WorldWideScience

Sample records for multiforme interim analysis

  1. Phase II Pilot Study of Bevacizumab in Combination with Temozolomide and Regional Radiation Therapy for Up-Front Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Interim Analysis of Safety and Tolerability

    International Nuclear Information System (INIS)

    Lai, Albert; Filka, Emese; McGibbon, Bruce; Nghiemphu, Phioanh Leia; Graham, Carrie; Yong, William H.; Mischel, Paul; Liau, Linda M.; Bergsneider, Marvin; Pope, Whitney; Selch, Michael; Cloughesy, Tim

    2008-01-01

    Purpose: To assess interim safety and tolerability of a 10-patient, Phase II pilot study using bevacizumab (BV) in combination with temozolomide (TMZ) and regional radiation therapy (RT) in the up-front treatment of patients with newly diagnosed glioblastoma. Methods and Materials: All patients received standard external beam regional RT of 60.0 Gy in 30 fractions started within 3 to 5 weeks after surgery. Concurrently TMZ was given daily at 75 mg/m 2 for 42 days during RT, and BV was given every 2 weeks at 10 mg/kg starting with the first day of RT/TMZ. After a 2-week interval upon completion of RT, the post-RT phase commenced with resumption of TMZ at 150 to 200 mg/m 2 for 5 days every 4 weeks and continuation of BV every 2 weeks. Results: For these 10 patients, toxicities were compiled until study discontinuation or up to ∼40 weeks from initial study treatment for those remaining on-study. In terms of serious immediate or delayed neurotoxicity, 1 patient developed presumed radiation-induced optic neuropathy. Among the toxicities that could be potentially treatment related, relatively high incidences of fatigue, myelotoxicity, wound breakdown, and deep venous thrombosis/pulmonary embolism were observed. Conclusion: The observed toxicities were acceptable to continue enrollment toward the overall target group of 70 patients. Preliminary efficacy analysis shows encouraging mean progression-free survival. At this time data are not sufficient to encourage routine off-label use of BV combined with TMZ/RT in the setting of newly diagnosed glioblastoma without longer follow-up, enrollment of additional patients, and thorough efficacy assessment

  2. Exploratory analysis of the copy number alterations in glioblastoma multiforme.

    Science.gov (United States)

    Freire, Pablo; Vilela, Marco; Deus, Helena; Kim, Yong-Wan; Koul, Dimpy; Colman, Howard; Aldape, Kenneth D; Bogler, Oliver; Yung, W K Alfred; Coombes, Kevin; Mills, Gordon B; Vasconcelos, Ana T; Almeida, Jonas S

    2008-01-01

    The Cancer Genome Atlas project (TCGA) has initiated the analysis of multiple samples of a variety of tumor types, starting with glioblastoma multiforme. The analytical methods encompass genomic and transcriptomic information, as well as demographic and clinical data about the sample donors. The data create the opportunity for a systematic screening of the components of the molecular machinery for features that may be associated with tumor formation. The wealth of existing mechanistic information about cancer cell biology provides a natural reference for the exploratory exercise. Glioblastoma multiforme DNA copy number data was generated by The Cancer Genome Atlas project for 167 patients using 227 aCGH experiments, and was analyzed to build a catalog of aberrant regions. Genome screening was performed using an information theory approach in order to quantify aberration as a deviation from a centrality without the bias of untested assumptions about its parametric nature. A novel Cancer Genome Browser software application was developed and is made public to provide a user-friendly graphical interface in which the reported results can be reproduced. The application source code and stand alone executable are available at (http://code.google.com/p/cancergenome) and (http://bioinformaticstation.org), respectively. The most important known copy number alterations for glioblastoma were correctly recovered using entropy as a measure of aberration. Additional alterations were identified in different pathways, such as cell proliferation, cell junctions and neural development. Moreover, novel candidates for oncogenes and tumor suppressors were also detected. A detailed map of aberrant regions is provided.

  3. Exploratory analysis of the copy number alterations in glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Pablo Freire

    Full Text Available The Cancer Genome Atlas project (TCGA has initiated the analysis of multiple samples of a variety of tumor types, starting with glioblastoma multiforme. The analytical methods encompass genomic and transcriptomic information, as well as demographic and clinical data about the sample donors. The data create the opportunity for a systematic screening of the components of the molecular machinery for features that may be associated with tumor formation. The wealth of existing mechanistic information about cancer cell biology provides a natural reference for the exploratory exercise.Glioblastoma multiforme DNA copy number data was generated by The Cancer Genome Atlas project for 167 patients using 227 aCGH experiments, and was analyzed to build a catalog of aberrant regions. Genome screening was performed using an information theory approach in order to quantify aberration as a deviation from a centrality without the bias of untested assumptions about its parametric nature. A novel Cancer Genome Browser software application was developed and is made public to provide a user-friendly graphical interface in which the reported results can be reproduced. The application source code and stand alone executable are available at (http://code.google.com/p/cancergenome and (http://bioinformaticstation.org, respectively.The most important known copy number alterations for glioblastoma were correctly recovered using entropy as a measure of aberration. Additional alterations were identified in different pathways, such as cell proliferation, cell junctions and neural development. Moreover, novel candidates for oncogenes and tumor suppressors were also detected. A detailed map of aberrant regions is provided.

  4. Solid waste burial grounds interim safety analysis

    International Nuclear Information System (INIS)

    Saito, G.H.

    1994-01-01

    This Interim Safety Analysis document supports the authorization basis for the interim operation and restrictions on interim operations for the near-surface land disposal of solid waste in the Solid Waste Burial Grounds. The Solid Waste Burial Grounds Interim Safety Basis supports the upgrade progress for the safety analysis report and the technical safety requirements for the operations in the Solid Waste Burial Grounds. Accident safety analysis scenarios have been analyzed based on the significant events identified in the preliminary hazards analysis. The interim safety analysis provides an evaluation of the operations in the Solid Waste Burial Grounds to determine if the radiological and hazardous material exposures will be acceptable from an overall health and safety standpoint to the worker, the onsite personnel, the public, and the environment

  5. Solid waste burial grounds interim safety analysis

    Energy Technology Data Exchange (ETDEWEB)

    Saito, G.H.

    1994-10-01

    This Interim Safety Analysis document supports the authorization basis for the interim operation and restrictions on interim operations for the near-surface land disposal of solid waste in the Solid Waste Burial Grounds. The Solid Waste Burial Grounds Interim Safety Basis supports the upgrade progress for the safety analysis report and the technical safety requirements for the operations in the Solid Waste Burial Grounds. Accident safety analysis scenarios have been analyzed based on the significant events identified in the preliminary hazards analysis. The interim safety analysis provides an evaluation of the operations in the Solid Waste Burial Grounds to determine if the radiological and hazardous material exposures will be acceptable from an overall health and safety standpoint to the worker, the onsite personnel, the public, and the environment.

  6. EMCS Retrofit Analysis - Interim Report

    Energy Technology Data Exchange (ETDEWEB)

    Diamond, R.C.; Salsbury, T.I.; Bell, G.C.; Huang, Y.J.; Sezgen, A.O.; Mazzucchi, R.; Romberger, J.

    1999-03-01

    This report presents the interim results of analyses carried out in the Phillip Burton Federal Building in San Francisco from 1996 to 1998. The building is the site of a major demonstration of the BACnet communication protocol. The energy management and control systems (EMCS) in the building were retrofitted with BACnet compatible controllers in order to integrate certain existing systems on one common network. In this respect, the project has been a success. Interoperability of control equipment from different manufacturers has been demonstrated in a real world environment. Besides demonstrating interoperability, the retrofits carried out in the building were also intended to enhance control strategies and capabilities, and to produce energy savings. This report presents analyses of the energy usage of HVAC systems in the building, control performance, and the reaction of the building operators. The report does not present an evaluation of the performance capabilities of the BACnet protocol. A monitoring system was installed in the building that parallels many of the EMCS sensors and data were archived over a three-year period. The authors defined pre-retrofit and post-retrofit periods and analyzed the corresponding data to establish the changes in building performance resulting from the retrofit activities. The authors also used whole-building energy simulation (DOE-2) as a tool for evaluating the effect of the retrofit changes. The results of the simulation were compared with the monitored data. Changes in operator behavior were assessed qualitatively with questionnaires. The report summarizes the findings of the analyses and makes several recommendations as to how to achieve better performance. They maintain that the full potential of the EMCS and associated systems is not being realized. The reasons for this are discussed along with possible ways of addressing this problem. They also describe a number of new technologies that could benefit systems of the type

  7. Decision on performing interim analysis for comparative clinical trials.

    Science.gov (United States)

    Pak, Kyongsun; Jacobus, Susanna; Uno, Hajime

    2017-09-01

    In randomized-controlled trials, interim analyses are often planned for possible early trial termination to claim superiority or futility of a new therapy. While unblinding is necessary to conduct the formal interim analysis in blinded studies, blinded data also have information about the potential treatment difference between the groups. We developed a blinded data monitoring tool that enables investigators to predict whether they observe such an unblinded interim analysis results that supports early termination of the trial. Investigators may skip some of the planned interim analyses if an early termination is unlikely. We specifically focused on blinded, randomized-controlled studies to compare binary endpoints of a new treatment with a control. Assuming one interim analysis is planned for early termination for superiority or futility, we conducted extensive simulation studies to assess the impact of the implementation of our tool on the size, power, expected number of interim analyses, and bias in the treatment effect. The numerical study showed the proposed monitoring tool does not affect size or power, but dramatically reduces the expected number of interim analyses when the effect of the treatment difference is small. The tool serves as a useful reference when interpreting the summary of the blinded data throughout the course of the trial, without losing integrity of the study. This tool could potentially save the study resources and budget by avoiding unnecessary interim analyses.

  8. Fire Hazards Analysis for the 200 Area Interim Storage Area

    International Nuclear Information System (INIS)

    JOHNSON, D.M.

    2000-01-01

    This documents the Fire Hazards Analysis (FHA) for the 200 Area Interim Storage Area. The Interim Storage Cask, Rad-Vault, and NAC-1 Cask are analyzed for fire hazards and the 200 Area Interim Storage Area is assessed according to HNF-PRO-350 and the objectives of DOE Order 5480 7A. This FHA addresses the potential fire hazards associated with the Interim Storage Area (ISA) facility in accordance with the requirements of DOE Order 5480 7A. It is intended to assess the risk from fire to ensure there are no undue fire hazards to site personnel and the public and to ensure property damage potential from fire is within acceptable limits. This FHA will be in the form of a graded approach commensurate with the complexity of the structure or area and the associated fire hazards

  9. Single-shell tank interim stabilization risk analysis

    International Nuclear Information System (INIS)

    Basche, A.D.

    1998-01-01

    The purpose of the Single-Shell Tank (SST) Interim Stabilization Risk Analysis is to provide a cost and schedule risk analysis of HNF-2358, Rev. 1, Single-Shell Tank Interim Stabilization Project Plan (Project Plan) (Ross et al. 1998). The analysis compares the required cost profile by fiscal year (Section 4.2) and revised schedule completion date (Section 4.5) to the Project Plan. The analysis also evaluates the executability of the Project Plan and recommends a path forward for risk mitigation

  10. Surprisal analysis of Glioblastoma Multiform (GBM) microRNA dynamics unveils tumor specific phenotype.

    Science.gov (United States)

    Zadran, Sohila; Remacle, Francoise; Levine, Raphael

    2014-01-01

    Gliomablastoma multiform (GBM) is the most fatal form of all brain cancers in humans. Currently there are limited diagnostic tools for GBM detection. Here, we applied surprisal analysis, a theory grounded in thermodynamics, to unveil how biomolecule energetics, specifically a redistribution of free energy amongst microRNAs (miRNAs), results in a system deviating from a non-cancer state to the GBM cancer -specific phenotypic state. Utilizing global miRNA microarray expression data of normal and GBM patients tumors, surprisal analysis characterizes a miRNA system response capable of distinguishing GBM samples from normal tissue biopsy samples. We indicate that the miRNAs contributing to this system behavior is a disease phenotypic state specific to GBM and is therefore a unique GBM-specific thermodynamic signature. MiRNAs implicated in the regulation of stochastic signaling processes crucial in the hallmarks of human cancer, dominate this GBM-cancer phenotypic state. With this theory, we were able to distinguish with high fidelity GBM patients solely by monitoring the dynamics of miRNAs present in patients' biopsy samples. We anticipate that the GBM-specific thermodynamic signature will provide a critical translational tool in better characterizing cancer types and in the development of future therapeutics for GBM.

  11. 5-ALA Fluorescence Image Guided Resection of Glioblastoma Multiforme: A Meta-Analysis of the Literature

    Directory of Open Access Journals (Sweden)

    Samy Eljamel

    2015-05-01

    Full Text Available Background: Glioblastoma multiforme (GBM is one of the most deadly cancers in humans. Despite recent advances in anti-cancer therapies, most patients with GBM die from local disease progression. Fluorescence image guided surgical resection (FIGR was recently advocated to enhance local control of GBM. This is meta-analyses of 5-aminolevulinic (5-ALA induced FIGR. Materials: Review of the literature produced 503 potential publications; only 20 of these fulfilled the inclusion criteria of this analysis, including a total of 565 patients treated with 5-ALA-FIGR reporting on its outcomes and 800 histological samples reporting 5-ALA-FIGR sensitivity and specificity. Results: The mean gross total resection (GTR rate was 75.4% (95% CI: 67.4–83.5, p < 0.001. The mean time to tumor progression (TTP was 8.1 months (95% CI: 4.7–12, p < 0.001. The mean overall survival gain reported was 6.2 months (95% CI: −1–13, p < 0.001. The specificity was 88.9% (95% CI: 83.9–93.9, p < 0.001 and the sensitivity was 82.6% (95% CI: 73.9–91.9, p < 0.001. Conclusion: 5-ALA-FIGR in GBM is highly sensitive and specific, and imparts significant benefits to patients in terms of improved GTR and TTP.

  12. Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis

    DEFF Research Database (Denmark)

    Home, Philip D; Pocock, Stuart J; Beck-Nielsen, Henning

    2007-01-01

    BACKGROUND: A recent meta-analysis raised concern regarding an increased risk of myocardial infarction and death from cardiovascular causes associated with rosiglitazone treatment of type 2 diabetes. METHODS: We conducted an unplanned interim analysis of a randomized, multicenter, open...... group). The primary end point was hospitalization or death from cardiovascular causes. RESULTS: Because the mean follow-up was only 3.75 years, our interim analysis had limited statistical power to detect treatment differences. A total of 217 patients in the rosiglitazone group and 202 patients...... in the control group had the adjudicated primary end point (hazard ratio, 1.08; 95% confidence interval [CI], 0.89 to 1.31). After the inclusion of end points pending adjudication, the hazard ratio was 1.11 (95% CI, 0.93 to 1.32). There were no statistically significant differences between the rosiglitazone...

  13. Analysis of Electronic Densities and Integrated Doses in Multiform Glioblastomas Stereotactic Radiotherapy

    International Nuclear Information System (INIS)

    Baron-Aznar, C.; Moreno-Jimenez, S.; Celis, M. A.; Ballesteros-Zebadua, P.; Larraga-Gutierrez, J. M.

    2008-01-01

    Integrated dose is the total energy delivered in a radiotherapy target. This physical parameter could be a predictor for complications such as brain edema and radionecrosis after stereotactic radiotherapy treatments for brain tumors. Integrated Dose depends on the tissue density and volume. Using CT patients images from the National Institute of Neurology and Neurosurgery and BrainScan(c) software, this work presents the mean density of 21 multiform glioblastomas, comparative results for normal tissue and estimated integrated dose for each case. The relationship between integrated dose and the probability of complications is discussed

  14. Radiation analysis for a generic centralized interim storage facility

    International Nuclear Information System (INIS)

    Gillespie, S.G.; Lopez, P.; Eble, R.G.

    1997-01-01

    This paper documents the radiation analysis performed for the storage area of a generic Centralized Interim Storage Facility (CISF) for commercial spent nuclear fuel (SNF). The purpose of the analysis is to establish the CISF Protected Area and Restricted Area boundaries by modeling a representative SNF storage array, calculating the radiation dose at selected locations outside the storage area, and comparing the results with regulatory radiation dose limits. The particular challenge for this analysis is to adequately model a large (6000 cask) storage array with a reasonable amount of analysis time and effort. Previous analyses of SNF storage systems for Independent Spent Fuel Storage Installations at nuclear plant sites (for example in References 5.1 and 5.2) had only considered small arrays of storage casks. For such analyses, the dose contribution from each storage cask can be modeled individually. Since the large number of casks in the CISF storage array make such an approach unrealistic, a simplified model is required

  15. Intraoperative MRI to guide the resection of primary supratentorial glioblastoma multiforme - a quantitative radiological analysis

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Jens P.; Rubach, Matthias; Schulz, Thomas; Dietrich, Juergen; Zimmer, Claus; Kahn, Thomas [University of Leipzig, Diagnostic Radiology, Leipzig (Germany); Trantakis, Christos; Winkler, Dirk; Renner, Christof [University of Leipzig, Department of Neurosurgery, Leipzig (Germany); Schober, Ralf; Geiger, Kathrin [University of Leipzig, Department of Neuropathology, Leipzig (Germany); Brosteanu, Oana [Coordination Centre for Clinical Trials, Leipzig (Germany)

    2005-07-01

    primary glioblastoma multiforme under intraoperative MR guidance as demonstrated is a possibility to achieve a more complete removal of the tumor than with conventional techniques. In our small but homogeneous patient group we found an increase in the median survival time in patients with MRI for complete tumor resection, and the overall surgical morbidity was low. (orig.)

  16. Increased intracranial pressure in a case of spinal cervical glioblastoma multiforme: analysis of these two rare conditions

    Directory of Open Access Journals (Sweden)

    C.M. de Castro-Costa

    1994-03-01

    Full Text Available The authors describe a rare case of increased intracranial hypertension consequent to a spinal cervical glioblastoma multiforme in a young patient. They analyse the physiopathology of intracranial hypertension in spinal tumors and the rarity of such kind of tumor in this location, and its clinico-pathological aspects.

  17. ATM and p53 combined analysis predicts survival in glioblastoma multiforme patients: A clinicopathologic study.

    Science.gov (United States)

    Romano, Francesco Jacopo; Guadagno, Elia; Solari, Domenico; Borrelli, Giorgio; Pignatiello, Sara; Cappabianca, Paolo; Del Basso De Caro, Marialaura

    2018-06-01

    Glioblastoma is one of the most malignant cancers, with a distinguishing dismal prognosis: surgery followed by chemo- and radiotherapy represents the current standard of care, and chemo- and radioresistance underlie disease recurrence and short overall survival of patients suffering from this malignancy. ATM is a kinase activated by autophosphorylation upon DNA doublestrand breaks arising from errors during replication, byproducts of metabolism, chemotherapy or ionizing radiations; TP53 is one of the most popular tumor suppressor, with a preeminent role in DNA damage response and repair. To study the effects of the immunohistochemical expression of p-ATM and p53 in glioblastoma patients, 21 cases were retrospectively examined. In normal brain tissue, p-ATM was expressed only in neurons; conversely, in tumors cells, the protein showed a variable cytoplasmic expression (score: +,++,+++), with being completely undetectable in three cases. Statistical analysis revealed that high p-ATM score (++/+++) strongly correlated to shorter survival (P = 0.022). No difference in overall survival was registered between p53 normally expressed (NE) and overexpressed (OE) glioblastoma patients (P = 0.669). Survival analysis performed on the results from combined assessment of the two proteins showed that patients with NE p53 /low pATM score had longer overall survival than the NE p53/ high pATM score counterpart. Cox-regression analysis confirmed this finding (HR = 0.025; CI 95% = 0.002-0.284; P = 0.003). Our study outlined the immunohistochemical expression of p-ATM/p53 in glioblastomas and provided data on their possible prognostic/predictive of response role. A "non-oncogene addiction" to ATM for NEp53 glioblastoma could be postulated, strengthening the rationale for development of ATM inhibiting drugs. © 2018 Wiley Periodicals, Inc.

  18. Global diffusion tensor imaging derived metrics differentiate glioblastoma multiforme vs. normal brains by using discriminant analysis: introduction of a novel whole-brain approach.

    Science.gov (United States)

    Roldan-Valadez, Ernesto; Rios, Camilo; Cortez-Conradis, David; Favila, Rafael; Moreno-Jimenez, Sergio

    2014-06-01

    Histological behavior of glioblastoma multiforme suggests it would benefit more from a global rather than regional evaluation. A global (whole-brain) calculation of diffusion tensor imaging (DTI) derived tensor metrics offers a valid method to detect the integrity of white matter structures without missing infiltrated brain areas not seen in conventional sequences. In this study we calculated a predictive model of brain infiltration in patients with glioblastoma using global tensor metrics. Retrospective, case and control study; 11 global DTI-derived tensor metrics were calculated in 27 patients with glioblastoma multiforme and 34 controls: mean diffusivity, fractional anisotropy, pure isotropic diffusion, pure anisotropic diffusion, the total magnitude of the diffusion tensor, linear tensor, planar tensor, spherical tensor, relative anisotropy, axial diffusivity and radial diffusivity. The multivariate discriminant analysis of these variables (including age) with a diagnostic test evaluation was performed. The simultaneous analysis of 732 measures from 12 continuous variables in 61 subjects revealed one discriminant model that significantly differentiated normal brains and brains with glioblastoma: Wilks' λ = 0.324, χ(2) (3) = 38.907, p tensor and linear tensor. These metrics might be clinically applied for diagnosis, follow-up, and the study of other neurological diseases.

  19. Terrestrial gravity data analysis for interim gravity model improvement

    Science.gov (United States)

    1987-01-01

    This is the first status report for the Interim Gravity Model research effort that was started on June 30, 1986. The basic theme of this study is to develop appropriate models and adjustment procedures for estimating potential coefficients from terrestrial gravity data. The plan is to use the latest gravity data sets to produce coefficient estimates as well as to provide normal equations to NASA for use in the TOPEX/POSEIDON gravity field modeling program.

  20. Radiotherapy Results of Brain Astrocytoma and Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Choi, Doo Ho; Kim, Il Han; Ha, Sung Whan; Chi, Je Geun

    1988-01-01

    A retrospective analysis was performed on 49 patients with astrocytoma of glioblastoma multiforme of brain who received postoperative radiotherapy in the period between February 1979 and December 1985. Fourteen patients had grade I astrocytoma, 11 patients grade II, 14 patients grade III, and 10 patients glioblastoma multiforme. Three year actuarial survival rates were 85.7%, 44.6% and 23.1% for grade I, II, and III astrocytomas, respectively. One and 2 year actuarial survival rates for patients with glioblastoma multiforme were 54.5% and 27.3%, respectively. Histologic grade, age, extent of operation and tumor location were revealed to be prognosticators

  1. Annex D-200 Area Interim Storage Area Final Safety Analysis Report [FSAR] [Section 1 and 2

    International Nuclear Information System (INIS)

    CARRELL, R.D.

    2002-01-01

    The 200 Area Interim Storage Area (200 Area ISA) at the Hanford Site provides for the interim storage of non-defense reactor spent nuclear fuel (SNF) housed in aboveground dry cask storage systems. The 200 Area ISA is a relatively simple facility consisting of a boundary fence with gates, perimeter lighting, and concrete and gravel pads on which to place the dry storage casks. The fence supports safeguards and security and establishes a radiation protection buffer zone. The 200 Area ISA is nominally 200,000 ft 2 and is located west of the Canister Storage Building (CSB). Interim storage at the 200 Area ISA is intended for a period of up to 40 years until the materials are shipped off-site to a disposal facility. This Final Safety Analysis Report (FSAR) does not address removal from storage or shipment from the 200 Area ISA. Three different SNF types contained in three different dry cask storage systems are to be stored at the 200 Area ISA, as follows: (1) Fast Flux Test Facility Fuel--Fifty-three interim storage casks (ISC), each holding a core component container (CCC), will be used to store the Fast Flux Test Facility (FFTF) SNF currently in the 400 Area. (2) Neutron Radiography Facility (NRF) TRIGA'--One Rad-Vault' container will store two DOT-6M3 containers and six NRF TRIGA casks currently stored in the 400 Area. (3) Commercial Light Water Reactor Fuel--Six International Standards Organization (ISO) containers, each holding a NAC-I cask4 with an inner commercial light water reactor (LWR) canister, will be used for commercial LWR SNF from the 300 Area. An aboveground dry cask storage location is necessary for the spent fuel because the current storage facilities are being shut down and deactivated. The spent fuel is being transferred to interim storage because there is no permanent repository storage currently available

  2. Annex D-200 Area Interim Storage Area Final Safety Analysis Report [FSAR] [Section 1 & 2

    Energy Technology Data Exchange (ETDEWEB)

    CARRELL, R D

    2002-07-16

    The 200 Area Interim Storage Area (200 Area ISA) at the Hanford Site provides for the interim storage of non-defense reactor spent nuclear fuel (SNF) housed in aboveground dry cask storage systems. The 200 Area ISA is a relatively simple facility consisting of a boundary fence with gates, perimeter lighting, and concrete and gravel pads on which to place the dry storage casks. The fence supports safeguards and security and establishes a radiation protection buffer zone. The 200 Area ISA is nominally 200,000 ft{sup 2} and is located west of the Canister Storage Building (CSB). Interim storage at the 200 Area ISA is intended for a period of up to 40 years until the materials are shipped off-site to a disposal facility. This Final Safety Analysis Report (FSAR) does not address removal from storage or shipment from the 200 Area ISA. Three different SNF types contained in three different dry cask storage systems are to be stored at the 200 Area ISA, as follows: (1) Fast Flux Test Facility Fuel--Fifty-three interim storage casks (ISC), each holding a core component container (CCC), will be used to store the Fast Flux Test Facility (FFTF) SNF currently in the 400 Area. (2) Neutron Radiography Facility (NRF) TRIGA'--One Rad-Vault' container will store two DOT-6M3 containers and six NRF TRIGA casks currently stored in the 400 Area. (3) Commercial Light Water Reactor Fuel--Six International Standards Organization (ISO) containers, each holding a NAC-I cask4 with an inner commercial light water reactor (LWR) canister, will be used for commercial LWR SNF from the 300 Area. An aboveground dry cask storage location is necessary for the spent fuel because the current storage facilities are being shut down and deactivated. The spent fuel is being transferred to interim storage because there is no permanent repository storage currently available.

  3. Interim analysis: A rational approach of decision making in clinical trial.

    Science.gov (United States)

    Kumar, Amal; Chakraborty, Bhaswat S

    2016-01-01

    Interim analysis of especially sizeable trials keeps the decision process free of conflict of interest while considering cost, resources, and meaningfulness of the project. Whenever necessary, such interim analysis can also call for potential termination or appropriate modification in sample size, study design, and even an early declaration of success. Given the extraordinary size and complexity today, this rational approach helps to analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. Such approach can also fill the gap by directing the resources toward relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals.

  4. Interim analysis: A rational approach of decision making in clinical trial

    Directory of Open Access Journals (Sweden)

    Amal Kumar

    2016-01-01

    Full Text Available Interim analysis of especially sizeable trials keeps the decision process free of conflict of interest while considering cost, resources, and meaningfulness of the project. Whenever necessary, such interim analysis can also call for potential termination or appropriate modification in sample size, study design, and even an early declaration of success. Given the extraordinary size and complexity today, this rational approach helps to analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. Such approach can also fill the gap by directing the resources toward relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals.

  5. Early post-treatment pseudo-progression amongst glioblastoma multiforme patients treated with radiotherapy and temozolomide: a retrospective analysis

    International Nuclear Information System (INIS)

    Gunjur, Ashray; Lau, Eddie; Taouk, Yamna; Ryan, Gail

    2011-01-01

    To evaluate the incidence and impact of early post-chemoradiation (cRT) 'pseudoprogression' (PsPD) amongst glioblastoma multiforme (GBM) patients treated with the current standard of care – 60 Gy conformal radiotherapy with concurrent low-dose temozolomide, followed by six cycles of high-dose temozolomide (the 'Stupp protocol'). Clinical notes and radiology reports for GBM patients treated as per the Stupp protocol were reviewed. PsPD was defined as apparent radiological progression on the first post-cRT scan, with further imaging within 3 months being stable or improving, while true early progression (ePD) was confirmed by continued progression in the subsequent 3 months following the first post-cRT scan. Of the 68 patients evaluated, 14 (21%) and 27 (40%) experienced PsPD and ePD, respectively; 3/14 (21%) patients experiencing PsPD and 14/27(52%), ePD were symptomatic for progression on first post-cRT follow-up (P = 0.096 for difference). Median survival for patients with ePD, PsPD and neither were 10.4, 27.4 and 13.0 months, respectively (P = 0.003 for ePD vs. PsPD, P = 0.19 for neither vs. PsPD groups). These data confirm a significant incidence of PsPD in post-cRT GBM patients, associated with improved median survival compared with those with neither ePD nor PsPD (not statistically significant). It appears likely that PsPD actually represents tumour response, conflicting with the traditional notion that increase in lesion size on contrast-enhanced imaging represents disease progression. Early post-cRT imaging should thus be interpreted with caution. Accompanying clinical symptoms are more commonly associated with ePD, but do not reliably distinguish PsPD from ePD.

  6. Pre-clinical analysis of changes in intra-cellular biochemistry of glioblastoma multiforme (GBM) cells due to c-Myc silencing.

    Science.gov (United States)

    Rajagopalan, Vishal; Vaidyanathan, Muthukumar; Janardhanam, Vanisree Arambakkam; Bradner, James E

    2014-10-01

    Glioblastoma Multiforme (GBM) is an aggressive form of brain Tumor that has few cures. In this study, we analyze the anti-proliferative effects of a new molecule JQ1 against GBMs induced in Wistar Rats. JQ1 is essentially a Myc inhibitor. c-Myc is also known for altering the biochemistry of a tumor cell. Therefore, the study is intended to analyze certain other oncogenes associated with c-Myc and also the change in cellular biochemistry upon c-Myc inhibition. The quantitative analysis of gene expression gave a co-expressive pattern for all the three genes involved namely; c-Myc, Bcl-2, and Akt. The cellular biochemistry analysis by transmission electron microscopy revealed high glycogen and lipid aggregation in Myc inhibited cells and excessive autophagy. The study demonstrates the role of c-Myc as a central metabolic regulator and Bcl-2 and Akt assisting in extending c-Myc half-life as well as in regulation of autophagy, so as to regulate cell survival on the whole. The study also demonstrates that transient treatment by JQ1 leads to aggressive development of tumor and therefore, accelerating death, emphasizing the importance of dosage fixation, and duration for clinical use in future.

  7. Additional EIPC Study Analysis: Interim Report on High Priority Topics

    Energy Technology Data Exchange (ETDEWEB)

    Hadley, Stanton W [ORNL

    2013-11-01

    Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations were developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 13 topics was developed for further analysis; this paper discusses the first five.

  8. Interim report on nuclear waste depository thermal analysis

    International Nuclear Information System (INIS)

    Altenbach, T.J.

    1978-01-01

    A thermal analysis of a deep geologic depository for spent nuclear fuel is being conducted. The TRUMP finite difference heat transfer code is used to analyze a 3-dimensional model of the depository. The model uses a unit cell consisting of one spent fuel canister buried in salt beneath a ventilated room in the depository. A base case was studied along with several parametric variations. It is concluded that this method is appropriate for analyzing the thermal response of the system, and that the most important parameter in determining the maximum temperatures is the canister heat generation rate. The effects of room ventilation and different depository media are secondary

  9. Novel multiform morphologies of hydroxyapatite: Synthesis and growth mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Mary, I. Reeta [Department of Nanoscience and Technology, Bharathiar University, Coimbatore 641046 (India); Department of Physics, Government Arts College, Coimbatore 641018 (India); Sonia, S.; Viji, S.; Mangalaraj, D.; Viswanathan, C. [Department of Nanoscience and Technology, Bharathiar University, Coimbatore 641046 (India); Ponpandian, N., E-mail: ponpandian@buc.edu.in [Department of Nanoscience and Technology, Bharathiar University, Coimbatore 641046 (India)

    2016-01-15

    Graphical abstract: - Highlights: • Novel multiform morphologies of hydroxyapatite from nanoscale building blocks. • Facile hydro/solvothermal method under mild reaction conditions without the necessity of post-annealing treatment. • Growth mechanism by Ostwald ripening and self-assembly processes. - Abstract: Morphological evolution of materials becomes a prodigious challenge due to their key role in defining their functional properties and desired applications. Herein, we report the synthesis of hydroxyapatite (HAp) microstructures with multiform morphologies, such as spheres, cubes, hexagonal rods and nested bundles constructed from their respective nanoscale building blocks via a simple cost effective hydro/solvothermal method. A possible formation mechanism of diverse morphologies of HAp has been presented. Structural analysis based on X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy confirms the purity of the HAp microstructures. The multiform morphologies of HAp were corroborated by using Field emission scanning electron microscope (FESEM).

  10. Thermal analysis of the unloading cell of the Spanish centralized interim storage facility (CISF)

    International Nuclear Information System (INIS)

    Perez Dominguez, J. R.; Perez Vara, R.; Huelamo Martinez, E.

    2016-01-01

    This article deals with the thermal analysis performed for the Untoading Cell of Spain Centralized Interim Storage Facility, CISF (ATC, in Spanish). The analyses are done using computational fluid dynamics (CFD) simulation, with the aim of obtaining the air flow required to remove the residual heat of the elements stored in the cell. Compliance with the admissible heat limits is checked with the results obtained in the various operation and accident modes. The calculation model is flexible enough to allow carrying out a number of sensitivity analyses with the different parameters involved in the process. (Author)

  11. Symptomatic treatment in multiple sclerosis-interim analysis of a nationwide registry.

    Science.gov (United States)

    Skierlo, S; Rommer, P S; Zettl, U K

    2017-04-01

    To analyze symptomatic treatment in patients with multiple sclerosis (MS). Multiple sclerosis is a chronic inflammatory disease of the central nervous system, with accumulating disability symptoms like spasticity, voiding disorders, depression, and pain might occur. The nationwide German MS registry was initiated 2001 under guidance of the German MS society (Deutsche MS Gesellschaft). This study was performed as an interim analysis to lay foundation for future work on this topic. A subcohort of 5113 patients was assessed for this interim analysis. The mean age of the patients was 45.3 years; mean EDSS was 4.2. More than two-third of the enrolled patients were females (70.9%). Most frequent symptoms were fatigue (60%), followed by spasticity (52.5%) and voiding disorders (51.7%). The likelihood of treatment was highest for epileptic disorders (68.8%), spasticity (68.5%), pain (60.7%), and depression (58.9%). Multivariate regression analysis showed that retirement was the strongest factor predictive for antispastic treatment (β=.061, P=.005). Almost all patients in this analysis suffer from symptoms due to advanced MS. Treatment for the various symptoms differed tremendously. The likelihood of treatment correlated with the availability of effective therapeutic agents. Clinicians should put more awareness on MS symptoms. Symptomatic treatment may improve quality of life. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Issues in data monitoring and interim analysis of trials.

    Science.gov (United States)

    Grant, A M; Altman, D G; Babiker, A B; Campbell, M K; Clemens, F J; Darbyshire, J H; Elbourne, D R; McLeer, S K; Parmar, M K B; Pocock, S J; Spiegelhalter, D J; Sydes, M R; Walker, A E; Wallace, S A

    2005-03-01

    included, although interaction with the DMCs of similar ongoing trials is controversial. A range of formal statistical approaches can be used, although this is only one of a number of considerations. DMCs usually reach decisions by consensus, but other approaches are sometimes used. The general, but not unanimous, view is that DMCs should be advisory rather than executive on the basis that it is the trial organisers who are ultimately responsible for the conduct of the trial. Some form of data monitoring should be considered for all RCTs, with reasons given where there is no DMC or when any member is not independent. An early DMC meeting is helpful, determining roles and responsibilities; planned operations can be agreed with investigators and sponsors/funders. A template for a DMC charter is suggested. Competing interests should be declared. DMC size (commonly three to eight people) is chosen to optimise performance. Members are usually independent and drawn from appropriate backgrounds, and some, particularly the chair, are experienced. A minimum frequency of meetings is usually agreed, with flexibility for more if needed. The DMC should understand and agree the statistical approach (and guidelines) chosen, with both the DMC statistician and analysis statistician competent to apply the method. A DMC's primary purpose is to ensure that continuing a trial according to its protocol is ethical, taking account of both individual and collective ethics. A broader remit in respect of wider ethical issues is controversial; arguably, these are primarily the responsibility of research ethics committees, trial steering committees and investigators. The DMC should know the range of recommendations or decisions open to it, in advance. A record should be kept describing the key issues discussed and the rationale for decisions taken. Errors are likely to be reduced if a DMC makes a thorough review of the evidence and has a clear understanding of how it should function, there is active

  13. Interim reliability evaluation program: analysis of the Arkansas Nuclear One. Unit 1 Nuclear Power Plant

    International Nuclear Information System (INIS)

    Kolb, G.J.; Kunsman, D.M.; Bell, B.J.

    1982-06-01

    This report represents the results of the analysis of Arkansas Nuclear One (ANO) Unit 1 nuclear power plant which was performed as part of the Interim Reliability Evaluation Program (IREP). The IREP has several objectives, two of which are achieved by the analysis presented in this report. These objectives are: (1) the identification, in a preliminary way, of those accident sequences which are expected to dominate the public health and safety risks; and (2) the development of state-of-the-art plant system models which can be used as a foundation for subsequent, more intensive applications of probabilistic risk assessment. The primary methodological tools used in the analysis were event trees and fault trees. These tools were used to study core melt accidents initiated by loss of coolant accidents (LOCAs) of six different break size ranges and eight different types of transients

  14. Cna 1 spent fuel element interim dry storage system thermal analysis

    International Nuclear Information System (INIS)

    Hilal, R. E; Garcia, J. C; Delmastro, D. F

    2006-01-01

    At the moment, the Atucha I Nuclear Power Plant (Cnea-I) located in the city of Lima, has enough room to store its spent fuel (Sf) in their two pools spent fuel until about 2015.In case of life extension a spend fuel element interim dry storage system is needed.Nucleolectrica Argentina S.A. (N A-S A) and the Comision Nacional de Energia Atomica (Cnea), have proposed different interim dry storage systems.These systems have to be evaluated in order to choose one of them.The present work's objective is the thermal analysis of one dry storage alternative for the Sf element of Cna 1.In this work a simple model was developed and used to perform the thermal calculations corresponding to the system proposed by Cnea.This system considers the store of sealed containers with 37 spent fuels in concrete modules.Each one of the containers is filled in the pool houses and transported to the module in a transference cask with lead walls.Fulfill the maximum cladding temperature requirement ( [es

  15. Lagrangian multiforms and multidimensional consistency

    Energy Technology Data Exchange (ETDEWEB)

    Lobb, Sarah; Nijhoff, Frank [Department of Applied Mathematics, University of Leeds, Leeds LS2 9JT (United Kingdom)

    2009-10-30

    We show that well-chosen Lagrangians for a class of two-dimensional integrable lattice equations obey a closure relation when embedded in a higher dimensional lattice. On the basis of this property we formulate a Lagrangian description for such systems in terms of Lagrangian multiforms. We discuss the connection of this formalism with the notion of multidimensional consistency, and the role of the lattice from the point of view of the relevant variational principle.

  16. Immobilized high-level waste interim storage alternatives generation and analysis and decision report

    International Nuclear Information System (INIS)

    CALMUS, R.B.

    1999-01-01

    This report presents a study of alternative system architectures to provide onsite interim storage for the immobilized high-level waste produced by the Tank Waste Remediation System (TWRS) privatization vendor. It examines the contract and program changes that have occurred and evaluates their impacts on the baseline immobilized high-level waste (IHLW) interim storage strategy. In addition, this report documents the recommended initial interim storage architecture and implementation path forward

  17. Cyclophilin B supports Myc and mutant p53-dependent survival of glioblastoma multiforme cells.

    Science.gov (United States)

    Choi, Jae Won; Schroeder, Mark A; Sarkaria, Jann N; Bram, Richard J

    2014-01-15

    Glioblastoma multiforme is an aggressive, treatment-refractory type of brain tumor for which effective therapeutic targets remain important to identify. Here, we report that cyclophilin B (CypB), a prolyl isomerase residing in the endoplasmic reticulum (ER), provides an essential survival signal in glioblastoma multiforme cells. Analysis of gene expression databases revealed that CypB is upregulated in many cases of malignant glioma. We found that suppression of CypB reduced cell proliferation and survival in human glioblastoma multiforme cells in vitro and in vivo. We also found that treatment with small molecule inhibitors of cyclophilins, including the approved drug cyclosporine, greatly reduced the viability of glioblastoma multiforme cells. Mechanistically, depletion or pharmacologic inhibition of CypB caused hyperactivation of the oncogenic RAS-mitogen-activated protein kinase pathway, induction of cellular senescence signals, and death resulting from loss of MYC, mutant p53, Chk1, and Janus-activated kinase/STAT3 signaling. Elevated reactive oxygen species, ER expansion, and abnormal unfolded protein responses in CypB-depleted glioblastoma multiforme cells indicated that CypB alleviates oxidative and ER stresses and coordinates stress adaptation responses. Enhanced cell survival and sustained expression of multiple oncogenic proteins downstream of CypB may thus contribute to the poor outcome of glioblastoma multiforme tumors. Our findings link chaperone-mediated protein folding in the ER to mechanisms underlying oncogenic transformation, and they make CypB an attractive and immediately targetable molecule for glioblastoma multiforme therapy.

  18. Interim restorations.

    Science.gov (United States)

    Gratton, David G; Aquilino, Steven A

    2004-04-01

    Interim restorations are a critical component of fixed prosthodontic treatment, biologically and biomechanically. Interim restoration serves an important diagnostic role as a functional and esthetic try-in and as a blueprint for the design of the definitive prosthesis. When selecting materials for any interim restoration, clinicians must consider physical properties, handling properties, patient acceptance, and material cost. Although no single material meets all the requirements and material classification alone of a given product is not a predictor of clinical performance, bis-acryl materials are typically best suited to single-unit restorations, and poly(methylmethacrylate) interim materials are generally ideal for multi-unit, complex, long-term, interim fixed prostheses. As with most dental procedures, the technique used for fabrication has a greater effect on the final result than the specific material chosen.

  19. INTERIM ANALYSIS OF THE CONTRIBUTION OF HIGH-LEVEL EVIDENCE FOR DENGUE VECTOR CONTROL.

    Science.gov (United States)

    Horstick, Olaf; Ranzinger, Silvia Runge

    2015-01-01

    This interim analysis reviews the available systematic literature for dengue vector control on three levels: 1) single and combined vector control methods, with existing work on peridomestic space spraying and on Bacillus thuringiensis israelensis; further work is available soon on the use of Temephos, Copepods and larvivorous fish; 2) or for a specific purpose, like outbreak control, and 3) on a strategic level, as for example decentralization vs centralization, with a systematic review on vector control organization. Clear best practice guidelines for methodology of entomological studies are needed. There is a need to include measuring dengue transmission data. The following recommendations emerge: Although vector control can be effective, implementation remains an issue; Single interventions are probably not useful; Combinations of interventions have mixed results; Careful implementation of vector control measures may be most important; Outbreak interventions are often applied with questionable effectiveness.

  20. Interim overdentures.

    Science.gov (United States)

    Fenton, A H

    1976-07-01

    The construction of an interim overdenture using existing removable partial dentures with natural tooth crowns and artificial teeth can be a simple and economical method of providing patients with dentures while tissues heal and teeth are prepared and restored. A more definite prognosis for both the patient and his remaining dentition can be established before the final overdenture is completed. The procedures necessary to provide three types of interim overdentures have been outlined. Patients tolerate this method of changing their dentitions extremely well.

  1. Annex D 200 Area Interim Storage Area Final Safety Analysis Report Volume 5 (FSAR) (Section 1 and 2)

    International Nuclear Information System (INIS)

    CARRELL, R.D.

    2003-01-01

    The 200 Area Interim Storage Area (200 Area ISA) at the Hanford Site provides for the interim storage of non-defense reactor spent nuclear fuel (SNF) housed in aboveground dry cask storage systems. The 200 Area ISA is a relatively simple facility consisting of a boundary fence with gates, perimeter lighting, and concrete and gravel pads on which to place the dry storage casks. The fence supports safeguards and security and establishes a radiation protection buffer zone. The 200 Area ISA is nominally 200,000 ft 2 and is located west of the Canister Storage Building (CSB). Interim storage at the 200 Area ISA is intended for a period of up to 40 years until the materials are shipped offsite to a disposal facility. This Final Safety Analysis Report (FSAR) does not address removal from storage or shipment from the 200 Area ISA. Three different SNF types contained in three different dry cask storage systems are to be stored at the 200 Area ISA, as follows: (1) Fast Flux Test Facility (FFTF) Fuel--Fifty-three interim storage casks (ISC), each holding a core component container (CCC), will be used to store the FFTF SNF currently in the 400 Area. (2) Neutron Radiography Facility (NRF)TRIGA--One Rad-Vault container stores two DOT-6M 3 containers and six NRF TRIGA casks. (3) Commercial Light Water Reactor Fuel--Six International Standards Organization (ISO) containers, each holding a NAC-1 cask with an inner commercial light water reactor (LWR) canister, are used for storing commercial LWR SNF from the 300 Area. An aboveground dry cask storage location is necessary for the spent fuel because the current storage facilities are being shut down and deactivated. The spent fuel is being transferred to interim storage because there is no permanent repository storage currently available

  2. Final hazard classification and auditable safety analysis for the 105-C Reactor Interim Safe Storage Project

    International Nuclear Information System (INIS)

    Rodovsky, T.J.; Larson, A.R.; Dexheimer, D.

    1996-12-01

    This document summarizes the inventories of radioactive and hazardous materials present in the 105-C Reactor Facility and the operations associated with the Interim Safe Storage Project which includes decontamination and demolition and interim safe storage of the remaining facility. This document also establishes a final hazard classification and verifies that appropriate and adequate safety functions and controls are in place to reduce or mitigate the risk associated with those operations

  3. Wave energy resource of Brazil: An analysis from 35 years of ERA-Interim reanalysis data

    Science.gov (United States)

    Araújo, Alex Maurício

    2017-01-01

    This paper presents a characterization of the wave power resource and an analysis of the wave power output for three (AquaBuoy, Pelamis and Wave Dragon) different wave energy converters (WEC) over the Brazilian offshore. To do so it used a 35 years reanalysis database from the ERA-Interim project. Annual and seasonal statistical analyzes of significant height and energy period were performed, and the directional variability of the incident waves were evaluated. The wave power resource was characterized in terms of the statistical parameters of mean, maximum, 95th percentile and standard deviation, and in terms of the temporal variability coefficients COV, SV e MV. From these analyses, the total annual wave power resource available over the Brazilian offshore was estimated in 89.97 GW, with largest mean wave power of 20.63 kW/m in the southernmost part of the study area. The analysis of the three WEC was based in the annual wave energy output and in the capacity factor. The higher capacity factor was 21.85% for Pelamis device at the southern region of the study area. PMID:28817731

  4. Sampling and analysis plan for Wayne Interim Storage Site (WISS), Wayne, New Jersey

    International Nuclear Information System (INIS)

    Brown, K.S.; Murray, M.E.; Rodriguez, R.E.

    1998-10-01

    This field sampling plan describes the methodology to perform an independent radiological verification survey and chemical characterization of a remediated area of the subpile at the Wayne Interim Storage Site, Wayne, New Jersey.Data obtained from collection and analysis of systematic and biased soil samples will be used to assess the status of remediation at the site and verify the final radiological status. The objective of this plan is to describe the methods for obtaining sufficient and valid measurements and analytical data to supplement and verify a radiological profile already established by the Project Remediation Management Contractor (PMC). The plan describes the procedure for obtaining sufficient and valid analytical data on soil samples following remediation of the first layer of the subpile. Samples will be taken from an area of the subpile measuring approximately 30 m by 80 m from which soil has been excavated to a depth of approximately 20 feet to confirm that the soil beneath the excavated area does not exceed radiological guidelines established for the site or chemical regulatory limits for inorganic metals. After the WISS has been fully remediated, the Department of Energy will release it for industrial/commercial land use in accordance with the Record of Decision. This plan provides supplemental instructions to guidelines and procedures established for sampling and analysis activities. Procedures will be referenced throughout this plan as applicable, and are available for review if necessary

  5. Wave energy resource of Brazil: An analysis from 35 years of ERA-Interim reanalysis data.

    Science.gov (United States)

    Espindola, Rafael Luz; Araújo, Alex Maurício

    2017-01-01

    This paper presents a characterization of the wave power resource and an analysis of the wave power output for three (AquaBuoy, Pelamis and Wave Dragon) different wave energy converters (WEC) over the Brazilian offshore. To do so it used a 35 years reanalysis database from the ERA-Interim project. Annual and seasonal statistical analyzes of significant height and energy period were performed, and the directional variability of the incident waves were evaluated. The wave power resource was characterized in terms of the statistical parameters of mean, maximum, 95th percentile and standard deviation, and in terms of the temporal variability coefficients COV, SV e MV. From these analyses, the total annual wave power resource available over the Brazilian offshore was estimated in 89.97 GW, with largest mean wave power of 20.63 kW/m in the southernmost part of the study area. The analysis of the three WEC was based in the annual wave energy output and in the capacity factor. The higher capacity factor was 21.85% for Pelamis device at the southern region of the study area.

  6. Final Hazard Classification and Auditable Safety Analysis for the 105-F Building Interim Safe Storage Project

    International Nuclear Information System (INIS)

    Rodovsky, T.J.; Bond, S.L.

    1998-07-01

    The auditable safety analysis (ASA) documents the authorization basis for the partial decommissioning and facility modifications to place the 105-F Building into interim safe storage (ISS). Placement into the ISS is consistent with the preferred alternative identified in the Record of Decision (58 FR). Modifications will reduce the potential for release and worker exposure to hazardous and radioactive materials, as well as lower surveillance and maintenance (S ampersand M) costs. This analysis includes the following: A description of the activities to be performed in the course of the 105-F Building ISS Project. An assessment of the inventory of radioactive and other hazardous materials within the 105-F Building. Identification of the hazards associated with the activities of the 105-F Building ISS Project. Identification of internally and externally initiated accident scenarios with the potential to produce significant local or offsite consequences during the 105-F Building ISS Project. Bounding evaluation of the consequences of the potentially significant accident scenarios. Hazard classification based on the bounding consequence evaluation. Associated safety function and controls, including commitments. Radiological and other employee safety and health considerations

  7. Wave energy resource of Brazil: An analysis from 35 years of ERA-Interim reanalysis data.

    Directory of Open Access Journals (Sweden)

    Rafael Luz Espindola

    Full Text Available This paper presents a characterization of the wave power resource and an analysis of the wave power output for three (AquaBuoy, Pelamis and Wave Dragon different wave energy converters (WEC over the Brazilian offshore. To do so it used a 35 years reanalysis database from the ERA-Interim project. Annual and seasonal statistical analyzes of significant height and energy period were performed, and the directional variability of the incident waves were evaluated. The wave power resource was characterized in terms of the statistical parameters of mean, maximum, 95th percentile and standard deviation, and in terms of the temporal variability coefficients COV, SV e MV. From these analyses, the total annual wave power resource available over the Brazilian offshore was estimated in 89.97 GW, with largest mean wave power of 20.63 kW/m in the southernmost part of the study area. The analysis of the three WEC was based in the annual wave energy output and in the capacity factor. The higher capacity factor was 21.85% for Pelamis device at the southern region of the study area.

  8. TSPO Imaging in Glioblastoma Multiforme

    DEFF Research Database (Denmark)

    Jensen, Per; Feng, Ling; Law, Ian

    2015-01-01

    -CLINDE is superior to (18)F-FET in predicting progression of glioblastoma multiforme (GBM) at follow-up. METHODS: Three patients with World Health Organization grade IV GBM were scanned with (123)I-CLINDE SPECT, (18)F-FET PET, and gadolinium-enhanced MR imaging. Molecular imaging data were compared with follow......-CLINDE (15%-30%). In contrast, VOIs of increased contrast enhancement at follow-up compared with baseline overlapped to a greater extent with baseline (123)I-CLINDE VOIs than (18)F-FET VOIs (21% vs. 8% and 72% vs. 55%). CONCLUSION: Our preliminary results suggest that TSPO brain imaging in GBM may...... be a useful tool for predicting tumor progression at follow-up and may be less susceptible to changes in blood-brain barrier permeability than (18)F-FET. Larger studies are warranted to test the clinical potential of TSPO imaging in GBM, including presurgical planning and radiotherapy....

  9. Re-use of pilot data and interim analysis of pivotal data in MRMC studies: a simulation study

    Science.gov (United States)

    Chen, Weijie; Samuelson, Frank; Sahiner, Berkman; Petrick, Nicholas

    2017-03-01

    Novel medical imaging devices are often evaluated with multi-reader multi-case (MRMC) studies in which radiologists read images of patient cases for a specified clinical task (e.g., cancer detection). A pilot study is often used to measure the effect size and variance parameters that are necessary for sizing a pivotal study (including sizing readers, non-diseased and diseased cases). Due to the practical difficulty of collecting patient cases or recruiting clinical readers, some investigators attempt to include the pilot data as part of their pivotal study. In other situations, some investigators attempt to perform an interim analysis of their pivotal study data based upon which the sample sizes may be re-estimated. Re-use of the pilot data or interim analyses of the pivotal data may inflate the type I error of the pivotal study. In this work, we use the Roe and Metz model to simulate MRMC data under the null hypothesis (i.e., two devices have equal diagnostic performance) and investigate the type I error rate for several practical designs involving re-use of pilot data or interim analysis of pivotal data. Our preliminary simulation results indicate that, under the simulation conditions we investigated, the inflation of type I error is none or only marginal for some design strategies (e.g., re-use of patient data without re-using readers, and size re-estimation without using the effect-size estimated in the interim analysis). Upon further verifications, these are potentially useful design methods in that they may help make a study less burdensome and have a better chance to succeed without substantial loss of the statistical rigor.

  10. Erythema multiforme associated with gemfibrozil monotherapy.

    Science.gov (United States)

    Yaçsar, Hamiyet Yilmaz; Ertuğrul, Ozden; Deniz, Coçskun

    2010-01-01

    A case of erythema multiforme associated with gemfibrozil monotherapy. A 46-year-old man with hyperlipidemia was treated with 600 mg gemfibrozil twice a day. On the fifth day of treatment, skin lesions consistent with erythema multiforme appeared. With the discontinuation of the treatment and start of a topical steroid treatment, the lesions recovered after 4 weeks. After 6 months, when gemfibrozil therapy was restarted, lesions reappeared on the fourth day of therapy. Lesions recovered again following the previous treatment strategies after 4 weeks. An objective casualty assessment suggests that erythema multiforme was probably related to gemfibrozil monotherapy. Patients starting gemfibrozil therapy should be warned about the occurrence of erythema multiforme in addition to previous reported and established side effects.

  11. Global Spent Fuel Logistics Systems Study (GSFLS). Volume 3A. GSFLS technical analysis (appendix). Interim report

    International Nuclear Information System (INIS)

    1978-01-01

    This report is a part of the interim report documentation for the Global Spent Fuel Logistics System (GSFLS) study. The technical and financial considerations underlying a global spent fuel logistics systems have been studied and are reported. The Pacific Basin is used as a model throughout this report; however the stated methodology and, in many cases, considerations and conclusions are applicable to other global regions. Spent fuel discharge profiles for Pacific Basin Countries were used to determine the technical systems requirements for alternative concepts. Functional analyses and flows were generated to define both system design requirements and logistics parameters. A technology review was made to ascertain the state-of-the-art of relevant GSFLS technical systems. Modular GSFLS facility designs were developed using the information generated from the functional analysis and technology review. The modular facility designs were used as a basis for siting and cost estimates for various GSFLS alternatives. Various GSFLS concepts were analyzed from a financial and economic perspective in order to provide total concepts costs and ascertain financial and economic sensitivities to key GSFLS variations. Results of the study include quantification of GSFLS facility and hardware requirements; drawings of relevant GSFLS facility designs; system cost estimates; financial reports - including user service charges; and comparative analyses of various GSFLS alternatives

  12. Global Spent Fuel Logistics Systems Study (GSFLS). Volume 3. GSFLS technical and financial analysis. Interim report

    International Nuclear Information System (INIS)

    1978-01-01

    This report is a part of the interim report documentation for the Global Spent Fuel Logistics System (GSFLS) study. The technical and financial considerations underlying a global spent fuel logistics systems have been studied and are reported herein. The Pacific Basin is used as a model throughout this report; however the stated methodology and, in many cases, considerations and conclusions are applicable to other global regions. Spent fuel discharge profiles for Pacific Basin Countries were used to determine the technical systems requirements for alternative concepts. Functional analyses and flows were generated to define both system design requirements and logistics parameters. A technology review was made to ascertain the state-of-the-art of relevant GSFLS technical systems. Modular GSFLS facility designs were developed using the information generated from the functional analysis and technology review. The modular facility designs were used as a basis for siting and cost estimates for various GSFLS alternatives. Various GSFLS concepts were analyzed from a financial and economic perspective in order to provide total concepts costs and ascertain financial and economic sensitivities to key GSFLS variations. Results of the study include quantification of GSFLS facility and hardware requirements; drawings of relevant GSFLS facility designs; system cost estimates; financial reports - including user service charges; and comparative analyses of various GSFLS alternatives

  13. Global Spent Fuel Logistics Systems Study (GSFLS). Volume 3A. GSFLS technical analysis (appendix). Interim report

    Energy Technology Data Exchange (ETDEWEB)

    Kriger, A.

    1978-01-31

    This report is a part of the interim report documentation for the Global Spent Fuel Logistics System (GSFLS) study. The technical and financial considerations underlying a global spent fuel logistics systems have been studied and are reported. The Pacific Basin is used as a model throughout this report; however the stated methodology and, in many cases, considerations and conclusions are applicable to other global regions. Spent fuel discharge profiles for Pacific Basin Countries were used to determine the technical systems requirements for alternative concepts. Functional analyses and flows were generated to define both system design requirements and logistics parameters. A technology review was made to ascertain the state-of-the-art of relevant GSFLS technical systems. Modular GSFLS facility designs were developed using the information generated from the functional analysis and technology review. The modular facility designs were used as a basis for siting and cost estimates for various GSFLS alternatives. Various GSFLS concepts were analyzed from a financial and economic perspective in order to provide total concepts costs and ascertain financial and economic sensitivities to key GSFLS variations. Results of the study include quantification of GSFLS facility and hardware requirements; drawings of relevant GSFLS facility designs; system cost estimates; financial reports - including user service charges; and comparative analyses of various GSFLS alternatives.

  14. Preparation of waste analysis plans under the Resource Conservation and Recovery Act (Interim guidance)

    International Nuclear Information System (INIS)

    1993-03-01

    This document is organized to coincide with the suggested structure of the actual Waste Analysis Plans (WAP) discussed in the previous section. The contents of the remaining eleven chapters and appendices that comprise this document are described below: Chapter 2 addresses waste streams, test parameters, and rationale for sampling and analytical method selection; test methods for analyzing parameters; proceduresfor collecting representative samples; and frequency of sample collection and analyses. These are the core WAP requirements. Chapter 3 addresses analysis requirements for waste received from off site. Chapter 4addresses additional requirements for ignitable, reactive, or incompatible wastes. Chapter 5 addresses unit-specific requirements. Chapter 6 addresses special procedures for radioactive mixed waste. Chapter 7 addresses wastes subject to the land disposal restrictions. Chapter 8 addresses QA/QC procedures. Chapter 9 compares the waste analysis requirements of an interim status facility with those of a permitted facility. Chapter 10 describes the petition process required for sampling and analytical procedures to deviate from accepted methods, such as those identified in promulgated regulations. Chapter 11 reviews the process for modification of WAPs as waste type or handling practices change at a RCRA permitted TSDF. Chapter 12 is the list of references that were used in the preparation of this guidance. Appendix A is a sample WAP addressing physical/chemical treatment and container storage. Appendix B is a sample WAP addressing an incinerator and tank systems. Appendix C discusses the relationship of the WAP to other permitting requirements and includes specific examples of how waste analysis is used to comply with certain parts of a RCRA permit. Appendix D contains the exact wording for the notification/certification requirements under theland disposal restrictions

  15. 1987 Federal interim storage fee study: A technical and economic analysis

    Energy Technology Data Exchange (ETDEWEB)

    1987-09-01

    This document is the latest in a series of reports that are published annually by Pacific Northwest Laboratory (PNL) for the US Department of Energy (DOE). This information in the report, which was prepared by E.R. Johnson Associates under subcontract to PNL, will be used by the DOE to establish a payment schedule for interim storage of spent nuclear fuel under the Federal Interim Storage (FIS) Program, which was mandated by the Nuclear Waste Policy Act of 1982. The information in this report will be used to establish the schedule of charges for FIS services for the year commencing January 1, 1988. 13 tabs.

