancer (≤4 cm) arising from a small-sized uterus. Between October 2008 and August 2011, 19 patients with Stage I-II cervical cancer (≤4 cm) were treated with external beam radiotherapy (EBRT) for the pelvis and CT-guided brachytherapy. Seven patients were treated with brachytherapy with standard loading of source-dwell positions and a fraction dose of 6 Gy at point A (conventional brachy-plan). The other 12 patients with a small uterus close to the rectum or small intestine were treated with brachytherapy with a point A dose-reduction to match D2cc of the rectum and <6 Gy as the dose constraint ('point A dose-reduced plan') instead of the 6-Gy plan at point A ('tentative 6-Gy plan'). The total doses from EBRT and brachytherapy were added up and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2). The median doses to the high-risk clinical target volume (HR-CTV) D90 in the conventional brachy-plan, tentative 6-Gy plan and point A dose-reduced plan were 62 GyEQD2, 80 GyEQD2 and 64 GyEQD2, respectively. The median doses of rectal D2cc in the corresponding three plans were 42 GyEQD2, 62 GyEQD2 and 51 GyEQD2, respectively. With a median follow-up period of 35 months, three patients developed Grade-1 late rectal complications and no patients developed local recurrence. Our preliminary results suggested that CT-guided brachytherapy using an individualized point A dose-reduced plan might be useful for reducing late rectal complications while maintaining primary tumor control.
Rades, Dirk; Huttenlocher, Stefan; Šegedin, Barbara; Perpar, Ana; Conde, Antonio J.; Garcia, Raquel; Veninga, Theo; Stalpers, Lukas J.A.; Cacicedo, Jon; Rudat, Volker; Schild, Steven E.
2015-10-01
Purpose: This study compared single-fraction to multi-fraction short-course radiation therapy (RT) for symptomatic metastatic epidural spinal cord compression (MESCC) in patients with limited survival prognosis. Methods and Materials: A total of 121 patients who received 8 Gy × 1 fraction were matched (1:1) to 121 patients treated with 4 Gy × 5 fractions for 10 factors including age, sex, performance status, primary tumor type, number of involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, pre-RT ambulatory status, and time developing motor deficits prior to RT. Endpoints included in-field repeated RT (reRT) for MESCC, overall survival (OS), and impact of RT on motor function. Univariate analyses were performed with the Kaplan-Meier method and log-rank test for in-field reRT for MESCC and OS and with the ordered-logit model for effect of RT on motor function. Results: Doses of 8 Gy × 1 fraction and 4 Gy × 5 fractions were not significantly different with respect to the need for in-field reRT for MESCC (P=.11) at 6 months (18% vs 9%, respectively) and 12 months (30% vs 22%, respectively). The RT regimen also had no significant impact on OS (P=.65) and post-RT motor function (P=.21). OS rates at 6 and 12 months were 24% and 9%, respectively, after 8 Gy × 1 fraction versus 25% and 13%, respectively, after 4 Gy × 5 fractions. Improvement of motor function was observed in 17% of patients after 8 Gy × 1 fraction and 23% after 4 Gy × 5 fractions, respectively. Conclusions: There were no significant differences with respect to need for in-field reRT for MESCC, OS, and motor function by dose fractionation regimen. Thus, 8 Gy × 1 fraction may be a reasonable option for patients with survival prognosis of a few months.
Antitumor activity of fermented noni exudates and its fractions
LI, JINHUA; CHANG, LENG-CHEE; WALL, MARISA; WONG, D.K.W.; YU, XIANZHONG; WEI, YANZHANG
2013-01-01
Noni has been extensively used in folk medicine by Polynesians for over 2000 year. Recent studies have shown that noni has a wide spectrum of therapeutic activities including inhibition of angiogenesis, anti-inflammatory effects and anti-cancer activities. Intraperitoneal (i.p.) injection of fermented noni exudates (fNE) were previously found to induce significant tumor rejection in a S180 mouse sarcoma tumor model, while natural killer (NK) cells were demonstrated to be markedly involved in fNE-induced antitumor activity. In this study, fNE was partitioned into three fractions and their antitumor effects were examined using i.p. injection or as water supplement. The in vivo animal study results showed that when delivered by i.p. injection, n-butanol fraction of fNE (BuOH) effectively rejected (100%) tumor challenge and eradicated existing tumors (75%). When delivered as a water supplement, 62.5% of the mice receiving the n-butanol or ethyl acetate fractions resisted tumor cells. The tumor-resistant mice effectively rejected more and higher doses of tumor challenge, indicating that the immune system was activated. The findings confirm those of an earlier study showing fNE to have anti-tumor activity and demonstrating that the n-butanol fraction of fNE contains active antitumor components, to be further identified. More importantly, the antitumor effect of fNE and its fractions as water supplements renders a significant potential for identifying novel and powerful new dietary products for cancer prevention. PMID:24649140
Antitumor activity of fermented noni exudates and its fractions.
Li, Jinhua; Chang, Leng-Chee; Wall, Marisa; Wong, D K W; Yu, Xianzhong; Wei, Yanzhang
2013-01-01
Noni has been extensively used in folk medicine by Polynesians for over 2000 year. Recent studies have shown that noni has a wide spectrum of therapeutic activities including inhibition of angiogenesis, anti-inflammatory effects and anti-cancer activities. Intraperitoneal (i.p.) injection of fermented noni exudates (fNE) were previously found to induce significant tumor rejection in a S180 mouse sarcoma tumor model, while natural killer (NK) cells were demonstrated to be markedly involved in fNE-induced antitumor activity. In this study, fNE was partitioned into three fractions and their antitumor effects were examined using i.p. injection or as water supplement. The in vivo animal study results showed that when delivered by i.p. injection, n-butanol fraction of fNE (BuOH) effectively rejected (100%) tumor challenge and eradicated existing tumors (75%). When delivered as a water supplement, 62.5% of the mice receiving the n-butanol or ethyl acetate fractions resisted tumor cells. The tumor-resistant mice effectively rejected more and higher doses of tumor challenge, indicating that the immune system was activated. The findings confirm those of an earlier study showing fNE to have anti-tumor activity and demonstrating that the n-butanol fraction of fNE contains active antitumor components, to be further identified. More importantly, the antitumor effect of fNE and its fractions as water supplements renders a significant potential for identifying novel and powerful new dietary products for cancer prevention.
Isotopic Fractionation by Gravitational Escape
NASA Astrophysics Data System (ADS)
Lammer, H. S. J.
2003-04-01
Present natural data bases for abundances of the isotopic compositions of noble gases, carbon and nitrogen inventories can be found in the Sun, the solar wind, meteorites and the planetary atmospheres and crustal reservoirs. Mass distributions in the various volatile reservoirs provide boundary conditions which must be satisfied in modelling the history of the present atmospheres. Such boundary conditions are constraints posed by comparison of isotopic ratios in primordial volatile sources with the isotopic pattern which was found on the planets and their satellites. Observations from space missions and Earth-based spectroscopic telescope observations of Venus, Mars and Saturn's major satellite Titan show that the atmospheric evolution of these planetary bodies to their present states was affected by processes capable of fractionating their elements and isotopes. The isotope ratios of D/H in the atmospheres of Venus and Mars indicate evidence for their planetary water inventories. Venus' H2O content may have been at least 0.3% of a terrestrial ocean. Analysis of the D/H ratio on Mars imply that a global H2O ocean with a depth of ≤ 30 m was lost since the end of hydrodynamic escape. Calculations of the time evolution of the 15N/14N isotope anomalies in the atmospheres of Mars and Titan show that the Martian atmosphere was at least ≥ 20 times denser than at present and that the mass of Titan's early atmosphere was about 30 times greater than its present value. A detailed study of gravitational fractionation of isotopes in planetary atmospheres furthermore indicates a much higher solar wind mass flux of the early Sun during the first half billion years.
[The effectiveness of fractionated exposure of sarcoma M-1 to gamma-radiation and fast neutrons].
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.