  16. 1987 Federal interim storage fee study: A technical and economic analysis

    International Nuclear Information System (INIS)

    1987-09-01

    This document is the latest in a series of reports that are published annually by Pacific Northwest Laboratory (PNL) for the US Department of Energy (DOE). This information in the report, which was prepared by E.R. Johnson Associates under subcontract to PNL, will be used by the DOE to establish a payment schedule for interim storage of spent nuclear fuel under the Federal Interim Storage (FIS) Program, which was mandated by the Nuclear Waste Policy Act of 1982. The information in this report will be used to establish the schedule of charges for FIS services for the year commencing January 1, 1988. 13 tabs

  17. Alternatives generation and analysis report for immobilized low-level waste interim storage architecture

    Energy Technology Data Exchange (ETDEWEB)

    Burbank, D.A., Westinghouse Hanford

    1996-09-01

    The Immobilized Low-Level Waste Interim Storage subproject will provide storage capacity for immobilized low-level waste product sold to the U.S. Department of Energy by the privatization contractor. This report describes alternative Immobilized Low-Level Waste storage system architectures, evaluation criteria, and evaluation results to support the Immobilized Low-Level Waste storage system architecture selection decision process.

  18. Prognostic value of interim FDG-PET in Hodgkin lymphoma : systematic review and meta-analysis

    NARCIS (Netherlands)

    Adams, Hugo J A; Nievelstein, Rutger A J; Kwee, Thomas C.

    2015-01-01

    This study aimed to systematically review and meta-analyse the value of interim (18) F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in predicting treatment failure in Hodgkin lymphoma. MEDLINE was systematically searched for original studies that used standardized international

  19. Thermal-hydraulic experiment and analysis for interim dry storage of spent nuclear fuel

    International Nuclear Information System (INIS)

    Yoo, Seung Hun

    2011-02-01

    The experimental and numerical studies of interim storages for nuclear spent fuels have been performed to investigate thermal-hydraulic characteristics of the dry storage systems and to propose new methodologies for the analysis and the design. Three separate researches have been performed in the present study: (a) Development of a scaling methodology and thermal-hydraulic experiment of a single spent fuel assembly simulating a dry storage cask: (b) Full-scope simulation of a dry storage cask by the use of Computational Fluid Dynamics (CFD) code: (c) Thermal-hydraulic design of a tunnel-type interim storage facility. In the first study, a scaling methodology has been developed to design a scaled-down canister. The scaling was performed in two steps. For the first step, the height of a spent fuel assembly was reduced from full height to half height. In order to consider the effect of height reduction on the natural convection, the scaling law of Ishii and Kataoka (1984) was employed. For the second step, the quantity of spent fuel assemblies was reduced from multiple assemblies to a single assembly. The scaling methodology was validated through the comparison with the experiment of the TN24P cask. The Peak Cladding Temperature (PCT), temperature gradients, and the axial and radial temperature distribution in the nondimensional forms were in good agreement with the experimental data. Based on the developed methodology, we have performed a single assembly experiment which was designed to simulate the full scale of the TN24P cask. The experimental data was compared with the CFD calculations. It turns out that their PCTs were less than the maximum allowable temperature for the fuel cladding and that the differences of their PCTs were agreed within 3 .deg. C, which was less than measurement uncertainty. In the second study, the full-scope simulations of the TN24P cask were performed by FLUENT. In order to investigate the sensitivity of the numerical and physical

  20. A new consideration for the heat transfer coefficient and an analysis of the thermal stress of the high-interim pressure turbine casing model

    International Nuclear Information System (INIS)

    Um, Dall Sun

    2004-01-01

    In real design of the high and interim pressure turbine casing, it is one of the important things to figure out its thermal strain exactly. In this paper, with the establishment of the new concept for the heat transfer coefficient of steam that is one of the factors in analysis of the thermal stress for turbine casing, an analysis was done for one of the high and interim pressure turbine casings in operating domestically. The sensitivity analysis of the heat transfer coefficient of steam to the thermal strain of the turbine casing was done with a 2-D simple model. The analysis was also done with switching of the material properties of the turbine casing and resulted in that the thermal strain of the turbine casing was not so sensitive to the heat transfer coefficient of steam. On the basis of this, 3-D analysis of the thermal strain for the high and interim pressure turbine casing was done

  1. Federal interim storage fee study for civilian spent nuclear fuel: a technical and economical analysis

    International Nuclear Information System (INIS)

    1983-07-01

    This report describes the study conducted by the Department of Energy (the Department) regarding payment charges for the federal interim storage (FIS) of spent fuel and presents the details of the study results. It describes the selection of a methodology for calculating a FIS fee schedule, sets forth the estimates of cost for construction and operation of FIS facilities, provides a range of estimates for the fee for FIS services, and identifies special contractual considerations associated with providing FIS services to authorized users. The fee is structured for a range of spent fuel capacities because of uncertainties regarding the schedule of availability and amount of spent fuel that may require and qualify for FIS. The results set forth in the report were used as a basis for development of the report entitled Payment Charges for Federal Interim Storage of Spent Nuclear Fuel from Civilian Nuclear Power Plants in the United States, dated July 1983

  2. The probabilistic risk analysis of external hazards of an interim storage for spent nuclear fuel in Olkiluoto

    International Nuclear Information System (INIS)

    Puukka, Tiia

    2014-01-01

    Due to natural disasters occurred in the world and the experiences perceived of the Fukushima nuclear accident, the particular knowledge of the role and influence of external hazards in the safety of interim storage of spent nuclear fuel has been emphasized. For that reason it is substantial that they are included in the probabilistic risk assessment (PRA) of the interim storage facility. This is also required by the Regulatory Guides issued by The Finnish Radiation and Nuclear Safety Authority STUK. To enhance safety culture and nuclear safety in Olkiluoto, The Finnish utility Teollisuuden Voima Oyj has recently completed an analysis of external natural (seismic events are studied as a separate analysis) and unintentional human-induced risks associated with the spent fuel pool cooling and decay heat removal systems as part of the full-scope PRA study for the interim storage of spent fuel (KPA store). The analysis had four goals to achieve: (1) to determine the definition of an initiating event in the context of the KPA store, (2) to identify all potential external hazards and hazard combinations, (3) to perform a qualitative screening analysis based on frequency-strength analysis and detailed plant responses analysis and (4) to model the hazards passed the screening analysis so that model can be used as a risk analysis tool in the risk informed decision making and operating procedures. The assessment carried out included the analysis of operation procedures of decay heat removal, the study of external hazards related initiating events included in the PRA of the OL1 and OL2 nuclear power plants and their dependencies on the initiating events of the KPA store. All external hazards related initiating events were modeled using fault tree linking method. The main result and conclusion of this study was that using the screening analysis, initiating events caused by external hazards that could lead to leakage of the spent fuel pools or that could pose a threat to the

  3. Analysis of the interim safe storage of reactors at the Hanford site

    International Nuclear Information System (INIS)

    Wang Hailiang

    2014-01-01

    The nine production reactors, i.e. B, C, D, DR, F, H, KE, KW and N, at the Hanford site are all water-cooled and graphite-moderated reactors with natural uranium fuel. In 1993, the U.S. Department of Energy (DOE) decided to put eight production reactors (except for B) into Interim Safe Storage (ISS) for 75 years followed by deferred one-piece removal. Reactor B will remain as a national historical landmark. By the end of 2013, six reactors C, F, D, DR, H and N had been successfully put into the ISS. Reactors KE and KW will be put into the ISS in the coming years. Taking reactor C as an example, this paper mainly talks about how to put the production reactors in the Interim Safe Storage, e.g. how to make site preparation, how to construct the safe storage enclosure (SSE) and how to perform surveillance and maintenance during the ISS period, etc. (authors)

  4. Value of information: interim analysis of a randomized, controlled trial of goal-directed hemodynamic treatment for aged patients.

    Science.gov (United States)

    Bartha, Erzsebet; Davidson, Thomas; Brodtkorb, Thor-Henrik; Carlsson, Per; Kalman, Sigridur

    2013-07-09

    A randomized, controlled trial, intended to include 460 patients, is currently studying peroperative goal-directed hemodynamic treatment (GDHT) of aged hip-fracture patients. Interim efficacy analysis performed on the first 100 patients was statistically uncertain; thus, the trial is continuing in accordance with the trial protocol. This raised the present investigation's main question: Is it reasonable to continue to fund the trial to decrease uncertainty? To answer this question, a previously developed probabilistic cost-effectiveness model was used. That model depicts (1) a choice between routine fluid treatment and GDHT, given uncertainty of current evidence and (2) the monetary value of further data collection to decrease uncertainty. This monetary value, that is, the expected value of perfect information (EVPI), could be used to compare future research costs. Thus, the primary aim of the present investigation was to analyze EVPI of an ongoing trial with interim efficacy observed. A previously developed probabilistic decision analytic cost-effectiveness model was employed to compare the routine fluid treatment to GDHT. Results from the interim analysis, published trials, the meta-analysis, and the registry data were used as model inputs. EVPI was predicted using (1) combined uncertainty of model inputs; (2) threshold value of society's willingness to pay for one, quality-adjusted life-year; and (3) estimated number of future patients exposed to choice between GDHT and routine fluid treatment during the expected lifetime of GDHT. If a decision to use GDHT were based on cost-effectiveness, then the decision would have a substantial degree of uncertainty. Assuming a 5-year lifetime of GDHT in clinical practice, the number of patients who would be subject to future decisions was 30,400. EVPI per patient would be €204 at a €20,000 threshold value of society's willingness to pay for one quality-adjusted life-year. Given a future population of 30,400 individuals

  5. Immobilized High-Level Waste (HLW) Interim Storage Alternative Generation and analysis and Decision Report - second Generation Implementing Architecture

    International Nuclear Information System (INIS)

    CALMUS, R.B.

    2000-01-01

    Two alternative approaches were previously identified to provide second-generation interim storage of Immobilized High-Level Waste (IHLW). One approach was retrofit modification of the Fuel and Materials Examination Facility (FMEF) to accommodate IHLW. The results of the evaluation of the FMEF as the second-generation IHLW interim storage facility and subsequent decision process are provided in this document

  6. Glioblastoma multiforme after radiotherapy for acromegaly

    Energy Technology Data Exchange (ETDEWEB)

    Piatt, J.H. Jr.; Blue, J.M.; Schold, S.C. Jr.; Burger, P.C.

    1983-07-01

    A case of glioblastoma multiforme that occurred 14 years after radiotherapy for acromegaly is presented. The striking correspondence between the anatomy of the tumor and the geometry of the radiation ports is suggestive of a causal relationship. Previously reported cases of radiation-associated glioma are reviewed, and a brief appraisal of the evidence for induction of these lesions by radiation is presented. The differentiation of radiation-associated neoplasms from radionecrosis is also discussed.

  7. Glioblastoma multiforme after radiotherapy for acromegaly

    International Nuclear Information System (INIS)

    Piatt, J.H. Jr.; Blue, J.M.; Schold, S.C. Jr.; Burger, P.C.

    1983-01-01

    A case of glioblastoma multiforme that occurred 14 years after radiotherapy for acromegaly is presented. The striking correspondence between the anatomy of the tumor and the geometry of the radiation ports is suggestive of a causal relationship. Previously reported cases of radiation-associated glioma are reviewed, and a brief appraisal of the evidence for induction of these lesions by radiation is presented. The differentiation of radiation-associated neoplasms from radionecrosis is also discussed

  8. Interim report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1985-06-01

    This Interim Report summarizes the research and development activities of the Superconducting Super Collider project carried out from the completion of the Reference Designs Study (May 1984) to June 1985. It was prepared by the SSC Central Design Group in draft form on the occasion of the DOE Annual Review, June 19--21, 1985. Now largely organized by CDG Divisions, the bulk of each chapter documents the progress and accomplishments to date, while the final section(s) describe plans for future work. Chapter 1, Introduction, provides a basic brief description of the SSC, its physics justification, its origins, and the R&D organization set up to carry out the work. Chapter 2 gives a summary of the main results of the R&D program, the tasks assigned to the four magnet R&D centers, and an overview of the future plans. The reader wishing a quick look at the SSC Phase I effort can skim Chapter 1 and read Chapter 2. Subsequent chapters discuss in more detail the activities on accelerator physics, accelerator systems, magnets and cryostats, injector, detector R&D, conventional facilities, and project planning and management. The magnet chapter (5) documents in text and photographs the impressive progress in successful construction of many model magnets, the development of cryostats with low heat leaks, and the improvement in current-carrying capacity of superconducting strand. Chapter 9 contains the budgets and schedules of the COG Divisions, the overall R&D program, including the laboratories, and also preliminary projections for construction. Appendices provide information on the various panels, task forces and workshops held by the CDG in FY 1985, a bibliography of COG and Laboratory reports on SSC and SSC-related work, and on private industrial involvement in the project.

  9. 1984 Federal Interim Storage fee study: a technical and economic analysis

    International Nuclear Information System (INIS)

    Engel, R.L.

    1984-07-01

    JAI examined alternative methods for structuring charges for Federal Interim Storage (FIS) services were examined and the conclusion reached that the combined interests of the Department and the users would be best served, and costs most appropriately recovered, by a two-part fee involving an Initial Payment upon execution of a contract for FIS services followed by a Final Payment upon delivery of the spent fuel to the Department. The Initial Payment would be an advance payment covering the pro rata share of preoperational costs, including (1) the capital costs of the required transfer facilities and storage area, (2) development costs, (3) government administrative costs including storage fund management, and (4) impact aid payments made in accordance with section 136(e) of the Act. The Final Payment would be made at the time of delivery of the spent fuel to the Department and would be calculated to cover the sum of the following: (1) any under-or over-estimation in the costs used to calculate the Initial Payment of the fee including savings due to rod consolidation), (2) module costs (i.e., storage casks, drywells, or silos), and (3) the total estimated cost of operation and decommissioning of the FIS facilities (including government administrative costs, storage fund management and impact aid). Charges for the transport of spent fuel from the reactor site to FIS facilities would be separately assessed at cost since these will be specific to each reactor site and destination

  10. Online Monitoring Technical Basis and Analysis Framework for Large Power Transformers; Interim Report for FY 2012

    Energy Technology Data Exchange (ETDEWEB)

    Nancy J. Lybeck; Vivek Agarwal; Binh T. Pham; Heather D. Medema; Kirk Fitzgerald

    2012-09-01

    The Light Water Reactor Sustainability program at Idaho National Laboratory (INL) is actively conducting research to develop and demonstrate online monitoring (OLM) capabilities for active components in existing Nuclear Power Plants. A pilot project is currently underway to apply OLM to Generator Step-Up Transformers (GSUs) and Emergency Diesel Generators (EDGs). INL and the Electric Power Research Institute (EPRI) are working jointly to implement the pilot project. The EPRI Fleet-Wide Prognostic and Health Management (FW-PHM) Software Suite will be used to implement monitoring in conjunction with utility partners: the Shearon Harris Nuclear Generating Station (owned by Duke Energy for GSUs, and Braidwood Generating Station (owned by Exelon Corporation) for EDGs. This report presents monitoring techniques, fault signatures, and diagnostic and prognostic models for GSUs. GSUs are main transformers that are directly connected to generators, stepping up the voltage from the generator output voltage to the highest transmission voltages for supplying electricity to the transmission grid. Technical experts from Shearon Harris are assisting INL and EPRI in identifying critical faults and defining fault signatures associated with each fault. The resulting diagnostic models will be implemented in the FW-PHM Software Suite and tested using data from Shearon-Harris. Parallel research on EDGs is being conducted, and will be reported in an interim report during the first quarter of fiscal year 2013.

  11. RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls

    Directory of Open Access Journals (Sweden)

    Noerholm Mikkel

    2012-01-01

    Full Text Available Abstract Background RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients. Methods Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N = 9 and normal controls (N = 7 were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N = 10 in both groups. Results Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes > 2-fold down in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size Conclusions Serum microvesicle RNA from patients with glioblastoma multiforme has significantly down-regulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size

  12. RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls

    International Nuclear Information System (INIS)

    Noerholm, Mikkel; Balaj, Leonora; Limperg, Tobias; Salehi, Afshin; Zhu, Lin Dan; Hochberg, Fred H; Breakefield, Xandra O; Carter, Bob S; Skog, Johan

    2012-01-01

    RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients. Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N = 9) and normal controls (N = 7) were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N = 10 in both groups). Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes > 2-fold down) in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size < 500 nt. Gene ontology of the down-regulated genes indicated these are coding for ribosomal proteins and genes related to ribosome production. Serum microvesicle RNA from patients with glioblastoma multiforme has significantly down-regulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size < 500 nt

  13. Randomized Clinical Trial Comparing Proton Beam Radiation Therapy with Transarterial Chemoembolization for Hepatocellular Carcinoma: Results of an Interim Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bush, David A., E-mail: dbush@llu.edu [Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California (United States); Smith, Jason C. [Department of Diagnostic Radiology, Loma Linda University Medical Center, Loma Linda, California (United States); Slater, Jerry D. [Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California (United States); Volk, Michael L. [Transplantation Institute and Liver Center, Loma Linda University Medical Center, Loma Linda, California (United States); Reeves, Mark E. [VA Loma Linda Health Care System, Loma Linda, California (United States); Cheng, Jason [Transplantation Institute and Liver Center, Loma Linda University Medical Center, Loma Linda, California (United States); Grove, Roger [Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California (United States); Vera, Michael E. de [Transplantation Institute and Liver Center, Loma Linda University Medical Center, Loma Linda, California (United States)

    2016-05-01

    Purpose: To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC). Methods and Materials: Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractions over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization. Results: At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group. Conclusions: This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are

  14. 1986 Federal Interim Storage fee study: a technical and economic analysis

    International Nuclear Information System (INIS)

    1986-09-01

    JAI examined alternative methods for structuring charges for federal interim storage (FIS) services and concluded that the combined interests of the Department and the users would be best served, and costs most appropriately recovered, by a two-part fee involving an Initial Payment upon execution of a contract for FIS services followed by a Final Payment upon delivery of the spent fuel to the Department. The Initial Payment would be an advance payment covering the pro rata share of preoperational costs, including (1) the capital costs of the required transfer facilities and storage area, (2) development costs, (3) government administrative costs including storage fund management, (4) impact aid payments made in accordance with Section 136(e) of the Act, and (5) module costs (i.e., storage casks, drywells or silos). The Final Payment would be made at the time of delivery of the spent fuel to the Department and would be calculated to cover the sum of the following: (1) any under- or over-estimation in the costs used to calculate the Initial Payment of the fee (including savings due to rod consolidation), and (2) the total estimated cost of operation and decommissioning of the FIS facilities (including government administrative costs, storage fund management and impact aid). The module costs were included in the Initial Payment to preclude the possible need to obtain appropriations for federal funds to support the purchase of the modules in advance of receipt of the Final Payment. Charges for the transport of spent fuel from the reactor site to FIS facilities would be separately assessed at actual cost since these will be specific to each reactor site and destination

  15. Erythema multiforme due to contact with laurel oil.

    Science.gov (United States)

    Athanasiadis, G I; Pfab, F; Klein, A; Braun-Falco, M; Ring, J; Ollert, M

    2007-08-01

    Erythema multiforme is a relatively common skin disorder. The best known cause is herpes simplex virus infection. We report the first case of erythema multiforme due to contact with laurel oil. The diagnosis was confirmed by the positive patch test to laurel oil, the histopathological studies of the lesions and the histopathological studies of the positive patch test to laurel oil.

  16. Multiform structures of SnO2 nanobelts

    International Nuclear Information System (INIS)

    Duan Junhong; Gong Jiangfeng; Huang Hongbo; Zhao Xiaoning; Cheng Guangxu; Yu Zhongzhen; Yang Shaoguang

    2007-01-01

    Multiform SnO 2 microstructures were synthesized by a facile thermal evaporation of tin grains. The product was characterized with a variety of techniques to obtain the structural and optical information. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images showed a large percentage of acute angle zigzag nanobelts with perfectly periodic morphology. High resolution transmission electron microscopy (HRTEM) images and selected area electron diffraction (SAED) patterns revealed that the zigzag nanobelts were single crystalline and their zone axis was along the [010] crystal direction. The growth mechanism of zigzag nanobelts was proposed based on TEM characterization and thermodynamic analysis. The zigzag nanobelts were deduced to be formed by changing the growth direction from [101-bar] to [101] or vice versa. The photoluminescence (PL) spectroscopy of the nanobelts showed a broad and strong luminescence emission centred at 550 nm

  17. Eritema multiforme mayor desencadenado por antimicrobianos

    Directory of Open Access Journals (Sweden)

    Ronaldo de Carvalho Raimundo

    2010-03-01

    Full Text Available El eritema multiforme, aparece como una enfermedad sistémica con la participación de la piel y las membranas mucosas en relación con varios factores como las infecciones bacterianas o virales, y en particular la administración de drogas, analgésicos y antibióticos en general. Se presenta un paciente masculino de 29 años de edad con eritema multiforme mayor desencadenado por antimicrobianos con la aparición de lesiones vesiculares-bulloso-ulcerosas en las regiones de los labios, encías, la lengua y la mucosa genital en tratamiento de una infección del tracto urinario con norfloxacino 400 mg por una semana. Fue realizado un tratamiento de soporte con el uso de colutorios para la higienización bucal y pomada a base de corticoide para protección de las úlceras, antihistamínicos y orientación nutricional de dieta líquida hipercalórica e hiperproteica. Este síndrome está caracterizado como un proceso eruptivo buloso agudo que compromete la calidad de vida del paciente y no hay pruebas de laboratorio específicas por lo que su diagnóstico debe estar basado en la revisión minuciosa de la anamnesis y en los hallazgos clínicos.

  18. Safety and effectiveness of certolizumab pegol in patients with rheumatoid arthritis: Interim analysis of post-marketing surveillance.

    Science.gov (United States)

    Kameda, Hideto; Nishida, Keiichiro; Nannki, Toshihiro; Watanabe, Akira; Oshima, Yukiya; Momohara, Shigaki

    2017-01-01

    Objective: To evaluate the safety and effectiveness of certolizumab pegol (CZP) in a real-world setting among Japanese patients with rheumatoid arthritis. Post-marketing surveillance data from 2,579 patients treated with CZP were analyzed. Adverse events (AEs) observed during the 24-week CZP treatment period were recorded. Disease activity was evaluated using DAS28-ESR and DAS28-CRP at baseline, Week 12, Week 24, or at withdrawal. The total period of exposure to CZP was 1313.8 patient-years (PY). AEs were reported in 658 (25.5%) patients, at an event rate (ER) of 73.68/100 PY. The most frequent serious AEs were pneumonia, herpes zoster, and interstitial lung disease, at ER per 100 PY of 2.06, 1.29, and 1.22, respectively. Mean disease activity scores at baseline, as measured by DAS28-ESR and DAS28-CRP, were 4.77 ± 1.34 and 4.21 ± 1.27, respectively. Mean changes from baseline at the last observation were -1.29 ± 1.46 and -1.30 ± 1.42, respectively. EULAR good or moderate responses were achieved in 65% of patients. Longer disease duration, prior biologics use, and treatment without MTX co-therapy were associated with EULAR no response. In this interim analysis, no new safety signals were observed. Clinical response to CZP was observed in approximately two thirds of patients.

  19. Statin use and survival following glioblastoma multiforme

    DEFF Research Database (Denmark)

    Gaist, David; Hallas, Jesper; Friis, Søren

    2014-01-01

    with glioblastoma multiforme (GBM). METHODS: We identified 1562 patients diagnosed with GBM during 2000-2009 from the Danish Cancer Registry and linked this cohort to Danish nationwide demographic and health registries. Within the GBM cohort, each patient recorded as using statins prior to diagnosis (defined as ≥2......-cause death associated with prediagnostic statin use. RESULTS: A total of 339 GBM patients were included in the analyses. Of these, 325 died during median follow-up of 6.9 months (interquartile range: 3.8-13.4 months). Prediagnostic statin use was associated with a reduced HR of death (0.79; 95% CI: 0......: 0.63-1.01). CONCLUSION: Long-term prediagnostic statin use may improve survival following GBM....

  20. Chlamydia pneumoniae infection-associated erythema multiforme

    Directory of Open Access Journals (Sweden)

    Shinsaku Imashuku

    2013-06-01

    Full Text Available There is a well-known correlation between Herpes simplex (HSV infection and erythema multiforme (EM. More recently, in Japan, it was found that Chlamydia pneumoniae (Cp may promote the development of EM. All cases of Cp infection-associated EM that had been diagnosed in our clinic over the past two years (from 2011 to 2012 were analyzed. Cp infection was diagnosed on the basis of a significant increase (>2.00 in anti-Cp IgM titers, as measured by the HITAZYME-ELISA test. There were 7 cases of Cp-EM, one male and 6 females. Median age was 13 years (range 3-29 years. It is recommended that the possible involvement of Cp infection, besides HSV or Mycoplasma pneumoniae infections, should be considered in all cases of EM.

  1. Glioblastoma Multiforme and Lipid Nanocapsules: A Review.

    Science.gov (United States)

    Aparicio-Blanco, Juan; Torres-Suárez, Ana-Isabel

    2015-08-01

    Epidemiological data on central nervous system disorders call for a focus on the major hindrance to brain drug delivery, blood-central nervous system barriers. Otherwise, there is little chance of improving the short-term survival of patients with diseases such as glioblastoma multiforme, which is one of the brain disorders associated with many years of life lost. Targetable nanocarriers for treating malignant gliomas are a unique way to overcome low chemotherapeutic levels at target sites devoid of systemic toxicity. This review describes the currently available targetable nanocarriers, focusing particularly on one of the newest nanocarriers, lipid nanocapsules. All of the strategies that are likely to be exploited by lipid nanocapsules to bypass blood-central nervous system barriers, including the most recent targeting approaches (mesenchymal cells), and novel administration routes (convection enhanced delivery) are discussed, together with their most remarkable achievements in glioma-implanted animal models. Although these systems are promising, much research remains to be done in this field.

  2. Glioblastoma Multiforme Presenting as Spontaneous Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Cagatay Ozdol

    2014-06-01

    Full Text Available Brain tumors with concomitant intracerebral hemorrhage are rarely encountered. Hemorrhage as the initial presentation of a brain tumour may pose some diagnostic problems, especially if the tumour is small or the hemorrhage is abundant. We present a 47-year-old man who admitted to the emergency department with sudden onset headache, right blurred vision and gait disturbance. A non-contrast cranial computerized tomography scan performed immediately after his admission revealed a well circumscribed right occipitoparietal haematoma with intense peripheral edema causing compression of the ipsilateral ventricles. On 6th hour of his admission the patient%u2019s neurological status deteriorated and he subsequently underwent emergent craniotomy and microsurgical evacuation of the haematoma. The histopathological examination of the mass was consistent with a glioblastoma multiforme. Neoplasms may be hidden behind each case of spontaneous intracerebral hemorrhage. Histological sampling and investigation is mandatory in the presence of preoperative radiological features suggesting a neoplasm.

  3. Comparisons of Cooperative and Non-Cooperative Students: An Analysis of Student Accounting System Data. Interim Report, June, 1981.

    Science.gov (United States)

    Frazier, Don

    The major purpose of this study was to identify unique effects of cooperative vocational education. This interim report is of results of the analyses of existing data bases. Comparisons of cooperative and non-cooperative vocational programs are made on the following variables: enrollments by age, sex and race, school status, work status,…

  4. Cost Sensitivity Analysis for Consolidated Interim Storage of Spent Fuel: Evaluating the Effect of Economic Environment Parameters

    Energy Technology Data Exchange (ETDEWEB)

    Cumberland, Riley M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Williams, Kent Alan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jarrell, Joshua J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Joseph, III, Robert Anthony [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-12-01

    This report evaluates how the economic environment (i.e., discount rate, inflation rate, escalation rate) can impact previously estimated differences in lifecycle costs between an integrated waste management system with an interim storage facility (ISF) and a similar system without an ISF.

  5. TCGA Workshop: Genomics and Biology of Glioblastoma Multiforme (GBM) - TCGA

    Science.gov (United States)

    The National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI) held a workshop entitled, “Genomics and Biology of Glioblastoma Multiforme (GBM),” to review the initial GBM data from the TCGA pilot project.

  6. Interim reliability-evaluation program: analysis of the Browns Ferry, Unit 1, nuclear plant. Appendix B - system descriptions and fault trees

    International Nuclear Information System (INIS)

    Mays, S.E.; Poloski, J.P.; Sullivan, W.H.; Trainer, J.E.; Bertucio, R.C.; Leahy, T.J.

    1982-07-01

    This report describes a risk study of the Browns Ferry, Unit 1, nuclear plant. The study is one of four such studies sponsored by the NRC Office of Research, Division of Risk Assessment, as part of its Interim Reliability Evaluation Program (IREP), Phase II. This report is contained in four volumes: a main report and three appendixes. Appendix B provides a description of Browns Ferry, Unit 1, plant systems and the failure evaluation of those systems as they apply to accidents at Browns Ferry. Information is presented concerning front-line system fault analysis; support system fault analysis; human error models and probabilities; and generic control circuit analyses

  7. Data Analysis of GPM Constellation Satellites-IMERG and ERA-Interim precipitation products over West of Iran

    Science.gov (United States)

    Sharifi, Ehsan; Steinacker, Reinhold; Saghafian, Bahram

    2016-04-01

    Precipitation is a critical component of the Earth's hydrological cycle. The primary requirement in precipitation measurement is to know where and how much precipitation is falling at any given time. Especially in data sparse regions with insufficient radar coverage, satellite information can provide a spatial and temporal context. Nonetheless, evaluation of satellite precipitation is essential prior to operational use. This is why many previous studies are devoted to the validation of satellite estimation. Accurate quantitative precipitation estimation over mountainous basins is of great importance because of their susceptibility to hazards. In situ observations over mountainous areas are mostly limited, but currently available satellite precipitation products can potentially provide the precipitation estimation needed for meteorological and hydrological applications. One of the newest and blended methods that use multi-satellites and multi-sensors has been developed for estimating global precipitation. The considered data set known as Integrated Multi-satellitE Retrievals (IMERG) for GPM (Global Precipitation Measurement) is routinely produced by the GPM constellation satellites. Moreover, recent efforts have been put into the improvement of the precipitation products derived from reanalysis systems, which has led to significant progress. One of the best and a worldwide used model is developed by the European Centre for Medium Range Weather Forecasts (ECMWF). They have produced global reanalysis daily precipitation, known as ERA-Interim. This study has evaluated one year of precipitation data from the GPM-IMERG and ERA-Interim reanalysis daily time series over West of Iran. IMERG and ERA-Interim yield underestimate the observed values while IMERG underestimated slightly and performed better when precipitation is greater than 10mm. Furthermore, with respect to evaluation of probability of detection (POD), threat score (TS), false alarm ratio (FAR) and probability

  8. Analysis of Dust Samples Collected from an In-Service Interim Storage System at the Maine Yankee Nuclear Site.

    Energy Technology Data Exchange (ETDEWEB)

    Bryan, Charles R.; Enos, David

    2016-10-01

    In July, 2016, the Electric Power Research Institute and industry partners performed a field test at the Maine Yankee Nuclear Site, located near Wiscasset, Maine. The primary goal of the field test was to evaluate the use of robots in surveying the surface of an in-service interim storage canister within an overpack; however, as part of the demonstration, dust and soluble salt samples were collected from horizontal surfaces within the interim storage system. The storage system is a vertical system made by NAC International, consisting of a steel-lined concrete overpack containing a 304 stainless steel (SS) welded storage canister. The canister did not contain spent fuel but rather greater-than-class-C waste, which did not generate significant heat, limiting airflow through the storage system. The surfaces that were sampled for deposits included the top of the shield plug, the side of the canister, and a shelf at the bottom of the overpack, just below the level of the pillar on which the canister sits. The samples were sent to Sandia National Laboratories for analysis. This report summarizes the results of those analyses. Because the primary goal of the field test was to evaluate the use of robots in surveying the surface of the canister within the overpack, collection of dust samples was carried out in a qualitative fashion, using paper filters and sponges as the sampling media. The sampling focused mostly on determining the composition of soluble salts present in the dust. It was anticipated that a wet substrate would more effectively extract soluble salts from the surface that was sampled, so both the sponges and the filter paper were wetted prior to being applied to the surface of the metal. Sampling was accomplished by simply pressing the damp substrate against the metal surface for two minutes, and then removing it. It is unlikely that the sampling method quantitatively collected dust or salts from the metal surface; however, both substrates did extract a

  9. Analysis and comparison of biomass pyrolysis/gasification condensates: an interim report

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, D.C.

    1985-09-01

    This report provides results of chemical and physical analysis of condensates from eleven biomass gasification and pyrolysis systems. The analyses were performed in order to provide more detailed data concerning these condensates for the different process research groups and to allow a determination of the differences in properties of the condensates as a function of reactor environment. The samples were representative of the various reactor configurations being researched within the Department of Energy, Biomass Thermochemical Conversion program. The condensates included tar phases, aqueous phases and, in some cases, both phases depending on the output of the particular reactor system. The analyses included gross compositional analysis (elemental analysis, ash, moisture), physical characterization (pour point, viscosity, density, heat of combustion, distillation), specific chemical analysis (gas chromatography/mass spectrometry, infrared spectrophotometry, proton and carbon-13 nuclear magnetic resonance spectrometry) and biological activity (Ames assay). The analytical data demonstrate the wide range of chemical composition of the organics recovered in the condensates and suggests a direct relationship between operating temperature and chemical composition of the condensates. A continuous pathway of thermal degradation of the tar components as a function of temperature is proposed. Variations in the chemical composition of the organic components in the tars are reflected in the physical properties of tars and phase stability in relation to water in the condensate. The biological activity appears to be limited to the tars produced at high temperatures as a result of formation of polycyclic aromatic hydrocarbons in high concentrations. 55 refs., 13 figs., 6 tabs.

  10. Diesel-generator reliability at nuclear power plants: data and preliminary analysis. Interim report

    International Nuclear Information System (INIS)

    McClymont, A.; McLagan, G.

    1982-06-01

    This report summarizes work performed under RP1233-1 relating to the collection and analysis of data pertaining to diesel generator reliability in nuclear power plants. Drawing from data collected on-site at plants, data supplied by utilites, and data from Licensee Event Reports (LERs), the report describes methods of deriving reliability estimates from data for use in probabilistic risk assessment and presents results when these methods are applied to data collected from 14 plants. Specifically, data are used to estimate diesel failure probabilities for failures to start and failure rates for failures to continue to run. A sampling theory approach and a Bayesian approach to failure probability estimation are compared. The data are used to derive estimates of diesel repair time for some plants, maintenance outages, and multiple diesel failure rates. In addition, a section is included that presents suggestions for failure-rate estimation when an accurate count of diesel start attempts at a plant is not available. The final section presents an analysis of diesel failures based on data from LERs, including a breakdown of failure event by subsystem, failure mode, and failure cause. Appendixes include detailed summaries of the data used in the analysis of previous sections

  11. Secure automated fabrication (SAF). Phase I interim report: a systems analysis

    International Nuclear Information System (INIS)

    1979-01-01

    An advanced Secure Automated Fabrication (SAF) System is being developed for mixed uranium and plutonium fuel fabrication. SAF System development will ultimately result in systems which maximize personnel radiation protection, restrict and control access to SNM material, improve containment and detection systems for nuclear materials, provide adequate SNM accountability and improve product uniformity and quality. A systems requirement analysis study was initiated to establish the consistent and objective set of requirements within which the choice among alternatives represents the balanced viewpoints of performance, achievability and risk

  12. Water Quality Analysis Study Pond and Interim Storage for Spent Fuel

    International Nuclear Information System (INIS)

    Dyah Sulistyani R; Husen Zamroni; Sudiyati

    2007-01-01

    Purification system of Storage facility of spent fuel which there is in Indonesia is integrated purification system. Reservoir pond of fuel contains approximately 995 m 3 demin water and in pond equipped with some of reservoir racks of spent fuel which must always avoid from factor-factor causing corrosion. In process of this purification system, water impurity which has been activation and also which is not is activation before will filtered and catch by passing of ion exchange so that will reduce conductivity and fuel coolant water activity. Water quality pond and canals links must fulfill specifications, among other: degree of acidity (pH) primary cooling water ranges from 5.5 and 6.5 ; its conductivity 1 - 8 μ S/cm, content analysis CI 0.03 - 0.06 ppm and NO 3 0.1 - 0.2 ppm, radionuclide activity Cs 137 742 Bq/l and Co 60 657 Bq/l and the temperature be kept of less than 40℃ to avoid from corrosion speed. (author)

  13. Biological contaminants and house characteristics : an interim analysis of data from the PEI study

    Energy Technology Data Exchange (ETDEWEB)

    Onysko, D.M. [DMO Associates (Canada); Ruest, K. [Canada Mortgage and Housing Corp., Ottawa, ON (Canada); Lawton, M. [Morrison Hershfield Ltd., Ottawa, ON (Canada); Miller, D. [Carleton Univ., Ottawa, ON (Canada); Fraser, B. [Jacques Whitford and Associates Limited, Ottawa, ON (Canada); Dale, R. [Health Canada, Ottawa, ON (Canada); Kazimierz, K.F.

    2005-07-01

    This paper discussed the results of a joint study on housing conditions, biological exposure and the health of infants in Prince Edward Island (PEI). The study was a longitudinal cohort investigation of the exposure of infants to biological materials in their home environments. Possible associations between housing data, biological data, operational circumstances and relevant family life style information were presented. A methodology of the study was presented, in which a total of 366 dwellings with newborn infants were monitored over a period of 6 years. All tests and inspections were presented, as well as the nature of variables in the study. House investigations included the following: housing and operational characteristics; variables related to the measure of molds in the air; mold areas as determined by visual inspection; the presence/absence of visible molds; past wetting events; and concentrations of endotoxins, ergosterol and allergens in various air and settled dust samples. It was concluded that there was support for the presumption that some housing characteristics were related to factors that may influence the health of occupants and their children. Moisture related concerns dominated the experimental design. Details of the following housing characteristics were summarized: ground moisture source coupling; operation of the residence by the occupant; analysis of dust samples; visible molds; and wetting events. It was concluded that further work is needed to review the final database in order to further correlate studies with the health of newborns who lived in the houses studied. 3 refs., 8 tabs., 4 figs.

  14. Eritema multiforme mayor desencadenado por antimicrobianos Big multiform erythema triggered by antimicrobials

    Directory of Open Access Journals (Sweden)

    Ronaldo de Carvalho Raimundo

    2010-03-01

    Full Text Available El eritema multiforme, aparece como una enfermedad sistémica con la participación de la piel y las membranas mucosas en relación con varios factores como las infecciones bacterianas o virales, y en particular la administración de drogas, analgésicos y antibióticos en general. Se presenta un paciente masculino de 29 años de edad con eritema multiforme mayor desencadenado por antimicrobianos con la aparición de lesiones vesiculares-bulloso-ulcerosas en las regiones de los labios, encías, la lengua y la mucosa genital en tratamiento de una infección del tracto urinario con norfloxacino 400 mg por una semana. Fue realizado un tratamiento de soporte con el uso de colutorios para la higienización bucal y pomada a base de corticoide para protección de las úlceras, antihistamínicos y orientación nutricional de dieta líquida hipercalórica e hiperproteica. Este síndrome está caracterizado como un proceso eruptivo buloso agudo que compromete la calidad de vida del paciente y no hay pruebas de laboratorio específicas por lo que su diagnóstico debe estar basado en la revisión minuciosa de la anamnesis y en los hallazgos clínicos.The multiform erythema appears as a systemic disease where skin and the mucous membranes have participation in relation to some factors such as bacterial or viral infections and in particular the drugs administration, analgesics and antibiotics in general. The aim of present paper was the presentation of case of big multiform erythema triggering by antimicrobials. Authors present the case of a male patient aged 29 with appearance of ulcerous bullous-vesicular lesions in lips, gums, tongue and genital mucosa under treatment with 400 mg norfloxacin due to urinary tract infection for a week. We made support treatment using mouthwashes for oral hygiene and corticoids ointment for ulcer protection, antihistaminics and nutritional guiding of a hypercaloric and hyperprotein liquid diet. This syndrome is characterized

  15. Analysis of removal of residual decay heat from interim storage facilities by means of the CFD program FLUENT

    International Nuclear Information System (INIS)

    Stratmann, W.; Hages, P.

    2004-01-01

    Within the scope of nuclear licensing procedures of on-site interim storage facilities for dual purpose casks it is necessary, among other things, to provide proof of sufficient removal of the residual decay heat emitted by the casks. The results of the analyses performed for this purpose define e.g. the boundary conditions for further thermal analyses regarding the permissible cask component temperatures or the maximum permissible temperatures of the fuel cladding tubes of the fuel elements stored in the casks. Up to now, for the centralized interim storage facilities in Germany such analyses were performed on the basis of experimental investigations using scaled-down storage geometries. In the engineering phase of the Lingen on-site interim storage facility, proof was furnished for the first time using the CFD (computational fluid dynamics) program FLUENT. The program FLUENT is an internationally recognized and comprehensively verified program for the calculation of flow and heat transport processes. Starting from a brief discussion of modeling and the different boundary conditions of the computation, this contribution presents various results regarding the temperatures of air, cask surfaces and storage facility components, the mass flows through the storage facility and the heat transfer at the cask surface. The interface point to the cask-specific analyses is defined to be the cask surface

  16. Immune phenotypes predict survival in patients with glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Haouraa Mostafa

    2016-09-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM, a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. Methods Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively. Results Using descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival. Conclusions Defined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.

  17. Clinical outcome and microvascular blood flow in VAC® - and Sorbalgon® -treated peri-vascular infected wounds in the groin after vascular surgery - an early interim analysis.

    Science.gov (United States)

    Acosta, Stefan; Monsen, Christina; Dencker, Magnus

    2013-08-01

    Vacuum-assisted wound closure (VAC(®)) therapy is considered to be superior to conventional dressings in the treatment of peri-vascular groin infections after vascular surgery at our department. Therefore, we performed an early interim analysis of the clinical outcomes in these seriously ill patients at risk of amputation and death. Patients were randomised to either VAC(®) (n = 5) or Sorbalgon(®) (n = 5; best alternative treatment) therapy after surgical debridement. Non-invasive, laser Doppler perfusion imaging (LDPI) studies of the skin adjacent to the undressed wound were performed after 14 days of wound treatment. There was no difference in LDPI values in VAC(®) versus Sorbalgon(®) treated patients (P = 0·46). One patient in the VAC(®) group suffered from two re-bleeding episodes, leading to vascular resection and transfemoral amputation and in the Sorbalgon(®) group two had a complete wound healing time of more than 4 months and one had a visible interposition bypass graft in the groin after 1 month of treatment. No patient died of the groin infection. Although not statistically proven, fewer wound treatment failures were recorded in the VAC(®) group, justifying this early interim analysis. LDPI studies were feasible. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

  18. A comprehensive characterization of mitochondrial DNA mutations in glioblastoma multiforme.

    Science.gov (United States)

    Vidone, Michele; Clima, Rosanna; Santorsola, Mariangela; Calabrese, Claudia; Girolimetti, Giulia; Kurelac, Ivana; Amato, Laura Benedetta; Iommarini, Luisa; Trevisan, Elisa; Leone, Marco; Soffietti, Riccardo; Morra, Isabella; Faccani, Giuliano; Attimonelli, Marcella; Porcelli, Anna Maria; Gasparre, Giuseppe

    2015-06-01

    Glioblastoma multiforme (GBM) is the most malignant brain cancer in adults, with a poor prognosis, whose molecular stratification still represents a challenge in pathology and clinics. On the other hand, mitochondrial DNA (mtDNA) mutations have been found in most tumors as modifiers of the bioenergetics state, albeit in GBM a characterization of the mtDNA status is lacking to date. Here, a characterization of the burden of mtDNA mutations in GBM samples was performed. First, investigation of tumor-specific vs. non tumor-specific mutations was carried out with the MToolBox bioinformatics pipeline by analyzing 45 matched tumor/blood samples, from whole genome or whole exome sequencing datasets obtained from The Cancer Genome Atlas (TCGA) consortium. Additionally, the entire mtDNA sequence was obtained in a dataset of 104 fresh-frozen GBM samples. Mitochondrial mutations with potential pathogenic interest were prioritized based on heteroplasmic fraction, nucleotide variability, and in silico prediction of pathogenicity. A preliminary biochemical analysis of the activity of mitochondrial respiratory complexes was also performed on fresh-frozen GBM samples. Although a high number of mutations was detected, we report that the large majority of them does not pass the prioritization filters. Therefore, a relatively limited burden of pathogenic mutations is indeed carried by GBM, which did not appear to determine a general impairment of the respiratory chain. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo

    Directory of Open Access Journals (Sweden)

    Grodzik M

    2011-11-01

    Full Text Available Marta Grodzik1, Ewa Sawosz1, Mateusz Wierzbicki1, Piotr Orlowski1, Anna Hotowy2, Tomasz Niemiec1, Maciej Szmidt3, Katarzyna Mitura4, André Chwalibog21Division of Biotechnology and Biochemistry of Nutrition, Warsaw University of Life Sciences, Warsaw, Poland; 2Department of Basic Animal and Veterinary Science, University of Copenhagen, Copenhagen, Denmark; 3Division of Histology and Embryology, Warsaw University of Life Sciences, Warsaw, Poland; 4Department of Biomedical Engineering, Koszalin University of Technology, Koszalin, PolandAbstract: The objective of the study was to determine the effect of carbon nanoparticles produced by different methods on the growth of brain tumor and the development of blood vessels. Glioblastoma multiforme cells were cultured on the chorioallantoic membrane of chicken embryo and after 7 days of incubation, were treated with carbon nanoparticles administered in ovo to the tumor. Both types of nanoparticles significantly decreased tumor mass and volume, and vessel area. Quantitative real-time polymerase chain reaction analysis showed downregulated fibroblast growth factor-2 and vascular endothelial growth factor expression at the messenger ribonucleic acid level. The present results demonstrate antiangiogenic activity of carbon nanoparticles, making them potential factors for anticancer therapy.Keywords: cancer, nanoparticle, embryo, angiogenesis, FGF-2, VEGF

  20. ANALYSIS OF DOSE RATES DURING REPLACEMENT OF MANIPULATORS IN THE FFTF INTERIM EXAMINATION and MAINTENANCE (IEM) CELL

    International Nuclear Information System (INIS)

    NELSON, J.V.

    2002-01-01

    Replacement of a master-slave manipulator in the Interim Examination and Maintenance Cell at the Fast Flux Test Facility was carried out in August 2001. This operation created a 178-mm opening in the thick concrete wall of the hot cell. To aid in radiological work planning, dose rates outside the penetration in the wall were predicted using MCNP(trademark) photon transport calculations. The predicted dose rate was 7.7 mrem/h, which was reasonably close to the value of 10.4 mrem/h inferred from measurements

  1. Evaluation of land surface model representation of phenology: an analysis of model runs submitted to the NACP Interim Site Synthesis

    Science.gov (United States)

    Richardson, A. D.; Nacp Interim Site Synthesis Participants

    2010-12-01

    Phenology represents a critical intersection point between organisms and their growth environment. It is for this reason that phenology is a sensitive and robust integrator of the biological impacts of year-to-year climate variability and longer-term climate change on natural systems. However, it is perhaps equally important that phenology, by controlling the seasonal activity of vegetation on the land surface, plays a fundamental role in regulating ecosystem processes, competitive interactions, and feedbacks to the climate system. Unfortunately, the phenological sub-models implemented in most state-of-the-art ecosystem models and land surface schemes are overly simplified. We quantified model errors in the representation of the seasonal cycles of leaf area index (LAI), gross ecosystem photosynthesis (GEP), and net ecosystem exchange of CO2. Our analysis was based on site-level model runs (14 different models) submitted to the North American Carbon Program (NACP) Interim Synthesis, and long-term measurements from 10 forested (5 evergreen conifer, 5 deciduous broadleaf) sites within the AmeriFlux and Fluxnet-Canada networks. Model predictions of the seasonality of LAI and GEP were unacceptable, particularly in spring, and especially for deciduous forests. This is despite an historical emphasis on deciduous forest phenology, and the perception that controls on spring phenology are better understood than autumn phenology. Errors of up to 25 days in predicting “spring onset” transition dates were common, and errors of up to 50 days were observed. For deciduous sites, virtually every model was biased towards spring onset being too early, and autumn senescence being too late. Thus, models predicted growing seasons that were far too long for deciduous forests. For most models, errors in the seasonal representation of deciduous forest LAI were highly correlated with errors in the seasonality of both GPP and NEE, indicating the importance of getting the underlying

  2. Micro RNAs as molecular markers of glioblastoma multiform

    Energy Technology Data Exchange (ETDEWEB)

    Farace, M G [Department Experimental Medicine and Biochemical Sciences, University of Tor Vergata, Rome (Italy); Finocchiaro, G [Istituto Neurologico Besta, Milan (Italy); Ricci Vitiani, L [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome (Italy)

    2009-07-01

    The aim of this project was to unravel the role that miR-221 and miR-222, of which we had already demonstrated the specific differential expression in glioblastoma multiforme compared to normal brain, play in the control of cell proliferation, with the ultimate goal to provide new insights in the molecular basis of cancer. The results of our research allowed to identify an important molecular target for miRNA-221 and miR-222, highly expressed in glioblastoma multiforme tissues and cell lines, and to precisely recognize the mRNA regions responsible for this regulation.

  3. Micro RNAs as molecular markers of glioblastoma multiform

    International Nuclear Information System (INIS)

    Farace, M.G.; Finocchiaro, G.; Ricci Vitiani, L.

    2009-01-01

    The aim of this project was to unravel the role that miR-221 and miR-222, of which we had already demonstrated the specific differential expression in glioblastoma multiforme compared to normal brain, play in the control of cell proliferation, with the ultimate goal to provide new insights in the molecular basis of cancer. The results of our research allowed to identify an important molecular target for miRNA-221 and miR-222, highly expressed in glioblastoma multiforme tissues and cell lines, and to precisely recognize the mRNA regions responsible for this regulation

  4. Interim Design Report

    CERN Document Server

    Choubey, S.; Goswami, S.; Berg, J.S.; Fernow, R.; Gallardo, J.C.; Gupta, R.; Kirk, H.; Simos, N.; Souchlas, N.; Ellis, M.; Kyberd, P.; Benedetto, E.; Fernandez-Martinez, E.; Efthymiopoulos, I.; Garoby, R.; Gilardoni, S.; Martini, M.; Prior, G.; Ballett, P.; Pascoli, S.; Bross, A.; Geer, S.; Johnstone, C.; Kopp, J.; Mokhov, N.; Morfin, J.; Neuffer, D.; Parke, S.; Popovic, M.; Strait, J.; Striganov, S.; Blondel, A.; Dufour, F.; Laing, A.; Soler, F.J.P; Lindner, M.; Schwetz, T.; Alekou, A.; Apollonio, M.; Aslaninejad, M.; Bontoiu, C.; Dornan, P.; Eccleston, R.; Kurup, A.; Long, K.; Pasternak, J.; Pozimski, J.; Bogacz, A.; Morozov, V.; Roblin, Y.; Bhattacharya, S.; Majumdar, D.; Mori, Y.; Planche, T.; Zisman, M.; Cline, D.; Stratakis, D.; Ding, X.; Coloma, P.; Donini, A.; Gavela, B.; Lopez Pavon, J.; Maltoni, M.; Bromberg, C.; Bonesini, M.; Hart, T.; Kudenko, Y.; Mondal, N.; Antusch, S.; Blennow, M.; Ota, T.; Abrams, R.J.; Ankenbrandt, C.M.; Beard, K.B.; Cummings, M.A.C.; Flanagan, G.; Johnson, R.P.; Roberts, T.J.; Yoshikawa, C.Y.; Migliozzi, P.; Palladino, V.; de Gouvea, A.; Graves, V.B.; Kuno, Y.; Peltoniemi, J.; Blackmore, V.; Cobb, J.; Witte, H.; Mezzetto, M.; Rigolin, S.; McDonald, K.T.; Coney, L.; Hanson, G.; Snopok, P.; Tortora, L.; Andreopoulos, C.; Bennett, J.R.J.; Brooks, S.; Caretta, O.; Davenne, T.; Densham, C.; Edgecock, R.; Kelliher, D.; Loveridge, P.; McFarland, A.; Machida, S.; Prior, C.; Rees, G.; Rogers, C.; Thomason, J.W.G.; Booth, C.; Skoro, G.; Karadzhov, Y.; Matev, R.; Tsenov, R.; Samulyak, R.; Mishra, S.R.; Petti, R.; Dracos, M.; Yasuda, O.; Agarwalla, S.K.; Cervera-Villanueva, A.; Gomez-Cadenas, J.J.; Hernandez, P.; Li, T.; Martin-Albo, J.; Huber, P.; Back, J.; Barker, G.; Harrison, P.; Meloni, D.; Tang, J.; Winter, W.

    2011-01-01

    The International Design Study for the Neutrino Factory (the IDS-NF) was established by the community at the ninth "International Workshop on Neutrino Factories, super-beams, and beta- beams" which was held in Okayama in August 2007. The IDS-NF mandate is to deliver the Reference Design Report (RDR) for the facility on the timescale of 2012/13. In addition, the mandate for the study [3] requires an Interim Design Report to be delivered midway through the project as a step on the way to the RDR. This document, the IDR, has two functions: it marks the point in the IDS-NF at which the emphasis turns to the engineering studies required to deliver the RDR and it documents baseline concepts for the accelerator complex, the neutrino detectors, and the instrumentation systems. The IDS-NF is, in essence, a site-independent study. Example sites, CERN, FNAL, and RAL, have been identified to allow site-specific issues to be addressed in the cost analysis that will be presented in the RDR. The choice of example sites shou...

  5. Transuranic waste storage and assay facility (TRUSAF) interim safety basis

    International Nuclear Information System (INIS)

    Gibson, K.D.

    1995-09-01

    The TRUSAF ISB is based upon current facility configuration and procedures. The purpose of the document is to provide the basis for interim operation or restrictions on interim operations and the authorization basis for the TRUSAF at the Hanford Site. The previous safety analysis document TRUSAF hazards Identification and Evaluation (WHC 1977) is superseded by this document

  6. Raman spectroscopy for diagnosis of glioblastoma multiforme

    Science.gov (United States)

    Clary, Candace Elise

    Glioblastoma multiforme (GBM), the most common and most fatal malignant brain tumor, is highly infiltrative and incurable. Although improved prognosis has been demonstrated by surgically resecting the bulk tumor, a lack of clear borders at the tumor margins complicates the selection decision during surgery. This dissertation investigates the potential of Raman spectroscopy for distinguishing between normal and malignant brain tissue and sets the groundwork for a surgical diagnostic guide for resection of gross malignant gliomas. These studies revealed that Raman spectroscopy was capable of discriminating between normal scid mouse brain tissue and human xenograft tumors induced in those mice. The spectra of normal and malignant tissue were normalized by dividing by the respective magnitudes of the peaks near 1440 cm -1. Spectral differences include the shape of the broad peaks near 1440 cm-1 and 1660 cm-1 and the relative magnitudes of the peaks at 1264 cm-1, 1287 cm-1, 1297 cm-1, 1556 cm -1, 1586 cm-1, 1614 cm-1, and 1683 cm-1. From these studies emerged questions regarding how to objectively normalize and compare spectra for future automation. Some differences in the Raman spectra were shown to be inherent in the disease states of the cells themselves via differences in the Raman spectra of normal human astrocytes in culture and cultured cells derived from GBM tumors. The spectra of astrocytes and glioma cells were normalized by dividing by the respective magnitudes of the peaks near 1450 cm-1. The differences between the Raman spectra of normal and transformed cells include the ratio of the 1450 cm-1/1650 cm-1 peaks and the relative magnitudes of the peaks at 1181 cm-1, 1191 cm-1, 1225 cm-1, 1263 cm -1, 1300 cm-1, 1336 cm-1, 1477 cm-1, 1494 cm-1, and 1695 cm -1. Previous Raman spectroscopic studies of biological cells have shown that the magnitude of the Raman signal decreases over time, indicating sample damage. Cells exposed to laser excitation at similar power

  7. Investigation of platinum nanoparticle properties against U87 glioblastoma multiforme

    DEFF Research Database (Denmark)

    Kutwin, Marta; Sawosz, Ewa; Jaworski, Slawomir

    2017-01-01

    a harmful influence on viability of U87 glioblastoma multiforme (GBM) cells, but also showed genotoxic properties as well as a pro-apoptotic effect on cancer cells. It was found that NP-Pt decreased the weight and volume of U87 GBM tumor tissue and caused pathomorphological changes in the ultrastructure...

  8. Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo

    DEFF Research Database (Denmark)

    Grodzik, Marta; Sawosz, Ewa; Wierzbicki, Mateusz

    2011-01-01

    The objective of the study was to determine the effect of carbon nanoparticles produced by different methods on the growth of brain tumor and the development of blood vessels. Glioblastoma multiforme cells were cultured on the chrioallantoic membrane of chicken embryo and after 7 days of incubati...

  9. Treatment outcome and prognostic factors of adult glioblastoma multiforme.

    Science.gov (United States)

    Ahmadloo, Niloofar; Kani, Amir-Abbas; Mohammadianpanah, Mohammad; Nasrolahi, Hamid; Omidvari, Shapour; Mosalaei, Ahmad; Ansari, Mansour

    2013-03-01

    This study aimed to report the characteristics, prognostic factors and treatment outcome of 223 patients with glioblastoma multiforme (GBM). This retrospective study was carried out by reviewing the medical records of 223 adult patients diagnosed at a tertiary academic hospital between 1990 and 2008. Patients' follow up ranged from 1 to 69 months (median 11 months). Surgery was attempted in all patients in whom complete resection in 15 patients (7%), subtotal resection in 77 patients (34%), partial resection in 73 patients (33%) and biopsy alone in 58 patients (26%) were done. In addition, we performed a literature review of PubMed to find out and analyze major related series. In all, we collected and analyzed the data of 33 major series including more than 11,000 patients with GBM. There were 141 men and 82 women. The median progression free- and overall survival were 6 (95% CI=5.711-8.289) and 11 (95% CI=9.304-12.696) months respectively. In univariate analysis for overall survival, age (P=0.003), tumor size (P<0.013), performance status (P<0.001), the extent of surgical resection (P=0.009), dose of radiation (P<0.001), and adjuvant chemotherapy (P<0.001) were prognostic factors. However, in multivariate analysis, only radiation dose, extent of surgical resection, and adjuvant chemotherapy were independent prognostic factors for overall survival. The prognosis of adult patients with GBM remains poor; however, complete surgical resection and adjuvant treatments improve progression-free and overall survival. Copyright © 2012. Production and hosting by Elsevier B.V.

  10. Treatment outcome and prognostic factors of adult glioblastoma multiforme

    International Nuclear Information System (INIS)

    Ahmadloo, N.; Mohammadianpanah, M.; Nasrolahi, H.; Omidvari, Sh.; Ansari, M.; Kani, A.A.; Mosalaei, A.

    2013-01-01

    Introduction: This study aimed to report the characteristics, prognostic factors and treatment outcome of 223 patients with glioblastoma multiforme (GBM). Subjects and method: This retrospective study was carried out by reviewing the medical records of 223 adult patients diagnosed at a tertiary academic hospital between 1990 and 2008. Patients’ follow up ranged from 1 to 69 months (median 11 months). Surgery was attempted in all patients in whom complete resection in 15 patients (7%), subtotal resection in 77 patients (34%), partial resection in 73 patients (33%) and biopsy alone in 58 patients (26%) were done. In addition, we performed a literature review of Pub Med to find out and analyze major related series. In all, we collected and analyzed the data of 33 major series including more than 11,000 patients with GB M. Results: There were 141 men and 82 women. The median progression free- and overall survival were 6 (95% Cl = 5.711-8.289) and 11 (95% Cl = 9.304-12.696) months respectively. In univariate analysis for overall survival, age (P = 0.003), tumor size (P < 0.013), performance status (P < 0.001), the extent of surgical resection (P - 0.009), dose of radiation (P < 0.001), and adjuvant chemotherapy (P < 0.001) were prognostic factors. However, in multivariate analysis, only radiation dose, extent of surgical resection, and adjuvant chemotherapy were independent prognostic factors for overall survival. Conclusion: The prognosis of adult patients with GBM remains poor; however, complete surgical resection and adjuvant treatments improve progression-free and overall survival

  11. Erythema multiforme as the result of taking carbamazepine

    Directory of Open Access Journals (Sweden)

    Maharani Laillyza Apriasari

    2010-06-01

    Full Text Available Background: Erythema multiforme is an acute mucocutaneus disease which is caused by the hypersensitivity reaction. It is characterized by target lesions on the skin or ulcerative oral lesion. Etiology of the disease is unknown, it is currently considered as immunologic disease. The triggering factors is the use of certain type of drugs like antibiotics, anticonvulsant, and NSAID. Most of the dentists do not know about it is mechanism, so a lot of people consider it as a malpractice. Purpose: This paper reported a case of a man, 46 years old which had ulcerative oral mucous, peeled and pain lips after taking carbamazepine drugs. Case: The clinical diagnosis of this case was erythema multiforme because of the hypersensitivity reaction as the result of taking carbamazepine. Case management: The final diagnosis based on anamnesis history of taking systemic drugs and clinical manifestation of erythema multiforme in the oral cavity. The drugs therapy that had been given were antihistamine, oral corticosteroid, gargle liquid contained of topical anesthetic, corticosteroid, and antibiotic. Conclusion: In this case, it can be concluded that erythema multiforme appeared was triggered by taking carbamazepine as the drug of choice for trigeminal neuralgia therapy. These drugs can cause type III hypersensitivity reaction. The final diagnosis based on anamnesis history of taking carbamazepine before lesions erupted and the characterized clinical manifestation.Latar belakang: Erythema multiforme adalah penyakit mukokutaneus akut yang menyerang kulit dan mukosa sebagai akibat dari reaksi hipersensitivitas. Secara karakteristik ditandai oleh lesi target pada kulit atau lesi ulserasi pada mukosa rongga mulut. Etiologi penyakit ini belum jelas, diduga karena adanya reaksi imunologi. Pencetusnya dikarenakan adanya pemakaian obat-obatan tertentu seperti antibiotik, antikonvulsan dan NSAID. Banyak dokter gigi kurang memahami mekanisme timbulnya penyakit ini, sehingga

  12. Evaluation of early imaging response criteria in glioblastoma multiforme

    International Nuclear Information System (INIS)

    Gladwish, Adam; Koh, Eng-Siew; Hoisak, Jeremy; Lockwood, Gina; Millar, Barbara-Ann; Mason, Warren; Yu, Eugene; Laperriere, Normand J; Ménard, Cynthia

    2011-01-01

    Early and accurate prediction of response to cancer treatment through imaging criteria is particularly important in rapidly progressive malignancies such as Glioblastoma Multiforme (GBM). We sought to assess the predictive value of structural imaging response criteria one month after concurrent chemotherapy and radiotherapy (RT) in patients with GBM. Thirty patients were enrolled from 2005 to 2007 (median follow-up 22 months). Tumor volumes were delineated at the boundary of abnormal contrast enhancement on T1-weighted images prior to and 1 month after RT. Clinical Progression [CP] occurred when clinical and/or radiological events led to a change in chemotherapy management. Early Radiologic Progression [ERP] was defined as the qualitative interpretation of radiological progression one month post-RT. Patients with ERP were determined pseudoprogressors if clinically stable for ≥6 months. Receiver-operator characteristics were calculated for RECIST and MacDonald criteria, along with alternative thresholds against 1 year CP-free survival and 2 year overall survival (OS). 13 patients (52%) were found to have ERP, of whom 5 (38.5%) were pseudoprogressors. Patients with ERP had a lower median OS (11.2 mo) than those without (not reached) (p < 0.001). True progressors fared worse than pseudoprogressors (median survival 7.2 mo vs. 19.0 mo, p < 0.001). Volume thresholds performed slightly better compared to area and diameter thresholds in ROC analysis. Responses of > 25% in volume or > 15% in area were most predictive of OS. We show that while a subjective interpretation of early radiological progression from baseline is generally associated with poor outcome, true progressors cannot be distinguished from pseudoprogressors. In contrast, the magnitude of early imaging volumetric response may be a predictive and quantitative metric of favorable outcome

  13. Automotive Mechanics Occupational Performance Survey. Interim Report.

    Science.gov (United States)

    Borcher, Sidney D.; Leiter, Paul B.

    The purpose of this federally-funded interim report is to present the results of a task inventory analysis survey of automotive mechanics completed by project staff within the Instructional Systems Design Program at the Center for Vocational and Technical Education. Intended for use in curriculum development for vocational education programs in…

  14. 340 waste handling facility interim safety basis

    Energy Technology Data Exchange (ETDEWEB)

    VAIL, T.S.

    1999-04-01

    This document presents an interim safety basis for the 340 Waste Handling Facility classifying the 340 Facility as a Hazard Category 3 facility. The hazard analysis quantifies the operating safety envelop for this facility and demonstrates that the facility can be operated without a significant threat to onsite or offsite people.

  15. ITER interim design report package documents

    International Nuclear Information System (INIS)

    1996-01-01

    This publication contains the Excerpt from the ITER Council (IC-8), the ITER Interim Design Report, Cost Review and Safety Analysis, ITER Site Requirements and ITER Site Design Assumptions and the Excerpt from the ITER Council (IC-9). 8 figs, 2 tabs

  16. 340 waste handling facility interim safety basis

    International Nuclear Information System (INIS)

    VAIL, T.S.

    1999-01-01

    This document presents an interim safety basis for the 340 Waste Handling Facility classifying the 340 Facility as a Hazard Category 3 facility. The hazard analysis quantifies the operating safety envelop for this facility and demonstrates that the facility can be operated without a significant threat to onsite or offsite people

  17. Interim reliability evaluation program (IREP)

    International Nuclear Information System (INIS)

    Carlson, D.D.; Murphy, J.A.

    1981-01-01

    The Interim Reliability Evaluation Program (IREP), sponsored by the Office of Nuclear Regulatory Research of the US Nuclear Regulatory Commission, is currently applying probabilistic risk analysis techniques to two PWR and two BWR type power plants. Emphasis was placed on the systems analysis portion of the risk assessment, as opposed to accident phenomenology or consequence analysis, since the identification of risk significant plant features was of primary interest. Traditional event tree/fault tree modeling was used for the analysis. However, the study involved a more thorough investigation of transient initiators and of support system faults than studies in the past and substantially improved techniques were used to quantify accident sequence frequencies. This study also attempted to quantify the potential for operator recovery actions in the course of each significant accident

  18. Advanced case of glioblastoma multiforme and pregnancy. An ethical dilemma.

    Science.gov (United States)

    Al-Rasheedy, Intisar M; Al-Hameed, Fahad M

    2015-10-01

    Glioblastoma multiforme (GBM) is the most common and malignant form of the glial tumors. Advanced and treated GBM is rarely associated with pregnancy for many reasons. Glioblastoma multiforme presenting during pregnancy carries unique challenges to the patient, baby, family, and health care providers. We describe an unusual case of advanced GBM that was treated with maximum doses of chemotherapy and radiations, and she became pregnant and presented at eighteenth weeks of gestation. Her medical management was associated with a significant ethical dilemma. We managed to deliver the baby safely through cesarean section at week 28 despite the critical condition of the mother. Unfortunately, the mother died 2 weeks post delivery. We concluded that although recurrent and treated GBM is rarely associated with pregnancy and carries dismal prognosis, but if it occurs, it can still be carried, and a multidisciplinary team work is the key for successful outcome.

  19. CMM Interim Check (U)

    Energy Technology Data Exchange (ETDEWEB)

    Montano, Joshua Daniel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-03-23

    Coordinate Measuring Machines (CMM) are widely used in industry, throughout the Nuclear Weapons Complex and at Los Alamos National Laboratory (LANL) to verify part conformance to design definition. Calibration cycles for CMMs at LANL are predominantly one year in length. Unfortunately, several nonconformance reports have been generated to document the discovery of a certified machine found out of tolerance during a calibration closeout. In an effort to reduce risk to product quality two solutions were proposed – shorten the calibration cycle which could be costly, or perform an interim check to monitor the machine’s performance between cycles. The CMM interim check discussed makes use of Renishaw’s Machine Checking Gauge. This off-the-shelf product simulates a large sphere within a CMM’s measurement volume and allows for error estimation. Data was gathered, analyzed, and simulated from seven machines in seventeen different configurations to create statistical process control run charts for on-the-floor monitoring.

  20. The Nord interim store

    International Nuclear Information System (INIS)

    Leushacke, D.F.; Rittscher, D.

    1996-01-01

    In line with the decision taken in 1990 to shut down and decommission the Greifswald and Rheinsberg Nuclear Power Stations, the waste management concept of the Energiewerke Nord is based on direct and complete decommissioning of the six shut down reactor units within the next fifteen years. One key element of this concept is the construction and use of the Zwischenlager Nord (Nord Interim Store, ZLN) for holding the existing nuclear fuels and for interim and decay storage of the radioactive materials arising in decommissioning and demolition. The owner and operator of the store is Energiewerke Nord GmbH. The interim store has the functions of a processing and Energiewerke Nord GmbH. The interim store has the functions of a processing and treatment station and buffer store for the flows of residues arising. As a radioactive waste management station, it accommodates nuclear fuels, radioactive waste or residues which are not treated any further. It is used as a buffer store to allow the materials accumulating in disassembly to be stored temporarily before or after treatment in order to ensure continuous loading of the treatment plants. When operated as a processing station, the ZLN is able to handle nearly all types of radioactive waste and residues arising, except for nuclear fuels. These installations allow the treatment of radioactive residues to be separated from the demolition work both physically and in time. The possibilities of interium storage and buffer storage of untreated waste and waste packages make for high flexibility in logistics and waste management strategy. (orig.) [de

  1. Tank Farm Interim Surface Barrier Materials And Runoff Alternatives Study

    International Nuclear Information System (INIS)

    Holm, M.J.

    2009-01-01

    This report identifies candidate materials and concepts for interim surface barriers in the single-shell tank farms. An analysis of these materials for application to the TY tank farm is also provided.

  2. Development of a probabilistic safety assessment framework for an interim dry storage facility subjected to an aircraft crash using best-estimate structural analysis

    Energy Technology Data Exchange (ETDEWEB)

    Almomani, Belal; Jang, Dong Chan [Dept. of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Lee, Sang Hoon [Dept. of Mechanical and Automotive Engineering, Keimyung University, Daegu (Korea, Republic of); Kang, Hyun Gook [Dept. of Mechanical, Aerospace and Nuclear Engineering, Rensselaer Polytechnic Institute, Troy (United States)

    2017-03-15

    Using a probabilistic safety assessment, a risk evaluation framework for an aircraft crash into an interim spent fuel storage facility is presented. Damage evaluation of a detailed generic cask model in a simplified building structure under an aircraft impact is discussed through a numerical structural analysis and an analytical fragility assessment. Sequences of the impact scenario are shown in a developed event tree, with uncertainties considered in the impact analysis and failure probabilities calculated. To evaluate the influence of parameters relevant to design safety, risks are estimated for three specification levels of cask and storage facility structures. The proposed assessment procedure includes the determination of the loading parameters, reference impact scenario, structural response analyses of facility walls, cask containment, and fuel assemblies, and a radiological consequence analysis with dose–risk estimation. The risk results for the proposed scenario in this study are expected to be small relative to those of design basis accidents for best-estimated conservative values. The importance of this framework is seen in its flexibility to evaluate the capability of the facility to withstand an aircraft impact and in its ability to anticipate potential realistic risks; the framework also provides insight into epistemic uncertainty in the available data and into the sensitivity of the design parameters for future research.

  3. Development of a Probabilistic Safety Assessment Framework for an Interim Dry Storage Facility Subjected to an Aircraft Crash Using Best-Estimate Structural Analysis

    Directory of Open Access Journals (Sweden)

    Belal Almomani

    2017-03-01

    Full Text Available Using a probabilistic safety assessment, a risk evaluation framework for an aircraft crash into an interim spent fuel storage facility is presented. Damage evaluation of a detailed generic cask model in a simplified building structure under an aircraft impact is discussed through a numerical structural analysis and an analytical fragility assessment. Sequences of the impact scenario are shown in a developed event tree, with uncertainties considered in the impact analysis and failure probabilities calculated. To evaluate the influence of parameters relevant to design safety, risks are estimated for three specification levels of cask and storage facility structures. The proposed assessment procedure includes the determination of the loading parameters, reference impact scenario, structural response analyses of facility walls, cask containment, and fuel assemblies, and a radiological consequence analysis with dose–risk estimation. The risk results for the proposed scenario in this study are expected to be small relative to those of design basis accidents for best-estimated conservative values. The importance of this framework is seen in its flexibility to evaluate the capability of the facility to withstand an aircraft impact and in its ability to anticipate potential realistic risks; the framework also provides insight into epistemic uncertainty in the available data and into the sensitivity of the design parameters for future research.

  4. Development of a probabilistic safety assessment framework for an interim dry storage facility subjected to an aircraft crash using best-estimate structural analysis

    International Nuclear Information System (INIS)

    Almomani, Belal; Jang, Dong Chan; Lee, Sang Hoon; Kang, Hyun Gook

    2017-01-01

    Using a probabilistic safety assessment, a risk evaluation framework for an aircraft crash into an interim spent fuel storage facility is presented. Damage evaluation of a detailed generic cask model in a simplified building structure under an aircraft impact is discussed through a numerical structural analysis and an analytical fragility assessment. Sequences of the impact scenario are shown in a developed event tree, with uncertainties considered in the impact analysis and failure probabilities calculated. To evaluate the influence of parameters relevant to design safety, risks are estimated for three specification levels of cask and storage facility structures. The proposed assessment procedure includes the determination of the loading parameters, reference impact scenario, structural response analyses of facility walls, cask containment, and fuel assemblies, and a radiological consequence analysis with dose–risk estimation. The risk results for the proposed scenario in this study are expected to be small relative to those of design basis accidents for best-estimated conservative values. The importance of this framework is seen in its flexibility to evaluate the capability of the facility to withstand an aircraft impact and in its ability to anticipate potential realistic risks; the framework also provides insight into epistemic uncertainty in the available data and into the sensitivity of the design parameters for future research

  5. A prospective PET study of patients with glioblastoma multiforme

    DEFF Research Database (Denmark)

    Andersen, Preben B.; Blinkenberg, M; Lassen, U

    2006-01-01

    OBJECTIVE: To study the post-surgical metabolic and structural cerebral changes in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS: We examined ten patients prospectively with newly diagnosed GBM. All patients were primarily treated with surgery, followed by chemotherapy...... compared with structural imaging in the prospective evaluation of GBM. We found a difference in metabolic increase and tumor growth between the two treatment regimens, although this finding has limited relevance due to the design of the study....

  6. Survival benefit of surgery in recurrent glioblastoma multiforme.

    Science.gov (United States)

    Choudry, Usama Khalid; Khan, Saad Akhtar; Shamim, Muhammad Shahzad

    2017-12-01

    There is an ongoing debate regarding role of surgery for recurrent glioblastoma multiforme (GBM). Older literature hinted at only modest survival benefits with surgery and a high rate of morbidity. However, more recent literature suggests better survival that may be attributed to better surgical techniques and better options in adjuvant treatment. Herein the authors review recent literature with regards to the possible role of surgery in recurrent GBM and also look into the key factors impacting second surgery. .

  7. A study of concurrent radiochemotherapy with paclitaxel in glioblastoma multiforme

    International Nuclear Information System (INIS)

    Julka, P.K.; Awasthy, B.S.; Rath, G.K.; Agarwal, S.; Varna, T.; Mahapatra, A.K.; Singh, R.

    2000-01-01

    Despite advances in neurosurgery and radiotherapy, the prognosis of patients with glioblastoma multiforme remains poor. Reports in the literature about the radiosensitizing properties of paclitaxel stimulated the authors to conduct a study using paclitaxel concurrently with radiation in a group of 18 patients who had residual disease postoperatively. Paclitaxel was delivered weekly as an intravenous infusion in a dose of 60 mg/m 2 along with radiation to the primary lesion. A total of 108 cycles of paclitaxel was given. All the patients tolerated the treatment well. The main side effects were haematological, and neuropathy which was self-limiting. The overall 1-year survival rate was 70%, with 12 patients alive at 13 months. The median survival has not yet been reached although it is more than 13 months. Thus, paclitaxel can be safely delivered concomitantly with radiation in patients with glioblastoma multiforme. Larger, randomized trials are required to establish the comparative efficacy of paclitaxel as a radiosensitizer in glioblastoma multiforme. Copyright (1999) Blackwell Science Pty Ltd

  8. CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Ganeshan, B.; Miles, K.A.; Shortman, R.; Afaq, A.; Ardeshna, K.M.; Groves, A.M.; Kayani, I.; Babikir, S.

    2017-01-01

    The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL. (orig.)

  9. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.

    Science.gov (United States)

    Dimopoulos, Meletios A; Goldschmidt, Hartmut; Niesvizky, Ruben; Joshua, Douglas; Chng, Wee-Joo; Oriol, Albert; Orlowski, Robert Z; Ludwig, Heinz; Facon, Thierry; Hajek, Roman; Weisel, Katja; Hungria, Vania; Minuk, Leonard; Feng, Shibao; Zahlten-Kumeli, Anita; Kimball, Amy S; Moreau, Philippe

    2017-10-01

    The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to compare overall survival between the two treatment groups. ENDEAVOR was a phase 3, open-label, randomised controlled trial in patients with relapsed or refractory multiple myeloma. Patients were recruited from 198 hospitals and outpatient clinics in 27 countries in Europe, North America, South America, and the Asia-Pacific region. Patients were aged 18 years or older, had relapsed or refractory multiple myeloma, and had received between one and three previous lines of therapy. Patients were randomly assigned (1:1) to receive carfilzomib and dexamethasone (carfilzomib group) or bortezomib and dexamethasone (bortezomib group) through a blocked randomisation scheme (block size of four), stratified by International Staging System stage, previous lines of treatment, previous proteasome inhibitor therapy, and planned route of bortezomib delivery if assigned to the bortezomib group. Carfilzomib (20 mg/m 2 on days 1 and 2 of cycle 1; 56 mg/m 2 thereafter) was given as a 30-min intravenous infusion on days 1, 2, 8, 9, 15, and 16 of 28-day cycles; bortezomib (1·3 mg/m 2 ) was given as an intravenous bolus or subcutaneous injection on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20 mg oral or intravenous infusion) was given on days 1, 2, 8, 9, 15, 16, 22, and 23 in the carfilzomib group and on days 1, 2, 4, 5, 8, 9, 11, and 12 in the bortezomib group. The primary endpoint of ENDEAVOR, progression-free survival, has been previously reported. A stratified log-rank test was used to compare overall survival between treatment groups for this prospectively planned second interim

  10. Sampling and analysis plan for the gunite and associated tanks interim remedial action, wall coring and scraping at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    International Nuclear Information System (INIS)

    1998-02-01

    This Sampling and Analysis Plan documents the procedures for collecting and analyzing wall core and wall scraping samples from the Gunite and Associated Tanks. These activities are being conducted to support the Comprehensive Environmental Response, Compensation, and Liability Act at the gunite and associated tanks interim remedial action at Oak Ridge National Laboratory in Oak Ridge, Tennessee. The sampling and analysis activities will be performed in concert with sludge retrieval and sluicing of the tanks. Wall scraping and/or wall core samples will be collected from each quadrant in each tank by using a scraping sampler and/or a coring drill deployed by the Houdini robot vehicle. Each sample will be labeled, transported to the Radioactive Materials Analytical Laboratory, and analyzed for physical and radiological characteristics, including total activity, gross alpha, gross beta, radioactive strontium and cesium, and other alpha- and gamma-emitting radionuclides. The data quality objectives process, based on US Environmental Protection Agency guidance, was applied to identify the objectives of this sampling and analysis. The results of the analysis will be used to (1) validate predictions of a strontium concrete diffusion model, (2) estimate the amount of radioactivity remaining in the tank shells, (3) provide information to correlate with measurements taken by the Gunite Tank Isotope Mapping Probe and the Characterization End Effector, and (4) estimate the performance of the wall cleaning system. This revision eliminates wall-scraping samples from all tanks, except Tank W-3. The Tank W-3 experience indicated that the wall scrapper does not collect sufficient material for analysis

  11. Evaluation of Extratropical Cyclone Precipitation in the North Atlantic Basin: An analysis of ERA-Interim, WRF, and two CMIP5 models.

    Science.gov (United States)

    Booth, James F; Naud, Catherine M; Willison, Jeff

    2018-03-01

    The representation of extratropical cyclones (ETCs) precipitation in general circulation models (GCMs) and a weather research and forecasting (WRF) model is analyzed. This work considers the link between ETC precipitation and dynamical strength and tests if parameterized convection affects this link for ETCs in the North Atlantic Basin. Lagrangian cyclone tracks of ETCs in ERA-Interim reanalysis (ERAI), the GISS and GFDL CMIP5 models, and WRF with two horizontal resolutions are utilized in a compositing analysis. The 20-km resolution WRF model generates stronger ETCs based on surface wind speed and cyclone precipitation. The GCMs and ERAI generate similar composite means and distributions for cyclone precipitation rates, but GCMs generate weaker cyclone surface winds than ERAI. The amount of cyclone precipitation generated by the convection scheme differs significantly across the datasets, with GISS generating the most, followed by ERAI and then GFDL. The models and reanalysis generate relatively more parameterized convective precipitation when the total cyclone-averaged precipitation is smaller. This is partially due to the contribution of parameterized convective precipitation occurring more often late in the ETC life cycle. For reanalysis and models, precipitation increases with both cyclone moisture and surface wind speed, and this is true if the contribution from the parameterized convection scheme is larger or not. This work shows that these different models generate similar total ETC precipitation despite large differences in the parameterized convection, and these differences do not cause unexpected behavior in ETC precipitation sensitivity to cyclone moisture or surface wind speed.

  12. Prognostic factors in glioblastoma multiforme. 10 years experience of a single institution

    International Nuclear Information System (INIS)

    Hulshof, M.C.C.M.; Schimmel, E.C.; Gonzalez, D.G.; Koot, R.W.; Bosch, D.A.; Dekker, F.

    2001-01-01

    Background: To analyze prognostic factors in patients with a glioblastoma multiforme treated in an academic institute over the last 10 years. Patients and method: From 1988 to 1998, 198 patients with pathologically confirmed glioblastoma multiforme were analyzed. Five radiation schedules were used mainly based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an interstitial iridium-192 (Ir-192) boost for selected patients with a good performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions for poor prognostic patients and 5. no irradiation. Results: Median survival was 16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively. No significant improvement in survival was encountered over the last 10 years. At multivariate analysis patients treated with a hypofractionated scheme showed a similar survival probability and duration of palliative effect compared to the conventionally fractionated group. The poor prognostic groups receiving radiotherapy had a highly significant better survival compared to the no-treatment group. Patients treated with an Ir-192 boost had a better median survival compared to a historical group matched on selection criteria but without boost treatment (16 vs 9.7 months, n.s.). However, survival at 2 years was similar. Analysis on pretreatment characteristics at multivariate analysis revealed age, neurological performance, addition of radiotherapy, total resection, tumor size post surgery and deterioration before start of radiotherapy (borderline) as significant prognostic factors for survival. Conclusion: Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors

  13. Interim storage study report

    Energy Technology Data Exchange (ETDEWEB)

    Rawlins, J.K.

    1998-02-01

    High-level radioactive waste (HLW) stored at the Idaho Chemical Processing Plant (ICPP) in the form of calcine and liquid and liquid sodium-bearing waste (SBW) will be processed to provide a stable waste form and prepare the waste to be transported to a permanent repository. Because a permanent repository will not be available when the waste is processed, the waste must be stored at ICPP in an Interim Storage Facility (ISF). This report documents consideration of an ISF for each of the waste processing options under consideration.

  14. Interim storage report

    International Nuclear Information System (INIS)

    Rawlins, J.K.

    1998-02-01

    High-level radioactive waste (HLW) stored at the Idaho Chemical Processing Plant (ICPP) in the form of calcine and liquid and liquid sodium-bearing waste (SBW) will be processed to provide a stable waste form and prepare the waste to be transported to a permanent repository. Because a permanent repository will not be available when the waste is processed, the waste must be stored at ICPP in an Interim Storage Facility (ISF). This report documents consideration of an ISF for each of the waste processing options under consideration

  15. ITER interim design report package and relevant documents

    International Nuclear Information System (INIS)

    1996-01-01

    This publication documents the technical basis which underlay the Interim Design Report, Cost Review and Safety Analysis submitted to the ITER Councils (IC-8 and IC-9) Records of decisions and the ''ITER Interim Design Report Package''. This publication contains ITER Site Requirements and ITER Site Design Assumptions, TAC-8 Report, SRG Report, CP's Report on Tentative Sequence of Events and Parties' Views on the IDR Package and Parties' Technical Comments on the IDR Package. Figs, tabs

  16. Prognostic value of plasma transforming growth factor-beta in patients with glioblastoma multiforme

    NARCIS (Netherlands)

    Hulshof, M. C.; Sminia, P.; Barten-van Rijbroek, A. D.; Gonzalez Gonzalez, D.

    2001-01-01

    We investigated whether the postoperative concentration of circulating transforming growth factor beta (TGF-beta) yields prognostic value in patients with glioblastoma multiforme (gbm). Blood was collected from 20 healthy volunteers and in 28 patients with mainly glioblastoma multiforme (gbm), both

  17. Erythema multiforme and persistent erythema as early cutaneous manifestations of Lyme disease

    NARCIS (Netherlands)

    Schuttelaar, M L; Laeijendecker, R; Heinhuis, R J; Van Joost, T

    1997-01-01

    We report two cases of borreliosis (Lyme disease) with unusual cutaneous manifestations, erythema multiforme, and persistent erythema. The lesions in both of our patients had distinctive histopathologic features. To our knowledge, this is the first report of erythema multiforme and persistent

  18. Recidiverende erythema multiforme udløst af herpes simplex-virus

    DEFF Research Database (Denmark)

    Vestergård Grejsen, Dorthe; Henningsen, Emil

    2012-01-01

    We describe two cases of recurrent erythema multiforme, both associated to infection with herpes simplex virus. The importance of subclinical herpes is illustrated. Antiviral and additional treatment is described.......We describe two cases of recurrent erythema multiforme, both associated to infection with herpes simplex virus. The importance of subclinical herpes is illustrated. Antiviral and additional treatment is described....

  19. Spent fuel interim storage

    International Nuclear Information System (INIS)

    Bilegan, Iosif C.

    2003-01-01

    The official inauguration of the spent fuel interim storage took place on Monday July 28, 2003 at Cernavoda NNP. The inaugural event was attended by local and central public authority representatives, a Canadian Government delegation as well as newsmen from local and central mass media and numerous specialists from Cernavoda NPP compound. Mr Andrei Grigorescu, State Secretary with the Economy and Commerce Ministry, underlined in his talk the importance of this objective for the continuous development of nuclear power in Romania as well as for Romania's complying with the EU practice in this field. Also the excellent collaboration between the Canadian contractor AECL and the Romanian partners Nuclear Montaj, CITON, UTI, General Concret in the accomplishment of this unit at the planned terms and costs. On behalf of Canadian delegation, spoke Minister Don Boudria. He underlined the importance which the Canadian Government affords to the cooperation with Romania aiming at specific objectives in the field of nuclear power such as the Cernavoda NPP Unit 2 and spent fuel interim storage. After traditional cutting of the inaugural ribbon by the two Ministers the festivities continued on the Cernavoda NPP Compound with undersigning the documents regarding the project completion and a press conference

  20. Hair-dye induced erythema multiforme like allergic contact dermatitis

    Directory of Open Access Journals (Sweden)

    Mrinal Gupta

    2017-04-01

    Full Text Available Erythema multiforme (EM is an acute, self limited skin disease characterized by the sudden eruption of symmetrical lesions in typical targetoid fashion usually confined to face and extremities. The most commonly implicated factors include infections like herpes simplex, mycoplasma, drugs like antibiotics and anticonvulsants and vaccinations. Contact dermatitis induced EM is a rarely reported entity. Herein we present a case of a 40 year old female who presented with EM due to contact sensitivity to p-Paraphenylenediamine (PPD, a common coloring agent in hair-dyes and a potent sensitizer. Till date, there have been only a few case reports of PPD induced EM.

  1. Japanese study of tofogliflozin with type 2 diabetes mellitus patients in an observational study of the elderly (J-STEP/EL): A 12-week interim analysis.

    Science.gov (United States)

    Utsunomiya, Kazunori; Shimmoto, Naoki; Senda, Masayuki; Kurihara, Yuji; Gunji, Ryoji; Kameda, Hiroyuki; Tamura, Masahiro; Mihara, Hanako; Kaku, Kohei

    2016-09-01

    Sodium-glucose co-transporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, but are associated with concerns about specific adverse drug reactions. We carried out a 1-year post-marketing surveillance of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus and here report the results of a 12-week interim analysis, focusing on adverse drug reactions of special interest. The present prospective observational study included all type 2 diabetes mellitus patients aged ≥65 years who started tofogliflozin during the first 3 months after its launch. Data on demographic and baseline characteristics, clinical course and adverse events were collected. Of 1,535 patients registered, 1,506 patients whose electronic case report forms were collected and who had at least one follow-up visit were included in the safety analysis at 12 weeks. A total of 178 of 1,506 patients (11.82%) had at least one adverse drug reaction to tofogliflozin. The incidence of adverse drug reactions of special interest (polyuria/pollakiuria, volume depletion-related events, urinary tract infection, genital infection, skin disorders and hypoglycemia) was 2.19, 2.32, 1.33, 1.13, 1.46 and 0.73%, respectively. No new safety concerns were identified. Among those evaluable for clinical effectiveness, the mean (standard deviation) glycated hemoglobin decreased from 7.65% (1.35%) at baseline to 7.25% (1.16%) at 12 weeks by 0.39% (0.94%; P type 2 diabetes mellitus during the early post-marketing period. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  2. Myelin structure is a key difference in the x-ray scattering signature between meningioma, schwannoma and glioblastoma multiforme

    International Nuclear Information System (INIS)

    Falzon, G; Pearson, S; Murison, R; Hall, C; Siu, K; Round, A; Schueltke, E; Kaye, A H; Lewis, R

    2007-01-01

    Small angle x-ray scattering (SAXS) patterns of benign and malignant brain tumour tissue were examined. Independent component analysis was used to find a feature set representing the images collected. A set of coefficients was then used to describe each image, which allowed the use of the statistical technique of flexible discriminant analysis to discover a hidden order in the data set. The key difference was found to be in the intensity and spectral content of the second and fourth order myelin scattering peaks. This has clearly demonstrated that significant differences in the structure of myelin exist in the highly malignant glioblastoma multiforme as opposed to the benign: meningioma and schwannoma

  3. Glioblastoma multiforme of the pineal region: case report Glioblastoma multiforme de região pineal: relato de caso

    Directory of Open Access Journals (Sweden)

    Emerson Leandro Gasparetto

    2003-06-01

    Full Text Available PURPOSE: pineal region tumors are uncommon, and comprise more frequently three categories: germ cell, parenchymal cell and glial tumors. Most pineal gliomas are low-grade astrocytomas. Glioblastoma multiforme, the most aggressive and common brain tumor, is extremely rare at this location with only few cases reported. CASE DESCRIPTION: a 29-year-old woman with a two month history of headache, nuchal pain, fever, nausea and seizures and physical examination showing nuchal rigidity, generalized hypotony, hypotrophy and hyper-reflexia, Babinski sign and left VI cranial par palsy. CT scan examination revealed a ill-defined hypodense lesion at the pineal region with heterogeneous contrast enhancement. MRI showed a lesion at the pineal region infiltrating the right thalamic region. The patient underwent a right craniotomy with partial resection of the mass. The histological examination of paraffin-embedded material defined the diagnosis of glioblastoma multiforme. Post-operative radiotherapy was indicated but the patient refused the treatment and died two months afterwards. CONCLUSION: in spite of its rarity at this location, glioblastoma multiforme should be considered in the differential diagnosis of aggressive lesions at the pineal region.OBJETIVO: Os tumores da região pineal são incomuns e podem ser divididos em três categorias de acordo com a sua origem: células germinativas, células do parênquima e células gliais. Em sua maioria, os gliomas de pineal são astrocitomas de baixo grau, sendo que o seu correspondente maligno, glioblastoma multiforme, é o mais comum e agressivo tumor encefálico e é extremamente raro nesta localização, com apenas alguns casos relatados na literatura. CASO: Mulher com 29 anos apresentando há 2 meses cefaléia, nucalgia, febre, náuseas e crises convulsivas. O exame físico mostrou rigidez de nuca, hipotonia, hipotrofia e hiperreflexia generalizadas, sinal de Babinski e paralisia do VI nervo craniano. A

  4. Prognostic significance of IDH 1 mutation in patients with glioblastoma multiforme.

    Science.gov (United States)

    Khan, Inamullah; Waqas, Muhammad; Shamim, Muhammad Shahzad

    2017-05-01

    Focus of brain tumour research is shifting towards tumour genesis and genetics, and possible development of individualized treatment plans. Genetic analysis shows recurrent mutation in isocitrate dehydrogenase (IDH1) gene in most Glioblastoma multiforme (GBM) cells. In this review we evaluated the prognostic significance of IDH 1 mutation on the basis of published evidence. Multiple retrospective clinical analyses correlate the presence of IDH1 mutation in GBM with good prognostic outcomes compared to wild-type IDH1. A systematic review reported similar results. Based on the review of current literature IDH1 mutation is an independent factor for longer overall survival (OS) and progression free survival (PFS) in GBM patients when compared to wild-type IDH1. The prognostic significance opens up new avenues for treatment.

  5. Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations.

    Science.gov (United States)

    Abernathy, Kristen; Burke, Jeremy

    2016-01-01

    Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

  6. ETF interim design review

    International Nuclear Information System (INIS)

    Steiner, D.; Rutherford, P.H.

    1980-01-01

    A three-day ETF Interim Design Review was conducted on July 23-25, 1980, at the Sheraton Potomac Inn in Rockville, Maryland. The intent of the review was to provide a forum for an in-depth assessment and critique of all facets of the ETF design by members of the fusion community. The review began with an opening plenary session at which an overview of the ETF design was presented by D. Steiner, manager of the ETF Design Center, complemented by a physics overview by P.H. Rutherford, chairman of the ETF/INTOR Physics Committee. This was followed by six concurrent review sessions over the next day and a half. The review closed with a plenary session at which the Design Review Board presented its findings. This document consists of the viewgraphs for the opening plenary session and an edited version of the presentations made by Steiner and Rutherford

  7. Interim geotechnical data report

    International Nuclear Information System (INIS)

    1986-01-01

    This issue, the Interim Geotechnical Field Data Report, presents information obtained from the geotechnical activities at the WIPP site underground facilities since the last quarterly report. It also includes cumulative plots which contain all previous data. Finally, it continues the geotechnical analyses and interpretations of the data. The GFDR is organized into two principal parts. The first part, Geotechnical Field Data, presents in graphical form all the data collected since April 1982 from the geomechanical instruments. Presented in the second part, Evaluation and Analyses, are preliminary interpretations and analyses of the data. In this report, continuing geotechnical assessment of all the facility features is presented. Also included in the second part are separate sections on evaluation and interpretation of the instrumentation measurements, and an updated description and evaluation of observed behavior of the underground openings

  8. Federal Interim Storage program

    International Nuclear Information System (INIS)

    Johnson, E.R.; McBride, J.A.

    1984-01-01

    The DOE has developed a program for providing Federal Interim Storage servies for spent nuclear fuel which complies with the requirements of the Nuclear Waste Policy Act of 1982. Although very little constructive activity in providing storage facilities can be undertaken by DOE until fuel has been certified by NRC as eligible for FIS, DOE planning and background information is such as to provide reasonable assurance that its obligations can be fulfilled when the required certifications have been issued. A fee structure providing fuel recovery of all costs associated with the FIS program, as required by the Act, has been developed. It provides for an equitable distribution of costs among users, based on the quantity of fuel requiring storage

  9. Impacts of the Interim Federal Health Program reforms: A stakeholder analysis of barriers to health care access and provision for refugees.

    Science.gov (United States)

    Antonipillai, Valentina; Baumann, Andrea; Hunter, Andrea; Wahoush, Olive; O'Shea, Timothy

    2017-11-09

    Changes to the Interim Federal Health Program (IFHP) in 2012 reduced health care access for refugees and refugee claimants, generating concerns among key stakeholders. In 2014, a new IFHP temporarily reinstated access to some health services; however, little is known about these changes, and more information is needed to map the IFHP's impact. This study explores barriers occurring during the time period of the IFHP reforms to health care access and provision for refugees. A stakeholder analysis, using 23 semi-structured interviews, was conducted to obtain insight into stakeholder perceptions of the 2014 reforms, as well as stakeholders' position and their influence to assess the acceptability of the IFHP changes. The majority of stakeholders expressed concerns about the 2014 IFHP changes as a result of the continuing barriers posed by the 2012 retrenchments and the emergence of new barriers to health care access and provision for refugees. Key barriers identified included lack of communication and awareness, lack of continuity and comprehensive care, negative political discourse and increased costs. A few stakeholders supported the reforms as they represented some, but limited, access to health care. Overall, the reforms to the IFHP in 2014 generated barriers to health care access and provision that contributed to confusion among stakeholders, the transfer of refugee health responsibility to provincial authorities and the likelihood of increased health outcome disparities, as refugees and refugee claimants chose to delay seeking health care. The study recommends that policy-makers engage with refugee health stakeholders to formulate a policy that improves health care provision and access for refugee populations.

  10. [Multicentric prospective randomized study evaluating the interest of intravaginal electro-stimulation at home for urinary incontinence after prior perineal reeducation. Interim analysis].

    Science.gov (United States)

    Lopès, P; Levy-Toledano, R; Chiarelli, P; Rimbault, F; Marès, P

    2014-03-01

    Perineal reeducation of stress urinary incontinence is beneficial in 80% of cases. However, patients have to perform self-retraining exercises of the perineal muscles at home, in order to maintain the benefit of the physiotherapy. The aim of this study is to assess the benefit of GYNEFFIK(®), a perineal electro-stimulator, during this home-care phase. Women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI) that responded to physiotherapy were included in this study in two parallel groups. The groups followed a self-reeducation program, with or without GYNEFFIK(®) electro-stimulation sessions. The comparison of the two groups was based on the rate of women for whom the benefit of the initial perineal reeducation was maintained (defined as non-worsening ICIQ and Ditrovie scales' score). According to the protocol, an interim analysis was performed on 95 patients (i.e. almost half of the expected sample size) who had had at least one evaluation under treatment, among which 44 patients had finished the study. The therapeutic benefit of the initial perineal reeducation was maintained in 87.8% of the GYNEFFIK(®) patient group, while it was maintained in 52.2% (P=0.0001) in the usual care group (i.e. who did not use electro-stimulation). Likewise, patient had a more favorable subjective impression when using GYNEFFIK(®) (83.7% versus 60.0% in the usual care group) as they felt that they improved during the study. In the GYNEFFIK(®) group, no increase in symptoms was reported, whereas almost one out of five patients in the usual care group felt that their condition had worsened. Copyright © 2014. Published by Elsevier SAS.

  11. Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma : Systematic review and meta-analysis

    NARCIS (Netherlands)

    Adams, Hugo J A; Kwee, Thomas C.

    2016-01-01

    This study aimed to systematically review and meta-analyze the prognostic value of interim 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone

  12. Nestin expression in the cell lines derived from glioblastoma multiforme

    International Nuclear Information System (INIS)

    Veselska, Renata; Kuglik, Petr; Cejpek, Pavel; Svachova, Hana; Neradil, Jakub; Loja, Tomas; Relichova, Jirina

    2006-01-01

    Nestin is a protein belonging to class VI of intermediate filaments that is produced in stem/progenitor cells in the mammalian CNS during development and is consecutively replaced by other intermediate filament proteins (neurofilaments, GFAP). Down-regulated nestin may be re-expressed in the adult organism under certain pathological conditions (brain injury, ischemia, inflammation, neoplastic transformation). Our work focused on a detailed study of the nestin cytoskeleton in cell lines derived from glioblastoma multiforme, because re-expression of nestin together with down-regulation of GFAP has been previously reported in this type of brain tumor. Two cell lines were derived from the tumor tissue of patients treated for glioblastoma multiforme. Nestin and other cytoskeletal proteins were visualized using imunocytochemical methods: indirect immunofluorescence and immunogold-labelling. Using epifluorescence and confocal microscopy, we described the morphology of nestin-positive intermediate filaments in glioblastoma cells of both primary cultures and the derived cell lines, as well as the reorganization of nestin during mitosis. Our most important result came through transmission electron microscopy and provided clear evidence that nestin is present in the cell nucleus. Detailed information concerning the pattern of the nestin cytoskeleton in glioblastoma cell lines and especially the demonstration of nestin in the nucleus represent an important background for further studies of nestin re-expression in relationship to tumor malignancy and invasive potential

  13. Thematic network on the analysis of thorium and its isotopes in workplace materials. Interim report on current research activity and future research needs

    International Nuclear Information System (INIS)

    Howe, A.; Rosen, P.; White, M.

    1999-12-01

    The task of Work Package 1 (WP 1) of the EC Thematic Network 'The analysis of thorium and its isotopes in workplace materials' was to prepare an 'Inventory of current research activities in participating member states concerning thorium analysis in the workplace and environment'. The specific objective of WP 1 was 'to identify common research areas and co-ordinate activity for better management of resources'. This was to be achieved by carrying out a survey of network and national laboratories to establish the extent of current and proposed research activity in the field, evaluation of survey by network members, and production of a report containing results and conclusions. A preliminary literature review revealed that the majority of thorium analysis is carried out by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) or a radiochemical technique, alpha counting and neutron activation being the most popular. In many instances there is a preconcentration or separation step, which usually involves an ion exchange column to isolate the thorium and remove the majority of the matrix. Papers concerned with the application of ICP-MS were found to feature prominently amongst recent publications, which is not surprising, as the technique is fairly newly established. Thorium was most commonly measured in geological matrixes, including soil and ores. On the basis of the results of the literature review and survey of research activity, the Network identified two key areas of priority for further research: sample preparation methods for thorium analysis; and traceable standards and certified reference materials for thorium analysis. The Network considered how best to distribute the results to interested parties to facilitate links between laboratories with common research areas, and decided that: at this stage, the findings should simply be published in the form of this interim report, which is freely available to all interested parties; the Network should continue to

  14. Concomitant semi-quantitative and visual analysis improves the predictive value on treatment outcome of interim 18F-fluorodeoxyglucose / Positron Emission Tomography in advanced Hodgkin lymphoma.

    Science.gov (United States)

    Biggi, Alberto; Bergesio, Fabrizio; Chauvie, Stephane; Bianchi, Andrea; Menga, Massimo; Fallanca, Federico; Hutchings, Martin; Gregianin, Michele; Meignan, Michel; Gallamini, Andrea

    2017-07-27

    Qualitative assessment using the Deauville five-point scale (DS) is the gold standard for interim and end-of treatment PET interpretation in lymphoma. In the present study we assessed the reliability and the prognostic value of different semi- quantitative (SQ) parameters in comparison with DS for interim PET (iPET) interpretation in Hodgkin lymphoma (HL). A cohort of 82 out of 260 patients with advanced stage HL enrolled in the International Validation Study (IVS), scored as 3 to 5 by the expert panel was included in the present report. Two nuclear medicine physicians blinded to patient history, clinical data and treatment outcome reviewed independently the iPET using the following parameters: DS, SUVMax, SUVPeak of the most active lesion, QMax (ratio of SUVMax of the lesion to liver SUVMax) and QRes (ratio of SUVPeak of the lesion to liver SUVMean). The optimal sensitivity, specificity, positive and negative predictive value to predict treatment outcome was calculated for all the above parameters with the Receiver Operator Characteristics analysis. The prognostic value of all parameters were similar, the best cut-off value being 4 for DS (Area Under the Curve, AUC, 0.81 CI95%: 0.72-0.90), 3.81 for SUVMax (AUC 0.82 CI95%: 0.73-0.91), 3.20 for SUVPeak (AUC 0.86 CI95%: 0.77-0.94), 1.07 for QMax (AUC 0.84 CI95%: 0.75-0.93) and 1.38 for QRes (AUC 0.84 CI95%: 0.75-0.93). The reproducibility of different parameters was similar as the inter-observer variability measured with Cohen's kappa were 0.93 (95% CI 0.84-1.01) for the DS, 0.88 (0.77-0.98) for SUVMax, 0.82 (0.70-0.95) for SUVPeak, 0.85 (0.74-0.97) for QRes and 0.78 (0.65-0.92) for QMax. Due to the high specificity of SUVPeak (0.87) and to the good sensitivity of DS (0.86), upon the use of both parameters the positive predictive value increased from 0.65 of the DS alone to 0.79. When both parameters were positive in iPET, 3-years Failure-Free Survival (FFS) was significantly lower compared to patients whose iPET was

  15. Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Ford, Judith M.; Seiferheld, Wendy; Alger, Jeffrey R.; Wu, Genevieve; Endicott, Thyra J.; Mehta, Minesh; Curran, Walter; Phan, See-Chun

    2007-01-01

    Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide

  16. In vivo radiation sensitivity of glioblastoma multiforme

    International Nuclear Information System (INIS)

    Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

    1995-01-01

    Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF 2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD 50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD 50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD 50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD 50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 ± 13.1 Gy. The TCD 50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 ± 6.4. The difference between the average TCD 50 of GBM and SCC was not significant. The STS and CC xenografts had TCD 50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD 50 in vivo and the SF 2 or D 0 in vitro. Conclusions: Our data on GBM xenografts showed a wide range of sensitivities to single dose

  17. In vivo radiation sensitivity of glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

    1995-04-30

    Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF{sub 2} values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD{sub 50} (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD{sub 50} of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD{sub 50} assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD{sub 50} values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 {+-} 13.1 Gy. The TCD{sub 50} values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 {+-} 6.4. The difference between the average TCD{sub 50} of GBM and SCC was not significant. The STS and CC xenografts had TCD{sub 50} values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD{sub 50} in vivo and the SF{sub 2} or D{sub 0} in vitro. Conclusions: Our data on GBM

  18. Interim Reliability Evaluation Program procedures guide

    International Nuclear Information System (INIS)

    Carlson, D.D.; Gallup, D.R.; Kolaczkowski, A.M.; Kolb, G.J.; Stack, D.W.; Lofgren, E.; Horton, W.H.; Lobner, P.R.

    1983-01-01

    This document presents procedures for conducting analyses of a scope similar to those performed in Phase II of the Interim Reliability Evaluation Program (IREP). It documents the current state of the art in performing the plant systems analysis portion of a probabilistic risk assessment. Insights gained into managing such an analysis are discussed. Step-by-step procedures and methodological guidance constitute the major portion of the document. While not to be viewed as a cookbook, the procedures set forth the principal steps in performing an IREP analysis. Guidance for resolving the problems encountered in previous analyses is offered. Numerous examples and representative products from previous analyses clarify the discussion

  19. Pantex Plant final safety analysis report, Zone 4 magazines. Staging or interim storage for nuclear weapons and components: Issue D

    Energy Technology Data Exchange (ETDEWEB)

    1993-04-01

    This Safety Analysis Report (SAR) contains a detailed description and evaluation of the significant environmental, safety, and health (ES&H) issues associated with the operations of the Pantex Plant modified-Richmond and steel arch construction (SAC) magazines in Zone 4. It provides (1) an overall description of the magazines, the Pantex Plant, and its surroundings; (2) a systematic evaluations of the hazards that could occur as a result of the operations performed in these magazines; (3) descriptions and analyses of the adequacy of the measures taken to eliminate, control, or mitigate the identified hazards; and (4) analyses of potential accidents and their associated risks.

  20. Analysis of Samples Collected from the Surface of Interim Storage Canisters at Calvert Cliffs in June 2017: Revision 01.

    Energy Technology Data Exchange (ETDEWEB)

    Bryan, Charles R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Schindelholz, Eric John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-11-01

    In June 2017, dust and salt samples were collected from the surface of Spent Nuclear Fuel (SNF) dry storage canisters at the Calvert Cliffs Nuclear Power Plant. The samples were delivered to Sandia National laboratories for analysis. Two types of samples were collected: filter-backed Scotch-Brite TM pads were used to collect dry dust samples for characterization of salt and dust morphologies and distributions; and Saltsmart TM test strips were used to collect soluble salts for determining salt surface loadings per unit area. After collection, the samples were sealed into plastic sleeves for shipping. Condensation within the sleeves containing the Scotch-Brite TM samples remobilized the salts, rendering them ineffective for the intended purpose, and also led to mold growth, further compromising the samples; for these reasons, the samples were not analyzed. The SaltSmart TM samples were unaffected and were analyzed by ion chromatography for major anions and cations. The results of those analyses are presented here.

  1. Permanent interstitial low-dose-rate brachytherapy for patients with low risk prostate cancer. An interim analysis of 312 cases

    Energy Technology Data Exchange (ETDEWEB)

    Badakhshi, Harun; Graf, Reinhold; Budach, Volker; Wust, Peter [University Hospital Berlin, Department for Radiation Oncology of Charite School of Medicine, Berlin (Germany)

    2015-04-01

    The biochemical relapse-free survival (bRFS) rate after treatment with permanent iodine-125 seed implantation (PSI) or combined seeds and external beam radiotherapy (COMB) for clinical stage T1-T2 localized prostate cancer is a clinically relevant endpoint. The goal of this work was to evaluate the influence of relevant patient- and treatment-related factors. The study population comprised 312 consecutive patients treated with permanent seed implantation. All patients were evaluable for analysis of overall survival (OS) and disease-specific survival (DSS), 230 for bRFS, of which 192 were in the PSI group and 38 in the COMB group. The prescribed minimum peripheral dose was 145 Gy for PSI, for COMB 110 Gy implant and external beam radiotherapy of 45 Gy. The median follow-up time was 33 months (range 8-66 months). bRFS was defined as a serum prostate-specific antigen (PSA) level ≤ 0.2 ng/ml at last follow-up. Overall, the actuarial bRFS at 50 months was 88.4 %. The 50-month bRFS rate for PSI and COMB was 90.9 %, and 77.2 %, respectively. In the univariate analysis, age in the categories ≤ 63 and > 63 years (p < 0.00), PSA nadir (≤ 0.5 ng/ml and > 0.5 ng/ml) and PSA bounce (yes/no) were the significant predicting factors for bRFS. None of the other patient and treatment variables (treatment modality, stage, PSA, Gleason score, risk group, number of risk factors, D90 and various other dose parameters) were found to be a statistically significant predictor of 50-month bRFS. The biochemical failure rates were low in this study. As a proof of principle, our large monocenteric analysis shows that low-dose-rate brachytherapy is an effective and safe procedure for patients with early stage prostate cancer. (orig.) [German] Das biochemisch rezidivfreie Ueberleben (bRFS) nach der Brachytherapie mit permanenter Iod-125-Seed-Implantation (PSI) oder in Kombination mit externer Radiotherapie (COMB) ist beim Patienten mit fruehem Prostatakarzinom (T1/T2) ein relevanter

  2. Analysis of Dust Samples Collected from an Unused Spent Nuclear Fuel Interim Storage Container at Hope Creek, Delaware.

    Energy Technology Data Exchange (ETDEWEB)

    Bryan, Charles R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Enos, David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-01

    In July, 2014, the Electric Power Research Institute and industry partners sampled dust on the surface of an unused canister that had been stored in an overpack at the Hope Creek Nuclear Generating Station for approximately one year. The foreign material exclusion (FME) cover that had been on the top of the canister during storage, and a second recently - removed FME cover, were also sampled. This report summarizes the results of analyses of dust samples collected from the unused Hope Creek canister and the FME covers. Both wet and dry samples of the dust/salts were collected, using SaltSmart(TM) sensors and Scotch - Brite(TM) abrasive pads, respectively. The SaltSmart(TM) samples were leached and the leachate analyzed chemically to determine the composition and surface load per unit area of soluble salts present on the canister surface. The dry pad samples were analyzed by X-ray fluorescence and by scanning electron microscopy to determine dust texture and mineralogy; and by leaching and chemical analysis to deter mine soluble salt compositions. The analyses showed that the dominant particles on the canister surface were stainless steel particles, generated during manufacturing of the canister. Sparse environmentally - derived silicates and aluminosilicates were also present. Salt phases were sparse, and consisted of mostly of sulfates with rare nitrates and chlorides. On the FME covers, the dusts were mostly silicates/aluminosilicates; the soluble salts were consistent with those on the canister surface, and were dominantly sulfates. It should be noted that the FME covers were w ashed by rain prior to sampling, which had an unknown effect of the measured salt loads and compositions. Sulfate salts dominated the assemblages on the canister and FME surfaces, and in cluded Ca - SO4 , but also Na - SO4 , K - SO4 , and Na - Al - SO4 . It is likely that these salts were formed by particle - gas conversion reactions, either

  3. Fracture analysis of CAD-CAM high-density polymers used for interim implant-supported fixed, cantilevered prostheses.

    Science.gov (United States)

    Yilmaz, Burak; Alp, Gülce; Seidt, Jeremy; Johnston, William M; Vitter, Roger; McGlumphy, Edwin A

    2018-01-06

    The load-to-fracture performance of computer-assisted design and computer-assisted manufacturing (CAD-CAM) high-density polymer (HDP) materials in cantilevers is unknown. The purposes of this in vitro study were to evaluate the load-to-fracture performance of CAD-CAM-fabricated HDPs and to compare that with performance of autopolymerized and injection-molded acrylic resins. Specimens from 8 different brands of CAD-CAM HDPs, including Brylic Solid (BS); Brylic Gradient (BG); AnaxCAD Temp EZ (AE); AnaxCAD Temp Plus (AP); Zirkonzahn Temp Basic (Z); GDS Tempo-CAD (GD); Polident (Po); Merz M-PM-Disc (MAT); an autopolymerized acrylic resin, Imident (Conv) and an injection-molded acrylic resin, SR-IvoBase High Impact (Inj) were evaluated for load-to-fracture analysis (n=5). CAD-CAM specimens were milled from poly(methyl methacrylate) (PMMA) blocks measuring 7 mm in buccolingual width, 8 mm in occlusocervical thickness, and 30 mm in length. A wax pattern was prepared in the same dimensions used for CAD-CAM specimens, flasked, and boiled out. Autopolymerizing acrylic resin was packed and polymerized in a pressure container for 30 minutes. An identical wax pattern was flasked and boiled out, and premeasured capsules were injected (SR-IvoBase) and polymerized under hydraulic pressure for 35 minutes for the injection-molded PMMA. Specimens were thermocycled 5000 times (5°C to 55°C) and fixed to a universal testing machine to receive static loads on the 10-mm cantilever, vertically at a 1 mm/min crosshead speed until fracture occurred. Maximum load-to-fracture values were recorded. ANOVA was used to analyze the maximum force values. Significant differences among materials were analyzed by using the Ryan-Einot-Gabriel-Welsch multiple range test (α=.05). Statistically significant differences were found among load-to-fracture values of different HDPs (PCAD-CAM polymer. GD and Po CAD-CAM materials had the highest load-to-fracture values. AE, AP, Z, MAT, and BS CAD-CAM polymers

  4. Evaluation of Wet Chemical ICP-AES Elemental Analysis Methods using Simulated Hanford Waste Samples-Phase I Interim Report

    International Nuclear Information System (INIS)

    Coleman, Charles J.; Edwards, Thomas B.

    2005-01-01

    The wet chemistry digestion method development for providing process control elemental analyses of the Hanford Tank Waste Treatment and Immobilization Plant (WTP) Melter Feed Preparation Vessel (MFPV) samples is divided into two phases: Phase I consists of: (1) optimizing digestion methods as a precursor to elemental analyses by ICP-AES techniques; (2) selecting methods with the desired analytical reliability and speed to support the nine-hour or less turnaround time requirement of the WTP; and (3) providing baseline comparison to the laser ablation (LA) sample introduction technique for ICP-AES elemental analyses that is being developed at the Savannah River National Laboratory (SRNL). Phase II consists of: (1) Time-and-Motion study of the selected methods from Phase I with actual Hanford waste or waste simulants in shielded cell facilities to ensure that the methods can be performed remotely and maintain the desired characteristics; and (2) digestion of glass samples prepared from actual Hanford Waste tank sludge for providing comparative results to the LA Phase II study. Based on the Phase I testing discussed in this report, a tandem digestion approach consisting of sodium peroxide fusion digestions carried out in nickel crucibles and warm mixed-acid digestions carried out in plastic bottles has been selected for Time-and-Motion study in Phase II. SRNL experience with performing this analytical approach in laboratory hoods indicates that well-trained cell operator teams will be able to perform the tandem digestions in five hours or less. The selected approach will produce two sets of solutions for analysis by ICP-AES techniques. Four hours would then be allocated for performing the ICP-AES analyses and reporting results to meet the nine-hour or less turnaround time requirement. The tandem digestion approach will need to be performed in two separate shielded analytical cells by two separate cell operator teams in order to achieve the nine-hour or less turnaround

  5. Market Efficiency Analysis at the Stockholm Stock Exchange: Measuring Intraday Stock Price Performance around Interim Reports of the OMXS30 Large Cap Stocks - An Event Study Approach

    OpenAIRE

    Tames Blanco, Juan Marcelo; Nsiah, Samuel Osei

    2010-01-01

    The purpose of this thesis is to perform event studies that determine the level of efficiency of twenty-two large cap stocks from the OMXS30 Index. Under the event study methodology, analysts’ expectations, the standard Capital Asset Pricing Model and a set of parametric tests are implemented. As a result, significant evidence is found on the existence of intraday abnormal returns at the exact moment of an interim report publication. However, further evidence on market corrections state effic...

  6. Glioblastoma multiforme of the cerebellum: description of three cases.

    Science.gov (United States)

    Luccarelli, G

    1980-01-01

    Only 43 cases of glioblastoma multiforme of the cerebellum have been reported in the literature. This report is based on the findings of 3 cerebellar glioblastomas in a review of 1,206 consecutive confirmed cases of glioblastoma operated on between 1947 and 1977 at the Istituto Neurologico of Milan, giving an incidence of 0.24%. Clinical features are similar to those of any other fast-growing subtentorial tumour. Neuroradiological studies, including CAT, are of little help in predicting the exact nature of these tumours before surgery. A correct diagnosis can be reached only by microscopic examination. Histological patterns appear in no way to differ from those of cerebral glioblastoma. The biological behaviour of these tumours is in all respects identical to that of glioblastoma of cerebral hemispheres.

  7. Cellular and subcellular distribution of BSH in human glioblastoma multiforme

    International Nuclear Information System (INIS)

    Neumann, M.; Gabel, D.

    2000-01-01

    The cellular and subcellular distribution of mercaptoundecahydrododecaborate (BSH) in seven glioblastoma multiforme tissue sections of six patients having received BSH prior to surgery was investigated by light, fluorescence and electron microscopy. With use of specific antibodies against BSH its localization could be found in tissue sections predominantly (approx. 90%) in the cytoplasm of GFAP-positive cells of all but one patient. The latter was significantly younger (33 years in contrast of 46-71 (mean 60) years). In none of the tissue sections BSH could be found to a significant amount in the cell nuclei. In contrast, electron microscopy studies show BSH as well associated with the cell membrane as with the chromatin in the nucleus. (author)

  8. Cerebellar giant cell glioblastoma multiforme in an adult

    Directory of Open Access Journals (Sweden)

    Sudhansu Sekhar Mishra

    2014-01-01

    Full Text Available Cerebellar glioblastoma multiforme (GBM is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

  9. Pediatric glioblastoma multiforme: A single-institution experience.

    Science.gov (United States)

    Ansari, Mansour; Nasrolahi, Hamid; Kani, Amir-Abbas; Mohammadianpanah, Mohammad; Ahmadloo, Niloofar; Omidvari, Shapour; Mosalaei, Ahmad

    2012-07-01

    Glioblastoma multiforme (GBM) is the most common astrocytoma in adults and has a poor prognosis, with a median survival of about 12 months. But, it is rare in children. We report our experience on the pediatric population (20 years or younger) with GBM. Twenty-three patients with GBM who were treated at our hospital during 1990-2008 were evaluated. The mean age was 15.2 years, and the majority of them (14/23) were male. All had received radiotherapy and some had also received chemotherapy. The mean survival was 16.0 months. Two cases survived more than 5 years. Age, radiation dose and performance status were significantly related to survival. GBM in pediatric patients were not very common in our center, and prognosis was unfavorable.

  10. Protocols for BNCT of glioblastoma multiforme at Brookhaven: Practical considerations

    Energy Technology Data Exchange (ETDEWEB)

    Chanana, A.D.; Coderre, J.A.; Joel, D.D.; Slatkin, D.N.

    1996-12-31

    In this report we discuss some issues considered in selecting initial protocols for boron neutron capture therapy (BNCT) of human glioblastoma multiforme. First the tolerance of normal tissues, especially the brain, to the radiation field. Radiation doses limits were based on results with human and animal exposures. Estimates of tumor control doses were based on the results of single-fraction photon therapy and single fraction BNCT both in humans and experimental animals. Of the two boron compounds (BSH and BPA), BPA was chosen since a FDA-sanctioned protocol for distribution in humans was in effect at the time the first BNCT protocols were written and therapy studies in experimental animals had shown it to be more effective than BSH.