Agwaramgbo, Amanze; Ilodigwe, Emmanuel Emeka; Ajaghaku, Daniel Lotanna; Onuorah, Maureen Ugochukwu; Mbagwu, Sonne Ikechukwu
2014-01-01
Gongronema latifolium fruit has wide application in ethnomedicine, especially in maintaining healthy living and general body healing. We therefore investigated the antioxidant, immunomodulatory activities, and safety of its ethanol extract and fractions. The in vitro antioxidant activities of the extract and fractions were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) test while in vivo activities were determined using carbon tetrachloride (CCL4) induced oxidative stress. Cell and humoral mediated immune responses were also evaluated together with toxicity studies. The extract, ethyl acetate, and methanol fractions showed inhibition of DPPH radical with IC50s 120, 90, and 60 μg/mL, respectively. Methanol fraction at 200 mg/kg produced significant (P < 0.05) inhibition of lipid peroxidation (MDA conc. 1.2 μmol/L) compared to control (2.8 μmol/L). Both ethyl acetate and methanol fractions at 200 mg/kg produced significant (P < 0.05) phagocytic index of 0.021 and 0.025, respectively, compared with control (0.01). Significant (P < 0.05) elevations of white blood cells, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were noticed on the 91st day at higher doses. Generally, this study justified the traditional use of G. latifolium fruit for general body healing and maintenance of healthy living. Long term administration is safe on the haematological and biochemical systems especially at lower doses and its toxicity at higher doses is reversible. PMID:27433504
Hof, Holger; Zgoda, Jacqueline; Nill, Simeon; Hoess, Angelika; Kopp-Schneider, Annette; Herfarth, Klaus; Debus, Juergen; Plathow, Christian
2010-08-01
Purpose: Normal tissue changes (NTC) of the normal lung parenchyma are commonly seen after stereotactic single-dose radiotherapy (radiosurgery) of lung tumors. The aim of this study was to investigate the extent and dynamics of NTCs after radiosurgery. Methods and Materials: Fifty lung tumors in 49 patients were treated with radiosurgery. Follow-up CTs were anatomically matched to the treatment planning CTs, incorporating the treatment plan and enabling spatial correlation of initial radiation dose distribution and subsequent NTCs of the lung. Lung parenchyma was divided into nine areas of different radiation dose exposures (range, 6-35 Gy). Areas were investigated and compared at different time points according to the development of NTCs. Results: Twenty-six patients developed NTCs during follow-up. The evaluation of the dependency of the extent of NTCs on the amount of radiation dose lead to a linear model for the fixed effects: Fraction of reacting volume =Intercept{sub T} +0.0208 * Dose ('Dose' should be given in Gy). Dose had a slope of 0.0208 (fraction of normal tissue reaction/Gy) (SE 0.000804, p < 0.0001), implying a significant correlation between dose level and the extent of NTC. Conclusion: For radiosurgery of lung tumors, a significant correlation of radiation dose and the extent of NTCs could be demonstrated. Using the introduced formula, a preview on the extent of NTCs to develop in normal lung parenchyma according to the dose level can be performed.
Zindler, Jaap D; Thomas, Charles R; Hahn, Stephen M; Hoffmann, Aswin L; Troost, Esther G C; Lambin, Philippe
2016-02-01
To obtain a favorable tradeoff between treatment benefits and morbidity ("therapeutic ratio"), radiotherapy (RT) dose is prescribed according to the tumor volume, with the goal of controlling the disease while respecting normal tissue tolerance levels. We propose a new paradigm for tumor dose prescription in stereotactic ablative radiotherapy (SABR) based on organ-at-risk (OAR) tolerance levels called isotoxic dose prescription (IDP), which is derived from experiences and limitations of conventionally fractionated radiotherapy. With IDP, the radiation dose is prescribed based on the predefined level of normal tissue complication probability of a nearby dose-limiting OAR at a prespecified dose-volume constraint. Simultaneously, the prescribed total tumor dose (TTD) is maximized to the technically highest achievable level in order to increase the local tumor control probability (TCP). IDP is especially relevant for tumors located at eloquent locations or for large tumors in which severe toxicity has been described. IDP will result in a lower RT dose or a treatment scheduled with more fractions if the OAR tolerance level is exceeded, and potential dose escalation occurs when the OAR tolerance level allows it and when it is expected to be beneficial (if TCP < 90%). For patients with small tumors at noneloquent sites, the current SABR dose prescription already results in high rates of local control at low toxicity rates. In this review, the concept of IDP is described in the context of SABR.