  11. The management of oral erythema multiforme in juvenile patient

    Directory of Open Access Journals (Sweden)

    Diah Savitri Ernawati

    2007-12-01

    Full Text Available Erythema multiforme is an acute inflammatory disease of the skin and mucous membranes that causes a variety of the skin lesionhence the name ‘multiforme’.The oral mucosa looks severely inflamed, but the feature are non specific and usually a biopsy is required in order to confirm the diagnosis. Cracked, bleeding, Crusted, swollen and ulcers of the lips is very characteristic of erythema multiforme, and lip involvement may cause significant morbidity. EM is assumed as an immune complex disorder which rises as a result of an immune response to an external agent such as herpes simplex virus or various drugs. We reported: 14-year girl, complained she suffered from painful oral ulceration for one week. One weeks advance the patient received a treatment of paracetamol and paramex for febris, headache and cough. Clinical examination of the skin showed no signs of cutaneous involvement. Other site such as the conjunctival, and genital were also free of lesions. The patients had several red-based superficial erosions on the upper and lower lips accompanied by crusting and bleeding. Intra oral findings showed multiple irregular erosions, ulcers and intense erythematous areas, mainly on the labial mucosa. The clinical diagnosis of EM was concluded by anamnesis and clinical appearance, with differential diagnosis of secondary herpes infection (herpes labialis and pemphigus vulgaris. Systemic and topical corticosteroid therapy is frequently used to treat EM Although it may partially suppress the disease. Objective: This report explains and describes the management of patients with EM which may help dentists to determine an accurate diagnosis to avoid further complication and to give medical intervention to the disease. Conclusion: Early recognition of this disease may prevent delayed diagnosis and incorrect treatment.

  12. Methods Data Qualification Interim Report

    International Nuclear Information System (INIS)

    Alessi, R. Sam; Grimmett, Tami; Vang, Leng; McGrath, Dave

    2010-01-01

    The overall goal of the Next Generation Nuclear Plant (NGNP) Data Management and Analysis System (NDMAS) is to maintain data provenance for all NGNP data including the Methods component of NGNP data. Multiple means are available to access data stored in NDMAS. A web portal environment allows users to access data, view the results of qualification tests and view graphs and charts of various attributes of the data. NDMAS also has methods for the management of the data output from VHTR simulation models and data generated from experiments designed to verify and validate the simulation codes. These simulation models represent the outcome of mathematical representation of VHTR components and systems. The methods data management approaches described herein will handle data that arise from experiment, simulation, and external sources for the main purpose of facilitating parameter estimation and model verification and validation (V and V). A model integration environment entitled ModelCenter is used to automate the storing of data from simulation model runs to the NDMAS repository. This approach does not adversely change the why computational scientists conduct their work. The method is to be used mainly to store the results of model runs that need to be preserved for auditing purposes or for display to the NDMAS web portal. This interim report demonstrates the currently development of NDMAS for Methods data and discusses data and its qualification that is currently part of NDMAS.

  13. Methods Data Qualification Interim Report

    Energy Technology Data Exchange (ETDEWEB)

    R. Sam Alessi; Tami Grimmett; Leng Vang; Dave McGrath

    2010-09-01

    The overall goal of the Next Generation Nuclear Plant (NGNP) Data Management and Analysis System (NDMAS) is to maintain data provenance for all NGNP data including the Methods component of NGNP data. Multiple means are available to access data stored in NDMAS. A web portal environment allows users to access data, view the results of qualification tests and view graphs and charts of various attributes of the data. NDMAS also has methods for the management of the data output from VHTR simulation models and data generated from experiments designed to verify and validate the simulation codes. These simulation models represent the outcome of mathematical representation of VHTR components and systems. The methods data management approaches described herein will handle data that arise from experiment, simulation, and external sources for the main purpose of facilitating parameter estimation and model verification and validation (V&V). A model integration environment entitled ModelCenter is used to automate the storing of data from simulation model runs to the NDMAS repository. This approach does not adversely change the why computational scientists conduct their work. The method is to be used mainly to store the results of model runs that need to be preserved for auditing purposes or for display to the NDMAS web portal. This interim report demonstrates the currently development of NDMAS for Methods data and discusses data and its qualification that is currently part of NDMAS.

  14. EUREKA study – the evaluation of real-life use of a biophotonic system in chronic wound management: an interim analysis

    Directory of Open Access Journals (Sweden)

    Romanelli M

    2017-12-01

    Full Text Available Marco Romanelli,1 Alberto Piaggesi,2 Giovanni Scapagnini,3 Valentina Dini,1 Agata Janowska,1 Elisabetta Iacopi,2 Carlotta Scarpa,4 Stéphane Fauverghe,5 Franco Bassetto4 1Wound Healing Research Unit, Division of Dermatology, School of Medicine, University of Pisa, Pisa, 2Diabetic Foot Section, Department of Medicine, University of Pisa, Pisa, 3Department of Medicine and Health Sciences, School of Medicine, University of Molise, Campobasso, 4Clinic of Plastic and Reconstructive Surgery, Padova University-Hospital, Padova, Italy; 5KLOX Technologies Inc., Laval, QC, Canada Objective: Interest has grown regarding photobiomodulation (PBM with low-level light therapy, which has been shown to positively affect the stages of the wound healing process. In a real-life context clinical setting, the objective of the EUREKA study was to investigate efficacy, safety, and quality of life associated with the use of a BioPhotonic gel (LumiHeal™ in the treatment of chronic wounds such as venous leg ulcers (VLUs, diabetic foot ulcers (DFUs, and pressure ulcers (PUs. This BioPhotonic gel represents a new, first-in-class emission spectrum of light, including fluorescence, to induce PBM and modulate healing.Design: The multicenter, prospective, interventional, uncontrolled, open-label study enrolled 100 patients in 12 wound centers in Italy. We performed an early interim analysis based on the first 33 subjects (13 VLU, 17 DFU, 3 PU in seven centers who completed the study.Main results: Seventeen patients (52% achieved total wound closure (full re-epithelialization for 2 weeks during the study period. Two patients (6% were considered “almost closed” (decrease of the wound area of more than 90% at study end and three others (9% were considered “ready for skin grafting”. No related serious adverse events were observed, and the compliance was excellent. After the treatment, the average time to “pain-free” was 11.9 days in the VLU group. Quality of life was

  15. Autopsy findings in a long-term survivor with glioblastoma multiforme. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Shozo; Endo, Yuzo; Takada, Koji; Usui, Masaaki; Hara, Mitsuru [Toranomon Hospital, Tokyo (Japan); Hirose, Takanori

    1998-02-01

    Autopsy detected no tumor tissues in a patient who died 6.5 years after the diagnosis of glioblastoma multiforme. A 54-year-old male developed left hemiparesis one month prior to admission. Computed tomography demonstrated a cystic lesion in the right frontal region with irregular ring-like enhancement. The tumor was extensively removed together with the surrounding tissues followed by irradiation (whole brain 32.4 Gy, local 28.8 Gy), and intravenous administration of interferon-{beta}. Histological examination confirmed the diagnosis of glioblastoma multiform. He died of accidental head trauma 6.5 years after surgery. Autopsy of the brain detected no evidence of glioblastoma multiform. The only findings were cerebral edema and hematoma caused by head trauma, as well as histological changes due to radiation damage. This case apparently confirms the histological disappearance of tumor tissue in a long-term survivor with glioblastoma multiform. (author)

  16. Autopsy findings in a long-term survivor with glioblastoma multiforme. Case report

    International Nuclear Information System (INIS)

    Yamada, Shozo; Endo, Yuzo; Takada, Koji; Usui, Masaaki; Hara, Mitsuru; Hirose, Takanori.

    1998-01-01

    Autopsy detected no tumor tissues in a patient who died 6.5 years after the diagnosis of glioblastoma multiforme. A 54-year-old male developed left hemiparesis one month prior to admission. Computed tomography demonstrated a cystic lesion in the right frontal region with irregular ring-like enhancement. The tumor was extensively removed together with the surrounding tissues followed by irradiation (whole brain 32.4 Gy, local 28.8 Gy), and intravenous administration of interferon-β. Histological examination confirmed the diagnosis of glioblastoma multiform. He died of accidental head trauma 6.5 years after surgery. Autopsy of the brain detected no evidence of glioblastoma multiform. The only findings were cerebral edema and hematoma caused by head trauma, as well as histological changes due to radiation damage. This case apparently confirms the histological disappearance of tumor tissue in a long-term survivor with glioblastoma multiform. (author)

  17. Proportion of false-positive lesions at interim and end-of-treatment FDG-PET in lymphoma as determined by histology: Systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com; Kwee, Thomas C.

    2016-11-15

    Purpose: To systematically review and meta-analyze the proportion of false-positive lesions at interim and end-of-treatment {sup 18}F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in lymphoma using biopsy as reference standard. Materials and methods: Medline was searched for original studies. Methodological quality of included studies was evaluated, and results were meta-analytically summarized using random effects (in case of interstudy heterogeneity [I{sup 2} ≤ 50%]) or fixed effects (in case of no interstudy heterogeneity [I{sup 2} > 50%]). Results: Eleven studies, comprising 139 patients who underwent biopsy of an FDG-avid lesion during or after completion of antilymphoma treatment, were included. Overall methodological quality was moderate. The proportion of false-positive results among all biopsied FDG-avid lesions at PET performed during of after completion of treatment ranged between 7.7% and 90.5% (the vast majority was due to inflammatory changes), with a weighted summary proportion (random effects, I{sup 2} = 75.7%) of 55.7% (95% confidence interval [CI]: 32.6–76.6%). There were no available studies on interim FDG-PET in Hodgkin lymphoma. The pooled summary false-positive proportions were 83.0% (95% CI: 72.0%–90.2%) for interim FDG-PET in non-Hodgkin lymphoma (fixed effects, I{sup 2} = 27.7%), 23.1% (95% CI: 4.7%–64.5%) for end-of-treatment FDG-PET in Hodgkin lymphoma (random effects; I{sup 2} = 67.1%), and 31.5% (95% CI: 3.9%–83.9%) for end-of-treatment FDG-PET in non-Hodgkin lymphoma (random effects, I{sup 2} = 68.3%). Conclusion: Both interim and end-of-treatment FDG-PET scans in patients with lymphoma suffer from a very high number of false-positive FDG-avid lesions. This finding, in combination with the previously reported high number of false-negative FGD-PET scans for residual disease detection, suggests that the role of interim and end-of-treatment FDG-PET should be reconsidered.

  18. 24 CFR 35.1330 - Interim controls.

    Science.gov (United States)

    2010-04-01

    ... Lead-Paint Hazard Evaluation and Hazard Reduction Activities § 35.1330 Interim controls. Interim..., cleanable covering or coating, such as metal coil stock, plastic, polyurethane, or linoleum. (3) Surfaces...

  19. Radioactive waste interim storage in Germany

    International Nuclear Information System (INIS)

    2015-12-01

    The short summary on the radioactive waste interim storage in Germany covers the following issues: importance of interim storage in the frame of radioactive waste management, responsibilities and regulations, waste forms, storage containers, transport of vitrified high-level radioactive wastes from the reprocessing plants, central interim storage facilities (Gorleben, Ahaus, Nord/Lubmin), local interim storage facilities at nuclear power plant sites, federal state collecting facilities, safety, radiation exposure in Germany.

  20. Prognostic factors in glioblastoma multiforme. 10 years experience of a single institution

    Energy Technology Data Exchange (ETDEWEB)

    Hulshof, M C.C.M.; Schimmel, E C; Gonzalez, D G [Amsterdam Univ. (Netherlands). Dept. of Radiotherapy; Koot, R W; Bosch, D A [Amsterdam Univ. (Netherlands). Dept. of Neurosurgery; Dekker, F [Amsterdam Univ. (Netherlands). Dept. of Epidemiology

    2001-06-01

    Background: To analyze prognostic factors in patients with a glioblastoma multiforme treated in an academic institute over the last 10 years. Patients and method: From 1988 to 1998, 198 patients with pathologically confirmed glioblastoma multiforme were analyzed. Five radiation schedules were used mainly based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an interstitial iridium-192 (Ir-192) boost for selected patients with a good performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions for poor prognostic patients and 5. no irradiation. Results: Median survival was 16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively. No significant improvement in survival was encountered over the last 10 years. At multivariate analysis patients treated with a hypofractionated scheme showed a similar survival probability and duration of palliative effect compared to the conventionally fractionated group. The poor prognostic groups receiving radiotherapy had a highly significant better survival compared to the no-treatment group. Patients treated with an Ir-192 boost had a better median survival compared to a historical group matched on selection criteria but without boost treatment (16 vs 9.7 months, n.s.). However, survival at 2 years was similar. Analysis on pretreatment characteristics at multivariate analysis revealed age, neurological performance, addition of radiotherapy, total resection, tumor size post surgery and deterioration before start of radiotherapy (borderline) as significant prognostic factors for survival. Conclusion: Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors

  1. 7 CFR 1735.75 - Interim financing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Interim financing. 1735.75 Section 1735.75... Involving Loan Funds § 1735.75 Interim financing. (a) A borrower may submit a written request for RUS approval of interim financing if it is necessary to close an acquisition before the loan to finance the...

  2. 7 CFR 1738.21 - Interim financing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Interim financing. 1738.21 Section 1738.21... Interim financing. (a) Upon notification by RUS that an applicant's application is considered complete, the applicant may enter into an interim financing agreement with a lender other than RUS or use its...

  3. Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial.

    Science.gov (United States)

    Basset-Seguin, Nicole; Hauschild, Axel; Grob, Jean-Jacques; Kunstfeld, Rainer; Dréno, Brigitte; Mortier, Laurent; Ascierto, Paolo A; Licitra, Lisa; Dutriaux, Caroline; Thomas, Luc; Jouary, Thomas; Meyer, Nicolas; Guillot, Bernard; Dummer, Reinhard; Fife, Kate; Ernst, D Scott; Williams, Sarah; Fittipaldo, Alberto; Xynos, Ioannis; Hansson, Johan

    2015-06-01

    The Hedgehog pathway inhibitor vismodegib has shown clinical benefit in patients with advanced basal cell carcinoma and is approved for treatment of patients with advanced basal cell carcinoma for whom surgery is inappropriate. STEVIE was designed to assess the safety of vismodegib in a situation similar to routine practice, with a long follow-up. In this multicentre, open-label trial, adult patients with histologically confirmed locally advanced basal cell carcinoma or metastatic basal cell carcinoma were recruited from regional referral centres or specialist clinics. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and adequate organ function. Patients with locally advanced basal cell carcinoma had to have been deemed ineligible for surgery. All patients received 150 mg oral vismodegib capsules once a day on a continuous basis in 28-day cycles. The primary objective was safety (incidence of adverse events until disease progression or unacceptable toxic effects), with assessments on day 1 of each treatment cycle (28 days) by principal investigator and coinvestigators at the site. Efficacy variables were assessed as secondary endpoints. The safety evaluable population included all patients who received at least one dose of study drug. Patients with histologically confirmed basal cell carcinoma who received at least one dose of study drug were included in the efficacy analysis. An interim analysis was pre-planned after 500 patients achieved 1 year of follow-up. This trial is registered with ClinicalTrials.gov, number NCT01367665. The study is still ongoing. Between June 30, 2011, and Nov 6, 2014, we enrolled 1227 patients. At clinical cutoff (Nov 6, 2013), 499 patients (468 with locally advanced basal cell carcinoma and 31 with metastatic basal cell carcinoma) had received study drug and had the potential to be followed up for 12 months or longer. Treatment was discontinued in 400 (80

  4. An interim report on the State of Nevada socioeconomic studies

    International Nuclear Information System (INIS)

    1989-06-01

    This Interim Report is a report on work in progress and presents findings from the research to date on the potential consequences of a repository for the citizens of Nevada. The research and findings in the Report have been subjected to rigorous peer review as part of the state's effort to insure independent, objective analysis that meets the highest professional standards. The basic research effort will continue through June 1990 and will enable the state to refine and clarify the findings presented in this Interim Report

  5. Activation of PPARγ mediates icaritin-induced cell cycle arrest and apoptosis in glioblastoma multiforme.

    Science.gov (United States)

    Liu, Yongji; Shi, Ling; Liu, Yuan; Li, Peng; Jiang, Guoping; Gao, Xiaoning; Zhang, Yongbin; Jiang, Chuanwu; Zhu, Weiping; Han, Hongxing; Ju, Fang

    2018-04-01

    Glioblastoma multiforme (GBM) is the most prevalent primary malignancy of the brain. This study was designed to investigate whether icaritin exerts anti-neoplastic activity against GBM in vitro. Cell Counting Kit-8 (CCK-8) assay was utilized to examine the viability of GBM cells. The apoptotic cell population was measured by flow cytometry analysis. Cell cycle distribution was detected by flow cytometry as well. Western blot analysis was performed to examine the level of biomarker proteins in GBM cells. Levels of PPARγ mRNA and protein were detected by qPCR and western blot analysis, respectively. To examine the role of PPARγ in the anti-neoplastic activity of icaritin, PPARγ antagonist GW9662 or PPARγ siRNA was used. The activity of PPARγ was determined by DNA binding and luciferase assays. Our findings revealed that icaritin markedly suppresses cell growth in a dose-dependent and time-dependent fashion. The cell population at the G0/G1 phase of the cell cycle was significantly increased following icaritin treatment. Meanwhile, icaritin promoted apoptotic cell death in T98G and U87MG cells. Further investigation showed upregulation of PPARγ played a key role in the anti-neoplastic activities of icaritin. Moreover, our result demonstrated activation of AMPK signaling by icaritin mediated the modulatory effect of icaritin on PPARγ. Our results suggest the PPARγ may mediate anti-neoplastic activities against GBM. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  6. Fast Flux Test Facility interim examination and maintenance cell: Past, present, and future

    International Nuclear Information System (INIS)

    Vincent, J.R.

    1990-09-01

    The Fast Flux Test Facility Interim Examination and Maintenance Cell was designed to perform interim examination and/or disassembly of experimental core components for final analysis elsewhere, as well as maintenance of sodium-wetted or neutron-activated internal reactor parts and plant support hardware. The Interim Examination and Maintenance Cell equipment developed and used for the first ten years of operation has been primarily devoted to the disassembly and examination of core component test assemblies. While no major reactor equipment has required remote repair or maintenance, the Interim Examina Examination and Maintenance Cell has served as the remote repair facility for its own in-cell equipment, and several innovative remote repairs have been accomplished. The Interim Examination and Maintenance Cell's demonstrated versatility has shown its capability to support a challenging future. 12 refs., 9 figs

  7. Interim report on the development and application of environmental mapped data digitization, encoding, analysis, and display software for the ALICE system. Volume II. [MAP, CHAIN, FIX, and DOUT, in FORTRAN IV for PDP-10

    Energy Technology Data Exchange (ETDEWEB)

    Amiot, L.W.; Lima, R.J.; Scholbrock, S.D.; Shelman, C.B.; Wehman, R.H.

    1979-06-01

    Volume I of An Interim Report on the Development and Application of Environmental Mapped Data Digitization, Encoding, Analysis, and Display Software for the ALICE System provided an overall description of the software developed for the ALICE System and presented an example of its application. The scope of the information presented in Volume I was directed both to the users and developers of digitization, encoding, analysis, and display software. Volume II presents information which is directly related to the actual computer code and operational characteristics (keys and subroutines) of the software. Volume II will be of more interest to developers of software than to users of the software. However, developers of software should be aware that the code developed for the ALICE System operates in an environment where much of the peripheral hardware to the PDP-10 is ANL/AMD built. For this reason, portions of the code may have to be modified for implementation on other computer system configurations. 11 tables.

  8. Altered expression of polycomb group genes in glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Gang Li

    Full Text Available The Polycomb group (PcG proteins play a critical role in histone mediated epigenetics which has been implicated in the malignant evolution of glioblastoma multiforme (GBM. By systematically interrogating The Cancer Genome Atlas (TCGA, we discovered widespread aberrant expression of the PcG members in GBM samples compared to normal brain. The most striking differences were upregulation of EZH2, PHF19, CBX8 and PHC2 and downregulation of CBX7, CBX6, EZH1 and RYBP. Interestingly, changes in EZH2, PHF19, CBX7, CBX6 and EZH1 occurred progressively as astrocytoma grade increased. We validated the aberrant expression of CBX6, CBX7, CBX8 and EZH2 in GBM cell lines by Western blotting and qRT-PCR, and further the aberrant expression of CBX6 in GBM tissue samples by immunohistochemical staining. To determine if there was functional significance to the diminished CBX6 levels in GBM, CBX6 was overexpressed in GBM cells resulting in decreased proliferative capacity. In conclusion, aberrant expression of PcG proteins in GBMs may play a role in the development or maintenance of the malignancy.

  9. Molecular Characteristics in MRI-classified Group 1 Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    William E Haskins

    2013-07-01

    Full Text Available Glioblastoma multiforme (GBM is a clinically and pathologically heterogeneous brain tumor. Previous study of MRI-classified GBM has revealed a spatial relationship between Group 1 GBM (GBM1 and the subventricular zone (SVZ. The SVZ is an adult neural stem cell niche and is also suspected to be the origin of a subtype of brain tumor. The intimate contact between GBM1 and the SVZ raises the possibility that tumor cells in GBM1 may be most related to SVZ cells. In support of this notion, we found that neural stem cell and neuroblast markers are highly expressed in GBM1. Additionally, we identified molecular characteristics in this type of GBM that include up-regulation of metabolic enzymes, ribosomal proteins, heat shock proteins, and c-Myc oncoprotein. As GBM1 often recurs at great distances from the initial lesion, the rewiring of metabolism and ribosomal biogenesis may facilitate cancer cells’ growth and survival during tumor migration. Taken together, combined our findings and MRI-based classification of GBM1 would offer better prediction and treatment for this multifocal GBM.

  10. Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

    Directory of Open Access Journals (Sweden)

    Maria-del-Mar Inda

    2014-01-01

    Full Text Available Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM, the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

  11. Glioblastoma multiforme: a look inside its heterogeneous nature.

    Science.gov (United States)

    Inda, Maria-Del-Mar; Bonavia, Rudy; Seoane, Joan

    2014-01-27

    Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

  12. Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

    International Nuclear Information System (INIS)

    Inda, Maria-del-Mar; Bonavia, Rudy; Seoane, Joan

    2014-01-01

    Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape

  13. Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

    Energy Technology Data Exchange (ETDEWEB)

    Inda, Maria-del-Mar, E-mail: mminda@vhio.net; Bonavia, Rudy [Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 119-129 Passeig Vall d’Hebron, Barcelona 08035 (Spain); Seoane, Joan [Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 119-129 Passeig Vall d’Hebron, Barcelona 08035 (Spain); Catalan Institution of Research and Advanced Studies (ICREA), Barcelona 08035 (Spain)

    2014-01-27

    Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

  14. Variegated colors of pediatric glioblastoma multiforme: what to expect?

    Directory of Open Access Journals (Sweden)

    Vivek Immanuel

    2017-08-01

    Full Text Available Malignant gliomas account for 35-45% of primary brain tumors; among these glioblastoma multiforme (GBM is the most common adult brain tumor constituting approximately 85%. Its incidence is quite less in the pediatric population and treatment of these patients is particularly challenging. Exposure to ionizing radiation is the only environmental factor found to have any significant association with GBM. Several genetic alterations associated with GBM in adults have been well documented such as epidermal growth factor receptor amplification, overexpression of mouse double minute 2 homolog also known as E3 ubiquitin-protein ligase, Phosphatase and tensin homolog gene mutation, loss of heterozygosity of chromosome 10p and isocitrate dehydrogenase-1 mutation. However, data on genetic mutations in pediatric GBM is still lacking. Exophytic brain stem gliomas are rare tumors and are usually associated with a poor prognosis. The most effective treatment in achieving long-term survival in such patients, is surgical excision of the tumor and then chemoradiotherapy followed by adjuvant chemotherapy by temozolomide. This schedule is the standard treatment for GBM patients. In view of the rarity of pediatric GBM, we report here a case of pontine GBM in a 5-year-old girl.

  15. Erythema multiforme and Stevens-Johnson syndrome following radiotherapy

    International Nuclear Information System (INIS)

    Yoshitake, Tadamasa; Nakamura, Katsumasa; Shioyama, Yoshiyuki

    2007-01-01

    Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS) are thought to be hypersensitivity syndromes with various causes, and radiotherapy might be one of the causes of these syndromes. We herein report two cases of EM/SJS following radiotherapy. The first case was a 63-year-old woman with breast cancer. At the end of postoperative radiotherapy with 60 Gy, severe pruritic erythema appeared in the irradiated area and spread over the whole body. She was diagnosed with EM by a skin biopsy. The second case was a 77-year-old woman with uterine cervical cancer who underwent postoperative radiotherapy. At a dose of 30.6 Gy, pruritic redness appeared in the irradiated area and the precordial region, and it became widespread rapidly with polymorphic transformation. Although without any histological confirmation, SJS was strongly suspected because of her pruritic conjunctivitis. Because both patients were given medicines during irradiation, radiotherapy may not be the only cause of EM/SJS. However, it should be noted that radiotherapy might trigger EM/SJS. (author)

  16. Students' interim literacies as a dynamic resource for teaching and ...

    African Journals Online (AJOL)

    This article explores the notion of 'interim literacies'by drawing on data from a research project which used linguistic and intertextual analysis of first year student writing in economics to investigate the intersection of academic discourse and student voice. This research has provided a rich set of data to illustrate the ways in ...

  17. Effectiveness Monitoring Report, MWMF Tritium Phytoremediation Interim Measures.

    Energy Technology Data Exchange (ETDEWEB)

    Hitchcock, Dan; Blake, John, I.

    2003-02-10

    This report describes and presents the results of monitoring activities during irrigation operations for the calendar year 2001 of the MWMF Interim Measures Tritium Phytoremediation Project. The purpose of this effectiveness monitoring report is to provide the information on instrument performance, analysis of CY2001 measurements, and critical relationships needed to manage irrigation operations, estimate efficiency and validate the water and tritium balance model.

  18. Prolonged survival when temozolomide is added to accelerated radiotherapy for glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Guckenberger, Matthias; Mayer, Mario; Sweeney, Reinhart A.; Flentje, Michael [University Hospital Wuerzburg (Germany). Dept. of Radiation Oncology; Buttmann, Mathias [University Hospital Wuerzburg (Germany). Dept. of Neurology; Vince, Giles H. [University Hospital Wuerzburg (Germany). Dept. of Neurosurgery

    2011-09-15

    The goal of this study was to evaluate accelerated radiotherapy with and without temozolomide (TMZ) for glioblastoma multiforme (GBM). This retrospective analysis evaluated 86 patients with histologically proven GBM who were treated with accelerated radiotherapy of 1.8 Gy twice daily to a total dose of 54 Gy within 3 weeks. Median age was 62 years and median Karnofsky index was 90. A total of 41 patients received radiotherapy only from 2002-2005 and 45 patients were treated with TMZ concomitantly and after radiotherapy from 2005-2007. Median overall survival (OS) was 12.5 months and 2-year OS was 15.4%. Patient characteristics were well balanced between the two groups except for better performance status (p = 0.05) and higher frequency of retreatment for the first recurrence (p = 0.02) in the TMZ group. Age at diagnosis (HR 2.83) and treatment with TMZ (HR 0.60) were correlated with OS in the multivariate analysis: treatment with and without TMZ resulted in median OS of 16 months and 11.3 months, respectively. Hematological toxicity grade > II was observed in 2/45 patients and 5/37 patients during simultaneous radiochemotherapy and adjuvant TMZ. TMZ added to accelerated radiotherapy for GBM resulted in prolonged overall survival with low rates of severe hematological toxicity. (orig.)

  19. Prolonged survival when temozolomide is added to accelerated radiotherapy for glioblastoma multiforme

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Mayer, Mario; Sweeney, Reinhart A.; Flentje, Michael; Buttmann, Mathias; Vince, Giles H.

    2011-01-01

    The goal of this study was to evaluate accelerated radiotherapy with and without temozolomide (TMZ) for glioblastoma multiforme (GBM). This retrospective analysis evaluated 86 patients with histologically proven GBM who were treated with accelerated radiotherapy of 1.8 Gy twice daily to a total dose of 54 Gy within 3 weeks. Median age was 62 years and median Karnofsky index was 90. A total of 41 patients received radiotherapy only from 2002-2005 and 45 patients were treated with TMZ concomitantly and after radiotherapy from 2005-2007. Median overall survival (OS) was 12.5 months and 2-year OS was 15.4%. Patient characteristics were well balanced between the two groups except for better performance status (p = 0.05) and higher frequency of retreatment for the first recurrence (p = 0.02) in the TMZ group. Age at diagnosis (HR 2.83) and treatment with TMZ (HR 0.60) were correlated with OS in the multivariate analysis: treatment with and without TMZ resulted in median OS of 16 months and 11.3 months, respectively. Hematological toxicity grade > II was observed in 2/45 patients and 5/37 patients during simultaneous radiochemotherapy and adjuvant TMZ. TMZ added to accelerated radiotherapy for GBM resulted in prolonged overall survival with low rates of severe hematological toxicity. (orig.)

  20. Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

    Science.gov (United States)

    Reardon, David A; Egorin, Merrill J; Quinn, Jennifer A; Rich, Jeremy N; Rich, Jeremy N; Gururangan, Sridharan; Gururangan, Idharan; Vredenburgh, James J; Desjardins, Annick; Sathornsumetee, Sith; Provenzale, James M; Herndon, James E; Dowell, Jeannette M; Badruddoja, Michael A; McLendon, Roger E; Lagattuta, Theodore F; Kicielinski, Kimberly P; Dresemann, Gregor; Sampson, John H; Friedman, Allan H; Salvado, August J; Friedman, Henry S

    2005-12-20

    We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

  1. Cyclophilin B Supports Myc and Mutant p53 Dependent Survival of Glioblastoma Multiforme Cells

    Science.gov (United States)

    Choi, Jae Won; Schroeder, Mark A.; Sarkaria, Jann N.; Bram, Richard J.

    2014-01-01

    Glioblastoma multiforme (GBM) is an aggressive, treatment-refractory type of brain tumor for which effective therapeutic targets remain important to identify. Here we report that cyclophilin B (CypB), a prolyl isomerase residing in the endoplasmic reticulum (ER), provides an essential survival signal in GBM cells. Analysis of gene expression databases revealed that CypB is upregulated in many cases of malignant glioma. We found that suppression of CypB reduced cell proliferation and survival in human GBM cells in vitro and in vivo. We also found that treatment with small molecule inhibitors of cyclophilins, including the approved drug cyclosporine, greatly reduced the viability of GBM cells. Mechanistically, depletion or pharmacologic inhibition of CypB caused hyperactivation of the oncogenic RAS-MAPK pathway, induction of cellular senescence signals, and death resulting from loss of MYC, mutant p53, Chk1 and JAK/STAT3 signaling. Elevated reactive oxygen species, ER expansion and abnormal unfolded protein responses in CypB-depleted GBM cells indicated that CypB alleviates oxidative and ER stresses and coordinates stress adaptation responses. Enhanced cell survival and sustained expression of multiple oncogenic proteins downstream of CypB may thus contribute to the poor outcome of GBM tumors. Our findings link chaperone-mediated protein folding in the ER to mechanisms underlying oncogenic transformation, and they make CypB an attractive and immediately targetable molecule for GBM therapy. PMID:24272483

  2. Hypofractionated High-Dose Irradiation with Positron Emission Tomography Data for the Treatment of Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Kazuhiro Miwa

    2014-01-01

    Full Text Available This research paper presents clinical outcomes of hypofractionated high-dose irradiation by intensity-modulated radiation therapy (Hypo-IMRT with 11C-methionine positron emission tomography (MET-PET data for the treatment of glioblastoma multiforme (GBM. A total of 45 patients with GBM were treated with Hypo-IMRT after surgery. Gross tumor volume (GTV was defined as the area of enhanced lesion on MRI, including MET-PET avid region; clinical target volume (CTV was the area with 5 mm margin surrounding the GTV; planning target volume (PTV was the area with 15 mm margin surrounding the CTV, including MET-PET moderate region. Hypo-IMRT was performed in 8 fractions; planning the dose for GTV was escalated to 68 Gy and that for CTV was escalated to 56 Gy, while keeping the dose delivered to the PTV at 40 Gy. Concomitant and adjuvant TMZ chemotherapy was administered. At a median follow-up of 18.7 months, median overall survival (OS was 20.0 months, and median progression-free survival was 13.0 months. The 1- and 2-year OS rates were 71.2% and 26.3%, respectively. Adjuvant TMZ chemotherapy was significantly predictive of OS on multivariate analysis. Late toxicity included 7 cases of Grade 3-4 radiation necrosis. Hypo-IMRT with MET-PET data appeared to result in favorable survival outcomes for patients with GBM.

  3. Chemotherapy followed by a combination of daily irradiation and carboplatine (CBDCA) in stage IIIB non small cell lung cancer (NSCLC) : first interim analysis of a phase II trial

    International Nuclear Information System (INIS)

    Bardet, E.; Douillard, J.Y.; Riviere, A.; Quoix, E.; Spaeth, D.; Ducolone, A.; Coudert, B.; Lagrange, J.L.; Chomy, P.; Tuchais, C.; Pellae-Cosset, B.; Henry-Amar, M.

    1996-01-01

    remission (PR), 21 had stable disease and 9 had failed (including 3 distant progressions) leading to an objective response (CR+PR) rate of 50%. Fifty patients were eligible for combination CBDCA and irradiation. Two patients died under therapy (1 from cerebral infarction, 1 from disease progression); the remaining 48 patients were treated according to the protocol (mean radiation dose 65.8 Gy; observed/theoretical CBDCA dose 99%) with hematological grade 3-4 toxicity in 15% of patients; other grade 3-4 toxicities were mucitis in 6%, nausea in 4% and diarrhea in 2% of patients. While 41 patients were eligible for adjuvant CT, it was given to 15 patients only, mainly because of previous experience of grade 3-4 hematological toxicity. Response to overall treatment could be estimated on 61 patients. Of these, 5 were in CR, 18 in PR, 6 had stable disease and 32 had failed or died. Therefore, at final evaluation, the objective response rate was 38% and the proportion of patients progression-free was 48%. The 1-year survival rate was 42% (95% confidence limits, 29 to 56%). Overall, 39 patients have died so far, 12 from local progression, 16 from distant progression, 5 from treatment-related death (3 aplasia, 1 hemorrhage, 1 during lung surgery), 5 from intercurrent disease (1 meningeal hemorrhage, 1 septic shock, 1 cachexia, 1 dementia, 1 suicide), and 1 from unknown cause. Conclusion : This interim analysis of 76 patients demonstrates that induction CT with NVB and CDDP followed by concominant daily irradiation and CBDCA can provide a local tumor control rate as high as 48% as well as high survival rate. These results, however, need longer follow-up to be confirmed. The contribution of CBDCA over local tumor control is now evaluating through a phase III trial comparing irradiation to concomitant daily CBDCA and irradiation (using the same scheme than described above) given after a less toxic induction CT (including NVB x 6, weekly, and CDDP x 2, monthly), and without adjuvant CT

  4. Chemotherapy followed by a combination of daily irradiation and carboplatine (CBDCA) in stage IIIB non small cell lung cancer (NSCLC) : first interim analysis of a phase II trial

    Energy Technology Data Exchange (ETDEWEB)

    Bardet, E; Douillard, J Y; Riviere, A; Quoix, E; Spaeth, D; Ducolone, A; Coudert, B; Lagrange, J L; Chomy, P; Tuchais, C; Pellae-Cosset, B; Henry-Amar, M

    1996-09-01

    (CR), 35 in partial remission (PR), 21 had stable disease and 9 had failed (including 3 distant progressions) leading to an objective response (CR+PR) rate of 50%. Fifty patients were eligible for combination CBDCA and irradiation. Two patients died under therapy (1 from cerebral infarction, 1 from disease progression); the remaining 48 patients were treated according to the protocol (mean radiation dose 65.8 Gy; observed/theoretical CBDCA dose 99%) with hematological grade 3-4 toxicity in 15% of patients; other grade 3-4 toxicities were mucitis in 6%, nausea in 4% and diarrhea in 2% of patients. While 41 patients were eligible for adjuvant CT, it was given to 15 patients only, mainly because of previous experience of grade 3-4 hematological toxicity. Response to overall treatment could be estimated on 61 patients. Of these, 5 were in CR, 18 in PR, 6 had stable disease and 32 had failed or died. Therefore, at final evaluation, the objective response rate was 38% and the proportion of patients progression-free was 48%. The 1-year survival rate was 42% (95% confidence limits, 29 to 56%). Overall, 39 patients have died so far, 12 from local progression, 16 from distant progression, 5 from treatment-related death (3 aplasia, 1 hemorrhage, 1 during lung surgery), 5 from intercurrent disease (1 meningeal hemorrhage, 1 septic shock, 1 cachexia, 1 dementia, 1 suicide), and 1 from unknown cause. Conclusion : This interim analysis of 76 patients demonstrates that induction CT with NVB and CDDP followed by concominant daily irradiation and CBDCA can provide a local tumor control rate as high as 48% as well as high survival rate. These results, however, need longer follow-up to be confirmed. The contribution of CBDCA over local tumor control is now evaluating through a phase III trial comparing irradiation to concomitant daily CBDCA and irradiation (using the same scheme than described above) given after a less toxic induction CT (including NVB x 6, weekly, and CDDP x 2, monthly

  5. ITER Conceptual design: Interim report

    International Nuclear Information System (INIS)

    1990-01-01

    This interim report describes the results of the International Thermonuclear Experimental Reactor (ITER) Conceptual Design Activities after the first year of design following the selection of the ITER concept in the autumn of 1988. Using the concept definition as the basis for conceptual design, the Design Phase has been underway since October 1988, and will be completed at the end of 1990, at which time a final report will be issued. This interim report includes an executive summary of ITER activities, a description of the ITER device and facility, an operation and research program summary, and a description of the physics and engineering design bases. Included are preliminary cost estimates and schedule for completion of the project

  6. Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an interim safety analysis of a multicenter, randomized, cross-over phase III trial of the 'Arbeitsgemeinschaft Internistische Onkologie'.

    Science.gov (United States)

    Boeck, Stefan; Vehling-Kaiser, Ursula; Waldschmidt, Dirk; Kettner, Erika; Märten, Angela; Winkelmann, Cornelia; Klein, Stefan; Kojouharoff, Georgi; Gauler, Thomas; Fischer von Weikersthal, Ludwig; Clemens, Michael R; Geissler, Michael; Greten, Tim F; Hegewisch-Becker, Susanna; Neugebauer, Sascha; Heinemann, Volker

    2010-01-01

    To date, only limited toxicity data are available for the combination of erlotinib with either capecitabine or gemcitabine as front-line therapy for advanced pancreatic cancer. Within a randomized phase III trial, 281 treatment-naive patients were randomly assigned between capecitabine (2000 mg/m/day, for 14 days, once every 3 weeks) plus erlotinib (150 mg/day, arm A) and gemcitabine (1000 mg/m as a 30-min infusion) plus erlotinib (150 mg/day, arm B). In case of treatment failure, patients were crossed over to a second-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was the time to treatment failure of second-line therapy (TTF2). This interim analysis of toxicity contains safety data from the first 127 randomized patients. During first-line therapy, patients received a median number of three treatment cycles (range 0-13) in both the arms. Regarding chemotherapy, a treatment delay was observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18 and 27% of treatment cycles, respectively. Erlotinib dose reductions were performed in 6 and 11% of all cycles. Grade 3/4 hematological toxicity was arms; major grade 3/4 toxicities in arms A and B were diarrhea (9 vs. 7%), skin rash (4 vs. 12%), and hand-foot syndrome (7 vs. 0%). No treatment-related death was observed. In conclusion, this interim safety analysis suggests that treatment with erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine.

  7. Agenda 21 interim balance, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Van Vuuren, D.P.; Bakkes, J.A.

    1997-10-01

    Five years after the `United Nations Conference on Environment and Development (UNCED)`, an interim balance was drawn up to see what was done to meet the ambitious challenges adopted in Agenda 21 during this conference. Such a balance is presented in this report and the complementary brochure, `Developments in Sustainability 1992-1997`, reflecting societal developments and changes in environmental quality, as well as changes in responses to environmental concerns. 24 figs., 12 tabs., 68 refs.

  8. Hitrex 1: an interim report on experimental and analytical work on BNL's zero power HTR

    Energy Technology Data Exchange (ETDEWEB)

    Beynon, A J; Kitching, S J; Lewis, T A; Waterson, R H

    1972-06-15

    This report presents interim experimental and theoretical results for the BNL Hitrex reactor. Reactivity effects and thermal and fast reaction rate distributions have been measured. Preliminary analysis has been performed, and some initial comparisons between theory and experiments made. (auth)

  9. Safety evaluation of interim stabilization of non-stabilized single-shell watch list tanks

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, S.M.

    1994-12-30

    The report provides a summation of the status of safety issues associated with interim stabilization of Watch List SSTs (organic, ferrocyanide, and flammable gas), as extracted from recent safety analyses, including the Tank Farms Accelerated Safety Analysis efforts.

  10. Safety evaluation of interim stabilization of non-stabilized single-shell watch list tanks

    International Nuclear Information System (INIS)

    Stahl, S.M.

    1994-01-01

    The report provides a summation of the status of safety issues associated with interim stabilization of Watch List SSTs (organic, ferrocyanide, and flammable gas), as extracted from recent safety analyses, including the Tank Farms Accelerated Safety Analysis efforts

  11. Prognostic relevance of cytochrome C oxidase in primary glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Corinne E Griguer

    Full Text Available Patients with primary glioblastoma multiforme (GBM have one of the lowest overall survival rates among cancer patients, and reliable biomarkers are necessary to predict patient outcome. Cytochrome c oxidase (CcO promotes the switch from glycolytic to OXPHOS metabolism, and increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure. Thus, we investigated the relationship between tumor CcO activity and the survival of patients diagnosed with primary GBM. A total of 84 patients with grade IV glioma were evaluated in this retrospective cohort study. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test, and univariate and multivariate analyses were performed with the Cox regression model. Mitochondrial CcO activity was determined by spectrophotometrically measuring the oxidation of cytochrome c. High CcO activity was detected in a subset of glioma tumors (∼30%, and was an independent prognostic factor for shorter progression-free survival and overall survival [P = 0.0087 by the log-rank test, hazard ratio = 3.57 for progression-free survival; P<0.001 by the log-rank test, hazard ratio = 10.75 for overall survival]. The median survival time for patients with low tumor CcO activity was 14.3 months, compared with 6.3 months for patients with high tumor CcO activity. High CcO activity occurs in a significant subset of high-grade glioma patients and is an independent predictor of poor outcome. Thus, CcO activity may serve as a useful molecular marker for the categorization and targeted therapy of GBMs.

  12. Identification of repaglinide as a therapeutic drug for glioblastoma multiforme

    International Nuclear Information System (INIS)

    Xiao, Zui Xuan; Chen, Ruo Qiao; Hu, Dian Xing; Xie, Xiao Qiang; Yu, Shang Bin; Chen, Xiao Qian

    2017-01-01

    Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a median survival time of only 14 months after treatment. It is urgent to find new therapeutic drugs that increase survival time of GBM patients. To achieve this goal, we screened differentially expressed genes between long-term and short-term survived GBM patients from Gene Expression Omnibus database and found gene expression signature for the long-term survived GBM patients. The signaling networks of all those differentially expressed genes converged to protein binding, extracellular matrix and tissue development as revealed in BiNGO and Cytoscape. Drug repositioning in Connectivity Map by using the gene expression signature identified repaglinide, a first-line drug for diabetes mellitus, as the most promising novel drug for GBM. In vitro experiments demonstrated that repaglinide significantly inhibited the proliferation and migration of human GBM cells. In vivo experiments demonstrated that repaglinide prominently prolonged the median survival time of mice bearing orthotopic glioma. Mechanistically, repaglinide significantly reduced Bcl-2, Beclin-1 and PD-L1 expression in glioma tissues, indicating that repaglinide may exert its anti-cancer effects via apoptotic, autophagic and immune checkpoint signaling. Taken together, repaglinide is likely to be an effective drug to prolong life span of GBM patients. - Highlights: • Gene expression signarue in long-term survived GBM patients are identified from Gene Expression Omnibus database. • Repaglinide is identified as a survival-related drug for GBM via drug repositioning in CMap. • Repaglinide effectively kills GBM cells, inhibits GBM cell migration and increases survival of mice bearing orthotopic glioma. • Repaglinide reduces Bcl-2, Beclin-1 and PD-L1 in GBM tissues.

  13. Transcranial sonography: integration into target volume definition for glioblastoma multiforme

    International Nuclear Information System (INIS)

    Vordermark, Dirk; Becker, Georg; Flentje, Michael; Richter, Susanne; Goerttler-Krauspe, Irene; Koelbl, Oliver

    2000-01-01

    Purpose: Recent studies indicate that transcranial sonography (TCS) reliably displays the extension of malignant brain tumors. The effect of integrating TCS into radiotherapy planning for glioblastoma multiforme (GBM) was investigated herein. Methods and Materials: Thirteen patients subtotally resected for GBM underwent TCS during radiotherapy planning and were conventionally treated (54 to 60 Gy). Gross tumor volumes (GTVs) and stereotactic boost planning target volumes (PTVs, 3-mm margin) were created, based on contrast enhancement on computed tomography (CT) only (PTV CT ) or the combined CT and TCS information (PTV CT+TCS ). Noncoplonar conformal treatment plans for both PTVs were compared. Tumor progression patterns and preoperative magnetic resonance imaging (MRI) were related to both PTVs. Results: A sufficient temporal bone window for TCS was present in 11 of 13 patients. GTVs as defined by TCS were considerably larger than the respective CT volumes: Of the composite GTV CT+TCS (median volume 42 ml), 23%, 13%, and 66% (medians) were covered by the overlap of both methods, CT only and TCS only, respectively. Median sizes of PTV CT and PTV CT+TCS were 34 and 74 ml, respectively. Addition of TCS to CT information led to a median increase of the volume irradiated within the 80% isodose by 32 ml (median factor 1.51). PTV CT+TCS volume was at median 24% of a 'conventional' MRI(T2)-based PTV. Of eight progressions analyzed, three and six occurred inside the 80% isodose of the plans for PTV CT and for PTV CT+TCS , respectively. Conclusion: Addition of TCS tumor volume to the contrast-enhancing CT volume in postoperative radiotherapy planning for GBM increases the treated volume by a median factor of 1.5. Since a high frequency of marginal recurrences is reported from dose-escalation trials of this disease, TCS may complement established methods in PTV definition

  14. Aplastic anemia as a cause of death in a patient with glioblastoma multiforme treated with temozolomide

    International Nuclear Information System (INIS)

    Kopecky, Jindrich; Priester, Peter; Slovacek, Ladislav; Petera, Jiri; Macingova, Zuzana; Kopecky, Otakar

    2010-01-01

    Background: Standard treatment of glioblastoma multiforme consists of postoperative radiochemotherapy with temozolomide, followed by a 6-month chemotherapy. Serious hematologic complications are rarely reported. Case Report and Results: The authors present the case of a 61-year-old female patient with glioblastoma multiforme treated with external-beam radiation therapy and concomitant temozolomide. After completion of treatment, the patient developed symptoms of serious aplastic anemia that eventually led to death due to prolonged neutro- and thrombocytopenia followed by infectious complications. Conclusion: Lethal complications following temozolomide are, per se, extremely rare, however, a total of four other cases of aplastic anemia have been reported in the literature so far. (orig.)

  15. Aplastic anemia as a cause of death in a patient with glioblastoma multiforme treated with temozolomide

    Energy Technology Data Exchange (ETDEWEB)

    Kopecky, Jindrich; Priester, Peter; Slovacek, Ladislav; Petera, Jiri; Macingova, Zuzana [Dept. of Clinical Oncology and Radiotherapy, Charles Univ. Hospital and Faculty of Medicine in Hradec Kralove (Czech Republic); Kopecky, Otakar [Clinical Oncology, Regional Hospital Nachod (Czech Republic)

    2010-08-15

    Background: Standard treatment of glioblastoma multiforme consists of postoperative radiochemotherapy with temozolomide, followed by a 6-month chemotherapy. Serious hematologic complications are rarely reported. Case Report and Results: The authors present the case of a 61-year-old female patient with glioblastoma multiforme treated with external-beam radiation therapy and concomitant temozolomide. After completion of treatment, the patient developed symptoms of serious aplastic anemia that eventually led to death due to prolonged neutro- and thrombocytopenia followed by infectious complications. Conclusion: Lethal complications following temozolomide are, per se, extremely rare, however, a total of four other cases of aplastic anemia have been reported in the literature so far. (orig.)

  16. Erythema multiforme like allergic contact dermatitis associated with laurel oil: a rare presentation.

    Science.gov (United States)

    Uzuncakmak, Tugba Kevser; Karadag, Ayse Serap; Izol, Belcin; Akdeniz, Necmettin; Cobanoglu, Bengu; Taskin, Secil

    2015-04-16

    Allergic contact dermatitis is a common skin disease, which affects approximately 20% of the population. This reaction may present with several clinical manifestations. Erythema multiforme-like allergic contact dermatitis is a rare type of non-eczematous contact dermatitis, which may lead to difficulty in diagnosis.Essential oil of Laurus nobilis is widely used in massage therapy for antiinflammatory and analgesic effects. Laurus nobilis induced contact dermatitis has been reported in the literature but an erythema multiforme-like presentation is rare.

  17. Tonsillary carcinoma after temozolomide treatment for glioblastoma multiforme: treatment-related or dual-pathology?

    Science.gov (United States)

    Binello, E; Germano, I M

    2009-08-01

    Glioblastoma multiforme is a primary malignant brain tumor with a prognosis of typically less than 2 years. Standard treatment paradigms include surgery, radiation therapy and temozolomide. Little data exists for temozolomide recommendations after the first 6 months. We present a case of a patient with glioblastoma multiforme treated with surgery, radiation and chronic temozolomide for 6 years. He continues to survive glioblastoma-recurrence-free, but developed tonsillary carcinoma. This case raises the question of whether this secondary solid-organ malignancy is treatment-related or dual pathology.

  18. Burn site groundwater interim measures work plan.

    Energy Technology Data Exchange (ETDEWEB)

    Witt, Jonathan L. (North Wind, Inc., Idaho Falls, ID); Hall, Kevin A. (North Wind, Inc., Idaho Falls, ID)

    2005-05-01

    This Work Plan identifies and outlines interim measures to address nitrate contamination in groundwater at the Burn Site, Sandia National Laboratories/New Mexico. The New Mexico Environment Department has required implementation of interim measures for nitrate-contaminated groundwater at the Burn Site. The purpose of interim measures is to prevent human or environmental exposure to nitrate-contaminated groundwater originating from the Burn Site. This Work Plan details a summary of current information about the Burn Site, interim measures activities for stabilization, and project management responsibilities to accomplish this purpose.

  19. Differential Expression of Circular RNAs in Glioblastoma Multiforme and Its Correlation with Prognosis

    Directory of Open Access Journals (Sweden)

    Junle Zhu

    2017-04-01

    Full Text Available OBJECTIVE: The present study aimed to explore the expression profiles of circular RNAs (circRNAs in glioblastoma multiforme (GBM in an attempt to identify potential core genes in the pathogenesis of this tumor. METHODS: Differentially expressed circRNAs were screened between tumor tissues from five GBM patients and five normal brain samples using Illumina Hiseq. Bioinformatics analysis was used to analyze their potential function. CircBRAF was further detected in different WHO grades glioma tissues and normal brain tissues. Kaplan-Meier curves and multivariate Cox's analysis were used to analyze the association between circBRAF expression level and prognosis of glioma patients. RESULTS: A total of 1411 differentially expressed circRNAs were identified in GBM patients including 206 upregulated circRNAs and 1205 downregulated circRNAs. Differential expression of circRNAs was closely associated with the biological process and molecular function. The downregulated circRNAs were mainly associated with ErbB and Neurotrophin signaling pathways. Moreover, the expression level of circBRAF in normal brain tissues was significantly higher than that in glioma tissues (P < .001. CircBRAF was significantly lower in glioma patients with high pathological grade (WHO III & IV than those with low grade (WHO I & II (P < .001. Cox analysis revealed that high circBRAF expression was an independent biomarker for predicting good progression-free survival and overall survival in glioma patients (HR = 0.413, 95% CI 0.201-0.849; HR = 0.299, 95% CI 0.135-0.661; respectively. CONCLUSION: The present study identified a profile of dysregulated circRNAs in GBM. Bioinformatics analysis showed that dysregulated circRNAs might be associated with tumorigenesis and development of GBM. In addition, circBRAF could severe as a biomarker for predicting pathological grade and prognosis in glioma patients.

  20. The prognostic significance of midline shift at presentation on survival in patients with glioblastoma multiforme

    International Nuclear Information System (INIS)

    Gamburg, Eugene S.; Regine, William F.; Patchell, Roy A.; Strottmann, James M.; Mohiuddin, Mohammed; Young, A. Byron

    2000-01-01

    Purpose: While patients with glioblastoma multiforme (GBM) who present with midline shift have a presumably worse prognosis, there is little literature evaluating the prognostic significance of this presentation in multivariate analysis in the context of other known prognostic factors. Methods and Materials: From March 1981 to September 1993, 219 patients underwent irradiation for intracranial glioma at our institution. One hundred fourteen patients with a diagnosis of a primary GBM were analyzed for the influence of the presence of midline shift at diagnosis on survival with respect to other known prognostic factors, including age, Karnofsky performance status (KPS), and extent of surgery. Eighty-five patients (74%) presented with midline shift. Surgical treatment consisted of subtotal/total resection in 86 patients (75%). Among patients presenting with midline shift, 68 (80%) underwent subtotal/total resection before irradiation. Results: Multivariate analysis of the entire cohort of patients found none of the potential prognostic factors analyzed to significantly influence survival. The overall median survival was 6 months. However, when multivariate analysis was limited to patients with a KPS of ≥ 70, only the presence of midline shift and age were found to significantly influence survival. Patients with a KPS ≥ 70 and with midline shift present at diagnosis had a median survival of 8 months, as compared to 14 months for those not having midline shift at presentation (p = 0.04). Patients with a KPS ≥ 70 and age > 50 years had a median survival of 5 months as compared to 11 months for those ≤ 50 (p 0.02). Conclusion: In this series, where 80% of patients who presented with a midline shift underwent decompressive resection of GBM before irradiation, the presence of midline shift at diagnosis remained an independent prognostic factor influencing survival among good performance status patients. While the role of decompressive surgery in this setting is

  1. Invariant delineation of nuclear architecture in glioblastoma multiforme for clinical and molecular association.

    Science.gov (United States)

    Chang, Hang; Han, Ju; Borowsky, Alexander; Loss, Leandro; Gray, Joe W; Spellman, Paul T; Parvin, Bahram

    2013-04-01

    Automated analysis of whole mount tissue sections can provide insights into tumor subtypes and the underlying molecular basis of neoplasm. However, since tumor sections are collected from different laboratories, inherent technical and biological variations impede analysis for very large datasets such as The Cancer Genome Atlas (TCGA). Our objective is to characterize tumor histopathology, through the delineation of the nuclear regions, from hematoxylin and eosin (H&E) stained tissue sections. Such a representation can then be mined for intrinsic subtypes across a large dataset for prediction and molecular association. Furthermore, nuclear segmentation is formulated within a multi-reference graph framework with geodesic constraints, which enables computation of multidimensional representations, on a cell-by-cell basis, for functional enrichment and bioinformatics analysis. Here, we present a novel method, multi-reference graph cut (MRGC), for nuclear segmentation that overcomes technical variations associated with sample preparation by incorporating prior knowledge from manually annotated reference images and local image features. The proposed approach has been validated on manually annotated samples and then applied to a dataset of 377 Glioblastoma Multiforme (GBM) whole slide images from 146 patients. For the GBM cohort, multidimensional representation of the nuclear features and their organization have identified 1) statistically significant subtypes based on several morphometric indexes, 2) whether each subtype can be predictive or not, and 3) that the molecular correlates of predictive subtypes are consistent with the literature. Data and intermediaries for a number of tumor types (GBM, low grade glial, and kidney renal clear carcinoma) are available at: http://tcga.lbl.gov for correlation with TCGA molecular data. The website also provides an interface for panning and zooming of whole mount tissue sections with/without overlaid segmentation results for quality

  2. Understanding cytoskeleton regulators in glioblastoma multiforme for therapy design

    Directory of Open Access Journals (Sweden)

    Masoumi S

    2016-09-01

    Full Text Available Samaneh Masoumi,1,*, Aditya Harisankar,2,* Aileen Gracias,3 Fabian Bachinger,1 Temesgen Fufa,1,4 Gayathri Chandrasekar,5 Frank Gaunitz,4 Julian Walfridsson,2 Satish S Kitambi1 1Department of Microbiology Tumor and Cell Biology, 2Center for Hematology and Regenerative Medicine, Department of Medicine, 3Department of Neuroscience, Karolinska Institutet, Solna, Sweden; 4Department of Neurosurgery, University Hospital, Leipzig, Germany; 5Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden *These authors contributed equally to this work Abstract: The cellular cytoskeleton forms the primary basis through which a cell governs the changes in size, shape, migration, proliferation, and forms the primary means through which the cells respond to their environment. Indeed, cell and tissue morphologies are used routinely not only to grade tumors but also in various high-content screening methods with an aim to identify new small molecules with therapeutic potential. This study examines the expression of various cytoskeleton regulators in glioblastoma multiforme (GBM. GBM is a very aggressive disease with a low life expectancy even after chemo- and radiotherapy. Cancer cells of GBM are notorious for their invasiveness, ability to develop resistance to chemo- and radiotherapy, and to form secondary site tumors. This study aims to gain insight into cytoskeleton regulators in GBM cells and to understand the effect of various oncology drugs, including temozolomide, on cytoskeleton regulators. We compare the expression of various cytoskeleton regulators in GBM-derived tumor and normal tissue, CD133-postive and -negative cells from GBM and neural cells, and GBM stem-like and differentiated cells. In addition, the correlation between the expression of cytoskeleton regulators with the clinical outcome was examined to identify genes associated with longer patient survival. This was followed by a small molecule screening with US Food and Drug

  3. Volumetric Spectroscopic Imaging of Glioblastoma Multiforme Radiation Treatment Volumes

    Energy Technology Data Exchange (ETDEWEB)

    Parra, N. Andres [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Maudsley, Andrew A. [Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida (United States); Gupta, Rakesh K. [Department of Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, Haryana (India); Ishkanian, Fazilat; Huang, Kris [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Walker, Gail R. [Biostatistics and Bioinformatics Core Resource, Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, Florida (United States); Padgett, Kyle [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida (United States); Roy, Bhaswati [Department of Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, Haryana (India); Panoff, Joseph; Markoe, Arnold [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Stoyanova, Radka, E-mail: RStoyanova@med.miami.edu [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States)

    2014-10-01

    Purpose: Magnetic resonance (MR) imaging and computed tomography (CT) are used almost exclusively in radiation therapy planning of glioblastoma multiforme (GBM), despite their well-recognized limitations. MR spectroscopic imaging (MRSI) can identify biochemical patterns associated with normal brain and tumor, predominantly by observation of choline (Cho) and N-acetylaspartate (NAA) distributions. In this study, volumetric 3-dimensional MRSI was used to map these compounds over a wide region of the brain and to evaluate metabolite-defined treatment targets (metabolic tumor volumes [MTV]). Methods and Materials: Volumetric MRSI with effective voxel size of ∼1.0 mL and standard clinical MR images were obtained from 19 GBM patients. Gross tumor volumes and edema were manually outlined, and clinical target volumes (CTVs) receiving 46 and 60 Gy were defined (CTV{sub 46} and CTV{sub 60}, respectively). MTV{sub Cho} and MTV{sub NAA} were constructed based on volumes with high Cho and low NAA relative to values estimated from normal-appearing tissue. Results: The MRSI coverage of the brain was between 70% and 76%. The MTV{sub NAA} were almost entirely contained within the edema, and the correlation between the 2 volumes was significant (r=0.68, P=.001). In contrast, a considerable fraction of MTV{sub Cho} was outside of the edema (median, 33%) and for some patients it was also outside of the CTV{sub 46} and CTV{sub 60}. These untreated volumes were greater than 10% for 7 patients (37%) in the study, and on average more than one-third (34.3%) of the MTV{sub Cho} for these patients were outside of CTV{sub 60}. Conclusions: This study demonstrates the potential usefulness of whole-brain MRSI for radiation therapy planning of GBM and revealed that areas of metabolically active tumor are not covered by standard RT volumes. The described integration of MTV into the RT system will pave the way to future clinical trials investigating outcomes in patients treated based on

  4. Surveillance on The Safety and Efficacy of Ambrisentan (Volibris Tablet 2.5 mg) in Patients with Pulmonary Arterial Hypertension in Real Clinical Practice: Post-marketing Surveillance (Interim Analysis Report).