Fractional Action Cosmology with Variable Order Parameter
NASA Astrophysics Data System (ADS)
El-Nabulsi, Rami Ahmad
2017-01-01
Fractional action cosmology with variable order parameter was constructed in this paper. Starting from a fractional weighted action which generalizes the fractional actionlike variational approach, a large number of cosmological dynamical equations are obtained depending on the mathematical type of the fractional order parameter. Through this paper, we selected two independent types which result on a number of cosmological scenarios and we discussed their dynamical consequences. It was observed that the present fractional cosmological formalism holds a large family of solutions and offers new features not found in the standard formalism and in many fundamental research papers.
Correlation Structure of Fractional Pearson Diffusions.
Leonenko, Nikolai N; Meerschaert, Mark M; Sikorskii, Alla
2013-09-01
The stochastic solution to a diffusion equations with polynomial coefficients is called a Pearson diffusion. If the first time derivative is replaced by a Caputo fractional derivative of order less than one, the stochastic solution is called a fractional Pearson diffusion. This paper develops an explicit formula for the covariance function of a fractional Pearson diffusion in steady state, in terms of Mittag-Leffler functions. That formula shows that fractional Pearson diffusions are long range dependent, with a correlation that falls off like a power law, whose exponent equals the order of the fractional derivative.
Correlation Structure of Fractional Pearson Diffusions
Leonenko, Nikolai N.; Meerschaert, Mark M.; Sikorskii, Alla
2013-01-01
The stochastic solution to a diffusion equations with polynomial coefficients is called a Pearson diffusion. If the first time derivative is replaced by a Caputo fractional derivative of order less than one, the stochastic solution is called a fractional Pearson diffusion. This paper develops an explicit formula for the covariance function of a fractional Pearson diffusion in steady state, in terms of Mittag-Leffler functions. That formula shows that fractional Pearson diffusions are long range dependent, with a correlation that falls off like a power law, whose exponent equals the order of the fractional derivative. PMID:24089586
Fractional Action Cosmology with Variable Order Parameter
NASA Astrophysics Data System (ADS)
El-Nabulsi, Rami Ahmad
2017-04-01
Fractional action cosmology with variable order parameter was constructed in this paper. Starting from a fractional weighted action which generalizes the fractional actionlike variational approach, a large number of cosmological dynamical equations are obtained depending on the mathematical type of the fractional order parameter. Through this paper, we selected two independent types which result on a number of cosmological scenarios and we discussed their dynamical consequences. It was observed that the present fractional cosmological formalism holds a large family of solutions and offers new features not found in the standard formalism and in many fundamental research papers.
Woody, Neil M.; Videtic, Gregory M.M.; Stephans, Kevin L.; Djemil, Toufik; Kim, Yongbok; Xia Ping
2012-05-01
Purpose: Recent studies with two fractionation schemes predicted that the volume of chest wall receiving >30 Gy (V30) correlated with chest wall pain after stereotactic body radiation therapy (SBRT) to the lung. This study developed a predictive model of chest wall pain incorporating radiobiologic effects, using clinical data from four distinct SBRT fractionation schemes. Methods and Materials: 102 SBRT patients were treated with four different fractionations: 60 Gy in three fractions, 50 Gy in five fractions, 48 Gy in four fractions, and 50 Gy in 10 fractions. To account for radiobiologic effects, a modified equivalent uniform dose (mEUD) model calculated the dose to the chest wall with volume weighting. For comparison, V30 and maximum point dose were also reported. Using univariable logistic regression, the association of radiation dose and clinical variables with chest wall pain was assessed by uncertainty coefficient (U) and C statistic (C) of receiver operator curve. The significant associations from the univariable model were verified with a multivariable mod