    Science.gov (United States)

    Takahashi, Tomohiko; Hayata, Satoru; Kobayashi, Akihiro; Onaka, Yuna; Ebihara, Takeshi; Hara, Terufumi

    2018-03-01

    Pulmonary arterial hypertension (PAH) is an intractable and rare disease and the accumulation of clinical evidence under real-world setting is needed. A post-marketing surveillance for the endothelin receptor antagonist ambrisentan (Volibris tablet) has been conducted by all-case investigation since September 2010. This paper is an interim report on the safety and efficacy of ambrisentan in 702 patients with PAH. PAH patients aged 15 years or older were subjected to the analysis. The safety analysis by overall cases or stratification of patient backgrounds and the efficacy analysis were investigated. Regarding patient characteristics, the 702 patients subjected to safety analysis included 543 (77.4%) women and 546 (77.8%) patients at WHO functional class II/III. The mean observational time was 392.7 days. A total of 324 adverse drug reaction (ADR) occurred in 204 (29.1%) patients. Common ADRs (≥ 2%) included anemia (4.6%), peripheral edema (4.1%), headache (3.6%), edema and face edema (2.6% each), abnormal hepatic function (2.3%), and epistaxis (2.1%). There were 82 serious ADRs occurring in 44 (6.3%) patients (385 serious adverse events in 184 (26.2%) patients). Although 11 (1.6%) interstitial lung disease (ILD) cases were reported, all were observed in patients with disease that may contribute to ILD and therefore it is difficult to assess if ambrisentan was associated with these events. There was no difference in safety in relation to the presence/absence of connective tissue disease-related PAH (CTD-PAH) or combination therapy. Among 677 patients subjected to efficacy analysis, those in whom hemodynamic status was determined before and after treatment showed improvement in the mean pulmonary arterial pressure and pulmonary vascular resistance after treatment. The interim results showed safety consistent with the known profile of ambrisentan in terms of the types and frequencies of ADRs in patients with PAH in real clinical practice, in comparison with

  5. Glioblastoma multiforme med intra- og ekstramedullær disseminering til spinalkanalen

    DEFF Research Database (Denmark)

    Hansson, Karin; Gutte Borgwardt, Henrik; Idris, Fadi

    2013-01-01

    Metastases to the spinal cord from glioblastoma multiforme (GBM) are uncommon, but important to have in mind when patients with a history of GBM present with symptoms that do not correlate with the primary disease pattern. We report a rare case, where a male with GBM, six months after tumour...

  6. Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme

    DEFF Research Database (Denmark)

    Muhic, Aida; Poulsen, Hans Skovgaard; Mau-Sørensen, Paul Morten

    2013-01-01

    glioblastoma multiforme (GBM) who had previously failed radiotherapy plus temozolomide as first-line therapy (STUPP), or the same regimen with subsequent bevacizumab-based therapy as second-line treatment (BEV). Patients with a performance status of 0-1, histologically proven GBM, and measurable disease (by...... GBM who had failed 1-2 prior lines of therapy....

  7. Clinical variables serve as prognostic factors in a model for survival from glioblastoma multiforme

    DEFF Research Database (Denmark)

    Michaelsen, Signe Regner; Christensen, Ib Jarle; Grunnet, Kirsten

    2013-01-01

    Although implementation of temozolomide (TMZ) as a part of primary therapy for glioblastoma multiforme (GBM) has resulted in improved patient survival, the disease is still incurable. Previous studies have correlated various parameters to survival, although no single parameter has yet been...

  8. On the Concepts and History of Glioblastoma Multiforme - Morphology, Genetics and Epigenetics

    Directory of Open Access Journals (Sweden)

    Stoyanov George St.

    2018-03-01

    Full Text Available Glioblastoma multiforme (GBM is a grade IV WHO malignant tumor with astrocytic differentiation. As one of the most common clinically diagnosed central nervous system (CNS oncological entries, there have been a wide variety of historical reports of the description and evolution of ideas regarding these tumors.

  9. Jacob's ladders, Riemann's oscillators, quotient of two oscillating multiforms and set of metamorphoses of this system

    OpenAIRE

    Moser, Jan

    2015-01-01

    In this paper we introduce complicated oscillating system, namely quotient of two multiforms based on Riemann-Siegel formula. We prove that there is an infinite set of metamorphoses of this system (=chrysalis) on critical line $\\sigma=\\frac 12$ into a butterfly (=infinite series of M\\" obius functions in the region of absolute convergence $\\sigma>1$).

  10. 76 FR 58790 - Notice of Interim Approval

    Science.gov (United States)

    2011-09-22

    ... to the customers. Rate Scenario 3--Original Cumberland Marketing Policy The third rate alternative... an interim basis to the customers. Rate Scenario 3--Original Cumberland Marketing Policy The third... allocated on an interim basis to the customers. Rate Scenario 3--Original Cumberland Marketing Policy The...

  11. Addendum to IFMIF-CDA interim report

    Energy Technology Data Exchange (ETDEWEB)

    Maekawa, Hiroshi; Ida, Mizuho [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; eds.

    1996-08-01

    During the second IFMIF-CDA Design Integration Workshop, the conceptual design and contents of `IFMIF-CDA Interim Report` were examined and discussed at both general and group meetings. Based on these discussion, the final IFMIF-CDA Report will be modified from the `Interim Report`. This report describes the outline of these modification. (author)

  12. Addendum to IFMIF-CDA interim report

    International Nuclear Information System (INIS)

    Maekawa, Hiroshi; Ida, Mizuho

    1996-08-01

    During the second IFMIF-CDA Design Integration Workshop, the conceptual design and contents of 'IFMIF-CDA Interim Report' were examined and discussed at both general and group meetings. Based on these discussion, the final IFMIF-CDA Report will be modified from the 'Interim Report'. This report describes the outline of these modification. (author)

  13. Fusion Breeder Program interim report

    International Nuclear Information System (INIS)

    Moir, R.; Lee, J.D.; Neef, W.

    1982-01-01

    This interim report for the FY82 Fusion Breeder Program covers work performed during the scoping phase of the study, December, 1981-February 1982. The goals for the FY82 study are the identification and development of a reference blanket concept using the fission suppression concept and the definition of a development plan to further the fusion breeder application. The context of the study is the tandem mirror reactor, but emphasis is placed upon blanket engineering. A tokamak driver and blanket concept will be selected and studied in more detail during FY83

  14. Involvement of miRNAs in the differentiation of human glioblastoma multiforme stem-like cells.

    Directory of Open Access Journals (Sweden)

    Beatriz Aldaz

    Full Text Available Glioblastoma multiforme (GBM-initiating cells (GICs represent a tumor subpopulation with neural stem cell-like properties that is responsible for the development, progression and therapeutic resistance of human GBM. We have recently shown that blockade of NFκB pathway promotes terminal differentiation and senescence of GICs both in vitro and in vivo, indicating that induction of differentiation may be a potential therapeutic strategy for GBM. MicroRNAs have been implicated in the pathogenesis of GBM, but a high-throughput analysis of their role in GIC differentiation has not been reported. We have established human GIC cell lines that can be efficiently differentiated into cells expressing astrocytic and neuronal lineage markers. Using this in vitro system, a microarray-based high-throughput analysis to determine global expression changes of microRNAs during differentiation of GICs was performed. A number of changes in the levels of microRNAs were detected in differentiating GICs, including over-expression of hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222, and down-regulation of hsa-miR-93 and hsa-miR-106a. Functional studies showed that miR-21 over-expression in GICs induced comparable cell differentiation features and targeted SPRY1 mRNA, which encodes for a negative regulator of neural stem-cell differentiation. In addition, miR-221 and miR-222 inhibition in differentiated cells restored the expression of stem cell markers while reducing differentiation markers. Finally, miR-29a and miR-29b targeted MCL1 mRNA in GICs and increased apoptosis. Our study uncovers the microRNA dynamic expression changes occurring during differentiation of GICs, and identifies miR-21 and miR-221/222 as key regulators of this process.

  15. SU-F-T-392: Superior Brainstem and Cochlea Sparing with VMAT for Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Briere, TM; McAleer, MF; Levy, LB; Yang, JN; Anderson, MD [Cancer Ctr., Houston, TX (United States)

    2016-06-15

    Purpose: Volumetric arc therapy (VMAT) can provide similar target coverage and normal tissue sparing as IMRT but with shorter treatment times. At our institution VMAT was adopted for the treatment glioblastoma multiforme (GBM) after a small number of test plans demonstrated its non-inferiority. In this study, we compare actual clinical treatment plans for a larger cohort of patients treated with either VMAT or IMRT. Methods: 90 GBM patients were included in this study, 45 treated with IMRT and 45 with VMAT. All planning target volumes (PTVs) were prescribed a dose of 50 Gy, with a simultaneous integrated boost to 60 Gy. Most IMRT plans used 5 non-coplanar beams, while most VMAT plans used 2 coplanar beams. Statistical analysis was performed using Fisher’s exact test or the Wilcoxon-Mann-Whitney rank sum test. Included in the analysis were patient and treatment characteristics as well as the doses to the target volumes and organs at risk. Results: Treatment times for the VMAT plans were reduced by 5 minutes compared with IMRT. The PTV coverage was similar, with at least 95% covered for all plans, while the median boost PTV dose differed by 0.1 Gy between the IMRT and VMAT cohorts. The doses to the brain, optic chiasm, optic nerves and eyes were not significantly different. The mean dose to the brainstem, however, was 9.4 Gy less with VMAT (p<0.001). The dose to the ipsilateral and contralateral cochleae were respectively 19.7 and 9.5 Gy less (p<0.001). Conclusion: Comparison of clinical treatment plans for separate IMRT and VMAT cohorts demonstrates that VMAT can save substantial treatment time while providing similar target coverage and superior sparing of the brainstem and cochleae. To our knowledge this is the first study to demonstrate this benefit of VMAT in the management of GBM.

  16. Marital status, treatment, and survival in patients with glioblastoma multiforme: a population based study.

    Science.gov (United States)

    Chang, Susan M; Barker, Fred G

    2005-11-01

    Social factors influence cancer treatment choices, potentially affecting patient survival. In the current study, the authors studied the interrelations between marital status, treatment received, and survival in patients with glioblastoma multiforme (GM), using population-based data. The data source was the Surveillance, Epidemiology, and End Results (SEER) Public Use Database, 1988-2001, 2004 release, all registries. Multivariate logistic, ordinal, and Cox regression analyses adjusted for demographic and clinical variables were used. Of 10,987 patients with GM, 67% were married, 31% were unmarried, and 2% were of unknown marital status. Tumors were slightly larger at the time of diagnosis in unmarried patients (49% of unmarried patients had tumors larger than 45 mm vs. 45% of married patients; P = 0.004, multivariate analysis). Unmarried patients were less likely to undergo surgical resection (vs. biopsy; 75% of unmarried patients vs. 78% of married patients) and were less likely to receive postoperative radiation therapy (RT) (70% of unmarried patients vs. 79% of married patients). On multivariate analysis, the odds ratio (OR) for resection (vs. biopsy) in unmarried patients was 0.88 (95% confidence interval [95% CI], 0.79-0.98; P = 0.02), and the OR for RT in unmarried patients was 0.69 (95% CI, 0.62-0.77; P Unmarried patients more often refused both surgical resection and RT. Unmarried patients who underwent surgical resection and RT were found to have a shorter survival than similarly treated married patients (hazard ratio for unmarried patients, 1.10; P = 0.003). Unmarried patients with GM presented with larger tumors, were less likely to undergo both surgical resection and postoperative RT, and had a shorter survival after diagnosis when compared with married patients, even after adjustment for treatment and other prognostic factors. (c) 2005 American Cancer Society.

  17. Interim and final storage casks

    International Nuclear Information System (INIS)

    Stumpfrock, L.; Kockelmann, H.

    2012-01-01

    The disposal of radioactive waste is a huge social challenge in Germany and all over the world. As is well known the search for a site for a final repository for high-level waste in Germany is not complete. Therefore, interim storage facilities for radioactive waste were built at plant sites in Germany. The waste is stored in these storage facilities in appropriate storage and transport casks until the transport in a final repository can be carried out. Licensing of the storage and transport casks aimed for use in the public space is done according to the traffic laws and for handling in the storage facility according to nuclear law. Taking into account the activity of the waste to be stored, different containers are in use, so that experience is available from the licensing and operation in interim storage facilities. The large volume of radioactive waste to be disposed of after the shut-down of power generation in nuclear power stations makes it necessary for large quantities of licensed storage and transport casks to be provided soon.

  18. Glass packages in interim storage

    International Nuclear Information System (INIS)

    Jacquet-Francillon, N.

    1994-10-01

    This report summarize the current state of knowledge concerning the behavior of type C waste packages consisting of vitrified high-level solutions produced by reprocessing spent fuel. The composition and the physical and chemical properties of the feed solutions are reviewed, and the vitrification process is described. Sodium alumino-borosilicate glass compositions are generally employed - the glass used at la Hague for LWR fuel solutions, for example, contains 45 % SiO 2 . The major physical, chemical, mechanical and thermal properties of the glass are reviewed. In order to allow their thermal power to diminish, the 3630 glass packages produced (as of January 1993) in the vitrification facilities at Marcoule and La Hague are placed in interim storage for several decades. The actual interim storage period has not been defined, as it is closely related to the concept and organization selected for the final destination of the packages: a geological repository. The glass behavior under irradiation is described. Considerable basic and applied research has been conducted to assess the aqueous leaching behavior of nuclear containment glass. The effects of various repository parameters (temperature, flow rate, nature of the environmental materials) have been investigated. The experimental findings have been used to specify a model describing the kinetics of aqueous corrosion of the glass. More generally all the ''source term'' models developed in France by the CEA or by ANDRA are summarized. (author). 152 refs., 33 figs

  19. Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, Arnulf; Vaupel, Peter; Stockinger, Marcus; Schmidberger, Heinz [University Medical Center, Department of Radiooncology and Radiotherapy, Mainz (Germany); Struss, Hans-Garlich [University Medical Center, Department of Laboratory Medicine, Mainz (Germany); Giese, Alf [University Medical Center, Department of Neurosurgery, Mainz (Germany)

    2014-10-15

    In comparison to normal brain tissue, glioblastomas exhibit significantly increased glucose uptake. Brain edema is a common complication during adjuvant chemoradiotherapy, leading to a requirement for glucocorticoid treatment. Glucocorticoid treatment frequently causes considerable deregulation of blood glucose levels. Therefore, episodes of hyperglycemia may contribute to radio- and/or chemoresistance. This study comprises a retrospective analysis of the influence of hyperglycemic episodes (HEs) during adjuvant therapy on the overall survival of 106 glioblastoma multiforme patients. The occurrence of one or more deregulated blood glucose value(s) > 10 mM is associated with a reduction in median overall survival from 16.7 to 8.8 months. A significantly poorer overall survival of patients with hyperglycemia could also be detected in subgroup analyses of patients with complete tumor resection and complete treatment according to the EORTC 22891/26891 trial protocol, as well as in a multivariate Cox proportional hazards analysis. A history of diabetes mellitus had no influence on prognosis. Our data suggest that the observed negative impact of elevated blood glucose levels on overall survival may not solely be explained by the patients' poorer general condition; the elevated blood glucose concentration itself may play a pathogenetic role. This could be due to increased activity of antioxidant systems, elevated expression of DNA damage response proteins and protection of hypoxic tumor cells against apoptosis combined with hypoxia-mediated radioresistance. A possible prognostic impact of elevated blood glucose levels during the period of adjuvant (chemo-) radiotherapy of glioblastoma should be evaluated in a prospective clinical trial. (orig.) [German] Glioblastome zeigen im Vergleich mit normalem Gehirngewebe eine deutlich vermehrte Glukoseaufnahme. Im Rahmen der adjuvanten Radio(chemo)therapie von Glioblastomen treten vielfach Hirnoedeme auf, die eine

  20. AGR-1 Data Qualification Interim Report

    International Nuclear Information System (INIS)

    Abbott, Machael

    2009-01-01

    Projects for the very-high-temperature reactor (VHTR) program provide data in support of Nuclear Regulatory Commission licensing of the VHTR. Fuel and materials to be used in the reactor are tested and characterized to quantify performance in high temperature and high fluence environments. The VHTR Program has established the NGNP Data Management and Analysis System (NDMAS) to ensure that VHTR data are (1) qualified for use, (2) stored in a readily accessible electronic form, and (3) analyzed to extract useful results. This document focuses on the first NDMAS objective. It describes the data streams associated with the first Advanced Gas Reactor (AGR-1) experiment, the processing of these data within NDMAS, and reports the interim FY09 qualification status of the AGR-1 data to date. Data qualification activities within NDMAS for specific types of data are determined by the data qualification category, which is assigned by the data generator, and include: (1) capture testing, to confirm that the data stored within NDMAS are identical to the raw data supplied, (2) accuracy testing, to confirm that the data are an accurate representation of the system or object being measured, and (3) documentation that the data were collected under an NQA-1 or equivalent QA program. The interim qualification status of the following four data streams is reported in this document: (1) fuel fabrication data, (2) fuel irradiation data, (3) fission product monitoring system (FPMS) data, and (4) Advanced Test Reactor (ATR) operating conditions data. A final report giving the NDMAS qualification status of all AGR-1 data (including cycle 145A) is planned for February 2010

  1. Interim safety basis compliance matrix for Trenches 31 and 34

    International Nuclear Information System (INIS)

    Ames, R.R.

    1994-01-01

    The tables provided in this document identify the specific requirements and basis for the administrative controls established in the Westinghouse Hanford Company (WHC) Solid Waste Burial Ground (SWBG) Interim Safety Basis (ISB) for operation of the Project W-025, Mixed Waste Lined Landfill (Trenches 31 and 34). The tables document the necessary controls and implementing procedures to ensure compliance with the requirements of the ISB. These requirements provide a basis for future Unreviewed Safety Questions (USQ) screening of applicable procedure changes, proposed physical modifications, tests, experiments, and occurrences. Table 1 provides the SWBG interim Operational Safety Requirements administrative controls matrix. The specific assumptions and commitments used in the safety analysis documents applicable to disposal of mixed wastes in Trenches 31 and 34 are provided in Table 2. Table 3 is provided to document the potential engineered and administrative mitigating features identified in the Preliminary Hazard Analysis (PHA) for disposal of mixed waste

  2. Radiation Therapy Dose Escalation for Glioblastoma Multiforme in the Era of Temozolomide

    Energy Technology Data Exchange (ETDEWEB)

    Badiyan, Shahed N.; Markovina, Stephanie; Simpson, Joseph R.; Robinson, Clifford G.; DeWees, Todd [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Tran, David D.; Linette, Gerry [Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri (United States); Jalalizadeh, Rohan [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Dacey, Ralph; Rich, Keith M.; Chicoine, Michael R.; Dowling, Joshua L.; Leuthardt, Eric C.; Zipfel, Gregory J.; Kim, Albert H. [Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri (United States); Huang, Jiayi, E-mail: jhuang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-11-15

    Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Methods and Materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.

  3. Impact of CD133 positive stem cell proportion on survival in patients with glioblastoma multiforme

    International Nuclear Information System (INIS)

    Kase, Marju; Minajeva, Ave; Niinepuu, Kristi; Kase, Sandra; Vardja, Markus; Asser, Toomas; Jaal, Jana

    2013-01-01

    The aim of the study was to assess the impact of CD133-positive (CD133+) cancer stem cell proportions on treatment results of glioblastoma multiforme (GBM) patients. Patients with GBM (n = 42) received postoperative radiotherapy (± chemotherapy). Surgically excised GBM tissue sections were immunohistochemically examined for CD133 expression. The proportions of CD133+ GBM cells were determined (%). The proportion of CD133+ GBM stem cells was established by 2 independent researchers whose results were in good accordance (R = 0.8, p < 0.01). Additionally, CD133 expression levels were correlated with patients overall survival. The proportion of CD133+ cells varied between patients, being from 0.5% to 82%. Mean and median proportions of CD133+ cells of the entire study group were 33% ± 24% (mean ± SD) and 28%, respectively. Clinical data do not support the association between higher proportion of stem cells and the aggressiveness of GBM. Median survival time of the study group was 10.0 months (95% CI 9.0–11.0). The survival time clearly depended on the proportion of CD133+ cells (log rank test, p = 0.02). Median survival times for patients with low (< median) and high (≥ median) proportion of CD133+ cells were 9.0 months (95% CI 7.6–10.5) and 12.0 months (95% CI 9.3–14.7), respectively. In multivariate analysis, the proportion of CD133+ cells emerged as a significant independent predictor for longer overall survival (HR 2.0, 95% CI 1.0–3.8, p = 0.04). In patients with higher stem cell proportion, significantly longer survival times after postoperative radiotherapy were achieved. Underlying reasons and possible higher sensitivity of GBM stem cells to fractionated radio-therapy should be clarified in further studies

  4. Pim1 kinase is upregulated in glioblastoma multiforme and mediates tumor cell survival

    Science.gov (United States)

    Herzog, Susann; Fink, Matthias Alexander; Weitmann, Kerstin; Friedel, Claudius; Hadlich, Stefan; Langner, Sönke; Kindermann, Katharina; Holm, Tobias; Böhm, Andreas; Eskilsson, Eskil; Miletic, Hrvoje; Hildner, Markus; Fritsch, Michael; Vogelgesang, Silke; Havemann, Christoph; Ritter, Christoph Alexander; Meyer zu Schwabedissen, Henriette Elisabeth; Rauch, Bernhard; Hoffmann, Wolfgang; Kroemer, Heyo Klaus; Schroeder, Henry; Bien-Möller, Sandra

    2015-01-01

    Background The current therapy for glioblastoma multiforme (GBM), the most aggressive and common primary brain tumor of adults, involves surgery and a combined radiochemotherapy that controls tumor progression only for a limited time window. Therefore, the identification of new molecular targets is highly necessary. Inhibition of kinases has become a standard of clinical oncology, and thus the oncogenic kinase Pim1 might represent a promising target for improvement of GBM therapy. Methods Expression of Pim1 and associated signaling molecules was analyzed in human GBM samples, and the potential role of this kinase in patients' prognosis was evaluated. Furthermore, we analyzed the in vivo role of Pim1 in GBM cell growth in an orthotopic mouse model and examined the consequences of Pim1 inhibition in vitro to clarify underlying pathways. Results In comparison with normal brain, a strong upregulation of Pim1 was demonstrated in human GBM samples. Notably, patients with short overall survival showed a significantly higher Pim1 expression compared with GBM patients who lived longer than the median. In vitro experiments with GBM cells and analysis of patients' GBM samples suggest that Pim1 regulation is dependent on epidermal growth factor receptor. Furthermore, inhibition of Pim1 resulted in reduced cell viability accompanied by decreased cell numbers and increased apoptotic cells, as seen by elevated subG1 cell contents and caspase-3 and -9 activation, as well as modulation of several cell cycle or apoptosis regulatory proteins. Conclusions Altogether, Pim1 could be a novel therapeutic target, which should be further analyzed to improve the outcome of patients with aggressive GBM. PMID:25155357

  5. A Non-randomized Controlled Trial of EMDR on Affective Symptoms in Patients With Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Monika Szpringer

    2018-05-01

    Full Text Available Glioblastoma multiforme (GBM is a highly aggressive brain cancer and its survival after diagnosis is less than 2 years. Therefore, GBM patients are especially prone to co-occurring psychological conditions such as anxiety and depressive disorders. Furthermore, aggressive medical therapies affect patients’ lives, undermining their sense of meaning and coherence. The main aim of this study was to determine the effectiveness of Eye Movement Desensitization and Reprocessing (EMDR therapy on anxiety, depression and sense of coherence in patients with GBM. Thirty-seven GBM-diagnosed women were included in this trial and received standard medical care. Of those, 18 patients were treated during 4 months with 10–12 individual EMDR sessions (60–90 minutes each. Nineteen GBM patients were used as a non-randomized control group as they consented to psychological evaluations but not to a psychotherapeutic intervention. The groups were homogeneous in terms of gender, age, educational level and treatment, but not in anxiety and depressive levels at baseline. All patients were evaluated at baseline, after treatment (4 months and at follow-up (further 4 months by the Hospital Anxiety and Depression Scale (HADS-M and the Sense of Coherence Scale (SOC-29. Caregivers in both groups were interviewed by the Patient Caregiver Questionnaire after 4 months follow-up. Statistical analyses were conducted using ANOVA statistics, correlation and regression analysis. Results showed a statistically significant decrease in the EMDR group in anxiety, depression and anger, when compared to the experimental group. EMDR therapy also had a positive impact upon the sense of coherence level in the experimental group, whereas in the control group this declined. Finally, the caregivers reported beneficial outcomes of the EMDR therapy with less anxiety- and anger-related behaviors in patients in the experimental group compared to the control group. This study is the first to show

  6. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial.

    Science.gov (United States)

    Clark, Richard E; Polydoros, Fotios; Apperley, Jane F; Milojkovic, Dragana; Pocock, Christopher; Smith, Graeme; Byrne, Jenny L; de Lavallade, Hugues; O'Brien, Stephen G; Coffey, Tony; Foroni, Letizia; Copland, Mhairi

    2017-07-01

    Discontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic myeloid leukaemia with deep molecular responses; however, patients with stable major molecular response (MMR), but not MR4, have not been studied, nor has the effect of treatment de-escalation rather than outright cessation. We aimed to examine the effects of treatment de-escalation as a prelude to complete cessation, not only in patients with MR4 or greater, but also in those with MMR but not MR4. We did this interim analysis of a non-randomised, phase 2 trial at 20 hospitals in the UK. We recruited patients (aged ≥18 years) with chronic myeloid leukaemia in first chronic phase who had received TKI for 3 years or more and were either in stable MR4 (BCR-ABL1:ABL1 ratio 0·1%) on two consecutive samples. The primary endpoint of this interim analysis was the proportion of patients who lost MMR on de-escalation and regained MMR on TKI resumption. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01804985. Between Dec 16, 2013 and April 10, 2015, we enrolled 174 patients into the MMR cohort (n=49) or the MR4 cohort (n=125). During the 12 months of half-dose therapy, 12 patients (7%) had molecular recurrence, all of whom regained MMR within 4 months of full-dose TKI resumption (median time to recovery 77 days). Recurrence was significantly lower in the MR4 cohort (three [2%; 90% CI 0·2-4·8] of 121 evaluable patients) than in the MMR cohort (nine [19%; 90% CI 9·5-28·0] of 48 evaluable patients; hazard ratio 0·12, 90% CI 0·04-0·37; p=0·0007), but was unrelated to previous TKI or TKI therapy duration. Adverse events (eg, lethargy, diarrhoea, rash, and nausea) improved during the first 3 months of de-escalation, though not thereafter. 16 serious adverse events were reported, including one fatality due to worsening pre-existing peripheral arterial occlusive disease in a patient who had received only imatinib. TKI de

  7. 13 CFR 120.890 - Source of interim financing.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Source of interim financing. 120... Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may use interim financing for all Project costs except the Borrower's contribution. Any source (including...

  8. DATA MINING METHODOLOGY FOR DETERMINING THE OPTIMAL MODEL OF COST PREDICTION IN SHIP INTERIM PRODUCT ASSEMBLY

    Directory of Open Access Journals (Sweden)

    Damir Kolich

    2016-03-01

    Full Text Available In order to accurately predict costs of the thousands of interim products that are assembled in shipyards, it is necessary to use skilled engineers to develop detailed Gantt charts for each interim product separately which takes many hours. It is helpful to develop a prediction tool to estimate the cost of interim products accurately and quickly without the need for skilled engineers. This will drive down shipyard costs and improve competitiveness. Data mining is used extensively for developing prediction models in other industries. Since ships consist of thousands of interim products, it is logical to develop a data mining methodology for a shipyard or any other manufacturing industry where interim products are produced. The methodology involves analysis of existing interim products and data collection. Pre-processing and principal component analysis is done to make the data “user-friendly” for later prediction processing and the development of both accurate and robust models. The support vector machine is demonstrated as the better model when there are a lower number of tuples. However as the number of tuples is increased to over 10000, then the artificial neural network model is recommended.

  9. CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Ganeshan, B.; Miles, K.A.; Shortman, R.; Afaq, A.; Ardeshna, K.M.; Groves, A.M.; Kayani, I. [University College London, Institute of Nuclear Medicine, London (United Kingdom); Babikir, S. [International Atomic Energy Agency (IAEA), Human Health Division, Nuclear Medicine and Diagnostic Imaging Section, Vienna (Austria)

    2017-03-15

    The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL. (orig.)

  10. 340 Waste Handling Facility interim safety basis

    International Nuclear Information System (INIS)

    Bendixsen, R.B.

    1995-01-01

    This document establishes the interim safety basis (ISB) for the 340 Waste Handling Facility (340 Facility). An ISB is a documented safety basis that provides a justification for the continued operation of the facility until an upgraded final safety analysis report is prepared that complies with US Department of Energy (DOE) Order 5480.23, Nuclear Safety Analysis Reports. The ISB for the 340 Facility documents the current design and operation of the facility. The 340 Facility ISB (ISB-003) is based on a facility walkdown and review of the design and operation of the facility, as described in the existing safety documentation. The safety documents reviewed, to develop ISB-003, include the following: OSD-SW-153-0001, Operating Specification Document for the 340 Waste Handling Facility (WHC 1990); OSR-SW-152-00003, Operating Limits for the 340 Waste Handling Facility (WHC 1989); SD-RE-SAP-013, Safety Analysis Report for Packaging, Railroad Liquid Waste Tank Cars (Mercado 1993); SD-WM-TM-001, Safety Assessment Document for the 340 Waste Handling Facility (Berneski 1994a); SD-WM-SEL-016, 340 Facility Safety Equipment List (Berneski 1992); and 340 Complex Fire Hazard Analysis, Draft (Hughes Assoc. Inc. 1994)

  11. Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan.

    Science.gov (United States)

    Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

    2017-09-01

    To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.

  12. DOE UST interim subsurface barrier technologies workshop

    International Nuclear Information System (INIS)

    1992-09-01

    This document contains information which was presented at a workshop regarding interim subsurface barrier technologies that could be used for underground storage tanks, particularly the tank 241-C-106 at the Hanford Reservation

  13. Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin

    International Nuclear Information System (INIS)

    Delattre, J.Y.; Safai, B.; Posner, J.B.

    1988-01-01

    In 15 months we encountered eight patients with intracranial tumors who developed erythema multiforme (EM) or erythema multiforme bullosa (Stevens-Johnson syndrome). All occurred shortly after use of phenytoin (DPH) and brain radiation therapy (WBRT). The clinical picture differed from the classic form of EM in that the erythema began on the scalp and spread to the extremities, progressing in three cases to extensive bullous formation. There were no cases of EM among patients who received either DPH or radiotherapy alone. The combination of DPH, WBRT, and tapering of steroids seems to predispose to EM. The pathogenesis of the disorder is probably immunologic. In the absence of seizures, anticonvulsants should not be given routinely to patients with brain tumors. When anticonvulsants are necessary in patients scheduled for WBRT, DPH may not be the drug of choice

  14. A simple route to synthesize multiform structures of tin oxide nanobelts and optical properties investigation

    International Nuclear Information System (INIS)

    Cheng Chuanwei; Xu Guoyue; Zhang Haiqian; Li Yingying; Luo Yan; Zhang Peigen

    2008-01-01

    Multiform structures of SnO 2 nanobelts including of zigzag, branching and straight structures have been synthesized by a simple molten-salt assisted route. The obtained samples were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM) and high resolution transmission electron microscope (HRTEM). The growth mechanism of zigzag nanobelts was proposed. A strong blue emission band centered in 425 nm was observed in the photoluminescence spectrum

  15. Parameter optimization for constructing competing endogenous RNA regulatory network in glioblastoma multiforme and other cancers.

    Science.gov (United States)

    Chiu, Yu-Chiao; Hsiao, Tzu-Hung; Chen, Yidong; Chuang, Eric Y

    2015-01-01

    In addition to direct targeting and repressing mRNAs, recent studies reported that microRNAs (miRNAs) can bridge up an alternative layer of post-transcriptional gene regulatory networks. The competing endogenous RNA (ceRNA) regulation depicts the scenario where pairs of genes (ceRNAs) sharing, fully or partially, common binding miRNAs (miRNA program) can establish coexpression through competition for a limited pool of the miRNA program. While the dynamics of ceRNA regulation among cellular conditions have been verified based on in silico and in vitro experiments, comprehensive investigation into the strength of ceRNA regulation in human datasets remains largely unexplored. Furthermore, pan-cancer analysis of ceRNA regulation, to our knowledge, has not been systematically investigated. In the present study we explored optimal conditions for ceRNA regulation, investigated functions governed by ceRNA regulation, and evaluated pan-cancer effects. We started by investigating how essential factors, such as the size of miRNA programs, the number of miRNA program binding sites, and expression levels of miRNA programs and ceRNAs affect the ceRNA regulation capacity in tumors derived from glioblastoma multiforme patients captured by The Cancer Genome Atlas (TCGA). We demonstrated that increased numbers of common targeting miRNAs as well as the abundance of binding sites enhance ceRNA regulation and strengthen coexpression of ceRNA pairs. Also, our investigation revealed that the strength of ceRNA regulation is dependent on expression levels of both miRNA programs and ceRNAs. Through functional annotation analysis, our results indicated that ceRNA regulation is highly associated with essential cellular functions and diseases including cancer. Furthermore, the highly intertwined ceRNA regulatory relationship enables constitutive and effective intra-function regulation of genes in diverse types of cancer. Using gene and microRNA expression datasets from TCGA, we successfully

  16. Salmonella enterica serovar Enteritidis brain abscess mimicking meningitis after surgery for glioblastoma multiforme: a case report and review of the literature.

    Science.gov (United States)

    Luciani, Léa; Dubourg, Grégory; Graillon, Thomas; Honnorat, Estelle; Lepidi, Hubert; Drancourt, Michel; Seng, Piseth; Stein, Andreas

    2016-07-07

    Salmonella brain abscess associated with brain tumor is rare. Only 11 cases have been reported to date. Here we report a case of brain abscess caused by Salmonella enterica serovar Enteritidis mimicking post-surgical meningitis in a patient with glioblastoma multiforme. A 60-year-old Algerian woman was admitted through an emergency department for a 4-day history of headache, nausea and vomiting, and behavioral disorders. Surgery for cerebral tumor excision was performed and histopathological analysis revealed glioblastoma multiforme. On the seventh day post-surgery, she presented a sudden neurological deterioration with a meningeal syndrome, confusion, and fever of 39.8°C. Her cerebrospinal fluid sample and blood cultures were positive for S. enterica Enteritidis. She was treated with ceftriaxone and ciprofloxacin. On the 17th day post-surgery, she presented a new neurological disorder and purulent discharge from the surgical wound. Brain computed tomography revealed a large cerebral abscess located at the operative site. Surgical drainage of the abscess was performed and microbial cultures of surgical deep samples were positive for the same S. enterica Enteritidis isolate. She recovered and was discharged 6 weeks after admission. In this case report, a brain abscess was initially diagnosed as Salmonella post-surgical meningitis before the imaging diagnosis of the brain abscess. The diagnosis of brain abscess should be considered in all cases of non-typhoidal Salmonella meningitis after surgery for brain tumor. Surgical brain abscess drainage followed by prolonged antibiotic treatment remains a major therapeutic option.

  17. What’s the clinical significance of adding diffusion and perfusion MRI in the differentiation of glioblastoma multiforme and solitary brain metastasis?

    Directory of Open Access Journals (Sweden)

    Amr F. Mourad

    2017-09-01

    Full Text Available Objective: To evaluate the additional diagnostic value of diffusion and perfusion MRI in the differentiation of glioblastoma multiforme (GBM and solitary brain metastasis. Patients and methods: This retrospective study included 24 patients with histologically proven brain tumors who underwent conventional MRI with analysis of diffusion (DWI and perfusion (PWI MRI findings of each tumor. The Apparent Diffusion Coefficient (ADC values were calculated in the minimum (ADC-MIN, mean (ADC-MEAN, and maximum (ADC-MAX in all the tumors and the peritumoral regions. The PWI data was expressed as maximum regional cerebral blood volume (rCBV of the tumors and peritumoral regions. Results: After adding diffusion and perfusion to conventional MRI findings, we found that the accuracy of differentiation between glioblastoma multiforme (GBM and solitary metastasis increased from 70% to 90%.There is a significant difference in DWI signal intensity between GBM and metastatic tumors (P < 0.05. The ADC values of GBM were lower than that of metastatic tumors. On perfusion MRI, the maximum rCBV of the peritumoral region (rCBVP of GBM was higher than that of brain metastases (P < 0.001. Conclusion: The addition of diffusion and perfusion to the MRI protocol increases the accuracy of differentiation between GBM and solitary brain metastasis and should be considered routinely. Keywords: Diffusion MRI, Perfusion MRI, GBM, Solitary brain metastases

  18. Metástases intrarraquidianas de glioblastoma multiforme supratentorial da infância: relato de caso Spinal cord metastatic glioblastoma multiforme of childhood: case report

    Directory of Open Access Journals (Sweden)

    Patricia Imperatriz Porto Rondinelli

    2002-09-01

    Full Text Available Relatamos o caso de uma menina de onze anos de idade com glioblastoma multiforme na região têmporo-parietal direita, completamente ressecado cirurgicamente, submetida a radioterapia craniana pós-operatória. Houve recaída três meses após, em topografia distante do sítio primário, na porção caudal do canal raquidiano. Após, ocorreu evolução rápida para o óbito. A propósito desse caso, discutimos nossa experiência quanto à conduta nesses tumores e a literatura sobre o assunto.We report the case of an eleven years-old girl with a right temporo-parietal glioblastoma multiforme. The tumor was totally resected on neurossurgery, and cranial radioteraphy was applied at next. The tumor recurred three months later, far from primary site, in the caudal portion of the spinal canal. Death occurred in less than one month later. Taking into account the data of this case, we discuss our experience in the management of such tumors and the literature on the subject.

  19. Hitrex 1: an interim report on experimental and analytical work on BNL's zero power HTR

    Energy Technology Data Exchange (ETDEWEB)

    Beynon, A.J.; Kitching, S.J.; Lewis, T.A.; Waterson, R.H.

    1972-06-15

    This report presents interim experimental and theoretical results for the BNL Hitrex reactor. Reactivity effects and thermal and fast reaction rate distributions have been measured. Preliminary analysis has been performed, and some initial comparisons between theory and experiments made. (auth)

  20. Interim Hanford Waste Management Plan

    International Nuclear Information System (INIS)

    1985-09-01

    The September 1985 Interim Hanford Waste Management Plan (HWMP) is the third revision of this document. In the future, the HWMP will be updated on an annual basis or as major changes in disposal planning at Hanford Site require. The most significant changes in the program since the last release of this document in December 1984 include: (1) Based on studies done in support of the Hanford Defense Waste Environmental Impact Statement (HDW-EIS), the size of the protective barriers covering contaminated soil sites, solid waste burial sites, and single-shell tanks has been increased to provide a barrier that extends 30 m beyond the waste zone. (2) As a result of extensive laboratory development and plant testing, removal of transuranic (TRU) elements from PUREX cladding removal waste (CRW) has been initiated in PUREX. (3) The level of capital support in years beyond those for which specific budget projections have been prepared (i.e., fiscal year 1992 and later) has been increased to maintain Hanford Site capability to support potential future missions, such as the extension of N Reactor/PUREX operations. The costs for disposal of Hanford Site defense wastes are identified in four major areas in the HWMP: waste storage and surveillance, technology development, disposal operations, and capital expenditures

  1. Interim Basis for PCB Sampling and Analyses

    International Nuclear Information System (INIS)

    BANNING, D.L.

    2001-01-01

    This document was developed as an interim basis for sampling and analysis of polychlorinated biphenyls (PCBs) and will be used until a formal data quality objective (DQO) document is prepared and approved. On August 31, 2000, the Framework Agreement for Management of Polychlorinated Biphenyls (PCBs) in Hanford Tank Waste was signed by the US. Department of Energy (DOE), the Environmental Protection Agency (EPA), and the Washington State Department of Ecology (Ecology) (Ecology et al. 2000). This agreement outlines the management of double shell tank (DST) waste as Toxic Substance Control Act (TSCA) PCB remediation waste based on a risk-based disposal approval option per Title 40 of the Code of Federal Regulations 761.61 (c). The agreement calls for ''Quantification of PCBs in DSTs, single shell tanks (SSTs), and incoming waste to ensure that the vitrification plant and other ancillary facilities PCB waste acceptance limits and the requirements of the anticipated risk-based disposal approval are met.'' Waste samples will be analyzed for PCBs to satisfy this requirement. This document describes the DQO process undertaken to assure appropriate data will be collected to support management of PCBs and is presented in a DQO format. The DQO process was implemented in accordance with the U.S. Environmental Protection Agency EPA QAlG4, Guidance for the Data Quality Objectives Process (EPA 1994) and the Data Quality Objectives for Sampling and Analyses, HNF-IP-0842/Rev.1 A, Vol. IV, Section 4.16 (Banning 1999)

  2. Outcome in elderly patients undergoing definitive surgery and radiation therapy for supratentorial glioblastoma multiforme at a tertiary care institution

    International Nuclear Information System (INIS)

    Mohan, Dasarahally S.; Suh, John H.; Phan, Jennifer L.; Kupelian, Patrick A.; Cohen, Bruce H.; Barnett, Gene H.

    1998-01-01

    Purpose: To determine the efficacy of definitive surgery and radiation in patients aged 70 years and older with supratentorial glioblastoma multiforme. Methods and Materials: We selected elderly patients (≥ 70 years) who had primary treatment for glioblastoma multiforme at our tertiary care institution from 1977 through 1996. The study group (n = 102) included 58 patients treated with definitive radiation, 19 treated with palliative radiation, and 25 who received no radiation. To compare our results with published findings, we grouped our patients according to the applicable prognostic categories developed by the Radiation Therapy Oncology Group (RTOG): RTOG group IV (n = 6), V (n = 70), and VI (n = 26). Patients were retrospectively assigned to prognostic group IV, V, or VI based on age, performance status, extent of surgery, mental status, neurologic function, and radiation dose. Treatment included surgical resection and radiation (n 49), biopsy alone (n = 25), and biopsy followed by radiation (n = 28). Patients were also stratified according to whether they were optimally treated (gross total or subtotal resection with postoperative definitive radiation) or suboptimally treated (biopsy, biopsy + radiation, surgery alone, or surgery + palliative radiation). Patients were considered to have a favorable prognosis (n = 39) if they were optimally treated and had a Karnofsky Performance Status (KPS) score of at least 70. Results: The median survival for patients according to RTOG groups IV, V, and VI was 9.2, 6.6, and 3.1 months, respectively (log-rank, p < 0.0004). The median overall survival was 5.3 months. The definitive radiation group (n = 58) had a median survival of 7.3 months compared to 4.5 months in the palliative radiation group (n = 19) and 1.2 months in the biopsy-alone group (p < 0.0001). Optimally treated patients had a median survival of 7.4 months compared to 2.4 months in those suboptimally treated (p < 0.0001). The favorable prognosis group had an

  3. The Predictive Value of Interim and Final [18F] Fluorodeoxyglucose Positron Emission Tomography after Rituximab-Chemotherapy in the Treatment of Non-Hodgkin's Lymphoma: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yuyuan Zhu

    2013-01-01

    Full Text Available Background and Purpose. The aim of this study is to determine the prognostic value of interim and final FDG-PET in major histotypes of B-cell NHL patients treated with rituximab containing-chemotherapy. Methods. We searched for articles published in English, limited to lymphoma, rituximab, and FDG-PET, and dedicated to deal with the impact on progression and survival. The log hazard ratios (HR and their variances were estimated. Results. A PubMed and Scopus review of published trials identified 13 studies of Progression-free survival (PFS and overall survival (OS which were set as the main outcome measures. The combined HRs of I-PET for PFS and OS in DLBCL were 4.4 (P=0.11 and 3.99 (P=0.46, respectively. The combined HRs of F-PET for PFS and OS in DLBCL were 5.91 (P=0.39 and 6.75 (P=0.92, respectively. Regarding to non-DLBCL with F-PET, the combined HRs of F-PET for PFS and OS were 4.05 (P=0.79 and 5.1 (P=0.51, respectively. No publication bias existed. Conclusion. In DLBCL, both I-PET and F-PET can be performed for survival and progression analysis. But in other B-cell subtypes such as follicular lymphoma (FL and mantle cell lymphoma (MCL, it would be necessary to perform F-PET for predictive purposes.

  4. Design review report FFTF interim storage cask

    International Nuclear Information System (INIS)

    Scott, P.L.

    1995-01-01

    Final Design Review Report for the FFTF Interim Storage Cask. The Interim Storage Cask (ISC) will be used for long term above ground dry storage of FFTF irradiated fuel in Core Component Containers (CCC)s. The CCC has been designed and will house assemblies that have been sodium washed in the IEM Cell. The Solid Waste Cask (SWC) will transfer a full CCC from the IEM Cell to the RSB Cask Loading Station where the ISC will be located to receive it. Once the loaded ISC has been sealed at the RSB Cask Loading Station, it will be transferred by facility crane to the DSWC Transporter. After the ISC has been transferred to the Interim Storage Area (ISA), which is yet to be designed, a mobile crane will be used to place the ISC in its final storage location

  5. CMM Interim Check Design of Experiments (U)

    Energy Technology Data Exchange (ETDEWEB)

    Montano, Joshua Daniel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-29

    Coordinate Measuring Machines (CMM) are widely used in industry, throughout the Nuclear Weapons Complex and at Los Alamos National Laboratory (LANL) to verify part conformance to design definition. Calibration cycles for CMMs at LANL are predominantly one year in length and include a weekly interim check to reduce risk. The CMM interim check makes use of Renishaw’s Machine Checking Gauge which is an off-the-shelf product simulates a large sphere within a CMM’s measurement volume and allows for error estimation. As verification on the interim check process a design of experiments investigation was proposed to test a couple of key factors (location and inspector). The results from the two-factor factorial experiment proved that location influenced results more than the inspector or interaction.

  6. Choosing a spent fuel interim storage system

    International Nuclear Information System (INIS)

    Roland, V.; Hunter, I.

    2001-01-01

    The Transnucleaire Group has developed different modular solutions to address spent fuel interim storage needs of NPP. These solutions, that are present in Europe, USA and Asia are metal casks (dual purpose or storage only) of the TN 24 family and the NUHOMS canister based system. It is not always simple for an operator to sort out relevant choice criteria. After explaining the basic designs involved on the examples of the TN 120 WWER dual purpose cask and the NUHOMS 56 WWER for WWER 440 spent fuel, we shall discuss the criteria that govern the choice of a given spent fuel interim storage system from the stand point of the operator. In conclusion, choosing and implementing an interim storage system is a complex process, whose implications can be far reaching for the long-term success of a spent fuel management policy. (author)

  7. HEXEREI: a multi-channel heat conduction convection code for use in transient thermal hydraulic analysis of high-temperature, gas-cooled reactors. Interim report

    International Nuclear Information System (INIS)

    Giles, G.E.; DeVault, R.M.; Turner, W.D.; Becker, B.R.

    1976-05-01

    A description is given of the development and verification of a generalized coupled conduction-convection, multichannel heat transfer computer program to analyze specific safety questions involving high temperature gas-cooled reactors (HTGR). The HEXEREI code was designed to provide steady-state and transient heat transfer analysis of the HTGR active core using a basic hexagonal mesh and multichannel coolant flow. In addition, the core auxiliary cooling systems were included in the code to provide more complete analysis of the reactor system during accidents involving reactor trip and cooling down on the auxiliary systems. Included are brief descriptions of the components of the HEXEREI code and sample HEXEREI analyses compared with analytical solutions and other heat transfer codes

  8. Eritema multiforme ampollar extenso asociado a infección por virus herpes simplex Extended Bullous Erythema Multiforme Associated To Herpes Simplex Virus Infection

    Directory of Open Access Journals (Sweden)

    A Elgueta-Noy

    2009-12-01

    Full Text Available El Eritema Multiforme (EM es una reacción cutánea aguda generalmente benigna y autolimitada, asociada a la infección por Virus Herpes Simplex (HSV. Se caracteriza por lesiones polimorfas y tipo diana en extremidades y mucosas. Presentamos un paciente de 22 años con pápulas, vesículas y ampollas, que evoluciona con un 90% de la superficie corporal comprometida en tres semanas. Se realizó una reacción de polimerasa en cadena para HSV, resultando positiva en una costra. La biopsia de piel y la tinción de inmunohistoquímica positiva para linfocitos T CD4, fueron compatibles con EM ampollar asociado a HSV. Destacamos la importancia de la correlación clínico patológica, apoyada por el estudio virológico, en el diagnóstico de este caso de presentación atípica. Los hallazgos de laboratorio confirmaron lo descrito en la literatura respecto de la patogenia del EM asociado a HSV.Erythema Multiforme (EM is a generally benign and self-limited acute cutaneous reaction, associated with Herpes Simplex Virus (HSV infection. It is characterized by polymorphic "target" lesions in extremities and mucosal tissues. We report a 22-year old patient with papules, vesicles and blisters, which evolved to cover 90% of the body in three weeks. We performed a PCR study for HSV, which was positive in a crust. A skin biopsy and positive immunohistochemical stain for LT CD4+ were compatible with bullous EM associated with HSV. We underline the importance of pathological clinical correlation, reinforced by a virological study, in the diagnosis of this case with atypical symptoms. The laboratory findings confirmed literature descriptions with respect to the pathogenicity of EM associated with HSV.

  9. Interim report for documentation of computer programs for crude oil profile analysis. [Codes, CV, CRULE, CPR, CIMPACT, ENT ADJ, REF VOLS, CIMP PRT, C MODEL, C PRINT

    Energy Technology Data Exchange (ETDEWEB)

    This report is summarizing the findings and documenting the programs developed by Economic Regulatory Administration (ERA) for the Crude Oil Profile Analysis. Based on a variety of estimates and assumptions from different sources, ERA developed a series of computer programs which generate a 24-month projection of the crude oil production in each of the price categories. AVANTE International Systems Corporation is contracted to provide an organized documentation for all of these data base, assumptions, estimation rationale and computing procedures.

  10. Interim Administrators in Higher Education: A National Study

    Science.gov (United States)

    Huff, Marie Thielke; Neubrander, Judy

    2015-01-01

    The focus of this paper is on the roles and experiences of interim administrators in higher education. A survey was given to current and recent interim administrators in four-year public universities and colleges across the United States. The goals were to identify the advantages and disadvantages of using and serving as interims, and to solicit…

  11. An Approach for Evaluating the Technical Quality of Interim Assessments

    Science.gov (United States)

    Li, Ying; Marion, Scott; Perie, Marianne; Gong, Brian

    2010-01-01

    Increasing numbers of schools and districts have expressed interest in interim assessment systems to prepare for summative assessments and to improve teaching and learning. However, with so many commercial interim assessments available, schools and districts are struggling to determine which interim assessment is most appropriate to their needs.…

  12. Lessons for outsourcing and interim management relationships.

    Science.gov (United States)

    Macko, W; Kostyack, P T

    1999-01-01

    Few decisions can affect an organization more than the selection of an outsourcing or interim management partner. More and more health care organizations face such decisions in today's competitive market in order to face new business needs. Making these relationships successful can be important for health care organizations seeking competitive advantages or seeking immediately accessible management support. These relationships, however, require careful partner selection and development. Success in outsourcing and interim management relationships is contingent upon a thorough selection process, a strong contract that has clearly and explicitly detailed responsibilities and a culture-sensitive business rapport between the client and selected partner.

  13. 216-T-4 interim stabilization final report

    International Nuclear Information System (INIS)

    Smith, D.L.

    1996-01-01

    This report provides a general description of the activities performed for the interim stabilization of the 216-T-4-1 ditch, 216-T-4-2 ditch, and 216-T-4-2 pond. Interim stabilization was required to reduce the amount of surface-contaminated acres and to minimize the migration of radioactive contamination. Work associated with the 216-T4-1 ditch and 216-T-4-2 pond was performed by the Radiation Area Remedial Action (RARA) Project. Work associated with the 216-T-4-2 ditch was done concurrently but was funded by Westinghouse Hanford Company (WHC) Tank Waste Remediation Systems (TWRS)

  14. COBRA-IV-I: an interim version of COBRA for thermal-hydraulic analysis of rod bundle nuclear fuel elements and cores

    Energy Technology Data Exchange (ETDEWEB)

    Wheeler, C.L.; Stewart, C.W.; Cena, R.J.; Rowe, D.S.; Sutey, A.M.

    1976-03-01

    The COBRA-IV-I computer code uses the subchannel analysis approach to determine the enthalpy and flow distribution in rod bundles for both steady-state and transient conditions. The steady-state and transient solution schemes used in COBRA-IIIC are still available in COBRA-IV-I as the implicit solution scheme option. In addition to these techniques, a new explicit solution scheme is now available which allows the calculation of severe transients involving flow reversals, recirculations, expulsion and reentry flows, with a pressure or flow boundary condition specified. Significant storage compaction and reduced running times have been achieved to allow the calculation of problems involving hundreds of subchannels.

  15. Predictive probability methods for interim monitoring in clinical trials with longitudinal outcomes.

    Science.gov (United States)

    Zhou, Ming; Tang, Qi; Lang, Lixin; Xing, Jun; Tatsuoka, Kay

    2018-04-17

    In clinical research and development, interim monitoring is critical for better decision-making and minimizing the risk of exposing patients to possible ineffective therapies. For interim futility or efficacy monitoring, predictive probability methods are widely adopted in practice. Those methods have been well studied for univariate variables. However, for longitudinal studies, predictive probability methods using univariate information from only completers may not be most efficient, and data from on-going subjects can be utilized to improve efficiency. On the other hand, leveraging information from on-going subjects could allow an interim analysis to be potentially conducted once a sufficient number of subjects reach an earlier time point. For longitudinal outcomes, we derive closed-form formulas for predictive probabilities, including Bayesian predictive probability, predictive power, and conditional power and also give closed-form solutions for predictive probability of success in a future trial and the predictive probability of success of the best dose. When predictive probabilities are used for interim monitoring, we study their distributions and discuss their analytical cutoff values or stopping boundaries that have desired operating characteristics. We show that predictive probabilities utilizing all longitudinal information are more efficient for interim monitoring than that using information from completers only. To illustrate their practical application for longitudinal data, we analyze 2 real data examples from clinical trials. Copyright © 2018 John Wiley & Sons, Ltd.

  16. Hemolytic anemia in two patients with glioblastoma multiforme: A possible interaction between vorinostat and dapsone.

    Science.gov (United States)

    Lewis, Jennifer A; Petty, William J; Harmon, Michele; Peacock, James E; Valente, Kari; Owen, John; Pirmohamed, Munir; Lesser, Glenn J

    2015-06-01

    Patients undergoing treatment for glioblastoma multiforme are routinely placed on prophylactic treatment for Pneumocystis jirovecii pneumonia because of significant therapy-induced lymphopenia. In patients with sulfa allergies, dapsone prophylaxis is often used due to its efficacy, long half-life, cost effectiveness, and general safety at low doses. However, dapsone may uncommonly induce a hemolytic anemia, particularly in patients deficient of glucose-6-phosphate dehydrogenase. This hemolysis is thought to be a result of oxidative stress on red blood cells induced by dapsone metabolites which produce reactive oxygen species that disrupt the red blood cell membrane and promote splenic sequestration. A single case report of dapsone-induced hemolytic anemia in a patient with glioblastoma multiforme has been reported. We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone. There are several potential mechanisms by which histone deacetylase inhibition may alter dapsone metabolism including changes in hepatic acetylation or N-glucuronidation leading to an increase in the bioavailability of dapsone's hematotoxic metabolites. In addition, vorinostat may lead to increased hemolysis through inhibition of heat shock protein-90, a chaperone protein that maintains the integrity of the red blood cell membrane cytoskeleton. The potential interaction between dapsone and vorinostat may have important clinical implications as more than 10 clinical trials evaluating drug combinations with vorinostat in patients with malignant glioma are either ongoing or planned in North America. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Erythema multiforme in a patient with recurrent non-hodgkins lymphoma/chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Siva Kumara Shankari

    2012-01-01

    Full Text Available Erythema multiforme major (EMM is a hypersensitivity reaction usually secondary to medications, viruses or other infections. Its presentation is fairly typical with a symmetrical distribution of vesicles, bullae or targeted lesions on the upper body, arms, legs, palms, feet and oral mucosa. The authors present a delineated case of EMM in association with chronic lymphocytic leukemia (CLL and non-Hodgkin′s lymphoma (NHL with a very unusual clinical presentation evolving overtime into a unique, almost dermatomal distribution. Typical therapies were not initially helpful and intravenous immunoglobulin antibody had to be administered.

  18. Primary pontine gliobastoma multiforme: A case report and review of the literature

    International Nuclear Information System (INIS)

    Baik, Ji Yeon; Baek, Hye Jin; Moon, Jin Il; Cho, Soo Buem; Choi, Bo Hwa; Bae, Kyung Soo; Jeon, Kyung Nyeo; Choi, Dae Seob; Shin, Hwa Seon

    2016-01-01

    Glioblastoma multiforme (GBM) most commonly occurs in the pons while it is rare in the brainstem. However, diagnosis of brainstem GBM can be difficult due to its rarity and nonspecific clinical manifestations. Herein, we presented a case of a 47-year-old female patient confirmed as primary pontine GBM by histopathological examination. This case highlights that GBM should be considered in the differential diagnosis of patients with a space-occupying lesion in the brainstem as well as the importance of a meticulous radiological review with clinical suspicion

  19. Primary pontine gliobastoma multiforme: A case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Baik, Ji Yeon; Baek, Hye Jin [Dept. of Radiology, Inje University College of Medicine, Haeundae Paik Hospital, Busan (Korea, Republic of); Moon, Jin Il; Cho, Soo Buem; Choi, Bo Hwa; Bae, Kyung Soo; Jeon, Kyung Nyeo [Dept. of Radiology, Gyeongsang National University School of Medicine, Gyeongsang National University Changwon Hospital, Changwon (Korea, Republic of); Choi, Dae Seob; Shin, Hwa Seon [Dept. of Radiology, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju (Korea, Republic of)

    2016-08-15

    Glioblastoma multiforme (GBM) most commonly occurs in the pons while it is rare in the brainstem. However, diagnosis of brainstem GBM can be difficult due to its rarity and nonspecific clinical manifestations. Herein, we presented a case of a 47-year-old female patient confirmed as primary pontine GBM by histopathological examination. This case highlights that GBM should be considered in the differential diagnosis of patients with a space-occupying lesion in the brainstem as well as the importance of a meticulous radiological review with clinical suspicion.

  20. A Phase 1 trial of intravenous boronophenylalanine-fructose complex in patients with glioblastoma multiforme

    International Nuclear Information System (INIS)

    Bergland, R.; Elowitz, E.; Chadha, M.; Coderre, J.A.; Joel, D.

    1996-01-01

    Boron neutron capture therapy (BNCT) of glioblastoma multiforme was initially performed at the Brookhaven National Laboratory in the early 1950's While this treatment for malignant brain tumors has continued in Japan, new worldwide interest has been stimulated by the development of new and more selective boron compounds. Boronophenylalanine (BPA) is a blood-brain barrier penetrating compound that has been used in BNCT of malignant melanomas. SPA has been employed experimentally in BNCT of rat gliosarcoma and has potential use in the treatment of human glioblastoma. As a preface to clinical BNCT trials, we studied the biodistribution of SPA in patients with glioblastoma

  1. Coexistence of meningioma and glioblastoma multiforme in a same patient: a case report

    International Nuclear Information System (INIS)

    Pereira, C.; Dumont, P.; Romero, P.C.; Lima, J.P.; Caldas, J.G.; Settanni, F.

    1991-01-01

    Tumoral collision has been defined as a coexistence of two or more central nervous system tumors histologically distinct, in a patient not harbouring a neuro-ectodermic disease (phakomatosis). Several theories exist for explaining this phenomenon but most of them assume that there is spacial proximity between the tumors and/or ionizing radiation effects. We report the case of coexistence of meningothelial meningioma and glioblastoma multiforme in a same patient, occurring in different hemispheres on different times. The tomographic aspects of the gliomatous lesion and the difficulty in differentiating by neuroimaging among high grade gliomas and recent hemorrhagic cerebral events are discussed. (author)

  2. Multiformity of inherent randomicity and visitation density in n symbolic dynamics

    International Nuclear Information System (INIS)

    Zhang Yagang; Wang Changjiang

    2007-01-01

    The multiformity of inherent randomicity and visitation density in n symbolic dynamics will be clarified in this paper. These stochastic symbolic sequences bear three features. The distribution of frequency, inter-occurrence times and the alignment of two random sequences are amplified in detail. The features of visitation density in surjective maps presents catholicity and the catholicity in n letters randomicity has the same measure foundation. We hope to offer a symbolic platform that satisfies these stochastic properties and to attempt to study certain properties of DNA base sequences, 20 amino acids symbolic sequences of proteid structure, and the time series that can be symbolic in finance market et al

  3. THE IMPORTANCE OF FINANCIAL INTERIM REPORTING FOR THE POSITION OF COMPANIES

    Directory of Open Access Journals (Sweden)

    Claudia‐Elena\tGRIGORAȘ‐ICHIM

    2015-12-01

    Full Text Available The importance that each company must grant to the strategic sources of information generates our concern for analysis of the interim financial reporting. In every enterprise, there are doubts on the usefulness of interim financial reports, given the following elements: the necessary time for their preparation (relatively long, their restricted character and the resources necessary to establish them. Finding a common solution to these problems and, implicitly, increasing the interest for interim financial reporting, can help to increase the economic performance of the company, either by reducing the unnecessary costs related to time, or by increasing communication and transparency with third parties. An appropriate management can act early in the direction of counteracting the negative effects in their company or prevention of any commercial or production failures, the overall economic trends in that field and increasing productivity. Starting from these premises, we propose a research in order to capture the main aspects related to the mentioned issues.

  4. Computational analysis of coupled fluid, heat, and mass transport in ferrocyanide single-shell tanks: FY 1994 interim report. Ferrocyanide Tank Safety Project

    International Nuclear Information System (INIS)

    McGrail, B.P.

    1994-11-01

    A computer modeling study was conducted to determine whether natural convection processes in single-shell tanks containing ferrocyanide wastes could generate localized precipitation zones that significantly concentrate the major heat-generating radionuclide, 137 Cs. A computer code was developed that simulates coupled fluid, heat, and single-species mass transport on a regular, orthogonal finite-difference grid. The analysis showed that development of a ''hot spot'' is critically dependent on the temperature dependence for the solubility of Cs 2 NiFe(CN) 6 or CsNaNiFe(CN) 6 . For the normal case, where solubility increases with increasing temperature, the net effect of fluid flow, heat, and mass transport is to disperse any local zones of high heat generation rate. As a result, hot spots cannot physically develop for this case. However, assuming a retrograde solubility dependence, the simulations indicate the formation of localized deposition zones that concentrate the 137 Cs near the bottom center of the tank where the temperatures are highest. Recent experimental studies suggest that Cs 2 NiFe(CN) 6 (c) does not exhibit retrograde solubility over the temperature range 25 degree C to 90 degree C and NaOH concentrations to 5 M. Assuming these preliminary results are confirmed, no natural mass transport process exists for generating a hot spot in the ferrocyanide single-shell tanks

  5. Effectiveness of interim remedial actions at a radioactive waste facility

    International Nuclear Information System (INIS)

    Devgun, J.S.; Beskid, N.J.; Peterson, J.M.; Seay, W.M.; McNamee, E.

    1989-01-01

    Over the past eight years, several interim remedial actions have been taken at the Niagara Falls Storage Site (NFSS), primarily to reduce radon and gamma radiation exposures and to consolidate radioactive waste into a waste containment facility. Interim remedial actions have included capping of vents, sealing of pipes, relocation of the perimeter fence (to limit radon risk), transfer and consolidation of waste, upgrading of storage buildings, construction of a clay cutoff wall (to limit the potential groundwater transport of contaminants), treatment and release of contaminated water, interim use of a synthetic liner, and emplacement of an interim clay cap. An interim waste containment facility was completed in 1986. 6 refs., 3 figs

  6. Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma: A Preplanned Interim Analysis of a Clinical Trial.

    Science.gov (United States)

    D'Angelo, Sandra P; Russell, Jeffery; Lebbé, Céleste; Chmielowski, Bartosz; Gambichler, Thilo; Grob, Jean-Jacques; Kiecker, Felix; Rabinowits, Guilherme; Terheyden, Patrick; Zwiener, Isabella; Bajars, Marcis; Hennessy, Meliessa; Kaufman, Howard L

    2018-03-22

    Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti-programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). To evaluate the efficacy and safety of avelumab as first-line treatment for patients with distant mMCC. JAVELIN Merkel 200 part B is an international, multicenter, single-arm, open-label clinical trial of first-line avelumab monotherapy. Eligible patients were adults with mMCC who had not received prior systemic treatment for metastatic disease. Patients were not selected for PD-L1 expression or Merkel cell polyomavirus status. Data were collected from April 15, 2016, to March 24, 2017, and enrollment is ongoing. Patients received avelumab, 10 mg/kg, by 1-hour intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxic effects, or withdrawal occurred. Tumor status was assessed every 6 weeks and evaluated by independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was durable response, defined as an objective response with a duration of at least 6 months. Secondary end points include best overall response, duration of response, progression-free survival, safety, and tolerability. As of March 24, 2017, 39 patients were enrolled (30 men and 9 women; median age, 75 years [range, 47-88 years]), with a median follow-up of 5.1 months (range, 0.3-11.3 months). In a preplanned analysis, efficacy was assessed in 29 patients with at least 3 months of follow-up; the confirmed objective response rate was 62.1% (95% CI, 42.3%-79.3%), with 14 of 18 responses (77.8%) ongoing at the time of analysis. In responding patients, the estimated proportion with duration of response of at

  7. Accelerated Partial Breast Irradiation With IMRT: New Technical Approach and Interim Analysis of Acute Toxicity in a Phase III Randomized Clinical Trial

    International Nuclear Information System (INIS)

    Livi, Lorenzo; Buonamici, Fabrizio Banci; Simontacchi, Gabriele; Scotti, Vieri; Fambrini, Massimiliano; Compagnucci, Antonella; Paiar, Fabiola; Scoccianti, Silvia; Pallotta, Stefania; Detti, Beatrice; Agresti, Benedetta; Talamonti, Cinzia; Mangoni, Monica; Bianchi, Simonetta; Cataliotti, Luigi; Marrazzo, Livia; Bucciolini, Marta; Biti, Giampaolo

    2010-01-01

    Purpose: To evaluate with a randomized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy (IMRT) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity. Methods and Materials: From September 2005, a randomized Phase III clinical trial has been conducted to compare conventional (tangential field) fractionated whole breast treatment (Arm A) with accelerated partial breast irradiation plus intensity-modulated radiotherapy (Arm B). For intensity-modulated radiotherapy, the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk. All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. Results: In September 2008, 259 patients were randomized and treated. The mean clinical target volume in Arm B was 44 cm 3 and the mean planning target volume was 123 cm 3 . The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21%. The rate of Grade 1 and Grade 2 acute skin toxicity was 22% and 19% in Arm A (Radiation Therapy Oncology Group scale), respectively. The tolerance in Arm B was excellent with only 5% Grade 1 and 0.8% Grade 2 acute skin toxicity. The planning constraints were fully satisfied in most patients. In a very few cases, this was not possible because of very unfavorable anatomy. Quality assurance procedures were performed according to our internal quality assurance protocol, with excellent results. Conclusion: In the present preliminary analysis, we have demonstrated that accelerated partial breast irradiation is feasible, with very low acute toxicity.

  8. High Temperature Materials Interim Data Qualification Report

    International Nuclear Information System (INIS)

    Lybeck, Nancy

    2010-01-01

    Projects for the very high temperature reactor (VHTR) Technology Development Office provide data in support of Nuclear Regulatory Commission licensing of the VHTR. Fuel and materials to be used in the reactor are tested and characterized to quantify performance in high temperature and high fluence environments. The VHTR program has established the NGNP Data Management and Analysis System (NDMAS) to ensure that VHTR data are qualified for use, stored in a readily accessible electronic form, and analyzed to extract useful results. This document focuses on the first NDMAS objective. It describes the High Temperature Materials characterization data stream, the processing of these data within NDMAS, and reports the interim FY2010 qualification status of the data. Data qualification activities within NDMAS for specific types of data are determined by the data qualification category assigned by the data generator. The High Temperature Materials data are being collected under NQA-1 guidelines, and will be qualified data. For NQA-1 qualified data, the qualification activities include: (1) capture testing, to confirm that the data stored within NDMAS are identical to the raw data supplied, (2) accuracy testing to confirm that the data are an accurate representation of the system or object being measured, and (3) documenting that the data were collected under an NQA-1 or equivalent Quality Assurance program. Currently, data from two test series within the High Temperature Materials data stream have been entered into the NDMAS vault: (1) Tensile Tests for Sm (i.e., Allowable Stress) Confirmatory Testing - 1,403,994 records have been inserted into the NDMAS database. Capture testing is in process. (2) Creep-Fatigue Testing to Support Determination of Creep-Fatigue Interaction Diagram - 918,854 records have been processed and inserted into the NDMAS database. Capture testing is in process.

  9. Interim storage of radioactive waste packages

    International Nuclear Information System (INIS)

    1998-01-01

    This report covers all the principal aspects of production and interim storage of radioactive waste packages. The latest design solutions of waste storage facilities and the operational experiences of developed countries are described and evaluated in order to assist developing Member States in decision making and design and construction of their own storage facilities. This report is applicable to any category of radioactive waste package prepared for interim storage, including conditioned spent fuel, high level waste and sealed radiation sources. This report addresses the following issues: safety principles and requirements for storage of waste packages; treatment and conditioning methods for the main categories of radioactive waste; examples of existing interim storage facilities for LILW, spent fuel and high level waste; operational experience of Member States in waste storage operations including control of storage conditions, surveillance of waste packages and observation of the behaviour of waste packages during storage; retrieval of waste packages from storage facilities; technical and administrative measures that will ensure optimal performance of waste packages subject to various periods of interim storage

  10. Disposal facility data for the interim performance

    International Nuclear Information System (INIS)

    Eiholzer, C.R.

    1995-01-01

    The purpose of this report is to identify and provide information on the waste package and disposal facility concepts to be used for the low-level waste tank interim performance assessment. Current concepts for the low-level waste form, canister, and the disposal facility will be used for the interim performance assessment. The concept for the waste form consists of vitrified glass cullet in a sulfur polymer cement matrix material. The waste form will be contained in a 2 x 2 x 8 meter carbon steel container. Two disposal facility concepts will be used for the interim performance assessment. These facility concepts are based on a preliminary disposal facility concept developed for estimating costs for a disposal options configuration study. These disposal concepts are based on vault type structures. None of the concepts given in this report have been approved by a Tank Waste Remediation Systems (TWRS) decision board. These concepts will only be used in th interim performance assessment. Future performance assessments will be based on approved designs

  11. 33 CFR 385.38 - Interim goals.

    Science.gov (United States)

    2010-07-01

    ..., monitoring and assessment; (ii) Be provided to the independent scientific review panel established in.... The interim goals shall be developed through the use of appropriate models and tools and shall provide... to be required to meet long-term hydrological and ecological restoration goals, based on best...

  12. Interim Storage Facility decommissioning. Final report

    International Nuclear Information System (INIS)

    Johnson, R.P.; Speed, D.L.

    1985-01-01

    Decontamination and decommissioning of the Interim Storage Facility were completed. Activities included performing a detailed radiation survey of the facility, removing surface and imbedded contamination, excavating and removing the fuel storage cells, restoring the site to natural conditions, and shipping waste to Hanford, Washington, for burial. The project was accomplished on schedule and 30% under budget with no measurable exposure to decommissioning personnel

  13. 19 CFR 354.8 - Interim sanctions.

    Science.gov (United States)

    2010-04-01

    ... reconsider imposition of interim sanctions on the basis of new and material evidence or other good cause... Secretary may petition a presiding official to impose such sanctions. (b) The presiding official may impose... person to return material previously provided by the Department and all other materials containing the...

  14. A Non-Traditional Interim Project.

    Science.gov (United States)

    Brown, Diane; Ward, Dorothy

    1980-01-01

    Describes a project initiated by the Foreign Language Department of Birmingham-Southern College for their Interim term and discusses an interdisciplinary course focusing on Medieval Europe. The course included presentations on German and French language and literature, as well as lectures on the arts, philosophy, and family life of the period.…

  15. LANDFILL BIOREACTOR PERFORMANCE, SECOND INTERIM REPORT

    Science.gov (United States)

    A bioreactor landfill is a landfill that is operated in a manner that is expected to increase the rate and extent of waste decomposition, gas generation, and settlement compared to a traditional landfill. This Second Interim Report was prepared to provide an interpretation of fie...

  16. Magnetic resonance imaging in 67 cases of glioblastoma multiform and occurrence of metastases

    International Nuclear Information System (INIS)

    Ferreira, Nelson Fortes; Barbosa, Marcelo; Amaral, Lazaro L. Faria do; Mendonca, Renato Adam; Lima, Sergio Santos

    2004-01-01

    The purpose of this paper is to demonstrate the main MRI characteristics of glioblastoma multiform (GBM), the most common CNS primary tumor, emphasizing its location and the occurrence of metastases. The MR imaging of 67 pathologically proven cases of glioblastoma multiform were retrospectively reviewed. The exams were realized in the period between 1995 and 2003, in one of three 1.5 Signa GE units (Milwaukee, WI). The ages of the patients ranged from 4 years to 86 years, mean 60 years, and the occurrence of the tumor was preponderant among men, with 39 cases (58%). The most common location was in the frontal lobes (47%) followed by the temporal lobes (18%) and the parietal lobes (16%). In 19% of the cases there were involvement of more than one site and long distance metastases were seen in 22% of the patients. According to the literature, the most common location of GBM was in the frontal lobe of older than 50 years old men. Metastases occurred in 22% of our cases. (author)

  17. New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection

    Science.gov (United States)

    Korbecki, Jan; Gutowska, Izabela; Kojder, Ireneusz; Jeżewski, Dariusz; Goschorska, Marta; Łukomska, Agnieszka; Lubkowska, Anna; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2018-01-01

    Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the ‘hallmarks of cancer’ in glioblastoma multiforme. Therefore, in the present work we describe the influence of these factors on the proliferation and apoptosis of neoplastic cells, cancer stem cells, angiogenesis, migration and invasion, and cancer immune evasion in a glioblastoma multiforme tumor. In particular, we discuss the effect of neurotensin, GDF-15, S1P (including the drug FTY720), and infection with CMV on tumor-associated macrophages (TAM), microglial cells, neutrophil and regulatory T cells (Treg), on the tumor microenvironment. In order to better understand the role of the aforementioned factors in tumoral processes, we outline the latest models of intratumoral heterogeneity in glioblastoma multiforme. Based on the most recent reports, we discuss the problems of multi-drug therapy in treating glioblastoma multiforme. PMID:29467963

  18. Differentiation of solitary brain metastasis from glioblastoma multiforme: a predictive multiparametric approach using combined MR diffusion and perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Adam Herman; Moser, Franklin G.; Maya, Marcel [Cedars-Sinai Medical Center, Department of Medical Imaging, Los Angeles, CA (United States); Erly, William; Nael, Kambiz [University of Arizona Medical Center, Department of Medical Imaging, Tucson, AZ (United States)

    2015-07-15

    Solitary brain metastasis (MET) and glioblastoma multiforme (GBM) can appear similar on conventional MRI. The purpose of this study was to identify magnetic resonance (MR) perfusion and diffusion-weighted biomarkers that can differentiate MET from GBM. In this retrospective study, patients were included if they met the following criteria: underwent resection of a solitary enhancing brain tumor and had preoperative 3.0 T MRI encompassing diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast (DSC) perfusion. Using co-registered images, voxel-based fractional anisotropy (FA), mean diffusivity (MD), K{sup trans}, and relative cerebral blood volume (rCBV) values were obtained in the enhancing tumor and non-enhancing peritumoral T2 hyperintense region (NET2). Data were analyzed by logistic regression and analysis of variance. Receiver operating characteristic (ROC) analysis was performed to determine the optimal parameter/s and threshold for predicting of GBM vs. MET. Twenty-three patients (14 M, age 32-78 years old) met our inclusion criteria. Pathology revealed 13 GBMs and 10 METs. In the enhancing tumor, rCBV, K{sup trans}, and FA were higher in GBM, whereas MD was lower, neither without statistical significance. In the NET2, rCBV was significantly higher (p = 0.05) in GBM, but MD was significantly lower (p < 0.01) in GBM. FA and K{sup trans} were higher in GBM, though not reaching significance. The best discriminative power was obtained in NET2 from a combination of rCBV, FA, and MD, resulting in an area under the curve (AUC) of 0.98. The combination of MR diffusion and perfusion matrices in NET2 can help differentiate GBM over solitary MET with diagnostic accuracy of 98 %. (orig.)

  19. Differentiation of solitary brain metastasis from glioblastoma multiforme: a predictive multiparametric approach using combined MR diffusion and perfusion

    International Nuclear Information System (INIS)

    Bauer, Adam Herman; Moser, Franklin G.; Maya, Marcel; Erly, William; Nael, Kambiz

    2015-01-01

    Solitary brain metastasis (MET) and glioblastoma multiforme (GBM) can appear similar on conventional MRI. The purpose of this study was to identify magnetic resonance (MR) perfusion and diffusion-weighted biomarkers that can differentiate MET from GBM. In this retrospective study, patients were included if they met the following criteria: underwent resection of a solitary enhancing brain tumor and had preoperative 3.0 T MRI encompassing diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast (DSC) perfusion. Using co-registered images, voxel-based fractional anisotropy (FA), mean diffusivity (MD), K trans , and relative cerebral blood volume (rCBV) values were obtained in the enhancing tumor and non-enhancing peritumoral T2 hyperintense region (NET2). Data were analyzed by logistic regression and analysis of variance. Receiver operating characteristic (ROC) analysis was performed to determine the optimal parameter/s and threshold for predicting of GBM vs. MET. Twenty-three patients (14 M, age 32-78 years old) met our inclusion criteria. Pathology revealed 13 GBMs and 10 METs. In the enhancing tumor, rCBV, K trans , and FA were higher in GBM, whereas MD was lower, neither without statistical significance. In the NET2, rCBV was significantly higher (p = 0.05) in GBM, but MD was significantly lower (p < 0.01) in GBM. FA and K trans were higher in GBM, though not reaching significance. The best discriminative power was obtained in NET2 from a combination of rCBV, FA, and MD, resulting in an area under the curve (AUC) of 0.98. The combination of MR diffusion and perfusion matrices in NET2 can help differentiate GBM over solitary MET with diagnostic accuracy of 98 %. (orig.)

  20. Temozolomide during radiotherapy of glioblastoma multiforme. Daily administration improves survival

    Energy Technology Data Exchange (ETDEWEB)

    Nachbichler, Silke Birgit; Schupp, Gabi; Ballhausen, Hendrik; Niyazi, Maximilian; Belka, Claus [LMU Munich, Department of Radiation Oncology, Munich (Germany)

    2017-11-15

    Temozolomide-(TMZ)-based chemoradiotherapy defines the current gold standard for the treatment of newly diagnosed glioblastoma. Data regarding the influence of TMZ dose density during chemoradiotherapy are currently not available. We retrospectively compared outcomes in patients receiving no TMZ, TMZ during radiotherapy on radiotherapy days only, and TMZ constantly 7 days a week. From 2002-2012, a total of 432 patients with newly diagnosed glioblastoma received radiotherapy in our department: 118 patients had radiotherapy alone, 210 had chemoradiotherapy with TMZ (75 mg/m{sup 2}) daily (7/7), and 104 with TMZ only on radiotherapy days (5/7). Radiotherapy was applied to a total dose of 60 Gy. Median survival after radiotherapy alone was 9.1 months, compared to 12.6 months with 5/7-TMZ and to 15.7 months with 7/7-TMZ. The 1-year survival rates were 33, 52, and 64%, respectively. Kaplan-Meier analysis showed a significant improvement of TMZ-7/7 vs. 5/7 (p = 0.01 by the log-rank test), while 5/7-TMZ was still superior to no TMZ at all (p = 0.02). Multivariate Cox regression showed a significant influence of TMZ regimen (p = 0.009) on hazard rate (+58% between groups) even in the presence of confounding factors age, sex, resection status, and radiotherapy dose concept. Our results confirm the findings of the EORTC/NCIC trial. It seems that also a reduced TMZ scheme can at first prolong the survival of glioblastoma patients, but not as much as the daily administration. (orig.) [German] Eine Temozolomid-(TMZ-)basierte Radiochemotherapie ist der gegenwaertige Goldstandard in der Behandlung von neu diagnostizierten Glioblastomen. Daten bezueglich des Einflusses der TMZ-Dosisdichte waehrend der Radiochemotherapie sind derzeit nicht vorhanden. Wir haben retrospektiv die Ergebnisse von Patienten verglichen, die entweder kein TMZ, TMZ zur Strahlentherapie nur an Bestrahlungstagen oder TMZ konstant 7 Tage/Woche erhalten hatten. Von 2002-2012 bekamen insgesamt 432 Patienten mit

  1. Interim FEP report for the safety assessment SR-Can

    Energy Technology Data Exchange (ETDEWEB)

    Skagius, Kristina (ed.) [Kemakta Konsult AB, Stockholm (Sweden)

    2004-08-01

    This report describes the work with identification and structuring of features, events and processes (FEPs) that has been carried out within the scope of the SR-Can safety assessment up to the time of the interim reporting of the project. The overall objective of the work is to develop a database of features, events and processes in a format that would facilitate both a systematic analysis of FEPs and documentation of the FEP analysis as well as facilitate revisions and updates to be made in connection with new safety assessments. This overall objective also includes the development of procedures for a systematic FEP analysis as well as to apply these procedures in order to arrive at an SR-Can version of the FEP database. The work started by implementing the content of the SR 97 Process report into a database format suitable for import and processing of FEP information from other sources. The SR 97 version of the database was systematically audited against the NEA database with Project FEPs, version 1.2. In addition, an earlier audit of the SR 97 process report against the interaction matrices developed for a deep repository of the KBS-3 type was revisited and updated. Relevant FEPs from the audit were sorted into three main categories in the SR-Can database i) FEPs related to the initial states of the repository system, ii) FEPs related to internal processes of the repository system, and iii) FEPs related to external impacts on the repository system. These groups of FEPs were further processed for making decisions on how to handle these FEPs in the assessment. Biosphere processes were not included in the SR 97 Process report and there is thus not the same basis for updating these descriptions as for the engineered barriers and the geosphere. All biosphere FEPs from the audit have therefore been compiled in a single category in the database, but remain to be further handled. FEPs were also categorised as irrelevant or as being related to methodology on a general

  2. Interim FEP report for the safety assessment SR-Can

    International Nuclear Information System (INIS)

    Skagius, Kristina

    2004-08-01

    This report describes the work with identification and structuring of features, events and processes (FEPs) that has been carried out within the scope of the SR-Can safety assessment up to the time of the interim reporting of the project. The overall objective of the work is to develop a database of features, events and processes in a format that would facilitate both a systematic analysis of FEPs and documentation of the FEP analysis as well as facilitate revisions and updates to be made in connection with new safety assessments. This overall objective also includes the development of procedures for a systematic FEP analysis as well as to apply these procedures in order to arrive at an SR-Can version of the FEP database. The work started by implementing the content of the SR 97 Process report into a database format suitable for import and processing of FEP information from other sources. The SR 97 version of the database was systematically audited against the NEA database with Project FEPs, version 1.2. In addition, an earlier audit of the SR 97 process report against the interaction matrices developed for a deep repository of the KBS-3 type was revisited and updated. Relevant FEPs from the audit were sorted into three main categories in the SR-Can database i) FEPs related to the initial states of the repository system, ii) FEPs related to internal processes of the repository system, and iii) FEPs related to external impacts on the repository system. These groups of FEPs were further processed for making decisions on how to handle these FEPs in the assessment. Biosphere processes were not included in the SR 97 Process report and there is thus not the same basis for updating these descriptions as for the engineered barriers and the geosphere. All biosphere FEPs from the audit have therefore been compiled in a single category in the database, but remain to be further handled. FEPs were also categorised as irrelevant or as being related to methodology on a general

  3. Spent fuel interim management: 1995 update

    International Nuclear Information System (INIS)

    Anderson, C.K.

    1995-01-01

    The problems of interim away-from-reactor spent fuel storage and storage in spent fuel pools at the reactor site are discussed. An overview of the state-of-the-art in the USA, Europe, and Japan is presented. The technical facilities for away-from-reactor storage are briefly described, including wet storage pools, interactive concrete systems, metallic containers, and passive concrete systems. Reprocessing technologies are mostly at the design stage only. It is predicted that during the 20 years to come, about 50 000 tonnes of spent fuel will be stored at reactor sites regardless of the advance of spent fuel reprocessing or interim storage projects. (J.B.). 4 tabs., 2 figs

  4. Pathways to deep decarbonization - Interim 2014 Report

    International Nuclear Information System (INIS)

    2014-01-01

    The interim 2014 report by the Deep Decarbonization Pathways Project (DDPP), coordinated and published by IDDRI and the Sustainable Development Solutions Network (SDSN), presents preliminary findings of the pathways developed by the DDPP Country Research Teams with the objective of achieving emission reductions consistent with limiting global warming to less than 2 deg. C. The DDPP is a knowledge network comprising 15 Country Research Teams and several Partner Organizations who develop and share methods, assumptions, and findings related to deep decarbonization. Each DDPP Country Research Team has developed an illustrative road-map for the transition to a low-carbon economy, with the intent of taking into account national socio-economic conditions, development aspirations, infrastructure stocks, resource endowments, and other relevant factors. The interim 2014 report focuses on technically feasible pathways to deep decarbonization

  5. Erythema multiforme

    Science.gov (United States)

    ... mouth sores that interferes with eating and drinking Antibiotics for skin infections Corticosteroids to control inflammation Medicines for eye symptoms Good hygiene and staying away from other people may ...

  6. Gaz de France interim financial report 2007

    International Nuclear Information System (INIS)

    2007-01-01

    This financial report contains the unaudited condensed financial statements of Gaz de France Group for the first half ended June 30, 2007, which were reviewed by the audit committee on August 27, 2007 and by the board of directors at its meeting on August 28, 2007. It includes forward-looking statements concerning the objectives, strategies, financial position, future operating results and the operations of Gaz de France Group. These statements reflect the Group's current perception of its activities and the markets in which it operates, as well as various estimates and assumptions considered to be reasonable. Content: interim management report (highlights of the first half of 2007, revenues and results for the period, financial structure, data on outstanding stock, outlook); interim consolidated financial statements (consolidated statements of income, consolidated balance sheets, consolidated statements of cash flows, recognized income and expenses, statements of changes in shareholders' equity, note to the consolidated financial statements); statement by the person responsible for the interim financial report; statutory auditors' report. (J.S.)

  7. Tribal child welfare. Interim final rule.

    Science.gov (United States)

    2012-01-06

    The Administration for Children and Families (ACF) is issuing this interim final rule to implement statutory provisions related to the Tribal title IV-E program. Effective October 1, 2009, section 479B(b) of the Social Security Act (the Act) authorizes direct Federal funding of Indian Tribes, Tribal organizations, and Tribal consortia that choose to operate a foster care, adoption assistance and, at Tribal option, a kinship guardianship assistance program under title IV-E of the Act. The Fostering Connections to Success and Increasing Adoptions Act of 2008 requires that ACF issue interim final regulations which address procedures to ensure that a transfer of responsibility for the placement and care of a child under a State title IV-E plan to a Tribal title IV-E plan occurs in a manner that does not affect the child's eligibility for title IV-E benefits or medical assistance under title XIX of the Act (Medicaid) and such services or payments; in-kind expenditures from third-party sources for the Tribal share of administration and training expenditures under title IV-E; and other provisions to carry out the Tribal-related amendments to title IV-E. This interim final rule includes these provisions and technical amendments necessary to implement a Tribal title IV-E program.

  8. The Interim Financial Statements: The Case of Greece

    OpenAIRE

    Rogdaki, E.I.; Kazantzis, Ch.

    1999-01-01

    The following paper refers to the accounting and auditing issues which emerge in the preparation of the interim financial statements of the companies: Firstly, the interim financial statements are defined as being the financial statements that provide useful information about the financial position and the financial results of a company which are realized and accrued during the fiscal year. The interim financial statements can be prepared on a monthly basis, on a quarterly basis or covering a...

  9. Simulation of glioblastoma multiforme (GBM) tumor cells using ising model on the Creutz Cellular Automaton

    Science.gov (United States)

    Züleyha, Artuç; Ziya, Merdan; Selçuk, Yeşiltaş; Kemal, Öztürk M.; Mesut, Tez

    2017-11-01

    Computational models for tumors have difficulties due to complexity of tumor nature and capacities of computational tools, however, these models provide visions to understand interactions between tumor and its micro environment. Moreover computational models have potential to develop strategies for individualized treatments for cancer. To observe a solid brain tumor, glioblastoma multiforme (GBM), we present a two dimensional Ising Model applied on Creutz cellular automaton (CCA). The aim of this study is to analyze avascular spherical solid tumor growth, considering transitions between non tumor cells and cancer cells are like phase transitions in physical system. Ising model on CCA algorithm provides a deterministic approach with discrete time steps and local interactions in position space to view tumor growth as a function of time. Our simulation results are given for fixed tumor radius and they are compatible with theoretical and clinic data.

  10. Current status and future therapeutic perspectives of glioblastoma multiforme (GBM) therapy: A review.

    Science.gov (United States)

    Anjum, Komal; Shagufta, Bibi Ibtesam; Abbas, Syed Qamar; Patel, Seema; Khan, Ishrat; Shah, Sayed Asmat Ali; Akhter, Najeeb; Hassan, Syed Shams Ul

    2017-08-01

    Glioblastoma multiforme (GBM) is the deadliest form of heterogeneous brain cancer. It affects an enormous number of patients every year and the survival is approximately 8 to 15 months. GBM has driven by complex signaling pathways and considered as a most challenging to treat. Standard treatment of GBM includes surgery, radiation therapy, chemotherapy and also the combined treatment. This review article described inter and intra- tumor heterogeneity of GMB. In addition, recent chemotherapeutic agents, with their mechanism of action have been defined. FDA-approved drugs also been focused over here and most importantly highlighting some natural and synthetic and novel anti- glioma agents, that are the main focus of researchers nowadays. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Primary glioblastoma multiforme of medulla oblongata: Case report and review of literature

    Science.gov (United States)

    Chotai, Silky P.; Moon, Hong-Joo; Kim, Joo-Han; Kim, Jong-Hyun; Kwon, Taek-Hyun

    2012-01-01

    Glioblastoma multiforme (GBM) is the most common glial tumor of the adult brain. However, the primary GBM of medulla oblongata is a rarity. To the best of our knowledge, only four cases of GBM of medulla oblongata have been reported so far in the literature, and this is the second report of conventional GBM of the medulla oblongata in adults. We describe a case of 51-year-old female, who presented with a heterogeneous mass with exophytic feature located in the caudal brain stem that was approached and a near total tumor removal was achieved by median suboccipital route. A literature review with emphasis on anatomical location, radiological and histopathological findings, extent of tumor resectibility, and outcome is included. PMID:22639691

  12. Role of 5-ALA in improving extent of tumour resection in patients with Glioblastoma Multiforme.

    Science.gov (United States)

    Waqas, Muhammad; Khan, Inamullah; Shamim, Muhammad Shahzad

    2017-10-01

    Goal of surgery for patients with Glioblastoma Multiforme (GBM) is gross total resection with no new neurological deficits. Surgical resection is often restricted due the difficulty in differentiating the tumour from surrounding normal brain using either naked eye, or standard intra-operative white light microscopy. GBM uptakes orally administered 5-ALA becomes fluorescent when viewed by a special light, and this property has been used to improve intra-operative tumour identification. This technique should therefore allow better extent of tumour resection. The hypothesis has been tested through several studies and even though most studies are of low quality, they strongly favour the use of 5- ALA in improving the extent of resection when compared to white light microscopy. A systematic review on the topic had a similar conclusion. Few studies have also hinted on a high false negative rate with the use of this technique..

  13. Comparing predictive models of glioblastoma multiforme built using multi-institutional and local data sources.

    Science.gov (United States)

    Singleton, Kyle W; Hsu, William; Bui, Alex A T

    2012-01-01

    The growing amount of electronic data collected from patient care and clinical trials is motivating the creation of national repositories where multiple institutions share data about their patient cohorts. Such efforts aim to provide sufficient sample sizes for data mining and predictive modeling, ultimately improving treatment recommendations and patient outcome prediction. While these repositories offer the potential to improve our understanding of a disease, potential issues need to be addressed to ensure that multi-site data and resultant predictive models are useful to non-contributing institutions. In this paper we examine the challenges of utilizing National Cancer Institute datasets for modeling glioblastoma multiforme. We created several types of prognostic models and compared their results against models generated using data solely from our institution. While overall model performance between the data sources was similar, different variables were selected during model generation, suggesting that mapping data resources between models is not a straightforward issue.

  14. Varicella zoster with erythema multiforme in a young girl: a rare association.

    Science.gov (United States)

    Kishore, B Nanda; Ankadavar, Nandini S; Kamath, Ganesh H; Martis, Jacintha

    2014-05-01

    Erythema multiforme (EM) is an acute, self-limited, mucocutaneous disorder regarded as a hypersensitivity reaction which is triggered by various factors like infection, drugs, and food. Infectious agents are considered to be a major cause of EM other than idiopathic cause. A young girl presented with fluid-filled lesions all over the body of 3 days duration with history of similar lesions with fever in her sibling 2 weeks prior to admission. This was followed by large fluid-filled lesions with halo 3 days thereafter over the trunk, extremities suggesting target lesions of EM. The diagnosis was confirmed by cytology and positive serology. Varicella zoster virus (VZV) has rarely been reported as an etiological agent, despite its high incidence in childhood. VZV as an etiology of EM in a young girl has not been reported so far. This case was reported for its rare association of EM and varicella zoster and also for its rare presentation in a young girl.

  15. Erythema Multiforme-Like Reaction Due to Rosewood: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Eylem Ceren

    2008-12-01

    Full Text Available Woods and their dusts can lead to various cutaneous reactions such as folliculitis, contact urticaria, irritant and allergic dermatitis. Erythema multiforme-like (EM cutaneous and respiratory system reactions such as astma and allergic rhinitis were also reported. The cutaneous reactions typically affect the areas such as the face, neck and arms exposed to the dust of the tree and usually occur on carpenters as occupational dermatitis\t. Rosewood is one of the most allergic varieties of the trees leading to contact dermatitis. It is a tropical tree and does not grow up in our country. It is especially used in the production of furniture and music instruments and imported from abroad to our country. A few cases of EM-like reaction were reported in 1976 and 1988 in the literature. Herein, two carpenters with severe EM-like skin reaction due to the rosewood, treated with systemic corticosteroids are reported for the first time in our country

  16. Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall

    Directory of Open Access Journals (Sweden)

    Li Shengwen

    2012-09-01

    Full Text Available Abstract Background The cancer stem cell (CSC hypothesis posits that deregulated neural stem cells (NSCs form the basis of brain tumors such as glioblastoma multiforme (GBM. GBM, however, usually forms in the cerebral white matter while normal NSCs reside in subventricular and hippocampal regions. We attempted to characterize CSCs from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall. Methods We described isolating CSCs from a GBM involving the lateral ventricles and characterized these cells with in vitro molecular biomarker profiling, cellular behavior, ex vivo and in vivo techniques. Results The patient’s MRI revealed a heterogeneous mass with associated edema, involving the left subventricular zone. Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. Recurrence of the tumor occurred shortly after the surgical resection. CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin, Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have been previously reported in the literature. Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also induced tumor formation when they were stereotactically transplanted into the brains of the immune-deficient NOD/SCID mice. Conclusions This brain tumor involving the neurogenic lateral ventricular wall was comprised of tumor-forming, CD133-positive cancer

  17. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report

    Directory of Open Access Journals (Sweden)

    Servadei Franco

    2010-04-01

    Full Text Available Abstract Background Management of glioblastoma multiforme (GBM has been difficult using standard therapy (radiation with temozolomide chemotherapy. The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI. Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter. Methods Prior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a restricted 4:1 (fat: carbohydrate + protein ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. The diet was supplemented with vitamins and minerals. Steroid medication (dexamethasone was removed during the course of the treatment. The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET. Results After two months treatment, the patient's body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy. Conclusion This is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed

  18. Compilation of interim technical research memoranda. Volume I

    International Nuclear Information System (INIS)

    Shanahan, W.R.

    1984-04-01

    Four interim technical research memoranda are presented that describe the results of numerical simulations designed to investigate the dynamics of energetic plasma beams propagating across magnetic fields

  19. Hanford Generic Interim Safety Basis

    Energy Technology Data Exchange (ETDEWEB)

    Lavender, J.C.

    1994-09-09

    The purpose of this document is to identify WHC programs and requirements that are an integral part of the authorization basis for nuclear facilities that are generic to all WHC-managed facilities. The purpose of these programs is to implement the DOE Orders, as WHC becomes contractually obligated to implement them. The Hanford Generic ISB focuses on the institutional controls and safety requirements identified in DOE Order 5480.23, Nuclear Safety Analysis Reports.

  20. Hanford Generic Interim Safety Basis

    International Nuclear Information System (INIS)

    Lavender, J.C.

    1994-01-01

    The purpose of this document is to identify WHC programs and requirements that are an integral part of the authorization basis for nuclear facilities that are generic to all WHC-managed facilities. The purpose of these programs is to implement the DOE Orders, as WHC becomes contractually obligated to implement them. The Hanford Generic ISB focuses on the institutional controls and safety requirements identified in DOE Order 5480.23, Nuclear Safety Analysis Reports

  1. Comparison of vitamins K1, K2 and K3 effects on growth of rat glioma and human glioblastoma multiforme cells in vitro.

    Science.gov (United States)

    Oztopçu, Pinar; Kabadere, Selda; Mercangoz, Ayşe; Uyar, Ruhi

    2004-09-01

    Glioblastoma multiforme is characterized as highly invasive and rapidly growing astrocytomas, and scientists have sought for efficient treatment against malignant gliomas for a long time. Therefore, we compared the respond of rat glioma (C6) and glioblastoma multiforme cells derived from two patients to vitamins K1, K2 and K3. The cells were exposed to 100, 250, 500, 750 and 1000 microM of vitamins K1 and K2, and 1, 10, 25, 50, 75 and 100 microM of vitamin K3 for 24 hours in an incubator atmosphere of 5% CO2, 37 degrees C and 100% humidity. Cell viability was estimated by MTT assay. Vitamin K1 showed no growth effect on all the glioma cells examined. Vitamin K2 did not cause any change in number of C6, however induced growth inhibition in a dose-dependent manner on glioblastoma multiforme. The IC50 values of vitamin K2 were 960 microM and 970 microM for glioblastoma multiforme, respectively. Vitamin K3 had also growth inhibitory effect in a dose-dependent manner on both C6 and glioblastoma multiforme. The IC50 values were 41 microM, 24 microM and 23 microM for vitamin K3, respectively. We concluded that vitamin K3 is more effective than vitamin K2 for inhibition of cancer cell growth, and might have an alternative value as an anticancer drug against glioblastoma multiforme.

  2. Interim report - geotechnical site assessment methodology. Vol.1

    International Nuclear Information System (INIS)

    Tunbridge, L.W.; Richards, L.R.

    1983-05-01

    An interim report summarizing the research conducted on geotechnical site assessment methodology at the Carwynnen test mine in Cornwall. The geological setting of the test site in the Cornubian granite batholith is described. The effect of structure imposed by discontinuities on the engineering behaviour of rock masses is discussed and the scanline survey method of obtaining data on discontinuities in the rock mass is described. The requirement for remote geophysical methods of characterizing the mass is discussed and initial experiments using seismic and ultrasonic velocity measurements are reported. Computer programs to perform statistical analysis of the discontinuity patterns are described. Overcoring and hydraulic fracturing methods of determining the in-situ stress are briefly described and the results of a programme of in-situ stress measurements using the overcoring method are reported. (author)

  3. Using optimization to improve radioactive waste interim storage

    International Nuclear Information System (INIS)

    Dellamano, J.C.; Sordi, G.M.

    2006-01-01

    In several countries where repository for final disposal is not constructed and in operation, the low level radioactive wastes are treated and stored. In some cases, interim storage can be extended for decades demanding special attention regarding security aspects. On the other hand, some packages contains very small quantities of radioactive material either by the long period of storage or by the rudimental segregation carried out when the radioactive waste were collected. This paper discuss the use of cost-benefit analysis as technique to aid decision making in order to evaluate the feasibility of to open the packages containing compactable solid radioactive wastes and to segregate these waste according to the classification that consider the recent clearance levels and exemption limits recommended by international organisms. (authors)

  4. Advanced nuclear reactor public opinion project. Interim report

    Energy Technology Data Exchange (ETDEWEB)

    Benson, B.

    1991-07-25

    This Interim Report summarizes the findings of our first twenty in-depth interviews in the Advanced Nuclear Reactor Public Opinion Project. We interviewed 6 industry trade association officials, 3 industry attorneys, 6 environmentalists/nuclear critics, 3 state officials, and 3 independent analysts. In addition, we have had numerous shorter discussions with various individuals concerned about nuclear power. The report is organized into the four categories proposed at our April, 1991, Advisory Group meeting: safety, cost-benefit analysis, science education, and communications. Within each category, some change of focus from that of the Advisory Group has been required, to reflect the findings of our interviews. This report limits itself to describing our findings. An accompanying memo draws some tentative conclusions.

  5. The Homestake Interim Laboratory and Homestake DUSEL

    Science.gov (United States)

    Lesko, Kevin T.

    2011-12-01

    The former Homestake gold mine in Lead South Dakota is proposed for the National Science Foundation's Deep Underground Science and Engineering Laboratory (DUSEL). The gold mine provides expedient access to depths in excess of 8000 feet below the surface (>7000 mwe). Homestake's long history of promoting scientific endeavours includes the Davis Solar Neutrino Experiment, a chlorine-based experiment that was hosted at the 4850 Level for more than 30 years. As DUSEL, Homestake would be uncompromised by competition with mining interests or other shared uses. The facility's 600-km of drifts would be available for conversion for scientific and educational uses. The State of South Dakota, under Governor Rounds' leadership, has demonstrated exceptionally strong support for Homestake and the creation of DUSEL. The State has provided funding totalling $46M for the preservation of the site for DUSEL and for the conversion and operation of the Homestake Interim Laboratory. Motivated by the strong educational and outreach potential of Homestake, the State contracted a Conversion Plan by world-recognized mine-engineering contractor to define the process of rehabilitating the facility, establishing the appropriate safety program, and regaining access to the facility. The State of South Dakota has established the South Dakota Science and Technology Authority to oversee the transfer of the Homestake property to the State and the rehabilitation and preservation of the facility. The Homestake Scientific Collaboration and the State of South Dakota's Science and Technology Authority has called for Letters of Interest from scientific, educational and engineering collaborations and institutions that are interested in hosting experiments and uses in the Homestake Interim Facility in advance of the NSF's DUSEL, to define experiments starting as early as 2007. The Homestake Program Advisory Committee has reviewed these Letters and their initial report has been released. Options for

  6. The Homestake Interim Laboratory and Homestake DUSEL

    International Nuclear Information System (INIS)

    Lesko, Kevin T.

    2011-01-01

    The former Homestake gold mine in Lead South Dakota is proposed for the National Science Foundation's Deep Underground Science and Engineering Laboratory (DUSEL). The gold mine provides expedient access to depths in excess of 8000 feet below the surface (>7000 mwe). Homestake's long history of promoting scientific endeavours includes the Davis Solar Neutrino Experiment, a chlorine-based experiment that was hosted at the 4850 Level for more than 30 years. As DUSEL, Homestake would be uncompromised by competition with mining interests or other shared uses. The facility's 600-km of drifts would be available for conversion for scientific and educational uses. The State of South Dakota, under Governor Rounds' leadership, has demonstrated exceptionally strong support for Homestake and the creation of DUSEL. The State has provided funding totalling $46M for the preservation of the site for DUSEL and for the conversion and operation of the Homestake Interim Laboratory. Motivated by the strong educational and outreach potential of Homestake, the State contracted a Conversion Plan by world-recognized mine-engineering contractor to define the process of rehabilitating the facility, establishing the appropriate safety program, and regaining access to the facility. The State of South Dakota has established the South Dakota Science and Technology Authority to oversee the transfer of the Homestake property to the State and the rehabilitation and preservation of the facility. The Homestake Scientific Collaboration and the State of South Dakota's Science and Technology Authority has called for Letters of Interest from scientific, educational and engineering collaborations and institutions that are interested in hosting experiments and uses in the Homestake Interim Facility in advance of the NSF's DUSEL, to define experiments starting as early as 2007. The Homestake Program Advisory Committee has reviewed these Letters and their initial report has been released. Options for

  7. 40 CFR 80.141 - Interim detergent gasoline program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Interim detergent gasoline program. 80... (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Detergent Gasoline § 80.141 Interim detergent gasoline... apply to: (i) All gasoline sold or transferred to a party who sells or transfers gasoline to the...

  8. 50 CFR 660.720 - Interim protection for sea turtles.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Interim protection for sea turtles. 660.720 Section 660.720 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... Migratory Fisheries § 660.720 Interim protection for sea turtles. (a) Until the effective date of §§ 660.707...

  9. 12 CFR 541.18 - Interim Federal savings association.

    Science.gov (United States)

    2010-01-01

    ... an existing savings and loan holding company or to facilitate any other transaction the Office may... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Interim Federal savings association. 541.18... REGULATIONS AFFECTING FEDERAL SAVINGS ASSOCIATIONS § 541.18 Interim Federal savings association. The term...

  10. Presidential Transition: The Experience of Two Community College Interim Presidents

    Science.gov (United States)

    Thompson, Matthew D.

    2010-01-01

    The purpose of this qualitative case study was to understand the experiences of two community college interim presidents, their characteristics, and how they led institutions following an abrupt presidential departure. There were two fundamental questions framing this research study, 1. How do two interim community college presidents lead…

  11. General certification procedure of enterprises and interim job enterprises

    CERN Document Server

    Int. At. Energy Agency, Wien

    2002-01-01

    This procedure defines the certification global process of enterprises employing workers of A or B category for nuclear facilities and interim job enterprises proposing workers of A or B category for nuclear facilities. This certification proves the enterprises ability to satisfy the specification ''E'' of the CEFRI and the interim job enterprises to satisfy the specification ''I'' of the CEFRI. (A.L.B.)

  12. 47 CFR 51.715 - Interim transport and termination pricing.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Interim transport and termination pricing. 51.715 Section 51.715 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER... Telecommunications Traffic § 51.715 Interim transport and termination pricing. (a) Upon request from a...

  13. Do Interim Assessments Reduce the Race and SES Achievement Gaps?

    Science.gov (United States)

    Konstantopoulos, Spyros; Li, Wei; Miller, Shazia R.; van der Ploeg, Arie

    2017-01-01

    The authors examined differential effects of interim assessments on minority and low socioeconomic status students' achievement in Grades K-6. They conducted a large-scale cluster randomized experiment in 2009-2010 to evaluate the impact of Indiana's policy initiative introducing interim assessments statewide. The authors used 2-level models to…

  14. 78 FR 49782 - Interim Staff Guidance on Changes During Construction

    Science.gov (United States)

    2013-08-15

    ... Construction AGENCY: Nuclear Regulatory Commission. ACTION: Draft interim staff guidance; request for comment... During Construction.'' This ISG provides guidance to the NRC staff on the Preliminary Amendment Request...-ISG-025 ``Interim Staff Guidance on Changes during Construction under 10 CFR Part 52'' is available...

  15. Central waste complex interim safety basis

    International Nuclear Information System (INIS)

    Cain, F.G.

    1995-01-01

    This interim safety basis provides the necessary information to conclude that hazards at the Central Waste Complex are controlled and that current and planned activities at the CWC can be conducted safely. CWC is a multi-facility complex within the Solid Waste Management Complex that receives and stores most of the solid wastes generated and received at the Hanford Site. The solid wastes that will be handled at CWC include both currently stored and newly generated low-level waste, low-level mixed waste, contact-handled transuranic, and contact-handled TRU mixed waste

  16. Interim supply in the electricity industry

    Energy Technology Data Exchange (ETDEWEB)

    Strassburg, W

    1977-06-01

    The interim supply or the so-called 'condition without a contract' can occur within the framework of energy supply in the relationship between 1) public utility and tariff customer, 2) public utility and the special last-in-line consumer, 3) supplying and distributing public utility, 4) public utility and territorial administrative body. The present contribution deals with the cases named under (3) and (4). Cases (1) and (2) were dealt with in a previous article. Relevant contract clauses and laws and their effects on contracting partners are discussed.

  17. Interim supply in the electricity industry

    Energy Technology Data Exchange (ETDEWEB)

    Strassburg, W

    1977-05-01

    The interim supply or the so-called 'condition without a contract' can occur within the framework of energy supply in the relationship between: 1) public utility and tariff customer, 2) public utility and the special last-in-line consumer, 3) supplying and distributing public utility, 4) public utility and territorial administrative body. The contribution at hand deals with the cases under 1) and 2); cases 3) and 4) are dealt with in an article to be published. Relevant contract clauses and laws and their effects on contracting partners are discussed. 41 references.

  18. National NIF Diagnostic Program Interim Management Plan

    International Nuclear Information System (INIS)

    Warner, B

    2002-01-01

    The National Ignition Facility (NIF) has the mission of supporting Stockpile Stewardship and Basic Science research in high-energy-density plasmas. To execute those missions, the facility must provide diagnostic instrumentation capable of observing and resolving in time events and radiation emissions characteristic of the plasmas of interest. The diagnostic instrumentation must conform to high standards of operability and reliability within the NIF environment. These exacting standards, together with the facility mission of supporting a diverse user base, has led to the need for a central organization charged with delivering diagnostic capability to the NIF. The National NIF Diagnostics Program (NNDP) has been set up under the aegis of the NIF Director to provide that organization authority and accountability to the wide user community for NIF. The funds necessary to perform the work of developing diagnostics for NIF will be allocated from the National NIF Diagnostics Program to the participating laboratories and organizations. The participating laboratories and organizations will design, build, and commission the diagnostics for NIF. Restricted availability of funding has had an adverse impact, unforeseen at the time of the original decision to projectize NIF Core Diagnostics Systems and Cryogenic Target Handing Systems, on the planning and initiation of these efforts. The purpose of this document is to provide an interim project management plan describing the organizational structure and management processes currently in place for NIF Core Diagnostics Systems. Preparation of a Program Execution Plan for NIF Core Diagnostics Systems has been initiated and a current draft is provided as Attachment 1 to this document. The National NIF Diagnostics Program Interim Management Plan provides a summary of primary design criteria and functional requirements, current organizational structure, tracking and reporting procedures, and current planning estimates of project scope

  19. Use of ERC-1671 Vaccine in a Patient with Recurrent Glioblastoma Multiforme after Progression during Bevacizumab Therapy: First Published Report.

    Science.gov (United States)

    Bota, Daniela A; Alexandru-Abrams, Daniela; Pretto, Chrystel; Hofman, Florence M; Chen, Thomas C; Fu, Beverly; Carrillo, Jose A; Schijns, Virgil Ejc; Stathopoulos, Apostolos

    2015-01-01

    Glioblastoma multiforme is a highy aggressive tumor that recurs despite resection, focal beam radiation, and temozolamide chemotherapy. ERC-1671 is an experimental treatment strategy that uses the patient's own immune system to attack the tumor cells. The authors report preliminary data on the first human administration of ERC-1671 vaccination under a single-patient, compassionate-use protocol. The patient survived for ten months after the vaccine administration without any other adjuvant therapy and died of complications related to his previous chemotherapies.

  20. Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Eriksen, Jesper Grau; Broholm, Helle

    2010-01-01

    , hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan...... of cetuximab. There is still an urgent need for one or more reliable and reproducible biomarkers able to predict the efficacy of anti-angiogenic therapy....

  1. Long-term Survival of Six Patients with Glioblastoma Multiforme: Case Series and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Shapour Omidvari

    2012-04-01

    Full Text Available The median overall survival in glioblastoma multiforme is usually less than one year. Long-term survival is rare and is seen in only 3%-6% of GBM patients. The present study reports the characteristics and treatment outcomes of six cases of glioblastoma multiforme with long-term survival. A literature review is also presented.Between 1990 and 2008, 217 glioblastoma multiforme patients have been treated at our center of which six cases (four males survived for three years or longer. The mean age of the six cases was 25.7 years. All patients received postoperative radiotherapy with a mean dose of 55 gray and four patients received nitrosourea-based chemotherapy.Patients' mean survival was 5.2 years. The results of this study and review of the literature have indicated that long-term (more than three years survival is exceptional and mainly observed in younger patients with good performance status and following complete surgical tumor resection.

  2. Difficult diagnosis of brainstem glioblastoma multiforme in a woman: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Lakhan Shaheen E

    2009-10-01

    Full Text Available Abstract Introduction Brainstem gliomas are rare in adults. They most commonly occur in the pons and are most likely to be high-grade lesions. The diagnosis of a high-grade brainstem glioma is usually reached due to the presentation of rapidly progressing brainstem, cranial nerve and cerebellar symptoms. These symptoms do, however, overlap with a variety of other central nervous system disorders. Magnetic resonance imaging is the radiographic modality of choice, but can still be misleading. Case presentation A 48-year-old Caucasian woman presented with headache and vomiting followed by cerebellar signs and confusion. Magnetic resonance imaging findings were suggestive of a demyelinating process, but the patient failed to respond to therapy. Her condition rapidly progressed and she died. At autopsy, a high-grade invasive pontine tumor was identified. Histological evaluation revealed glioblastoma multiforme. Conclusion While pontine gliomas are rare in adults, those that do occur tend to be high-grade and rapidly progressive. Progression of symptoms from non-specific findings of headache and vomiting to rapid neurological deterioration, as occurred in our patient, is common in glioblastoma multiforme. While radiographic findings are often suggestive of the underlying pathology, this case represents the possibility of glioblastoma multiforme presenting as a deceptively benign appearing lesion.

  3. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Costello Joseph F

    2008-06-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells. Methods We used quantitative RT-PCR to assess microRNA expression in high-grade astrocytomas and adult mouse neural stem cells. To assess the function of candidate microRNAs in high-grade astrocytomas, we transfected miR mimics to cultured-mouse neural stem cells, -mouse oligodendroglioma-derived stem cells, -human glioblastoma multiforme-derived stem cells and -glioblastoma multiforme cell lines. Cellular differentiation was assessed by immunostaining, and cellular proliferation was determined using fluorescence-activated cell sorting. Results Our studies revealed that expression levels of microRNA-124 and microRNA-137 were significantly decreased in anaplastic astrocytomas (World Health Organization grade III and glioblastoma multiforme (World Health Organization grade IV relative to non-neoplastic brain tissue (P erbB tumors and cluster of differentiation 133+ human glioblastoma multiforme-derived stem cells (SF6969. Transfection of microRNA-124 or microRNA-137 also induced G1 cell cycle arrest in U251 and SF6969 glioblastoma multiforme cells, which was associated with decreased expression of cyclin-dependent kinase 6 and phosphorylated retinoblastoma (pSer 807/811 proteins. Conclusion microRNA-124 and microRNA-137 induce differentiation of adult mouse neural stem cells, mouse

  4. SU-F-R-17: Advancing Glioblastoma Multiforme (GBM) Recurrence Detection with MRI Image Texture Feature Extraction and Machine Learning

    Energy Technology Data Exchange (ETDEWEB)

    Yu, V; Ruan, D; Nguyen, D; Kaprealian, T; Chin, R; Sheng, K [UCLA School of Medicine, Los Angeles, CA (United States)

    2016-06-15

    Purpose: To test the potential of early Glioblastoma Multiforme (GBM) recurrence detection utilizing image texture pattern analysis in serial MR images post primary treatment intervention. Methods: MR image-sets of six time points prior to the confirmed recurrence diagnosis of a GBM patient were included in this study, with each time point containing T1 pre-contrast, T1 post-contrast, T2-Flair, and T2-TSE images. Eight Gray-level co-occurrence matrix (GLCM) texture features including Contrast, Correlation, Dissimilarity, Energy, Entropy, Homogeneity, Sum-Average, and Variance were calculated from all images, resulting in a total of 32 features at each time point. A confirmed recurrent volume was contoured, along with an adjacent non-recurrent region-of-interest (ROI) and both volumes were propagated to all prior time points via deformable image registration. A support vector machine (SVM) with radial-basis-function kernels was trained on the latest time point prior to the confirmed recurrence to construct a model for recurrence classification. The SVM model was then applied to all prior time points and the volumes classified as recurrence were obtained. Results: An increase in classified volume was observed over time as expected. The size of classified recurrence maintained at a stable level of approximately 0.1 cm{sup 3} up to 272 days prior to confirmation. Noticeable volume increase to 0.44 cm{sup 3} was demonstrated at 96 days prior, followed by significant increase to 1.57 cm{sup 3} at 42 days prior. Visualization of the classified volume shows the merging of recurrence-susceptible region as the volume change became noticeable. Conclusion: Image texture pattern analysis in serial MR images appears to be sensitive to detecting the recurrent GBM a long time before the recurrence is confirmed by a radiologist. The early detection may improve the efficacy of targeted intervention including radiosurgery. More patient cases will be included to create a generalizable

  5. The challenges facing the long term interim storage

    Energy Technology Data Exchange (ETDEWEB)

    Iracane, D. [CEA Sacaly, Dir. de la Simulation et des Outils Experimentaux-DSOE, 91 - Gif sur Yvette (France); Marvy, A. [CEA Saclay, Dir. du Developpement et de l' Innovation Nucleares-DDIN, 91 - Gif Sur Yvette (France)

    2001-07-01

    In France electricity generation by means of commercial nuclear power plants has come to a point where it contributes to the national demand at a level of 80%. The safety performance of the production system has also reached a high level of both maturity and reliability taking advantage of the cumulative effect of a 30 years long learning experience and ever more stringent safety requirements. The policy to reprocess spent fuel has been overriding but no final decision has yet been made regarding the ultimate disposition of the waste streams. Although studies on deep geological disposal are ongoing, France is also looking at whether and under which conditions a long-term interim storage may provide an effective flexibility to the fuel cycle back-end. We discuss thereafter the needs and the paramount objectives of this latter R and D program. Results are being framed as potential guiding criteria for decision makers and various stakeholders. In first part, we propose a general analysis which emphasises that a long term interim storage is more than a classical nuclear facility because it explicitly requires long-lasting control and creates a burden for Society during many generations. Then, in second part, we offer an overview of the technical results from the R and D program as they stand at the time of writing. As an answer to the Government request, a strong emphasis has been put on this research for three years. Conclusion is an attempt to outline the societal context in which future decisions will have to be made. (author)

  6. The challenges facing the long term interim storage

    International Nuclear Information System (INIS)

    Iracane, D.; Marvy, A.

    2001-01-01

    In France electricity generation by means of commercial nuclear power plants has come to a point where it contributes to the national demand at a level of 80%. The safety performance of the production system has also reached a high level of both maturity and reliability taking advantage of the cumulative effect of a 30 years long learning experience and ever more stringent safety requirements. The policy to reprocess spent fuel has been overriding but no final decision has yet been made regarding the ultimate disposition of the waste streams. Although studies on deep geological disposal are ongoing, France is also looking at whether and under which conditions a long-term interim storage may provide an effective flexibility to the fuel cycle back-end. We discuss thereafter the needs and the paramount objectives of this latter R and D program. Results are being framed as potential guiding criteria for decision makers and various stakeholders. In first part, we propose a general analysis which emphasises that a long term interim storage is more than a classical nuclear facility because it explicitly requires long-lasting control and creates a burden for Society during many generations. Then, in second part, we offer an overview of the technical results from the R and D program as they stand at the time of writing. As an answer to the Government request, a strong emphasis has been put on this research for three years. Conclusion is an attempt to outline the societal context in which future decisions will have to be made. (author)

  7. Operations and Maintenance Concept Plan for the Immobilized High Level Waste (IHLW) Interim Storage Facility

    Energy Technology Data Exchange (ETDEWEB)

    JANIN, L.F.

    2000-08-30

    This O&M Concept looks at the future operations and maintenance of the IHLW/CSB interim storage facility. It defines the overall strategy, objectives, and functional requirements for the portion of the building to be utilized by Project W-464. The concept supports the tasks of safety basis planning, risk mitigation, alternative analysis, decision making, etc. and will be updated as required to support the evolving design.

  8. Operations and Maintenance Concept Plan for the Immobilized High-Level Waste (IHLW) Interim Storage Facility

    International Nuclear Information System (INIS)

    JANIN, L.F.

    2000-01-01

    This OandM Concept looks at the future operations and maintenance of the IHLW/CSB interim storage facility. It defines the overall strategy, objectives, and functional requirements for the portion of the building to be utilized by Project W-464. The concept supports the tasks of safety basis planning, risk mitigation, alternative analysis, decision making, etc. and will be updated as required to support the evolving design

  9. Flammable gas deflagration consequence calculations for the tank waste remediation system basis for interim operation

    Energy Technology Data Exchange (ETDEWEB)

    Van Vleet, R.J., Westinghouse Hanford

    1996-08-13

    This paper calculates the radiological dose consequences and the toxic exposures for deflagration accidents at various Tank Waste Remediation System facilities. These will be used in support of the Tank Waste Remediation System Basis for Interim Operation.The attached SD documents the originator`s analysis only. It shall not be used as the final or sole document for effecting changes to an authorization basis or safety basis for a facility or activity.

  10. Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling

    Directory of Open Access Journals (Sweden)

    Hernández-Moneo Jose-Luis

    2006-09-01

    Full Text Available Abstract Background Conventional cytogenetic and comparative genomic hybridization (CGH studies in brain malignancies have shown that glioblastoma multiforme (GBM is characterized by complex structural and numerical alterations. However, the limited resolution of these techniques has precluded the precise identification of detailed specific gene copy number alterations. Results We performed a genome-wide survey of gene copy number changes in 20 primary GBMs by CGH on cDNA microarrays. A novel amplicon at 4p15, and previously uncharacterized amplicons at 13q32-34 and 1q32 were detected and are analyzed here. These amplicons contained amplified genes not previously reported. Other amplified regions containg well-known oncogenes in GBMs were also detected at 7p12 (EGFR, 7q21 (CDK6, 4q12 (PDGFRA, and 12q13-15 (MDM2 and CDK4. In order to identify the putative target genes of the amplifications, and to determine the changes in gene expression levels associated with copy number change events, we carried out parallel gene expression profiling analyses using the same cDNA microarrays. We detected overexpression of the novel amplified genes SLA/LP and STIM2 (4p15, and TNFSF13B and COL4A2 (13q32-34. Some of the candidate target genes of amplification (EGFR, CDK6, MDM2, CDK4, and TNFSF13B were tested in an independent set of 111 primary GBMs by using FISH and immunohistological assays. The novel candidate 13q-amplification target TNFSF13B was amplified in 8% of the tumors, and showed protein expression in 20% of the GBMs. Conclusion This high-resolution analysis allowed us to propose novel candidate target genes such as STIM2 at 4p15, and TNFSF13B or COL4A2 at 13q32-34 that could potentially contribute to the pathogenesis of these tumors and which would require futher investigations. We showed that overexpression of the amplified genes could be attributable to gene dosage and speculate that deregulation of those genes could be important in the development

  11. The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial.

    Science.gov (United States)

    Sultanem, Khalil; Patrocinio, Horacio; Lambert, Christine; Corns, Robert; Leblanc, Richard; Parker, William; Shenouda, George; Souhami, Luis

    2004-01-01

    Despite major advances in treatment modalities, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. Exploring hypofractionated regimens to replace the standard 6-week radiotherapy schedule is an attractive strategy as an attempt to prevent accelerated tumor cell repopulation. There is equally interest in dose escalation to the gross tumor volume where the majority of failures occur. We report our preliminary results using hypofractionated intensity-modulated accelerated radiotherapy regimen in the treatment of patients with GBM. Between July 1998 and December 2001, 25 patients with histologically proven diagnosis of GBM, Karnofsky performance status > or =60, and a postoperative tumor volume step-and-shoot technique), 60 Gy in 20 daily fractions of 3 Gy each were given to the GTV, whereas the planning target volume received a minimum of 40 Gy in 20 fractions of 2 Gy each at its periphery. Treatments were delivered over a 4-week period using 5 daily fractions per week. Dose was prescribed at the isocenter (ICRU point). Three beam angles were used in all of the cases. Treatments were well tolerated. Acute toxicity was limited to increased brain edema during radiotherapy in 2 patients who were on tapering doses of corticosteroids. This was corrected by increasing the steroid dose. At a median follow-up of 8.8 months, no late toxicity was observed. One patient experienced visual loss at 9 months after completion of treatment. MRI suggested nonspecific changes to the optic chiasm. On review of the treatment plan, the total dose to the optic chiasm was confirmed to be equal to or less than 40 Gy in 20 fractions. When Radiation Therapy Oncology Group recursive partitioning analysis was used, 10 patients were class III-IV, and 15 patients were class V-VI. To date, 21 patients have had clinical and/or radiologic evidence of disease progression, and 16 patients have died. The median survival was 9.5 months (range: 2.8-22.9 months), the 1-year survival

  12. Phase II Radiation therapy oncology group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme

    International Nuclear Information System (INIS)

    Langer, Corey J.; Ruffer, James; Rhodes, Harker; Paulus, Rebecca; Murray, Kevin; Movsas, Benjamin; Curran, Walter

    2001-01-01

    Purpose: Fractionated external beam radiotherapy (EBRT) ± carmustine (BCNU) is the standard of care for patients with glioblastoma multiforme (GBM), but survival results remain poor. Preclinical studies indicate synergy between RT and paclitaxel (TAX) in astrocytoma cell lines. Phase I studies in GBM have demonstrated a maximum tolerated dose for TAX of 225 mg/m 2 /3 h/week x 6, during EBRT, with no exacerbation of typical RT-induced toxicities. The Radiation Therapy Oncology Group (RTOG) therefore mounted a Phase II study to determine the feasibility and efficacy of conventional EBRT and concurrent weekly TAX at its MTD. Patients and Methods: Sixty-two patients with histologic diagnosis of GBM were enrolled from 8/16/96 through 3/21/97 in a multi-institutional Phase II trial of EBRT and TAX 225 mg/m 2 /3 h (1-3 h before EBRT), administered the first treatment day of each RT week. Total EBRT dose was 60 Gy (200 cGy/fraction), 5 days per week. A smaller treatment field, to include gross disease plus a margin only, was used after 46 Gy. Results: Sixty-one patients (98%) were evaluable. Median age was 55 years (range, 28-78). Seventy-four percent were ≥50 years. Recursive partitioning analysis (RPA) Classes III, IV, V, VI included 10 (17%), 21 (34%), 25 (41%), and 5 (8%) patients, respectively. Gross total resection was performed in only 16%. There was no Grade 3 or 4 neutropenia or thrombocytopenia. Hypersensitivity reactions precluding further use of TAX occurred in 4 patients. There were 2 instances of late neurotoxicity (4% Grade 3 or 4). Ninety-one percent of patients received treatment per protocol. Seventy-seven percent completed prescribed treatment (6 weeks). Of 35 patients with measurable disease, CR/PR was observed in 23%, MR in 17%, and SD in 43%. Seventeen percent demonstrated progression at first follow-up. Median potential follow-up time is 20 months. Median survival is 9.7 months, with median survivals for RPA classes III, IV, V, and VI of 16.3, 10

  13. Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme.

    Science.gov (United States)

    Bien-Möller, Sandra; Lange, Sandra; Holm, Tobias; Böhm, Andreas; Paland, Heiko; Küpper, Johannes; Herzog, Susann; Weitmann, Kerstin; Havemann, Christoph; Vogelgesang, Silke; Marx, Sascha; Hoffmann, Wolfgang; Schroeder, Henry W S; Rauch, Bernhard H

    2016-03-15

    A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P1-S1P5) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient´s survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P1, S1P2, S1P3 and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P1 and S1P2 with patient´s survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P1 and S1P2. The participation of S1P1 and S1P2 in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells.In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation.

  14. Combined stereotactic biopsy and stepping-source interstitial irradiation of glioblastoma multiforme.

    Science.gov (United States)

    Brehmer, Stefanie; Guthier, Christian V; Clausen, Sven; Schneider, Frank; Schulte, Dirk-Michael; Benker, Matthias; Bludau, Frederic; Glatting, Gerhard; Marx, Alexander; Schmiedek, Peter; Hesser, Jürgen; Wenz, Frederik; Giordano, Frank A

    2018-04-01

    Patients diagnosed with glioblastoma multiforme receiving stereotactic biopsy only either due to tumor localization or impaired clinical status face a devastating prognosis with very short survival times. One strategy to provide an initial cytoreductive and palliative therapy at the time of the stereotactic biopsy is interstitial irradiation through the pre-defined trajectory of the biopsy channel. We designed a novel treatment planning system and evaluated the treatment potential of a fixed-source and a stepping-source algorithm for interstitial radiosurgery on non-spherical glioblastoma in direct adjacency to risk structures. Using both setups, we show that radiation doses delivered to 100% of the gross tumor volume shifts from sub-therapeutic (10-12 Gy) to sterilizing single doses (25-30 Gy) when using the stepping source algorithm due to improved sparing of organs-at-risk. Specifically, the maximum doses at the brain stem were 100% of the PTV dose when a fixed central source and 38% when a stepping-source algorithm was used. We also demonstrated precision of intracranial target points and stability of superficial and deep trajectories using both a phantom and a body donor study. Our setup now for the first time provides a basis for a clinical proof-of-concept trial and may widen palliation options for patients with limited life expectancy that should not undergo time-consuming therapies.

  15. Patterns of failure for glioblastoma multiforme following limited-margin radiation and concurrent temozolomide

    International Nuclear Information System (INIS)

    Gebhardt, Brian J; Dobelbower, Michael C; Ennis, William H; Bag, Asim K; Markert, James M; Fiveash, John B

    2014-01-01

    To analyze patterns of failure in patients with glioblastoma multiforme (GBM) treated with limited-margin radiation therapy and concurrent temozolomide. We hypothesize that patients treated with margins in accordance with Adult Brain Tumor Consortium guidelines (ABTC) will demonstrate patterns of failure consistent with previous series of patients treated with 2–3 cm margins. A retrospective review was performed of patients treated at the University of Alabama at Birmingham for GBM between 2000 and 2011. Ninety-five patients with biopsy-proven disease and documented disease progression after treatment were analyzed. The initial planning target volume includes the T1-enhancing tumor and surrounding edema plus a 1 cm margin. The boost planning target volume includes the T1-enhancing tumor plus a 1 cm margin. The tumors were classified as in-field, marginal, or distant if greater than 80%, 20-80%, or less than 20% of the recurrent volume fell within the 95% isodose line, respectively. The median progression-free survival from the time of diagnosis to documented failure was 8 months (range 3–46). Of the 95 documented recurrences, 77 patients (81%) had an in-field component of treatment failure, 6 (6%) had a marginal component, and 27 (28%) had a distant component. Sixty-three patients (66%) demonstrated in-field only recurrence. The low rate of marginal recurrence suggests that wider margins would have little impact on the pattern of failure, validating the use of limited margins in accordance ABTC guidelines

  16. The Radiologic Features of Cystic versus Noncystic Glioblastoma Multiforme as Significant Prognostic Factors

    International Nuclear Information System (INIS)

    Choi, Seung Joon; Hwang, Hee Young; Kim, Na Rae; Lee, Sheen Woo; Kim, Jeong Ho; Choi, Hye Young; Kim, Hyung Sik

    2010-01-01

    The purpose of this study was to determine the preoperative radiological characteristic and survival differences of glioblastoma multiforme (GBM) with and without cysts. Twenty-one GBMs were collected retrospectively; these tumors were pathologic confirmed as GBM. Based on the preoperative MR imaging, we compared the cystic GBMs with the noncystic GBMs according to the the tumor size, the tumor interface, the tumor wall thickness and peritumoral edema. Seven cases were classified as cystic GBMs and fourteen were noncystic GBMs. The cystic GBMs had a well-defined tumor interface, a less than 2 cm thickness of the tumor wall and less than 40 cm 3 thick peritumoral edema as compared to that of the noncystic GBMs. There was a statistically significant difference in age between the patients with cystic tumors and those with noncystic tumors. For the patients with cystic GBMs and noncystic GBMs, median survival time after surgery was 43.8 months and 12.5 months, respectively. The cystic GBMs had a well-defined tumor interface, a thin wall and minimal edema, as compared with that of the noncystic GBMs. The patients with cystic GBMs were significantly younger and they had more favorable survival outcomes than did the patients with noncystic GBMs

  17. Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study

    Directory of Open Access Journals (Sweden)

    Cristina Ferrari

    2015-01-01

    Full Text Available Glioblastoma multiforme (GBM is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [64Cu]CuCl2. To evaluate the potential theranostic role of [64Cu]CuCl2 in GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [64Cu]CuCl2 to simulate single- and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy.

  18. Glioblastoma multiforme and papillary thyroid carcinoma - A rare combination of multiple primary malignancies

    Directory of Open Access Journals (Sweden)

    Swaroopa Pulivarthi

    2015-01-01

    Full Text Available We are describing a 19-year-old white woman who presented with two synchronous primary cancers, namely glioblastoma multiforme and papillary thyroid cancer. The patient was admitted with dizziness, headache, and vomiting. CT head revealed acute intraparenchymal hematoma in the right cingulate gyrus and the splenium of the corpus callosum. Carotid and cerebral angiogram were unremarkable. MRI of the brain demonstrated a non-enhancing and non-hemorrhagic component of the lesion along the lateral margin of the hemorrhage just medial to the atrium of the right lateral ventricle that was suspicious for a tumor or metastasis. Brain biopsy confirmed it as glioblastoma mutiforme. CT chest was done to rule out primary cancer that revealed a 11 mm hypodense lesion in the left lobe of the thyroid and ultrasound-guided fine-needle aspiration biopsy confirmed it as papillary thyroid carcinoma. We should evaluate for multiple primary malignancies in young patients who are found to have primary index cancer.

  19. Association of Glioblastoma Multiforme Stem Cell Characteristics, Differentiation, and Microglia Marker Genes with Patient Survival

    Directory of Open Access Journals (Sweden)

    Sandra Bien-Möller

    2018-01-01

    Full Text Available Patients with glioblastoma multiforme (GBM are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin as well as differentiation and microglia markers (GFAP, Iba1, and Sparc in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed. At mRNA level, ABCG2 and CD95 were reduced, GFAP was unchanged; all other investigated markers were increased in GBM. At protein level, CD44, ELF4, Nanog, Nestin, and Sparc were elevated in GBM, but only CD133 and Nestin were strongly associated with survival time. In addition, ABCG2 and GFAP expression was decreased in LN18 neurospheres whereas CD44, CD95, CD133, ELF4, Nanog, Nestin, and Sparc were upregulated. Altogether only CD133 and Nestin were associated with survival rates. This raises concerns regarding the suitability of the other target structures as prognostic markers, but makes both CD133 and Nestin candidates for GBM therapy. Nevertheless, a search for more specific marker proteins is urgently needed.

  20. Glioblastoma multiforme subterfuge as acute cerebral hemorrhage: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Seidu A. Richard

    2018-04-01

    Full Text Available Hemorrhagic related Glioblastoma multiforme (GBM are rare and characterizes with severe clinical scuffle. The etiology of this presentation although not well known is believed to be multifactorial. We present a case as well as review on the pathogenesis of evolution of the hematoma into ring enhancing features of GBM on imaging studies. We present a case of 28 years old man who suddenly went into coma for 9 hours preceded with seizures that latest for 10 minutes. He had no focal neurological signs. CT-Scans images indicated acute cerebral hemorrhage near the frontal horn of the left ventricle with brain edema about the hemorrhagic lesion and MRI done a week later revealed a cerebral ring enhancing lesion. The lesion was partially resected during surgery and immunohistochemical staining confirmed GBM (WHO, grade 4. The diagnosis of intratumoral hemorrhage in GBM was very challenging at the initial stages but with time the hematoma evolved into ring enhancing images typical of GBM. It’s not every intracranial hematoma that is of pure vascular origin.

  1. A Pilot Safety Study of Lenalidomide and Radiotherapy for Patients With Newly Diagnosed Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Drappatz, Jan; Wong, Eric T.; Schiff, David; Kesari, Santosh; Batchelor, Tracy T.; Doherty, Lisa; LaFrankie, Debra Conrad; Ramakrishna, Naren; Weiss, Stephanie; Smith, Sharon T.; Ciampa, Abigail; Zimmerman, Jennifer; Ostrowsky, Louis; David, Karly; Norden, Andrew

    2009-01-01

    Purpose: To define the maximum tolerated dose (MTD) of lenalidomide, an analogue of thalidomide with enhanced immunomodulatory and antiangiogenic properties and a more favorable toxicity profile, in patients with newly diagnosed glioblastoma multiforme (GBM) when given concurrently with radiotherapy. Patients and Methods: Patients with newly diagnosed GBM received radiotherapy concurrently with lenalidomide given for 3 weeks followed by a 1-week rest period and continued lenalidomide until tumor progression or unacceptable toxicity. Dose escalation occurred in groups of 6. Determination of the MTD was based on toxicities during the first 12 weeks of therapy. The primary endpoint was toxicity. Results: Twenty-three patients were enrolled, of whom 20 were treated and evaluable for both toxicity and tumor response and 2 were evaluable for toxicity only. Common toxicities included venous thromboembolic disease, fatigue, and nausea. Dose-limiting toxicities were eosinophilic pneumonitis and transaminase elevations. The MTD for lenalidomide was determined to be 15 mg/m 2 /d. Conclusion: The recommended dose for lenalidomide with radiotherapy is 15 mg/m 2 /d for 3 weeks followed by a 1-week rest period. Venous thromboembolic complications occurred in 4 patients, and prophylactic anticoagulation should be considered

  2. Improved Outcomes with Intensity Modulated Radiation Therapy Combined with Temozolomide for Newly Diagnosed Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Noel J. Aherne

    2014-01-01

    Full Text Available Purpose. Glioblastoma multiforme (GBM is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months. We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

  3. Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

    Science.gov (United States)

    Aherne, Noel J; Benjamin, Linus C; Horsley, Patrick J; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M R; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S; Lee, Yvonne L; McKay, Michael J; Shakespeare, Thomas P

    2014-01-01

    Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

  4. The development of glioblastoma multiforme reactive monoclonal antibodies and their use in drug targeting

    International Nuclear Information System (INIS)

    Klaich, G.M.

    1989-01-01

    The objectives of this project were to develop monoclonal antibodies reactive with the tumor glioblastoma multiforme and to use them to study and develop new treatment modalities for this disease. A tumor antigen enriched immunogen, prepared by immunoaffinity chromatography, was compared to a whole tumor homogenate immunogen with the difference in the yield of tumor reactive, normal brain unreactive monoclonal antibodies proving to be significant. Monoclonal antibody A7, reactive with tumor tissue but unreactive with normal tissue, was isotyped to be an IgG2a immunoglobulin and could be purified to electrophoretic homogeneity by using serum-free culture conditions and protein A sepharose chromatography. Monoclonal antibody A7 is noncytotoxic as measured by the 3 H-nicotinamide release assay and binds to a 138 kd membrane antigen which is not internalized. Localization studies using 14 C-labeled monoclonal antibody A7 and the U-87 MG nude mouse xenograft model resulted in a tumor:serum ratio of 1.25:1.0 as compared to 0.29:1.0 for the negative control. A monoclonal antibody A7-doxorubicin immunoconjugate proved to be more cytotoxic than free doxorubicin in vitro while lethality studies using Swiss mice demonstrated the lack of toxicity of the immunoconjugate as compared to free doxorubicin. In vivo chemotherapy studies using the U-87 MG nude mouse xenograft failed to demonstrate any immunoconjugate anti-tumor activity which may be attributable to the route of administration

  5. Semi-automated segmentation of a glioblastoma multiforme on brain MR images for radiotherapy planning.

    Science.gov (United States)

    Hori, Daisuke; Katsuragawa, Shigehiko; Murakami, Ryuuji; Hirai, Toshinori

    2010-04-20

    We propose a computerized method for semi-automated segmentation of the gross tumor volume (GTV) of a glioblastoma multiforme (GBM) on brain MR images for radiotherapy planning (RTP). Three-dimensional (3D) MR images of 28 cases with a GBM were used in this study. First, a sphere volume of interest (VOI) including the GBM was selected by clicking a part of the GBM region in the 3D image. Then, the sphere VOI was transformed to a two-dimensional (2D) image by use of a spiral-scanning technique. We employed active contour models (ACM) to delineate an optimal outline of the GBM in the transformed 2D image. After inverse transform of the optimal outline to the 3D space, a morphological filter was applied to smooth the shape of the 3D segmented region. For evaluation of our computerized method, we compared the computer output with manually segmented regions, which were obtained by a therapeutic radiologist using a manual tracking method. In evaluating our segmentation method, we employed the Jaccard similarity coefficient (JSC) and the true segmentation coefficient (TSC) in volumes between the computer output and the manually segmented region. The mean and standard deviation of JSC and TSC were 74.2+/-9.8% and 84.1+/-7.1%, respectively. Our segmentation method provided a relatively accurate outline for GBM and would be useful for radiotherapy planning.

  6. Quality of Radiomic Features in Glioblastoma Multiforme: Impact of Semi-Automated Tumor Segmentation Software.

    Science.gov (United States)

    Lee, Myungeun; Woo, Boyeong; Kuo, Michael D; Jamshidi, Neema; Kim, Jong Hyo

    2017-01-01

    The purpose of this study was to evaluate the reliability and quality of radiomic features in glioblastoma multiforme (GBM) derived from tumor volumes obtained with semi-automated tumor segmentation software. MR images of 45 GBM patients (29 males, 16 females) were downloaded from The Cancer Imaging Archive, in which post-contrast T1-weighted imaging and fluid-attenuated inversion recovery MR sequences were used. Two raters independently segmented the tumors using two semi-automated segmentation tools (TumorPrism3D and 3D Slicer). Regions of interest corresponding to contrast-enhancing lesion, necrotic portions, and non-enhancing T2 high signal intensity component were segmented for each tumor. A total of 180 imaging features were extracted, and their quality was evaluated in terms of stability, normalized dynamic range (NDR), and redundancy, using intra-class correlation coefficients, cluster consensus, and Rand Statistic. Our study results showed that most of the radiomic features in GBM were highly stable. Over 90% of 180 features showed good stability (intra-class correlation coefficient [ICC] ≥ 0.8), whereas only 7 features were of poor stability (ICC NDR ≥1), while above 35% of the texture features showed poor NDR (software tools provided sufficiently reliable tumor segmentation and feature stability; thus helping to overcome the inherent inter-rater and intra-rater variability of user intervention. However, certain aspects of feature quality, including NDR and redundancy, need to be assessed for determination of representative signature features before further development of radiomics.

  7. Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme-A systematic review.

    Science.gov (United States)

    Mahajan-Thakur, Shailaja; Bien-Möller, Sandra; Marx, Sascha; Schroeder, Henry; Rauch, Bernhard H

    2017-11-17

    The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq, and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its receptors in GBM. We further highlight the current insights into the signaling pathways considered fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.

  8. Erythema multiforme-like eruption from a slimming drug preparation cutaneous adverse drug reaction

    Directory of Open Access Journals (Sweden)

    Linda Tognetti

    2011-01-01

    Full Text Available We report a case of a 34-year-old woman presenting with an erythema multiforme (EM-like eruption. Lesions developed after a 12-day treatment with a slimming drug preparation (food integrator with thermogenic activity and a herbal remedy (pilosella tincture. Serological investigations excluded viral or bacterial infections. Patch testing with galenic preparations of both drugs demonstrated sensitization to the slimming drug preparation. According to literature reports and immune-chemical properties, those components that are likely to have triggered the skin eruption are clorazepate dipotassium and theobromine. Their interaction with other two constituents such as pseudoephedrine hydrochloride and dehydrocholic acid may have caused the adverse reaction by means of a summation effect. There are no reports specifically about EM caused by a slimming drug preparation and no studies have identified thermogenic pills as cause of EM/EM-like eruption. Weight-loss compounds in slimming preparations should be kept in mind as a possible cause of drug-induced EM-like eruption.

  9. Short course of radiation therapy in elderly patients with multiform glioblastoma

    International Nuclear Information System (INIS)

    Idbaih, A.; Taillibert, S.; Simon, J.M.; Lopez, S.; Lang, P.; Toubiana, T.; Feuvret, L.; Mazeron, J.J.; Idbaih, A.; Taillibert, S.; Psimaras, D.; Delattre, J.Y.; Schneble, H.M.

    2008-01-01

    Purpose: The optimal schedule of irradiation in elderly patients suffering from glioblastoma multiform (G.B.M.) is unsettled. Materials and methods: This study reviewed the charts of 28 consecutive G.B.M. patients aged 70 years or more with a Karnofsky Performance Status (K.P.S.) greater than or equal to 70 who received a short course of radiotherapy (40 grays in 15 fractions over three weeks). Results: The median age at surgery was 74.6 years (range, 70.1 - 85.7). No patient received prior or concomitant chemotherapy. The median progression-free survival and overall survival were 21.6 weeks (95% CI, 17.0 - 39.9) and 50.6 weeks (95% CI, 26.3 - 62.0), respectively. Even within a narrow range (< 90 or = 90), K.P.S. remained a prognostic factor (p = 0.03). Tolerance appeared acceptable in terms of K.P.S. changes and corticosteroid use during radiation therapy. Conclusion: These results support the efficacy of short schedule radiotherapy for G.B.M. in elderly patients with a good K.P.S.. (authors)

  10. The PEP-3-KLH (CDX-110) vaccine in glioblastoma multiforme patients

    Science.gov (United States)

    Heimberger, Amy B.; Sampson, John H

    2009-01-01

    Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively resulting in non-specific toxicity. Immune targeting of tumor-specific mutations may allow for more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation that is widely expressed on GBM and other neoplasms and its expression enhances tumorigenicity. This in-frame deletion mutation splits a codon resulting in a novel glycine at the fusion junction producing a tumor-specific epitope target for cellular or humoral immunotherapy. We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction (PEPvIII-KLH/CDX-110) is an efficacious immunotherapy in syngeneic murine models. In this review, we summarize our results in GBM patients targeting this mutation in multiple, multi-institutional Phase II immunotherapy trials. These trials demonstrated that a selected population of GBM patients who received the vaccines targeting EGFRvIII had an unexpectedly long survival time. Further therapeutic strategies and potential pitfalls using this approach are discussed. PMID:19591631

  11. Can high-dose fotemustine reverse MGMT resistance in glioblastoma multiforme?

    Science.gov (United States)

    Gallo, Chiara; Buonerba, Carlo; Di Lorenzo, Giuseppe; Romeo, Valeria; De Placido, Sabino; Marinelli, Alfredo

    2010-11-01

    Glioblastoma multiforme (GBM), the highest grade malignant glioma, is associated with a grim prognosis-median overall survival is in the range 12-15 months, despite optimum treatment. Surgery to the maximum possible extent, external beam radiotherapy, and systemic temozolomide chemotherapy are current standard treatments for newly diagnosed GBM, with intracerebral delivery of carmustine wafers (Gliadel). Unfortunately, the effectiveness of chemotherapy can be hampered by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT), which confers resistance both to temozolomide and nitrosoureas, for example fotemustine and carmustine. MGMT activity can be measured by PCR and immunohistochemistry, with the former being the current validated technique. High-dose chemotherapy can deplete MGMT levels in GBM cells and has proved feasible in various trials on temozolomide, in both newly diagnosed and recurrent GBM. We here report the unique case of a GBM patient, with high MGMT expression by immunohistochemistry, who underwent an experimental, high-dose fotemustine schedule after surgery and radiotherapy. Although treatment caused two episodes of grade 3-4 thrombocytopenia, a complete response and survival of more than three years were achieved, with a 30% increase in dose intensity compared with the standard fotemustine schedule.

  12. Radiotherapy and chemotherapy with or without carbogen and nicotinamide in inoperable biopsy-proven glioblastoma multiforme

    International Nuclear Information System (INIS)

    Simon, Jean-Marc; Noeel, Georges; Chiras, Jacques; Khe, H.-X.; Delattre, Jean-Yves; Baillet, Francois; Mazeron, Jean-Jacques

    2003-01-01

    Background: Nicotinamide and carbogen have been shown to enhance the radiation effect in tumour models. Purpose: Prospective evaluation of the toxicity and efficacy of carbogen and nicotinamide with external beam radiotherapy in the management of inoperable glioblastoma. Patients and methods: From April 1995 to December 1997, 33 patients with inoperable biopsy-proven glioblastoma multiforme (GBM) were enrolled in a phase II trial, to undergo radiotherapy (59.4 Gy in 1.8 Gy/fraction), intra-arterial cerebral chemotherapy (ACNU 100 mg/m 2 , three cycles), carbogen breathing (15 l/min), and nicotinamide (85 mg/kg). This experimental group was compared to a control group of 38 patients with inoperable GBM treated with radiotherapy and three cycles of nitrosourea-based chemotherapy from January 1990 to March 1995, in our institution. Results: In the experimental group, carbogen breathing was well tolerated, but only 51.5% of patients completed daily nicotinamide over the 6.5-week treatment period. Nausea and vomiting were the most frequent side effects of nicotinamide. No significant difference in overall survival was observed among the two treatment groups: median survival times were 36.7 and 35.3 weeks for patients treated with carbogen and nicotinamide, and for those treated in the control group, respectively. Conclusion: The association of carbogen and nicotinamide with radiotherapy is feasible, but tolerable only in 51.5% of patients with GBM. Carbogen and nicotinamide did not appear to modify the evolution of glioblastoma

  13. Subcutaneous tissue metastasis from glioblastoma multiforme: A case report and review of the literature.

    Science.gov (United States)

    Frade Porto, Natalia; Delgado Fernández, Juan; García Pallero, María de Los Ángeles; Penanes Cuesta, Juan Ramón; Pulido Rivas, Paloma; Gil Simoes, Ricardo

    2018-05-16

    Glioblastoma multiforme is the most common primary brain tumor, despite an aggressive clinical course, less than 2% of patients develop extraneural metastasis. We present a 72-year-old male diagnosed with a right temporal glioblastoma due to headache. He underwent total gross resection surgery and after that the patient was treated with adyuvant therapy. Five months after the patient returned with trigeminal neuralgia, and MRI showed an infratemporal cranial mass which infiltrates masticator space, the surrounding bone, the temporal muscle and superior cervical and parotid lymph nodes. The patient underwent a new surgery reaching partial resection of the temporal lesion. After that the patient continued suffering from disabling trigeminal neuralgia, that's why because of the bad clinical situation and the treatment failure we decided to restrict therapeutic efforts. The patient died 3 weeks after the diagnosis of extracranial metastasis. Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Radiotherapy with concurrent or sequential temozolomide in elderly patients with glioblastoma multiforme

    International Nuclear Information System (INIS)

    Hashem, Sameh A.; Salem, Ahmed; Al-Rashdan, Abdulla

    2012-01-01

    The objective of this article was to evaluate therapeutic outcomes of elderly patients with glioblastoma multiforme (GBM) treated by surgery followed by combined modality therapy and compare achievable outcomes to those of a younger age population. Seventy-eight adult patients with histologically confirmed grade IV astrocytoma were treated at King Hussein Cancer Center (Amman, Jordan) between September 2004 and December 2008. Records were retrospectively reviewed and included 55 males and 23 females between 19 and 78 years of age (median age 50 years). This case series included 20 patients aged 60 years or older. All patients underwent craniotomy followed radiotherapy and concurrent or sequential temozolomide. The follow-up ranged from 1 to 56 months (median 9.4 months). The median survival for the whole cohort was 13.8 months. The median survival for patients less than 60 years was 14.3 months and for patients 60 years or older was 12.3 months (P = 0.19). Among elderly patients, radical surgical resection (P = 0.002), concurrent delivery of chemoradiation (0.041) and radiotherapy dose ≥5400 cGy (P = 0.0001) conferred statistically significant improvements in overall survival. Management of GBM in elderly patients should include maximal surgical resection followed by radiotherapy and temozolomide whenever medically feasible. Outcomes comparable to those obtained in younger age groups can be expected. Our results indicate that concurrent chemoradiation is superior to sequential chemoradiation in these patients.

  15. ORAL LESIONS OF DRUG INDUCED ERYTHEMA MULTIFORME and ndash; REPORT OF THREE CASES

    Directory of Open Access Journals (Sweden)

    Shruthi Hegde

    2013-09-01

    Full Text Available Abstract: Erythema multiforme (EM is an acute, self-limited, and sometimes recurring skin condition considered to be a hypersensitivity reaction associated with certain infections and medications. A range of medications can trigger the EM. Non-steroidal anti-inflammatory drugs (NSAIDS which are most commonly prescribed for pain relief can also produce rare adverse reactions such as EM. EM is clinically characterized by a and lsquo; and lsquo;minor'' form and a and lsquo; and lsquo;major'' form. Only few reports have stated about oral EM as the third variant of EM. However it is unclear whether EM involving only oral mucosa is a separate entity or is a part of minor form of EM. In this report three cases of EM are discussed , in which two cases involved exclusively oral mucosal lesions and in one case skin manifestations along with oral mucosa was observed. Also the uncommon adverse effects of NSAIDS is highlighted in this report along with its management. [J Contemp Med 2013; 3(3.000: 193-196

  16. Association of Glioblastoma Multiforme Stem Cell Characteristics, Differentiation, and Microglia Marker Genes with Patient Survival

    Science.gov (United States)

    Balz, Ellen; Herzog, Susann; Plantera, Laura; Vogelgesang, Silke; Seifert, Carolin; Bialke, Angela; Venugopal, Chitra; Singh, Sheila K.; Hoffmann, Wolfgang; Schroeder, Henry W. S.

    2018-01-01

    Patients with glioblastoma multiforme (GBM) are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs) are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin) as well as differentiation and microglia markers (GFAP, Iba1, and Sparc) in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed. At mRNA level, ABCG2 and CD95 were reduced, GFAP was unchanged; all other investigated markers were increased in GBM. At protein level, CD44, ELF4, Nanog, Nestin, and Sparc were elevated in GBM, but only CD133 and Nestin were strongly associated with survival time. In addition, ABCG2 and GFAP expression was decreased in LN18 neurospheres whereas CD44, CD95, CD133, ELF4, Nanog, Nestin, and Sparc were upregulated. Altogether only CD133 and Nestin were associated with survival rates. This raises concerns regarding the suitability of the other target structures as prognostic markers, but makes both CD133 and Nestin candidates for GBM therapy. Nevertheless, a search for more specific marker proteins is urgently needed. PMID:29535786

  17. Patterns of failure for glioblastoma multiforme following concurrent radiation and temozolomide

    International Nuclear Information System (INIS)

    Dobelbower, Michael C.; Burnett, Omer L. III; Haytt, Mark D.; Fiveash, John B.; Nordal, Robert A.; Nabors, Louis B.; Markert, James M.

    2011-01-01

    To analyse patterns of failure in patients with glioblastoma multiforme treated with concurrent radiation and temozolomide. A retrospective review of patients treated with concurrent radiation and temozolomide was performed. Twenty patients treated at the University of Alabama at Birmingham, with biopsy-proven disease, documented disease progression after treatment, and adequate radiation dosimetry and imaging records were included in the study. Patients generally received 46 Gy to the primary tumour and surrounding oedema plus 1 cm, and 60 Gy to the enhancing tumour plus 1 cm. MRIs documenting failure after therapy were fused to the original treatment plans. Contours of post-treatment tumour volumes were generated from MRIs showing tumour failure and were overlaid onto the original isodose curves. The recurrent tumours were classified as in-field, marginal or regional. Recurrences were also evaluated for distant failure. Of the 20 documented failures, all patients had some component of failure at the primary site. Eighteen patients (90%) failed in-field, 2 patients (10%) had marginal failures, and no regional failures occurred. Four patients (20%) had a component of distant failure in which an independent satellite lesion was located completely outside of the 95% isodose curve. Radiation concurrent with temozolomide appears to be associated with a moderate risk of distant brain failure in addition to the high rate of local failure. The risk of distant failure was consistent with that observed with radiation alone, suggesting that temozolomide does not act to reduce distant brain failure but to improve local control.

  18. In silico studies on marine actinomycetes as potential inhibitors for Glioblastoma multiforme

    Science.gov (United States)

    Kirubakaran, Palani; Kothapalli, Roopa; Singh, Kh Dhanachandra; Nagamani, Selvaraman; Arjunan, Subramanian; Muthusamy, Karthikeyan

    2011-01-01

    Glioblastoma multiforme (GBM) is considered to be the most common and often deadly disorder which affects the brain. It is caused by the over expression of proteins such as ephrin type-A receptor 2 (EphA2), epidermal growth factor receptor (EGFR) and EGFRvIII. These 3 proteins are considered to be the potential therapeutic targets for GBM. Among these, EphA2 is reported to be over-expressed in ˜90% of GBM. Herein we selected 35 compounds from marine actinomycetes, 5 in vitro and in vivo studied drug candidates and 4 commercially available drugs for GBM which were identified from literature and analysed by using comparative docking studies. Based on the glide scores and other in silico parameters available in Schrödinger, two selected marine actinomycetes compounds which include Tetracenomycin D and Chartreusin exhibited better binding energy among all the compounds studied in comparative docking. In this study we have demonstrated the inhibition of the 3 selected targets by the two bioactive compounds from marine actinomycetes through in-silico docking studies. Furthermore molecular dynamics simulation were also been performed to check the stability and the amino acids interacted with the 3 molecular targets (EphA2 receptor, EGFR, EGFRvIII) for GBM. Our results suggest that Tetracinomycin D and Chartreusin are the novel and potential inhibitor for the treatment of GBM. PMID:21584184

  19. ω-3 and ω-6 Fatty Acids Modulate Conventional and Atypical Protein Kinase C Activities in a Brain Fatty Acid Binding Protein Dependent Manner in Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Marwa E. Elsherbiny

    2018-04-01

    Full Text Available Glioblastoma multiforme (GBM is a highly infiltrative brain cancer with a dismal prognosis. High levels of brain fatty acid binding protein (B-FABP are associated with increased migration/infiltration in GBM cells, with a high ratio of arachidonic acid (AA to docosahexaenoic acid (DHA driving B-FABP-mediated migration. Since several protein kinase Cs (PKCs are overexpressed in GBM and linked to migration, we explored a possible relationship between B-FABP and levels/activity of different PKCs, as a function of AA and DHA supplementation. We report that ectopic expression of B-FABP in U87 cells alters the levels of several PKCs, particularly PKCζ. Upon analysis of PKCζ RNA levels in a panel of GBM cell lines and patient-derived GBM neurospheres, we observed a trend towards moderate positive correlation (r = 0.624, p = 0.054 between B-FABP and PKCζ RNA levels. Analysis of PKC activity in U87 GBM cells revealed decreased typical PKC activity (23.4% in B-FABP-expressing cells compared with nonexpressing cells, with no difference in novel and atypical PKC activities. AA and DHA modulated both conventional and atypical PKC activities in a B-FABP-dependent manner, but had no effect on novel PKC activity. These results suggest that conventional and atypical PKCs are potential downstream effectors of B-FABP/fatty acid-mediated alterations in GBM growth properties.

  20. Sustainable Solutions for Nuclear used Fuels Interim Storage

    International Nuclear Information System (INIS)

    Arslan, Marc; Favet, Dominique; Issard, Herve; Le Jemtel, Amaury; Drevon, Caroline

    2014-01-01

    AREVA has a unique experience in providing sustainable solutions for used fuel management, fitted with the needs of different customers in the world and with regulation in different countries. These solutions entail both recycling and interim storage technologies. In a first part, we will describe the various types of solutions for Interim Storage of UNF that have been implemented around the world for interim storage at reactor or centralized Pad solution in canisters dry storage, vault type storages for dry storage, dry storage of transportation casks (dual purpose) pools for wet storage, The experience for all these different families of interim storages in which AREVA is involved is extensive and will be discussed with respect to the new challenges: increase of the duration of the interim storage (long term interim storage) increase of burn up of the fuels In a second part of the presentation, special recycling features will be presented. In that case, interim storage of the used fuels is ensured in pools. This provides in the long term good conditions for the behaviour of the fuel and its retrievability. With recycling, the final waste (Universal Canister of vitrified fission products and compacted hulls and end pieces): is stable and licensed in many countries for the final disposal (France, UK, Belgium, NL, Switzerland, Germany, Japan, upcoming: Spain, Australia, Italy). Presents neither safety criticality risks nor proliferation risks (AREVA conditioned HLW and LL-ILW are free of IAEA safeguard constraints thanks to AREVA process high recovery and purification yields). It can therefore be safely stored in interim storage for more than 100 years before final disposal. Some economic considerations will also be discussed. In particular, in the case of long term interim storage of used fuels, there are growing uncertainties regarding the future needs of repackaging and transportation, which can result in future cost overruns. Meanwhile, in the recycling policy

  1. Retention of long-term interim restorations with sodium fluoride enriched interim cement

    Science.gov (United States)

    Strash, Carolyn

    Purpose: Interim fixed dental prostheses, or "provisional restorations", are fabricated to restore teeth when definitive prostheses are made indirectly. Patients undergoing extensive prosthodontic treatment frequently require provisionalization for several months or years. The ideal interim cement would retain the restoration for as long as needed and still allow for ease of removal. It would also avoid recurrent caries by preventing demineralization of tooth structure. This study aims to determine if adding sodium fluoride varnish to interim cement may assist in the retention of interim restorations. Materials and methods: stainless steel dies representing a crown preparation were fabricated. Provisional crowns were milled for the dies using CAD/CAM technology. Crowns were provisionally cemented onto the dies using TempBond NE and NexTemp provisional cements as well as a mixture of TempBond NE and Duraphat fluoride varnish. Samples were stored for 24h then tested or thermocycled for 2500 or 5000 cycles before being tested. Retentive strength of each cement was recorded using a universal testing machine. Results: TempBond NE and NexTemp cements performed similarly when tested after 24h. The addition of Duraphat significantly decreased the retention when added to TempBond NE. NexTemp cement had high variability in retention over all tested time periods. Thermocycling for 2500 and 5000 cycles significantly decreased the retention of all cements. Conclusions: The addition of Duraphat fluoride varnish significantly decreased the retention of TempBond NE and is therefore not recommended for clinical use. Thermocycling significantly reduced the retention of TempBond NE and NexTemp. This may suggest that use of these cements for three months, as simulated in this study, is not recommended.

  2. PROJECT W-551 INTERIM PRETREATMENT SYSTEM PRECONCEPTUAL CANDIDATE TECHNOLOGY DESCRIPTIONS

    Energy Technology Data Exchange (ETDEWEB)

    MAY TH

    2008-08-12

    The Office of River Protection (ORP) has authorized a study to recommend and select options for interim pretreatment of tank waste and support Waste Treatment Plant (WTP) low activity waste (LAW) operations prior to startup of all the WTP facilities. The Interim Pretreatment System (IPS) is to be a moderately sized system which separates entrained solids and 137Cs from tank waste for an interim time period while WTP high level waste vitrification and pretreatment facilities are completed. This study's objective is to prepare pre-conceptual technology descriptions that expand the technical detail for selected solid and cesium separation technologies. This revision includes information on additional feed tanks.

  3. Hierarchies of belief and interim rationalizability

    Directory of Open Access Journals (Sweden)

    Jeffrey C. Ely

    2006-03-01

    Full Text Available In games with incomplete information, conventional hierarchies of belief are incomplete as descriptions of the players' information for the purposes of determining a player's behavior. We show by example that this is true for a variety of solution concepts. We then investigate what is essential about a player's information to identify behavior. We specialize to two player games and the solution concept of interim rationalizability. We construct the universal type space for rationalizability and characterize the types in terms of their beliefs. Infinite hierarchies of beliefs over conditional beliefs, which we call Delta-hierarchies, are what turn out to matter. We show that any two types in any two type spaces have the same rationalizable sets in all games if and only if they have the same Delta-hierarchies.

  4. Interim report and accounts 1993/94

    International Nuclear Information System (INIS)

    1993-01-01

    An interim set of accounts and reports is presented here for 1993/1994 for the health science company Amersham International. The company's research programs focus on developments in life science research, nuclear medicine and industrial quality and safety assurance, with particular expertise in the application of radioactivity to labelling and detection at the molecular level. This report which covers the half-year to 30 September 1993 shows promising financial results, with turnover, operating profits and earnings per share all having risen. All life science markets report growth although difficult trading conditions are being reported in Europe. Two products in the Healthcare business have achieved progress, a pain palliation agent for bone metastases has been launched in the United States, and European approval has been gained for a new technetium based heart imaging agent. Further growth is expected for the company. (UK)

  5. Safety regulations for radioisotopes, etc. (interim report)

    International Nuclear Information System (INIS)

    1980-01-01

    An (interim) report by an ad hoc expert committee to the Nuclear Safety Commission, on the safety regulations for radioisotopes, etc., was presented. For the utilization of radioisotopes, etc., there is the Law Concerning Prevention of Radiation Injury Due to Radioisotopes, etc. with the advances in this field and the improvement in international standards, the regulations by the law have been examined. After explaining the basic ideas of the regulations, the problems and countermeasures in the current regulations are described: legal system, rationalization in permission procedures and others, inspection on RI management, the system of the persons in charge of radiation handling, RI transport, low-level radioactive wastes, consumer goods, definitions of RIs, radiation and sealed sources, regulations by group partitioning, RI facilities, system of personnel exposure registration, entrusting of inspection, etc. to private firms, and reduction in the works for permission among governmental offices. (author)

  6. Criticality safety evaluation for long term storage of FFTF fuel in interim storage casks

    International Nuclear Information System (INIS)

    Richard, R.F.

    1995-01-01

    It has been postulated that a degradation phenomenon, referred to as ''hot cell rot'', may affect irradiated FFTF mixed plutonium-uranium oxide (MOX) fuel during dry interim storage. ''Hot cell rot'' refers to a variety of phenomena that degrade fuel pin cladding during exposure to air and inert gas environments. It is thought to be a form of caustic stress corrosion cracking or environmentally assisted cracking. Here, a criticality safety analysis was performed to address the effect of the ''hot cell rot'' phenomenon on the long term storage of irradiated FFTF fuel in core component containers. The results show that seven FFTF fuel assemblies or six Ident-69 pin containers stored in core component containers within interim storage casks will remain safely subcritical

  7. FedEx Gasoline Hybrid Electric Delivery Truck Evaluation: 6-Month Interim Report

    Energy Technology Data Exchange (ETDEWEB)

    Barnitt, R.

    2010-05-01

    This interim report presents partial (six months) results for a technology evaluation of gasoline hybrid electric parcel delivery trucks operated by FedEx in and around Los Angeles, CA. A 12 month in-use technology evaluation comparing in-use fuel economy and maintenance costs of GHEVs and comparative diesel parcel delivery trucks was started in April 2009. Comparison data was collected and analyzed for in-use fuel economy and fuel costs, maintenance costs, total operating costs, and vehicle uptime. In addition, this interim report presents results of parcel delivery drive cycle collection and analysis activities as well as emissions and fuel economy results of chassis dynamometer testing of a gHEV and a comparative diesel truck at the National Renewable Energy Laboratory's (NREL) ReFUEL laboratory. A final report will be issued when 12 months of in-use data have been collected and analyzed.

  8. Functions and requirements document for interim store solidified high-level and transuranic waste

    Energy Technology Data Exchange (ETDEWEB)

    Smith-Fewell, M.A., Westinghouse Hanford

    1996-05-17

    The functions, requirements, interfaces, and architectures contained within the Functions and Requirements (F{ampersand}R) Document are based on the information currently contained within the TWRS Functions and Requirements database. The database also documents the set of technically defensible functions and requirements associated with the solidified waste interim storage mission.The F{ampersand}R Document provides a snapshot in time of the technical baseline for the project. The F{ampersand}R document is the product of functional analysis, requirements allocation and architectural structure definition. The technical baseline described in this document is traceable to the TWRS function 4.2.4.1, Interim Store Solidified Waste, and its related requirements, architecture, and interfaces.

  9. Interim Hanford Waste Management Technology Plan

    International Nuclear Information System (INIS)

    1985-09-01

    The Interim Hanford Waste Management Technology Plan (HWMTP) is a companion document to the Interim Hanford Waste Management Plan (HWMP). A reference plan for management and disposal of all existing and certain projected future radioactive Hanford Site Defense Wastes (HSDW) is described and discussed in the HWMP. Implementation of the reference plan requires that various open technical issues be satisfactorily resolved. The principal purpose of the HWMTP is to present detailed descriptions of the technology which must be developed to close each of the technical issues associated with the reference plan identified in the HWMP. If alternative plans are followed, however, technology development efforts including costs and schedules must be changed accordingly. Technical issues addressed in the HWMTP and HWMP are those which relate to disposal of single-shell tank wastes, contaminated soil sites, solid waste burial sites, double-shell tank wastes, encapsulated 137 CsCl and 90 SrF 2 , stored and new solid transuranic (TRU) wastes, and miscellaneous wastes such as contaminated sodium metal. Among the high priority issues to be resolved are characterization of various wastes including early determination of the TRU content of future cladding removal wastes; completion of development of vitrification (Hanford Waste Vitrification Plant) and grout technology; control of subsidence in buried waste sites; and development of criteria and standards including performance assessments of systems proposed for disposal of HSDW. Estimates of the technology costs shown in this report are made on the basis that all identified tasks for all issues associated with the reference disposal plan must be performed. Elimination of, consolidation of, or reduction in the scope of individual tasks will, of course, be reflected in corresponding reduction of overall technology costs

  10. CXCR4 expression varies significantly among different subtypes of glioblastoma multiforme (GBM) and its low expression or hypermethylation might predict favorable overall survival.

    Science.gov (United States)

    Ma, Xinlong; Shang, Feng; Zhu, Weidong; Lin, Qingtang

    2017-09-01

    CXCR4 is an oncogene in glioblastoma multiforme (GBM) but the mechanism of its dysregulation and its prognostic value in GBM have not been fully understood. Bioinformatic analysis was performed by using R2 and the UCSC Xena browser based on data from GSE16011 in GEO datasets and in GBM cohort in TCGA database (TCGA-GBM). Kaplan Meier curves of overall survival (OS) were generated to assess the association between CXCR4 expression/methylation and OS in patients with GBM. GBM patients with high CXCR4 expression had significantly worse 5 and 10 yrs OS (p GBM subtypes, there was an inverse relationship between overall DNA methylation and CXCR4 expression. CXCR4 expression was significantly lower in CpG island methylation phenotype (CIMP) group than in non CIMP group. Log rank test results showed that patients with high CXCR4 methylation (first tertile) had significantly better 5 yrs OS (p = 0.038). CXCR4 expression is regulated by DNA methylation in GBM and its low expression or hypermethylation might indicate favorable OS in GBM patients.

  11. Strategic Review of Medical Training and Career Structure Interim Report

    OpenAIRE

    Department of Health (Ireland)

    2013-01-01

    Click here to download Strategic Review of Medical Training and Career Structure Interim Report PDF 44kb Click here to download Strategic Review of Medical Training and Career Structure Terms of Reference PDF 59KB

  12. Fuel Supply Shutdown Facility Interim Operational Safety Requirements

    International Nuclear Information System (INIS)

    BENECKE, M.W.

    2000-01-01

    The Interim Operational Safety Requirements for the Fuel Supply Shutdown (FSS) Facility define acceptable conditions, safe boundaries, bases thereof, and management of administrative controls to ensure safe operation of the facility

  13. Interim research assessment 2003-2005 - Computer Science

    NARCIS (Netherlands)

    Mouthaan, A.J.; Hartel, Pieter H.

    This report primarily serves as a source of information for the 2007 Interim Research Assessment Committee for Computer Science at the three technical universities in the Netherlands. The report also provides information for others interested in our research activities.

  14. Interim Feed The Future Population Based Assessment of Cambodia

    Data.gov (United States)

    US Agency for International Development — This is the interim population based survey of Feed the Future in Cambodia for 2015. The data is split into survey modules. Modules A through C includes location...

  15. EPA's Revised Interim Financial Assistance Conflict of Interest Policy

    Science.gov (United States)

    EPA has established the following revised interim policy governing disclosure of actual and potential conflicts of interest (COI Policy) by applicants for, and recipients of, federal financial assistance awards from EPA.

  16. Interim report on long range plan for nuclear physics

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    The interim report on the updated NSAC Long Range Plan for Nuclear Physics will be presented to the community for discussion and comment before submission to the funding agencies. The presentation will be coordinated by E. Moniz chair of NSAC

  17. TWRS HLW interim storage facility search and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Calmus, R.B., Westinghouse Hanford

    1996-05-16

    The purpose of this study was to identify and provide an evaluation of interim storage facilities and potential facility locations for the vitrified high-level waste (HLW) from the Phase I demonstration plant and Phase II production plant. In addition, interim storage facilities for solidified separated radionuclides (Cesium and Technetium) generated during pretreatment of Phase I Low-Level Waste Vitrification Plant feed was evaluated.

  18. K basins interim remedial action health and safety plan

    Energy Technology Data Exchange (ETDEWEB)

    DAY, P.T.

    1999-09-14

    The K Basins Interim Remedial Action Health and Safety Plan addresses the requirements of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA), as they apply to the CERCLA work that will take place at the K East and K West Basins. The provisions of this plan become effective on the date the US Environmental Protection Agency issues the Record of Decision for the K Basins Interim Remedial Action, currently planned in late August 1999.

  19. Interim Report by Asia International Grid Connection Study Group

    Science.gov (United States)

    Omatsu, Ryo

    2018-01-01

    The Asia International Grid Connection Study Group Interim Report examines the feasibility of developing an international grid connection in Japan. The Group has investigated different cases of grid connections in Europe and conducted research on electricity markets in Northeast Asia, and identifies the barriers and challenges for developing an international grid network including Japan. This presentation introduces basic contents of the interim report by the Study Group.

  20. Materials behavior in interim storage of spent fuel

    International Nuclear Information System (INIS)

    Johnson, A.B. Jr.; Bailey, W.J.; Gilbert, E.R.; Inman, S.C.

    1982-01-01

    Interim storage has emerged as the only current spent-fuel management method in the US and is essential in all countries with nuclear reactors. Materials behavior is a key aspect in licensing interim-storage facilities for several decades of spent-fuel storage. This paper reviews materials behavior in wet storage, which is licensed for light-water reactor (LWR) fuel, and dry storage, for which a licensing position for LWR fuel is developing

  1. Interim Safety Basis for Fuel Supply Shutdown Facility

    International Nuclear Information System (INIS)

    BENECKE, M.W.

    2000-01-01

    This ISB, in conjunction with the IOSR, provides the required basis for interim operation or restrictions on interim operations and administrative controls for the facility until a SAR is prepared in accordance with the new requirements or the facility is shut down. It is concluded that the risks associated with tha current and anticipated mode of the facility, uranium disposition, clean up, and transition activities required for permanent closure, are within risk guidelines

  2. Phase I trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme.

    Science.gov (United States)

    Grossmann, Kenneth F; Colman, Howard; Akerley, Wallace A; Glantz, Michael; Matsuoko, Yuko; Beelen, Andrew P; Yu, Margaret; De Groot, John F; Aiken, Robert D; Olson, Jeffrey J; Olsen, Jeffery J; Evans, Brent A; Jensen, Randy L

    2012-11-01

    Verubulin (MPC-6827) is a microtubule-destabilizing agent that achieves high concentrations in the brain. Verubulin disrupts newly formed blood vessels in xenografts. We determined the safety and tolerability of verubulin administered in combination with carboplatin in patients with relapsed glioblastoma multiforme (GBM). Three pre-selected doses of verubulin were tested: 2.1, 2.7, and 3.3 mg/m(2) in a standard "3+3" design. Verubulin was given every second week of a 6-week cycle in the 2.1 mg/m(2) cohort or weekly for 3 weeks of a 4-week cycle in subsequent cohorts. Carboplatin was administered intravenously at an area under the curve (AUC) dosage 4 every 2 weeks for the 2.1 mg/m(2) cohort or on day 1 of each 4-week cycle in subsequent cohorts. Nineteen patients with GBM in first or second relapse were enrolled. Four patients (21 %) experienced a grade 3 or greater verubulin- or carboplatin-related adverse event, including hypesthesia, cerebral ischemia, anemia, and thrombocytopenia. The mean plasma half life of verubulin was 3.2 h (SD = 0.82). Two patients achieved at least a partial response by Macdonald criteria. One of these patients remains progression free and off treatment more than 24 months beyond his initiation of verubulin. Five patients had stable disease. Median progression-free survival (PFS) across all patients was 8 weeks, and the 6-month PFS rate was 21 %. The combination of verubulin at the previously determined single-agent maximum tolerated dose of 3.3 mg/m(2) with carboplatin in patients with recurrent/refractory GBM is safe and well tolerated. In this patient population with a highly vascularized tumor, no cerebral hemorrhage was observed.

  3. Acquired MET expression confers resistance to EGFR inhibition in a mouse model of glioblastoma multiforme.

    Science.gov (United States)

    Jun, H J; Acquaviva, J; Chi, D; Lessard, J; Zhu, H; Woolfenden, S; Bronson, R T; Pfannl, R; White, F; Housman, D E; Iyer, L; Whittaker, C A; Boskovitz, A; Raval, A; Charest, A

    2012-06-21

    Glioblastoma multiforme (GBM) is an aggressive brain tumor for which there is no cure. Overexpression of wild-type epidermal growth factor receptor (EGFR) and loss of the tumor suppressor genes Ink4a/Arf and PTEN are salient features of this deadly cancer. Surprisingly, targeted inhibition of EGFR has been clinically disappointing, demonstrating an innate ability for GBM to develop resistance. Efforts at modeling GBM in mice using wild-type EGFR have proven unsuccessful to date, hampering endeavors at understanding molecular mechanisms of therapeutic resistance. Here, we describe a unique genetically engineered mouse model of EGFR-driven gliomagenesis that uses a somatic conditional overexpression and chronic activation of wild-type EGFR in cooperation with deletions in the Ink4a/Arf and PTEN genes in adult brains. Using this model, we establish that chronic activation of wild-type EGFR with a ligand is necessary for generating tumors with histopathological and molecular characteristics of GBMs. We show that these GBMs are resistant to EGFR kinase inhibition and we define this resistance molecularly. Inhibition of EGFR kinase activity using tyrosine kinase inhibitors in GBM tumor cells generates a cytostatic response characterized by a cell cycle arrest, which is accompanied by a substantial change in global gene expression levels. We demonstrate that an important component of this pattern is the transcriptional activation of the MET receptor tyrosine kinase and that pharmacological inhibition of MET overcomes the resistance to EGFR inhibition in these cells. These findings provide important new insights into mechanisms of resistance to EGFR inhibition and suggest that inhibition of multiple targets will be necessary to provide therapeutic benefit for GBM patients.

  4. Human glioblastoma multiforme: p53 reactivation by a novel MDM2 inhibitor.

    Directory of Open Access Journals (Sweden)

    Barbara Costa

    Full Text Available Cancer development and chemo-resistance are often due to impaired functioning of the p53 tumor suppressor through genetic mutation or sequestration by other proteins. In glioblastoma multiforme (GBM, p53 availability is frequently reduced because it binds to the Murine Double Minute-2 (MDM2 oncoprotein, which accumulates at high concentrations in tumor cells. The use of MDM2 inhibitors that interfere with the binding of p53 and MDM2 has become a valid approach to inhibit cell growth in a number of cancers; however little is known about the efficacy of these inhibitors in GBM. We report that a new small-molecule inhibitor of MDM2 with a spirooxoindolepyrrolidine core structure, named ISA27, effectively reactivated p53 function and inhibited human GBM cell growth in vitro by inducing cell cycle arrest and apoptosis. In immunoincompetent BALB/c nude mice bearing a human GBM xenograft, the administration of ISA27 in vivo activated p53, inhibited cell proliferation and induced apoptosis in tumor tissue. Significantly, ISA27 was non-toxic in an in vitro normal human cell model and an in vivo mouse model. ISA27 administration in combination with temozolomide (TMZ produced a synergistic inhibitory effect on GBM cell viability in vitro, suggesting the possibility of lowering the dose of TMZ used in the treatment of GBM. In conclusion, our data show that ISA27 releases the powerful antitumor capacities of p53 in GBM cells. The use of this MDM2 inhibitor could become a novel therapy for the treatment of GBM patients.

  5. 23Na-MRI of recurrent glioblastoma multiforme after intraoperative radiotherapy: technical note

    International Nuclear Information System (INIS)

    Haneder, Stefan; Buesing, Karen A.; Schoenberg, Stefan O.; Ong, Melissa M.; Giordano, Frank A.; Wenz, Frederik; Konstandin, Simon; Schad, Lothar R.; Brehmer, Stefanie; Schmiedek, Peter

    2015-01-01

    We report the first case of an intraoperative radiotherapy (IORT) in a patient with recurrent glioblastoma multiforme (GBM) who was followed up with a novel magnetic resonance imaging (MRI) method - 23 Na-MRI - in comparison to a standard contrast-enhanced 1 H-MRI and 18 F-FET-PET. A 56-year-old female patient with diagnosed GBM in July 2012 underwent tumor resection, radiochemotherapy, and three cycles of chemotherapy. After a relapse, 6 months after the initial diagnosis, an IORT was recommended which was performed in March 2013 using the INTRABEAM system (Carl Zeiss Meditec AG, Germany) with a 3-cm applicator and a surface dose of 20 Gy. Early post-operative contrast-enhanced and 1-month follow-up 1 H-MRI and a 18 F-FET-PET were performed. In addition, an IRB-approved 23 Na-MRI was performed on a 3.0-T MR scanner (MAGNETOM TimTrio, Siemens Healthcare, Germany). After re-surgery and IORT in March 2013, only a faint contrast enhancement but considerable surrounding edema was visible at the medio-posterior resection margins. In April 2013, new and progressive contrast enhancement, edema, 23 Na content, and increased uptake in the 18 F-FET-PET were visible, indicating tumor recurrence. Increased sodium content within the area of contrast enhancement was found in the 23 Na-MRI, but also exceeding this area, very similar to the increased uptake depicted in the 18 F-FET-PET. The clearly delineable zone of edema in both examinations exhibits a lower 23 Na content compared to areas with suspected proliferating tumor tissue. 23 Na-MRI provided similar information in the suspicious area compared to 18 F-FET-PET, exceeding conventional 1 H-MRI. Still, 23 Na-MRI remains an investigational technique, which is worth to be further evaluated. (orig.)

  6. Phase I/II Trial of Hyperfractionated Concomitant Boost Proton Radiotherapy for Supratentorial Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Mizumoto, Masashi; Tsuboi, Koji; Igaki, Hiroshi; Yamamoto, Tetsuya; Takano, Shingo; Oshiro, Yoshiko; Hayashi, Yasutaka; Hashii, Haruko; Kanemoto, Ayae; Nakayama, Hidetsugu; Sugahara, Shinji; Sakurai, Hideyuki; Matsumura, Akira; Tokuuye, Koichi

    2010-01-01

    Purpose: To evaluate the safety and efficacy of postoperative hyperfractionated concomitant boost proton radiotherapy with nimustine hydrochloride for supratentorial glioblastoma multiforme (GBM). Methods and Materials: Twenty patients with histologically confirmed supratentorial GBM met the following criteria: (1) a Karnofsky performance status of ≥60; (2) the diameter of the enhanced area before radiotherapy was ≤40 cm; and (3) the enhanced area did not extend to the brain stem, hypothalamus, or thalamus. Magnetic resonance imaging (MRI) T 2 -weighted high area (clinical tumor volume 3 [CTV3]) was treated by x-ray radiotherapy in the morning (50.4 Gy in 28 fractions). More than 6 hours later, 250 MeV proton beams were delivered to the enhanced area plus a 10-mm margin (CTV2) in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume (CTV1) in the latter half (23.1 GyE in 14 fraction). The total dose to the CTV1 was 96.6 GyE. Nimustine hydrochloride (80 mg/m2) was administered during the first and fourth weeks. Results: Acute toxicity was mainly hematologic and was controllable. Late radiation necrosis and leukoencephalopathy were each seen in one patient. The overall survival rates after 1 and 2 years were 71.1% and 45.3%, respectively. The median survival period was 21.6 months. The 1- and 2-year progression-free survival rates were 45.0% and 15.5%, respectively. The median MRI change-free survival was 11.2 months. Conclusions: Hyperfractionated concomitant boost proton radiotherapy (96.6 GyE in 56 fractions) for GBM was tolerable and beneficial if the target size was well considered. Further studies are warranted to pursue the possibility of controlling border region recurrences.

  7. The addition of temozolomide does not change the pattern of progression glioblastoma multiforme post-radiotherapy

    International Nuclear Information System (INIS)

    Gunjur, Ashray; Bressel, Mathias; Ryan, Gail

    2012-01-01

    To determine whether the pattern of progressive disease (PD) for glioblastoma multiforme (GBM) patients has changed with the introduction of the current standard of care protocol – postoperative conformal radiotherapy to a dose of 60 Gray in 30 fractions with concurrent low-dose (75–100 mg/m 2 ) temozolomide, followed by six cycles of adjuvant high-dose (150–200 mg/m 2 ) temozolomide – as compared with radiotherapy alone. For GBM patients commencing combined modality treatment between October 2005 and August 2009, the MRI scan confirming progression (if any) was co-registered with the original planning CT scan, and progression site(s) marked. Coverage of the composite progression volume (PDvol) by the original 95% prescription isodose volume was obtained from dose-volume histogram (DVH) data, and assigned as ‘central’, ‘in field’, ‘marginal’ and ‘out of field’, corresponding to >95%, >80%, 20–80% and <20% coverage. Of 68 consecutive patients identified, 54 (79.4%) had documented PD. Of the 47 (87%) evaluable patients, 43 (91%) had in field progression with 36 (77%) of these being central. Of the remaining four cases, three (6%) had marginal progression, and only one patient (2%) had out of field progression. Median overall and progression-free survival were 11.6 and 6.6 months, respectively. The pattern of progression in our GBM patients does not appear to have been altered by the addition of temozolomide. The overwhelming majority of first PD occurred within the original radiotherapy planning target volume, as is the case in patients treated with radiotherapy alone. Major changes to radiotherapy volumes are not indicated, with alternative strategies required to improve outcomes.

  8. Quality of radiomic features in glioblastoma multiforme: Impact of semi-automated tumor segmentation software

    International Nuclear Information System (INIS)

    Lee, Myung Eun; Kim, Jong Hyo; Woo, Bo Yeong; Ko, Micheal D.; Jamshidi, Neema

    2017-01-01

    The purpose of this study was to evaluate the reliability and quality of radiomic features in glioblastoma multiforme (GBM) derived from tumor volumes obtained with semi-automated tumor segmentation software. MR images of 45 GBM patients (29 males, 16 females) were downloaded from The Cancer Imaging Archive, in which post-contrast T1-weighted imaging and fluid-attenuated inversion recovery MR sequences were used. Two raters independently segmented the tumors using two semi-automated segmentation tools (TumorPrism3D and 3D Slicer). Regions of interest corresponding to contrast-enhancing lesion, necrotic portions, and non-enhancing T2 high signal intensity component were segmented for each tumor. A total of 180 imaging features were extracted, and their quality was evaluated in terms of stability, normalized dynamic range (NDR), and redundancy, using intra-class correlation coefficients, cluster consensus, and Rand Statistic. Our study results showed that most of the radiomic features in GBM were highly stable. Over 90% of 180 features showed good stability (intra-class correlation coefficient [ICC] ≥ 0.8), whereas only 7 features were of poor stability (ICC NDR ≥1), while above 35% of the texture features showed poor NDR (< 1). Features were shown to cluster into only 5 groups, indicating that they were highly redundant. The use of semi-automated software tools provided sufficiently reliable tumor segmentation and feature stability; thus helping to overcome the inherent inter-rater and intra-rater variability of user intervention. However, certain aspects of feature quality, including NDR and redundancy, need to be assessed for determination of representative signature features before further development of radiomics

  9. Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide.

    Science.gov (United States)

    Topkan, Erkan; Selek, Ugur; Ozdemir, Yurday; Yildirim, Berna A; Guler, Ozan C; Ciner, Fuat; Mertsoylu, Huseyin; Tufan, Kadir

    2018-04-25

    To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS). Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP L and albumin > 35 g/L; GPS-1: CRP L and albumin L or CRP > 10 mg/L and albumin > 35 g/L; and GPS-2: CRP > 10 mg/L and albumin L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes. A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.

  10. Differential Radiosensitizing Potential of Temozolomide in MGMT Promoter Methylated Glioblastoma Multiforme Cell Lines

    International Nuclear Information System (INIS)

    Nifterik, Krista A. van; Berg, Jaap van den; Stalpers, Lukas J.A.; Lafleur, M. Vincent M.; Leenstra, Sieger; Slotman, Ben J.; Hulsebos, Theo J.M.; Sminia, Peter

    2007-01-01

    Purpose: To investigate the radiosensitizing potential of temozolomide (TMZ) for human glioblastoma multiforme (GBM) cell lines using single-dose and fractionated γ-irradiation. Methods and Materials: Three genetically characterized human GBM cell lines (AMC-3046, VU-109, and VU-122) were exposed to various single (0-6 Gy) and daily fractionated doses (2 Gy per fraction) of γ-irradiation. Repeated TMZ doses were given before and concurrent with irradiation treatment. Immediately plated clonogenic cell-survival curves were determined for both the single-dose and the fractionated irradiation experiments. To establish the net effect of clonogenic cell survival and cell proliferation, growth curves were determined, expressed as the number of surviving cells. Results: All three cell lines showed MGMT promoter methylation, lacked MGMT protein expression, and were sensitive to TMZ. The isotoxic TMZ concentrations used were in a clinically feasible range of 10 μmol/L (AMC-3046), 3 μmol/L (VU-109), and 2.5 μmol/L (VU-122). Temozolomide was able to radiosensitize two cell lines (AMC 3046 and VU-122) using single-dose irradiation. A reduction in the number of surviving cells after treatment with the combination of TMZ and fractionated irradiation was seen in all three cell lines, but only AMC 3046 showed a radiosensitizing effect. Conclusions: This study on TMZ-sensitive GBM cell lines shows that TMZ can act as a radiosensitizer and is at least additive to γ-irradiation. Enhancement of the radiation response by TMZ seems to be independent of the epigenetically silenced MGMT gene

  11. Glioblastoma multiforme in Klippel-Trenaunay-Weber syndrome: a case report.

    Science.gov (United States)

    Yilmaz, Tevfik; Cikla, Ulas; Kirst, Alice; Baskaya, Mustafa K

    2015-04-17

    Klippel-Trenaunay-Weber syndrome (KTWS) is a rare syndrome in which patients usually present with cutaneous hemangiomas, venous varicosities, and bone and soft tissue hypertrophy of the affected limb. Intracranial lesions in patients with KTWS are extremely rare, and are generally reported as single cases in the literature. We describe a rare case, where a patient with KTWS was found with a hemorrhagic grade IV astrocytoma. Although central nervous system abnormalities such as intracranial aneurysms and cerebral and spinal cord cavernomas have been described in patients with KTWS, to the best of our knowledge, this is the first report of an association between glioblastoma multiforme (grade IV astrocytoma) and KTWS in the English-language medical literature. A 61-year-old white Caucasian man with a history of KTWS presented with seizures. Left upper and lower extremity hypertrophy, left foot, leg and ear gigantism and left-sided abdominal capillary hemangiomas were noted in the physical examination. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) were obtained, showing a heterogeneous lesion in the cingulate gyrus, with peripheral and central areas of T1 hyperintensity and layering T2 hypointensity consistent with a hemorrhage. A right parasagittal frontal craniotomy was performed with an interhemispheric approach. We had difficulty controlling the bleeding with bipolar electrocautery during surgery and finally were able to stop the bleeding using surgicel and gelfoam. Postoperative cranial CT and MRI scans showed intraparenchymal hemorrhage centered within the medial right frontal lobe. There was no increase in hematoma size in consecutive CT scans. Co-occurrence of vascular abnormalities with KWTS should be taken into consideration to avoid perilous preoperative and postoperative complications.

  12. Quality of radiomic features in glioblastoma multiforme: Impact of semi-automated tumor segmentation software

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myung Eun; Kim, Jong Hyo [Center for Medical-IT Convergence Technology Research, Advanced Institutes of Convergence Technology, Seoul National University, Suwon (Korea, Republic of); Woo, Bo Yeong [Dept. of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon (Korea, Republic of); Ko, Micheal D.; Jamshidi, Neema [Dept. of Radiological Sciences, University of California, Los Angeles, Los Angeles (United States)

    2017-06-15

    The purpose of this study was to evaluate the reliability and quality of radiomic features in glioblastoma multiforme (GBM) derived from tumor volumes obtained with semi-automated tumor segmentation software. MR images of 45 GBM patients (29 males, 16 females) were downloaded from The Cancer Imaging Archive, in which post-contrast T1-weighted imaging and fluid-attenuated inversion recovery MR sequences were used. Two raters independently segmented the tumors using two semi-automated segmentation tools (TumorPrism3D and 3D Slicer). Regions of interest corresponding to contrast-enhancing lesion, necrotic portions, and non-enhancing T2 high signal intensity component were segmented for each tumor. A total of 180 imaging features were extracted, and their quality was evaluated in terms of stability, normalized dynamic range (NDR), and redundancy, using intra-class correlation coefficients, cluster consensus, and Rand Statistic. Our study results showed that most of the radiomic features in GBM were highly stable. Over 90% of 180 features showed good stability (intra-class correlation coefficient [ICC] ≥ 0.8), whereas only 7 features were of poor stability (ICC < 0.5). Most first order statistics and morphometric features showed moderate-to-high NDR (4 > NDR ≥1), while above 35% of the texture features showed poor NDR (< 1). Features were shown to cluster into only 5 groups, indicating that they were highly redundant. The use of semi-automated software tools provided sufficiently reliable tumor segmentation and feature stability; thus helping to overcome the inherent inter-rater and intra-rater variability of user intervention. However, certain aspects of feature quality, including NDR and redundancy, need to be assessed for determination of representative signature features before further development of radiomics.

  13. The suppression of manganese superoxide dismutase decreased the survival of human glioblastoma multiforme T98G cells

    Directory of Open Access Journals (Sweden)

    Novi S. Hardiany

    2017-05-01

    Full Text Available Background: Glioblastoma multiforme (GBM is a primary malignant brain tumor which has poor prognosis. High incidence of oxidative stress-based therapy resistance could be related to the high antioxidant status of GBM cells. Our previous study has reported that manganese superoxide dismutase (MnSOD antioxidant expression was significantly higher in high grade glioma than in low grade. The aim of this study was to analyze the impact of MnSOD suppression toward GBM cell survival.Methods: This study is an experimental study using human glioblastoma multiforme T98G cell line. Suppression of MnSOD expression was performed using in vitro transfection MnSOD-siRNA. The MnSOD expression was analyzed by measuring the mRNA using real time RT-PCR, protein using ELISA technique, and specific activity of enzyme using inhibition of xantine oxidase. Concentration of reactive oxygen species (ROS intracellular was determined by measuring superoxide radical and hydrogen peroxide. Cell survival was analyzed by measuring viability, proliferation, and cell apoptosis.Results: In vitro transfection of MnSOD-siRNA suppressed the mRNA, protein, and specific activity of MnSOD. This treatment significantly increased the concentration of superoxide radical; however, it did not influence the concentration of hydrogen peroxide. Moreover, viability MnSOD-suppressing cell significantly decreased, accompanied by increase of cell apoptosis without affecting cell proliferation.Conclusion: The suppression of MnSOD expression leads to decrease glioblastoma multiforme cell survival, which was associated to the increase of cell apoptotic.

  14. The “Great Masquerader" Strikes Again: Secondary Syphilis Presentation with Erythema Multiforme (EM-Like Lesions

    Directory of Open Access Journals (Sweden)

    Adi Brom

    2014-12-01

    Full Text Available Syphilis is a sexually transmitted disease known to present with highly variable manifestations, especially when left untreated. Patients who present to Internal Medicine Departments with fever and a rash are always a diagnostic challenge since mild viral diseases and life-threatening bacterial infections may manifest themselves similarly. In the following case presentation, we describe a patient with 1 month’s duration of fever and rash on the palms of the hand and soles of the feet, in the form of erythema multiforme (EM-like lesions. His disease was diagnosed as secondary syphilis, once again justifying its name: the “great masquerader".

  15. Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Eriksen, Jesper Grau; Broholm, Helle

    2010-01-01

    , hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan....... Of the 37 patients with available tumor tissue, 29 were evaluable for response. We concurrently performed immunohistochemical stainings on tumor tissue from 21 GBM patients treated with bevacizumab and irinotecan. We found a tendency of correlation between the hypoxia-related markers, indicating...

  16. Level of Notch activation determines the effect on growth and stem cell-like features in glioblastoma multiforme neurosphere cultures

    DEFF Research Database (Denmark)

    Kristoffersen, Karina; Villingshøj, Mette; Poulsen, Hans Skovgaard

    2013-01-01

    Brain cancer stem-like cells (bCSC) are cancer cells with neural stem cell (NSC)-like properties found in glioblastoma multiforme (GBM) and they are assigned a central role in tumor initiation, progression and relapse. The Notch pathway is important for maintenance and cell fate decisions...... in the normal NSC population. Notch signaling is often deregulated in GBM and recent results suggest that this pathway plays a significant role in bCSC as well. We therefore wished to further elucidate the role of Notch activation in GBM-derived bCSC....

  17. Treatment of newly diagnosed glioblastoma multiforme with carmustine, cisplatin and etoposide followed by radiotherapy. A phase II study

    DEFF Research Database (Denmark)

    Lassen, U; Kristjansen, P E; Wagner, A

    1999-01-01

    fractions. Twenty-nine patients with newly diagnosed glioblastoma multiforme (GBM), mean age 50 (27-66) and performance status (PS) 0-2 were included. Using the Macdonald criteria 33% had partial remission (PR), 41% stable disease (SD) and 26% progressive disease (PD) after chemotherapy. After additional...... (6.0-9.1) and median survival was 11.4 months (10.1-12.7). We conclude that this regimen is effective and feasible in patients with GBM. The short course pre-irradiatory chemotherapy may be less cumbersome than adjuvant chemotherapy and the regimen may be even more active in grade III gliomas....

  18. Transgenic nude mouse with green fluorescent protein expression-based human glioblastoma multiforme animal model with EGFR expression and invasiveness.

    Science.gov (United States)

    Tan, Guo-Wei; Lan, Fo-Lin; Gao, Jian-Guo; Jiang, Cai-Mou; Zhang, Yi; Huang, Xiao-Hong; Ma, Yue-Hong; Shao, He-Dui; He, Xue-Yang; Chen, Jin-Long; Long, Jian-Wu; Xiao, Hui-Sheng; Guo, Zhi-Tong; Diao, Yi

    2012-08-01

    Previously, we developed an orthotopic xenograft model of human glioblastoma multiforme (GBM) with high EGFR expression and invasiveness in Balb/c nu/nu nude mice. Now we also developed the same orthotopic xenograft model in transgenic nude mice with green fluorescent protein (GFP) expression. The present orthotopic xenografts labeled by phycoerythrin fluorescing red showed high EGFR expression profile, and invasive behavior under a bright green-red dual-color fluorescence background. A striking advantage in the present human GBM model is that the change of tumor growth can be observed visually instead of sacrificing animals in our further antitumor therapy studies.

  19. EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

    Science.gov (United States)

    Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

    2011-03-01

    Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

  20. Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme

    DEFF Research Database (Denmark)

    Hofland, Kenneth F; Hansen, Steinbjørn; Sorensen, Morten

    2014-01-01

    BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated...... from febrile neutropenia whereas non-hematological toxicity was manageable. CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS....

  1. Boron neutron capture therapy (BNCT) for glioblastoma multiforme using the epithermal neutron beam at the Brookhaven Medical Research Reactor

    International Nuclear Information System (INIS)

    Capala, J.; Diaz, A.Z.; Chadha, M.

    1997-01-01

    The abstract describes evaluation of boron neutron capture therapy (BNCT) for two groups of glioblastoma multiforme patients. From September 1994 to February 1996 15 patients have been treated. In September 1997 another 34 patients were examined. Authors determined a safe starting dose for BNCT using epithermal neutrons and BPA-F. They have also evaluated adverse effects of BNCT at this starting dose. Therapeutic effectiveness of this starting dose has been evaluated. No significant side effects from BPA-F infusion or BNCT treatment were observed in normal brains

  2. Prospective study evaluating the radiosensitizing effect of reduced doses of temozolomide in the treatment of Egyptian patients with glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Gaber M

    2013-10-01

    Full Text Available May Gaber, Hanan Selim, Tamer El-NahasDepartment of Clinical Oncology, Cairo University, Cairo, EgyptPurpose: In view of the documented toxicity of continuous daily radiosensitizer doses of temozolomide concomitant with radiation in the treatment of glioblastoma multiforme, we aimed to compare it with a different schedule of abbreviated radiosensitizer dosing.Patients and methods: This was a randomized prospective study comparing toxicity and survival in 60 Egyptian patients with glioblastoma multiforme. Patients in arm I received temozolomide at a dose of 75 mg/m2 daily with radiotherapy for 42 days, starting 4 weeks after surgery and reaching to a total radiation dose of 60 Gy/30 Fractions/6 weeks, while patients in arm II received temozolomide at a dose of 75 mg/m2 concomitantly with the same radiotherapy schedule daily in the first and last weeks of the same radiotherapy program.Results: Common grade 1–2 adverse events were malaise in 28 patients (46.7%, followed by alopecia (40% and nausea (26.7%. Grade 3–4 convulsion and decreased level of consciousness was seen in only four patients who were all from arm I. The median progression-free survival (PFS for the entire study population was 10.6 months (95% confidence interval [CI] 7.3–14, and PFS at 12 months was 32%. The median PFS in arm I was 8.8 months (95% CI 5.9–11.7 and in arm II 11.5 months (95% CI 8.9–14.2, and PFS at 12 months for both arms was 32% and 30% respectively (P=0.571. The median overall survival (OS of the whole group of patients was 14.2 months (95% CI 13–15.5, and OS was 70% at 12 months and 25% at 18 months. The median OS for patients in arm I was 12.3 months (95% CI 7.7–16.9, whereas in arm II it was 14.3 months (95% CI 14–14.7 (P=0.83.Conclusion: Reduced radiosensitizer dosing of temozolomide concomitant with radiotherapy in glioblastoma multiforme exhibited comparable efficacy with a classic continuous daily schedule, though with better tolerability

  3. Boron neutron capture therapy (BNCT) for glioblastoma multiforme using the epithermal neutron beam at the Brookhaven Medical Research Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Capala, J. [Brookhaven National Lab., Upton, NY (United States); Diaz, A.Z.; Chadha, M. [Univ. Hospital, State Univ. of New York, NY (United States)] [and others

    1997-12-31

    The abstract describes evaluation of boron neutron capture therapy (BNCT) for two groups of glioblastoma multiforme patients. From September 1994 to February 1996 15 patients have been treated. In September 1997 another 34 patients were examined. Authors determined a safe starting dose for BNCT using epithermal neutrons and BPA-F. They have also evaluated adverse effects of BNCT at this starting dose. Therapeutic effectiveness of this starting dose has been evaluated. No significant side effects from BPA-F infusion or BNCT treatment were observed in normal brains.

  4. A Procedure for Structural Weight Estimation of Single Stage to Orbit Launch Vehicles (Interim User's Manual)

    Science.gov (United States)

    Martinovic, Zoran N.; Cerro, Jeffrey A.

    2002-01-01

    This is an interim user's manual for current procedures used in the Vehicle Analysis Branch at NASA Langley Research Center, Hampton, Virginia, for launch vehicle structural subsystem weight estimation based on finite element modeling and structural analysis. The process is intended to complement traditional methods of conceptual and early preliminary structural design such as the application of empirical weight estimation or application of classical engineering design equations and criteria on one dimensional "line" models. Functions of two commercially available software codes are coupled together. Vehicle modeling and analysis are done using SDRC/I-DEAS, and structural sizing is performed with the Collier Research Corp. HyperSizer program.

  5. Application of NUREG/CR-5999 interim fatigue curves to selected nuclear power plant components

    International Nuclear Information System (INIS)

    Ware, A.G.; Morton, D.K.; Nitzel, M.E.

    1995-03-01

    Recent test data indicate that the effects of the light water reactor (LWR) environment could significantly reduce the fatigue resistance of materials used in the reactor coolant pressure boundary components of operating nuclear power plants. Argonne National Laboratory has developed interim fatigue curves based on test data simulating LWR conditions, and published them in NUREG/CR-5999. In order to assess the significance of these interim fatigue curves, fatigue evaluations of a sample of the components in the reactor coolant pressure boundary of LWRs were performed. The sample consists of components from facilities designed by each of the four U.S. nuclear steam supply system vendors. For each facility, six locations were studied, including two locations on the reactor pressure vessel. In addition, there are older vintage plants where components of the reactor coolant pressure boundary were designed to codes that did not require an explicit fatigue analysis of the components. In order to assess the fatigue resistance of the older vintage plants, an evaluation was also conducted on selected components of three of these plants. This report discusses the insights gained from the application of the interim fatigue curves to components of seven operating nuclear power plants

  6. Release of radionuclides following severe accident in interim storage facility. Source term determination

    International Nuclear Information System (INIS)

    Morandi, S.; Mariani, M.; Giacobbo, F.; Covini, R.

    2006-01-01

    Among the severe accidents that can cause the release of radionuclides from an interim storage facility, with a consequent relevant radiological impact on the population, there is the impact of an aircraft on the facility. In this work, a safety assessment analysis for the case of an aircraft crash into an interim storage facility is tackled. To this aim a methodology, based upon DOE, IAEA and NUREG standard procedures and upon conservative yet realistic hypothesis, has been developed in order to evaluate the total radioactivity, source term, released to the biosphere in consequence of the impact, without recurring to the use of complicated numerical codes. The procedure consists in the identification of the accidental scenarios, in the evaluation of the consequent damage to the building structures and to the waste packages and in the determination of the total release of radionuclides through the building-atmosphere interface. The methodology here developed has been applied to the case of an aircraft crash into an interim storage facility currently under design. Results show that in case of perforation followed by a fire incident the total released activity would be greater of some orders of magnitude with respect to the case of mere perforation. (author)

  7. An interim report on the Zenith Exponential Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Absalom, R M; Cameron, I R; Kinchin, G H; Sanders, J E; Wilson, D J [Atomic Energy Establishment, Winfrith, Dorchester, Dorset (United Kingdom)

    1959-06-15

    The following memorandum gives an interim account of the exponential experiments with Zenith-type fuel elements being carried out at Winfrith. Results quoted are still subject to revision: however it is hoped that the description of the work at this stage will stimulate discussion and suggestions for further measurements before the experiment is dismantled later in the year. The measurements are being undertaken in order to form some initial understanding of the reactor physics of uranium 235-thorium-graphite systems of the type later to be studied in Zenith. There have been no previous investigations of this type of system in the U.K. though measurements on enriched uranium-graphite systems have been reported from the U.S.A.. A practical result of the measurements will be a revision of the estimated critical loadings for Zenith, since the exponential systems studied cover the range of loadings proposed for the first critical assemblies. The theoretical work on these systems includes a two-group analysis being carried on in the Zenith group and a multigroup analysis being made by the H.T.G.C. Technical Assessments Group, including a Monte Carlo study of resonance capture.

  8. Immunotherapy for recurrent malignant glioma: an interim report on survival.

    Science.gov (United States)

    Ingram, M; Buckwalter, J G; Jacques, D B; Freshwater, D B; Abts, R M; Techy, G B; Miyagi, K; Shelden, C H; Rand, R W; English, L W

    1990-12-01

    We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.

  9. E-Area Performance Assessment Interim Measures Assessment FY2005

    Energy Technology Data Exchange (ETDEWEB)

    Stallings, M

    2006-01-31

    After major changes to the limits for various disposal units of the E-Area Low Level Waste Facility (ELLWF) last year, no major changes have been made during FY2005. A Special Analysis was completed which removes the air pathway {sup 14}C limit from the Intermediate Level Vault (ILV). This analysis will allow the disposal of reactor moderator deionizers which previously had no pathway to disposal. Several studies have also been completed providing groundwater transport input for future special analyses. During the past year, since Slit Trenches No.1 and No.2 were nearing volumetric capacity, they were operationally closed under a preliminary closure analysis. This analysis was performed using as-disposed conditions and data and showed that concrete rubble from the demolition of 232-F was acceptable for disposal in the STs even though the latest special analysis for the STs had reduced the tritium limits so that the inventory in the rubble exceeded limits. A number of special studies are planned during the next years; perhaps the largest of these will be revision of the Performance Assessment (PA) for the ELLWF. The revision will be accomplished by incorporating special analyses performed since the last PA revision as well as revising analyses to include new data. Projected impacts on disposal limits of more recent studies have been estimated. No interim measures will be applied during this year. However, it is being recommended that tritium disposals to the Components-in-Grout (CIG) Trenches be suspended until a limited Special Analysis (SA) currently in progress is completed. This SA will give recommendations for optimum placement of tritiated D-Area tower waste. Further recommendations for tritiated waste placement in the CIG Trenches will be given in the upcoming PA revision.

  10. Evaluation of ERA-Interim precipitation data in complex terrain

    Science.gov (United States)

    Gao, Lu; Bernhardt, Matthias; Schulz, Karsten

    2013-04-01

    Precipitation controls a large variety of environmental processes, which is an essential input parameter for land surface models e.g. in hydrology, ecology and climatology. However, rain gauge networks provides the necessary information, are commonly sparse in complex terrains, especially in high mountainous regions. Reanalysis products (e.g. ERA-40 and NCEP-NCAR) as surrogate data are increasing applied in the past years. Although they are improving forward, previous studies showed that these products should be objectively evaluated due to their various uncertainties. In this study, we evaluated the precipitation data from ERA-Interim, which is a latest reanalysis product developed by ECMWF. ERA-Interim daily total precipitation are compared with high resolution gridded observation dataset (E-OBS) at 0.25°×0.25° grids for the period 1979-2010 over central Alps (45.5-48°N, 6.25-11.5°E). Wet or dry day is defined using different threshold values (0.5mm, 1mm, 5mm, 10mm and 20mm). The correspondence ratio (CR) is applied for frequency comparison, which is the ratio of days when precipitation occurs in both ERA-Interim and E-OBS dataset. The result shows that ERA-Interim captures precipitation occurrence very well with a range of CR from 0.80 to 0.97 for 0.5mm to 20mm thresholds. However, the bias of intensity increases with rising thresholds. Mean absolute error (MAE) varies between 4.5 mm day-1 and 9.5 mm day-1 in wet days for whole area. In term of mean annual cycle, ERA-Interim almost has the same standard deviation of the interannual variability of daily precipitation with E-OBS, 1.0 mm day-1. Significant wet biases happened in ERA-Interim throughout warm season (May to August) and dry biases in cold season (November to February). The spatial distribution of mean annual daily precipitation shows that ERA-Interim significant underestimates precipitation intensity in high mountains and northern flank of Alpine chain from November to March while pronounced

  11. Interim main report of the safety assessment SR-Can

    Energy Technology Data Exchange (ETDEWEB)

    Hedin, Allan [and others

    2004-08-01

    This document is an interim report on the safety assessment SR-Can (SR in the acronym stands for Safety Report and Can is short for canister). The final SR-Can report will support SKB's application to build an Encapsulation plant for spent nuclear fuel and is to be produced in 2006. The purpose of the present interim report is to demonstrate the methodology for safety assessment so that it can be reviewed before it is used in a license application. The assessment relates to the KBS-3 disposal concept in which copper canisters with a cast iron insert containing spent nuclear fuel are surrounded by bentonite clay and deposited at approximately 500 m depth in saturated, granitic rock. Preliminary data from the Forsmark site, presently being investigated by SKB as one of the candidate for a KBS-3 repository are used to some extent as examples. However, the collected data are yet too sparse to allow an evaluation of safety for this site. An important aim of this report is to demonstrate the proper handling of requirements on the safety assessment in applicable regulations. Therefore, regulations issued by the Swedish Nuclear Power Inspectorate and the Swedish Radiation Protection Authority are duplicated in an Appendix. The principal acceptance criterion requires that 'the annual risk of harmful effects after closure does not exceed 10{sup -6} for a representative individual in the group exposed to the greatest risk'. 'Harmful effects' refer to cancer and hereditary effects. Following the introductory chapter 1, this report outlines the methodology for the SR-Can assessment in chapter 2, and presents in chapters 3, 4 and 5 the initial state of the system and the plans and methods for handling external influences and internal processes, respectively. Function indicators are introduced in chapter 6 and a preliminary evaluation of these is given in chapter 7. The material presented in the first seven chapters is utilised in the scenario selection in chapter 8

  12. Interim main report of the safety assessment SR-Can

    Energy Technology Data Exchange (ETDEWEB)

    Hedin, Allan (ed.) [and others

    2004-08-01

    This document is an interim report on the safety assessment SR-Can (SR in the acronym stands for Safety Report and Can is short for canister). The final SR-Can report will support SKB's application to build an Encapsulation plant for spent nuclear fuel and is to be produced in 2006. The purpose of the present interim report is to demonstrate the methodology for safety assessment so that it can be reviewed before it is used in a license application. The assessment relates to the KBS-3 disposal concept in which copper canisters with a cast iron insert containing spent nuclear fuel are surrounded by bentonite clay and deposited at approximately 500 m depth in saturated, granitic rock. Preliminary data from the Forsmark site, presently being investigated by SKB as one of the candidate for a KBS-3 repository are used to some extent as examples. However, the collected data are yet too sparse to allow an evaluation of safety for this site. An important aim of this report is to demonstrate the proper handling of requirements on the safety assessment in applicable regulations. Therefore, regulations issued by the Swedish Nuclear Power Inspectorate and the Swedish Radiation Protection Authority are duplicated in an Appendix. The principal acceptance criterion requires that 'the annual risk of harmful effects after closure does not exceed 10{sup -6} for a representative individual in the group exposed to the greatest risk'. 'Harmful effects' refer to cancer and hereditary effects. Following the introductory chapter 1, this report outlines the methodology for the SR-Can assessment in chapter 2, and presents in chapters 3, 4 and 5 the initial state of the system and the plans and methods for handling external influences and internal processes, respectively. Function indicators are introduced in chapter 6 and a preliminary evaluation of these is given in chapter 7. The material presented in the first seven chapters is utilised in the scenario selection

  13. Interim main report of the safety assessment SR-Can

    International Nuclear Information System (INIS)

    Hedin, Allan

    2004-08-01

    This document is an interim report on the safety assessment SR-Can (SR in the acronym stands for Safety Report and Can is short for canister). The final SR-Can report will support SKB's application to build an Encapsulation plant for spent nuclear fuel and is to be produced in 2006. The purpose of the present interim report is to demonstrate the methodology for safety assessment so that it can be reviewed before it is used in a license application. The assessment relates to the KBS-3 disposal concept in which copper canisters with a cast iron insert containing spent nuclear fuel are surrounded by bentonite clay and deposited at approximately 500 m depth in saturated, granitic rock. Preliminary data from the Forsmark site, presently being investigated by SKB as one of the candidate for a KBS-3 repository are used to some extent as examples. However, the collected data are yet too sparse to allow an evaluation of safety for this site. An important aim of this report is to demonstrate the proper handling of requirements on the safety assessment in applicable regulations. Therefore, regulations issued by the Swedish Nuclear Power Inspectorate and the Swedish Radiation Protection Authority are duplicated in an Appendix. The principal acceptance criterion requires that 'the annual risk of harmful effects after closure does not exceed 10 -6 for a representative individual in the group exposed to the greatest risk'. 'Harmful effects' refer to cancer and hereditary effects. Following the introductory chapter 1, this report outlines the methodology for the SR-Can assessment in chapter 2, and presents in chapters 3, 4 and 5 the initial state of the system and the plans and methods for handling external influences and internal processes, respectively. Function indicators are introduced in chapter 6 and a preliminary evaluation of these is given in chapter 7. The material presented in the first seven chapters is utilised in the scenario selection in chapter 8. Hydrogeological

  14. The EMEFS model evaluation. An interim report

    Energy Technology Data Exchange (ETDEWEB)

    Barchet, W.R. [Pacific Northwest Lab., Richland, WA (United States); Dennis, R.L. [Environmental Protection Agency, Research Triangle Park, NC (United States); Seilkop, S.K. [Analytical Sciences, Inc., Durham, NC (United States); Banic, C.M.; Davies, D.; Hoff, R.M.; Macdonald, A.M.; Mickle, R.E.; Padro, J.; Puckett, K. [Atmospheric Environment Service, Downsview, ON (Canada); Byun, D.; McHenry, J.N. [Computer Sciences Corp., Research Triangle Park, NC (United States); Karamchandani, P.; Venkatram, A. [ENSR Consulting and Engineering, Camarillo, CA (United States); Fung, C.; Misra, P.K. [Ontario Ministry of the Environment, Toronto, ON (Canada); Hansen, D.A. [Electric Power Research Inst., Palo Alto, CA (United States); Chang, J.S. [State Univ. of New York, Albany, NY (United States). Atmospheric Sciences Research Center

    1991-12-01

    The binational Eulerian Model Evaluation Field Study (EMEFS) consisted of several coordinated data gathering and model evaluation activities. In the EMEFS, data were collected by five air and precipitation monitoring networks between June 1988 and June 1990. Model evaluation is continuing. This interim report summarizes the progress made in the evaluation of the Regional Acid Deposition Model (RADM) and the Acid Deposition and Oxidant Model (ADOM) through the December 1990 completion of a State of Science and Technology report on model evaluation for the National Acid Precipitation Assessment Program (NAPAP). Because various assessment applications of RADM had to be evaluated for NAPAP, the report emphasizes the RADM component of the evaluation. A protocol for the evaluation was developed by the model evaluation team and defined the observed and predicted values to be used and the methods by which the observed and predicted values were to be compared. Scatter plots and time series of predicted and observed values were used to present the comparisons graphically. Difference statistics and correlations were used to quantify model performance. 64 refs., 34 figs., 6 tabs.

  15. Design criteria for the 200-ZP-1 interim remedial measure

    International Nuclear Information System (INIS)

    Mudge, J.F.; Olson, J.W.

    1995-08-01

    The Interim Remedial Measure Proposed Plan for the 200-ZP-1 Operable Unit recommended a pump and treat action to contain contaminated groundwater and limit further degradation of groundwater due to elevated concentrations of carbon tetrachloride, chloroform, and trichloroethylene in the 200-ZP-1 Operable Unit. This design criteria document defines the Project. The Project encompasses: site preparation; development of groundwater wells for monitoring, extraction, and injection; extraction and injection equipment; construction of a treatment system with support buildings/utilities; management; engineering design, analysis, and reporting; and operation and maintenance. A groundwater pump and treat system, hereafter the System, will be composed of extraction wells, a piping network, treatment equipment, water storage, and injection wells. Based upon engineering judgment, the selected technology in the proposed plan (DOE-RL 1994a) is air stripping of the organic contaminants followed by vapor-phase adsorption onto granulated activated carbon (GAC); liquid-phase GAC may be required as a polishing step. The Treatment Equipment refers to air stripping towers, adsorption vessels, water pumps, air blowers, instrumentation, and control devices which will be procured as a turn-key system

  16. Peer Review of the Waste Package Material Performance Interim Report

    International Nuclear Information System (INIS)

    J. A. Beavers; T. M. Devine, Jr.; G. S. Frankel; R. H. Jones; R. G. Kelly; R. M. Latanision; J. H. Payer

    2001-01-01

    At the request of the U.S. Department of Energy, Bechtel SAIC Company, LLC, formed the Waste Package Materials Performance Peer Review Panel (the Panel) to review the technical basis for evaluating the long-term performance of waste package materials in a proposed repository at Yucca Mountain, Nevada. This is the interim report of the Panel; a final report will be issued in February 2002. In its work to date, the Panel has identified important issues regarding waste package materials performance. In the remainder of its work, the Panel will address approaches and plans to resolve these issues. In its review to date, the Panel has not found a technical basis to conclude that the waste package materials are unsuitable for long-term containment at the proposed Yucca Mountain Repository. Nevertheless, significant technical issues remain unsettled and, primarily because of the extremely long life required for the waste packages, there will always be some uncertainty in the assessment. A significant base of scientific and engineering knowledge for assessing materials performance does exist and, therefore, the likelihood is great that uncertainty about the long-term performance can be substantially reduced through further experiments and analysis

  17. Immunohistochemically determined total epidermal growth factor receptor levels not of prognostic value in newly diagnosed glioblastoma multiforme: Report from the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Chakravarti, Arnab; Seiferheld, Wendy; Tu Xiaoyu; Wang Huijun; Zhang Huazhong; Ang, K. Kian; Hammond, Elizabeth; Curran, Walter; Mehta, Minesh

    2005-01-01

    Purpose: The Radiation Therapy Oncology Group (RTOG) performed an analysis of patterns of immunohistochemically detected total epidermal growth factor receptor (EGFR) protein expression levels and their prognostic significance on archival tissue in newly diagnosed glioblastoma multiforme (GBM) patients from prior prospective RTOG clinical trials. Methods and materials: Patients in this study had been treated on previous RTOG GBM trials (RTOG 7401, 7918, 8302, 8409, 9006, 9305, 9602, and 9806). Tissue microarrays were prepared from 155 patients enrolled in these trials. These specimens were stained using a mouse monoclonal antibody specific for the extracellular binding domain of EGFR to detect total EGFR (including both wild-type phosphorylated and wild-type unphosphorylated isoforms with some cross-reactivity with EGFRvIII). The intensity of total EGFR protein expression was measured by computerized quantitative image analysis using the SAMBA 4000 Cell Image Analysis System. The parameters measured were the mean optical densities over the labeled areas and the staining index, which represents the proportion of stained area relative to the mean stain concentration. Both parameters were correlated with the clinical outcome. Results: No differences in either overall or progression-free survival could be demonstrated by the mean optical density class or mean optical density quartile or the staining index of total EGFR immunostaining among the representative RTOG GBM cases. Conclusion: Total EGFR protein expression levels, as measured immunohistochemically, do not appear to be of prognostic value in newly diagnosed GBM patients. Given the accumulating clinical evidence of the activity of anti-EGFR agents in GBM and the preclinical data suggesting the important role of downstream mediators as effectors of EGFR signaling, the RTOG is conducting additional investigations into the prognostic value of activation patterns of EGFR signaling, both at the level of the receptor

  18. Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.

    Science.gov (United States)

    Moser, Joanna J; Fritzler, Marvin J; Rattner, Jerome B

    2014-01-01

    Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors. Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium. Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously

  19. {sup 23}Na-MRI of recurrent glioblastoma multiforme after intraoperative radiotherapy: technical note

    Energy Technology Data Exchange (ETDEWEB)

    Haneder, Stefan; Buesing, Karen A.; Schoenberg, Stefan O.; Ong, Melissa M. [Heidelberg University, Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Giordano, Frank A.; Wenz, Frederik [University of Heidelberg, Department of Radiation Oncology, University Medical Center Mannheim, Mannheim (Germany); Konstandin, Simon; Schad, Lothar R. [Heidelberg University, Computer Assisted Clinical Medicine, Mannheim (Germany); Brehmer, Stefanie; Schmiedek, Peter [Heidelberg University, Department of Neurosurgery, University Medical Center Mannheim, Mannheim (Germany)

    2015-03-01

    We report the first case of an intraoperative radiotherapy (IORT) in a patient with recurrent glioblastoma multiforme (GBM) who was followed up with a novel magnetic resonance imaging (MRI) method - {sup 23}Na-MRI - in comparison to a standard contrast-enhanced {sup 1}H-MRI and {sup 18}F-FET-PET. A 56-year-old female patient with diagnosed GBM in July 2012 underwent tumor resection, radiochemotherapy, and three cycles of chemotherapy. After a relapse, 6 months after the initial diagnosis, an IORT was recommended which was performed in March 2013 using the INTRABEAM system (Carl Zeiss Meditec AG, Germany) with a 3-cm applicator and a surface dose of 20 Gy. Early post-operative contrast-enhanced and 1-month follow-up {sup 1}H-MRI and a {sup 18}F-FET-PET were performed. In addition, an IRB-approved {sup 23}Na-MRI was performed on a 3.0-T MR scanner (MAGNETOM TimTrio, Siemens Healthcare, Germany). After re-surgery and IORT in March 2013, only a faint contrast enhancement but considerable surrounding edema was visible at the medio-posterior resection margins. In April 2013, new and progressive contrast enhancement, edema, {sup 23}Na content, and increased uptake in the {sup 18}F-FET-PET were visible, indicating tumor recurrence. Increased sodium content within the area of contrast enhancement was found in the {sup 23}Na-MRI, but also exceeding this area, very similar to the increased uptake depicted in the {sup 18}F-FET-PET. The clearly delineable zone of edema in both examinations exhibits a lower {sup 23}Na content compared to areas with suspected proliferating tumor tissue. {sup 23}Na-MRI provided similar information in the suspicious area compared to {sup 18}F-FET-PET, exceeding conventional {sup 1}H-MRI. Still, {sup 23}Na-MRI remains an investigational technique, which is worth to be further evaluated. (orig.)

  20. Feasibility of extreme dose escalation for glioblastoma multiforme using 4π radiotherapy

    International Nuclear Information System (INIS)

    Nguyen, Dan; Rwigema, Jean-Claude M; Yu, Victoria Y; Kaprealian, Tania; Kupelian, Patrick; Selch, Michael; Lee, Percy; Low, Daniel A; Sheng, Ke

    2014-01-01

    Glioblastoma multiforme (GBM) frequently recurs at the same location after radiotherapy. Further dose escalation using conventional methods is limited by normal tissue tolerance. 4π non-coplanar radiotherapy has recently emerged as a new potential method to deliver highly conformal radiation dose using the C-arm linacs. We aim to study the feasibility of very substantial GBM dose escalation while maintaining normal tissue tolerance using 4π. 11 GBM patients previously treated with volumetric modulated arc therapy (VMAT/RapidArc) on the NovalisTx™ platform to a prescription dose of either 59.4 Gy or 60 Gy were included. All patients were replanned with 30 non-coplanar beams using a 4π radiotherapy platform, which inverse optimizes both beam angles and fluence maps. Four different prescriptions were used including original prescription dose and PTV (4πPTV PD ), 100 Gy to the PTV and GTV (4πPTV 100Gy ), 100 Gy to the GTV only while maintaining prescription dose to the rest of the PTV (4πGTV 100Gy ), and a 5 mm margin expansion plan (4πPTV PD+5mm ). OARs included in the study are the normal brain (brain – PTV), brainstem, chiasm, spinal cord, eyes, lenses, optical nerves, and cochleae. The 4π plans resulted in superior dose gradient indices, as indicated by >20% reduction in the R50, compared to the clinical plans. Among all of the 4π cases, when compared to the clinical plans, the maximum and mean doses were significantly reduced (p < 0.05) by a range of 47.01-98.82% and 51.87-99.47%, respectively, or unchanged (p > 0.05) for all of the non-brain OARs. Both the 4πPTV PD and 4π GTV 100GY plans reduced the mean normal brain mean doses. 4π non-coplanar radiotherapy substantially increases the dose gradient outside of the PTV and better spares critical organs. Dose escalation to 100 Gy to the GTV or additional margin expansion while meeting clinical critical organ dose constraints is feasible. 100 Gy to the PTV result in higher normal brain doses but may

  1. The future role of personalized medicine in the treatment of glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Jing Li

    2010-08-01

    Full Text Available Jing Li1,2, Chunhui Di1,2, Austin K Mattox1,2, Linda Wu1,2, D Cory Adamson1,2,3,41Preston Robert Tisch Brain Tumor Center, Duke Medical Center, Durham, North Carolina, USA; 2Department of Surgery (Neurosurgery, Duke Medical Center, Durham, North Carolina, USA; 3Department of Neurobiology, Duke Medical Center, Durham, North Carolina, USA; 4Neurosurgery Section, Durham VA Medical Center, Durham, North Carolina, USAAbstract: Glioblastoma multiforme (GBM remains one of the most malignant primary central nervous system tumors. Personalized therapeutic approaches have not become standard of care for GBM, but science is fast approaching this goal. GBM’s heterogeneous genomic landscape and resistance to radiotherapy and chemotherapy make this tumor one of the most challenging to treat. Recent advances in genome-wide studies and genetic profiling show that there is unlikely to be a single genetic or cellular event that can be effectively targeted in all patients. Instead, future therapies will likely require personalization for each patient’s tumor genotype or proteomic profile. Over the past year, many investigations specifically focused simultaneously on strategies to target oncogenic pathways, angiogenesis, tumor immunology, epigenomic events, glioma stem cells (GSCs, and the highly migratory glioma cell population. Combination therapy targeting multiple pathways is becoming a fast growing area of research, and many studies put special attention on small molecule inhibitors. Because GBM is a highly vascular tumor, therapy that directs monoclonal antibodies or small molecule tyrosine kinase inhibitors toward angiogenic factors is also an area of focus for the development of new therapies. Passive, active, and adoptive immunotherapies have been explored by many studies recently, and epigenetic regulation of gene expression with microRNAs is also becoming an important area of study. GSCs can be useful targets to stop tumor recurrence and

  2. Industrial complementarities between interim storage and reversible geological repository - 59237

    International Nuclear Information System (INIS)

    Hoorelbeke, Jean-Michel

    2012-01-01

    The French Act voted in 2006 made the choice of deep geological disposal as the reference option for the long term management of high level (HLW) and intermediate level long-lived waste. The CIGEO repository project aims at avoiding or limiting burden to future generations, which could not be achieved by the extension in time of interim storage. The reversibility as provided by the Act will maintain a liberty of choice for waste management on a duration which is comparable to new storage facility. Interim storage is required to accommodate waste as long as the repository is not available. The commissioning of the repository in 2025 will not suppress needs for interim storage. The paper describes the complementarities between existing and future interim storage facilities and the repository project: repository operational issues and planning, HLW thermal decay, support for the reversibility, etc. It shows opportunities to prepare a global optimization of waste management including the utilization at best of storage capacities and the planning of waste emplacement in the repository in such a way to facilitate operational conditions and to limit cost. Preliminary simulations of storage-disposal scenarios are presented. Thanks to an optimal use of the waste management system, provision can be made for a progressive increase of waste emplacement flow during the first operation phase of the repository. It is then possible to stabilize the industrial activity level of the repository site. An optimal utilization of interim storage can also limit the diversity of waste packages emplaced simultaneously, which facilitates the operation of the repository. 60 years minimum interim storage duration is generally required with respect to HLW thermal output. Extending this interim storage period may reduce the underground footprint of the repository. Regarding reversibility, the capability to manage waste packages potentially retrieved from the repository should be analyzed. The

  3. Permitting plan for the high-level waste interim storage

    International Nuclear Information System (INIS)

    Deffenbaugh, M.L.

    1997-01-01

    This document addresses the environmental permitting requirements for the transportation and interim storage of solidified high-level waste (HLW) produced during Phase 1 of the Hanford Site privatization effort. Solidified HLW consists of canisters containing vitrified HLW (glass) and containers that hold cesium separated during low-level waste pretreatment. The glass canisters and cesium containers will be transported to the Canister Storage Building (CSB) in a U.S. Department of Energy (DOE)-provided transportation cask via diesel-powered tractor trailer. Tri-Party Agreement (TPA) Milestone M-90 establishes a new major milestone, and associated interim milestones and target dates, governing acquisition and/or modification of facilities necessary for: (1) interim storage of Tank Waste Remediation Systems (TWRS) immobilized HLW (IHLW) and other canistered high-level waste forms; and (2) interim storage and disposal of TWRS immobilized low-activity tank waste (ILAW). An environmental requirements checklist and narrative was developed to identify the permitting path forward for the HLW interim storage (HLWIS) project (See Appendix B). This permitting plan will follow the permitting logic developed in that checklist

  4. Next Generation Melter Optioneering Study - Interim Report

    International Nuclear Information System (INIS)

    Gray, M.F.; Calmus, R.B.; Ramsey, G.; Lomax, J.; Allen, H.

    2010-01-01

    The next generation melter (NOM) development program includes a down selection process to aid in determining the recommended vitrification technology to implement into the WTP at the first melter change-out which is scheduled for 2025. This optioneering study presents a structured value engineering process to establish and assess evaluation criteria that will be incorporated into the down selection process. This process establishes an evaluation framework that will be used progressively throughout the NGM program, and as such this interim report will be updated on a regular basis. The workshop objectives were achieved. In particular: (1) Consensus was reached with stakeholders and technology providers represented at the workshop regarding the need for a decision making process and the application of the D 2 0 process to NGM option evaluation. (2) A framework was established for applying the decision making process to technology development and evaluation between 2010 and 2013. (3) The criteria for the initial evaluation in 2011 were refined and agreed with stakeholders and technology providers. (4) The technology providers have the guidance required to produce data/information to support the next phase of the evaluation process. In some cases it may be necessary to reflect the data/information requirements and overall approach to the evaluation of technology options against specific criteria within updated Statements of Work for 2010-2011. Access to the WTP engineering data has been identified as being very important for option development and evaluation due to the interface issues for the NGM and surrounding plant. WRPS efforts are ongoing to establish precisely data that is required and how to resolve this Issue. It is intended to apply a similarly structured decision making process to the development and evaluation of LAW NGM options.

  5. Postoperative treatment of glioblastoma multiforme with radiation therapy plus concomitant and adjuvant temozolomide : A mono-institutional experience of 215 patients

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Julka

    2013-01-01

    Full Text Available Objective: To study the clinical results and prognostic factors of patients with glioblastoma multiforme (GBM treated by postoperative radiation therapy (PORT and concomitant temozolomide followed by adjuvant temozolomide. Methods: From 2005 to 2008, 215 patients (median age 48 years with GBM were treated with PORT plus temozolomide chemotherapy. Radiation therapy (RT was employed with a dose of 60 Gy in 30 fractions over 6 weeks by conventional fractionation with concomitant temozolomide (75 mg/m 2 /day. Adjuvant therapy consisted of 6 cycles of temozolomide (150 mg/m 2 for 5 days, 28 days cycle. The primary end point of the study was overall survival (OS, and the secondary end points were progression free survival (PFS and toxicity. OS was determined with respect to different variables to study the prognostic significance. Results: Median follow up was 11 months (range 2-50 months. Median OS and PFS were 13 months and 11 months respectively. The 1-year and 2-year OS was 44% and 18% respectively. There was no statistical significant impact of age, sex, KP score, anatomical location and extent of surgery. Presentation without seizures (on univariate analysis and 6 cycles of adjuvant temozolomide therapy (on univariate as well as multivariate analysis were found significant prognostic factors. Sixteen patients developed grade III-IV neutropenia/thrombocytopenia during the course of RT. Conclusion: Our results authenticate the role of concomitant and adjuvant temozolomide chemotherapy in combination with PORT for the management of GBM patients. We strongly recommend complete 6 cycle of adjuvant temozolomide since it significantly improved the survival in our study.

  6. Surface characterization of polymers used in fabrication of interim prostheses after treatment with photopolymerized glaze

    International Nuclear Information System (INIS)

    Santos, Daniela Micheline dos; Commar, Betina Chiarelo; Rocha Bonatto, Liliane da; Freitas da Silva, Emily Vivianne; Sônego, Mariana Vilela; Rangel, Elidiane Cipriano; Pesqueira, Aldieris Alves; Goiato, Marcelo Coelho

    2017-01-01

    The material used for interim prostheses fabrication must present excellent physical properties for greater longevity in the face of environmental conditions, which can occur in the oral cavity. The purpose of this study was to evaluate the effect of a photopolymerized glaze on the physical and mechanical properties of polymers used for the fabrication of interim prostheses, before and after thermocycling and immersion in staining solutions. One hundred samples of composite and acrylic resins were fabricated: Dencor chemically activated acrylic resin (CAAR) (n = 20) and heat-polymerized acrylic resin (HPAR) (n = 20), Charisma (n = 20), Structur (n = 20), and Protemp (n = 20). A mechanical polishing was performed on half of the samples, and a chemical polishing was performed on the remaining samples. Subsequently, all samples were submitted to thermocycling and immersion in coffee staining solution for 21 days. Analysis of color and microhardness, as well as atomic force microscopy (AFM), scanning electron microscopy (SEM), and energy dispersive x-ray spectrometry (EDS) were performed. The data were submitted to repeated-measures analysis of variance (ANOVA), followed by the Tukey test (α = 0.05) and the Student t-test (α = 0.05). It was verified that the glaze decreased the chromatic alteration values, and increased the microhardness values of the samples, with the exception of the Charisma resin. The samples that did not receive chemical polishing had the greatest number of surface irregularities. This study concluded that the groups with glaze presented less color alteration. In addition, Charisma and Structur resins exhibited the greatest chromatic stability. As to the microhardness, the values were greater when the samples were treated with the glaze, with the exception of the Charisma group. - Highlights: • Polymers used in fabrication of interim prostheses were analyzed. • The influence of a chemical polishing on these polymers was analyzed.

  7. Surface characterization of polymers used in fabrication of interim prostheses after treatment with photopolymerized glaze

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Daniela Micheline dos, E-mail: danielamicheline@foa.unesp.br [Department of Dental Materials and Prosthodontics, Aracatuba Dental School, Univ Estadual Paulista (UNESP), José Bonifácio St., 1193, Aracatuba, São Paulo 16015-050 (Brazil); Commar, Betina Chiarelo; Rocha Bonatto, Liliane da; Freitas da Silva, Emily Vivianne; Sônego, Mariana Vilela [Department of Dental Materials and Prosthodontics, Aracatuba Dental School, Univ Estadual Paulista (UNESP), José Bonifácio St., 1193, Aracatuba, São Paulo 16015-050 (Brazil); Rangel, Elidiane Cipriano [Technological Plasma Laboratory (LaPTec), Experimental Campus of Sorocaba, Univ Estadual Paulista (UNESP), Tres de Março Av., 511, Sorocaba, Sao Paulo, 18087-180 (Brazil); Pesqueira, Aldieris Alves; Goiato, Marcelo Coelho [Department of Dental Materials and Prosthodontics, Aracatuba Dental School, Univ Estadual Paulista (UNESP), José Bonifácio St., 1193, Aracatuba, São Paulo 16015-050 (Brazil)

    2017-02-01

    The material used for interim prostheses fabrication must present excellent physical properties for greater longevity in the face of environmental conditions, which can occur in the oral cavity. The purpose of this study was to evaluate the effect of a photopolymerized glaze on the physical and mechanical properties of polymers used for the fabrication of interim prostheses, before and after thermocycling and immersion in staining solutions. One hundred samples of composite and acrylic resins were fabricated: Dencor chemically activated acrylic resin (CAAR) (n = 20) and heat-polymerized acrylic resin (HPAR) (n = 20), Charisma (n = 20), Structur (n = 20), and Protemp (n = 20). A mechanical polishing was performed on half of the samples, and a chemical polishing was performed on the remaining samples. Subsequently, all samples were submitted to thermocycling and immersion in coffee staining solution for 21 days. Analysis of color and microhardness, as well as atomic force microscopy (AFM), scanning electron microscopy (SEM), and energy dispersive x-ray spectrometry (EDS) were performed. The data were submitted to repeated-measures analysis of variance (ANOVA), followed by the Tukey test (α = 0.05) and the Student t-test (α = 0.05). It was verified that the glaze decreased the chromatic alteration values, and increased the microhardness values of the samples, with the exception of the Charisma resin. The samples that did not receive chemical polishing had the greatest number of surface irregularities. This study concluded that the groups with glaze presented less color alteration. In addition, Charisma and Structur resins exhibited the greatest chromatic stability. As to the microhardness, the values were greater when the samples were treated with the glaze, with the exception of the Charisma group. - Highlights: • Polymers used in fabrication of interim prostheses were analyzed. • The influence of a chemical polishing on these polymers was analyzed.

  8. Interim process report for the safety assessment SR-Can

    International Nuclear Information System (INIS)

    Sellin, Patrick

    2004-08-01

    This report is a documentation of buffer processes identified as relevant to the long-term safety of a KBS-3 repository. The report is part of the interim reporting of the safety assessment SR-Can, see further the Interim main report. The final SR-Can reporting will support SKB's application to build an Encapsulation plant for spent nuclear fuel and is to be produced in 2006. The purpose of this report is to document the scientific knowledge of the processes to a level required for an adequate treatment in the safety assessment. The documentation is thus from a scientific point of not exhaustive since such a treatment is neither necessary for the purposes of the safety assessment nor possible within the scope of an assessment. The purpose is further to determine the handling of each process in the safety assessment and to demonstrate how uncertainties are taken care of, given the suggested handling. The process documentation in the SR 97 version of the Process report is a starting point for this SR-Can interim version. As further described in the Interim main report, the list of relevant processes has been reviewed and slightly extended by comparison to other databases. Furthermore, the backfill has been included as a system part of its own, rather than being described together with the buffer as in SR 97. Apart from giving an interim account of the documentation and handling of buffer processes in SR-Can, this report is meant to serve as a template for the forthcoming documentation of processes occurring in other parts of the repository system. A complete list of processes can be found in the Interim FEP report for the safety assessment SR-Can. All material presented in this document is preliminary in nature and will possibly be updated as the SR-Can project progresses

  9. Single-shell tank interim stabilization project plan

    Energy Technology Data Exchange (ETDEWEB)

    Ross, W.E.

    1998-03-27

    Solid and liquid radioactive waste continues to be stored in 149 single-shell tanks at the Hanford Site. To date, 119 tanks have had most of the pumpable liquid removed by interim stabilization. Thirty tanks remain to be stabilized. One of these tanks (C-106) will be stabilized by retrieval of the tank contents. The remaining 29 tanks will be interim stabilized by saltwell pumping. In the summer of 1997, the US Department of Energy (DOE) placed a moratorium on the startup of additional saltwell pumping systems because of funding constraints and proposed modifications to the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) milestones to the Washington State Department of Ecology (Ecology). In a letter dated February 10, 1998, Final Determination Pursuant to Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) in the Matter of the Disapproval of the DOE`s Change Control Form M-41-97-01 (Fitzsimmons 1998), Ecology disapproved the DOE Change Control Form M-41-97-01. In response, Fluor Daniel Hanford, Inc. (FDH) directed Lockheed Martin Hanford Corporation (LNMC) to initiate development of a project plan in a letter dated February 25, 1998, Direction for Development of an Aggressive Single-Shell Tank (SST) Interim Stabilization Completion Project Plan in Support of Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement). In a letter dated March 2, 1998, Request for an Aggressive Single-Shell Tank (SST) Interim Stabilization Completion Project Plan, the DOE reaffirmed the need for an aggressive SST interim stabilization completion project plan to support a finalized Tri-Party Agreement Milestone M-41 recovery plan. This project plan establishes the management framework for conduct of the TWRS Single-Shell Tank Interim Stabilization completion program. Specifically, this plan defines the mission needs and requirements; technical objectives and approach; organizational structure, roles, responsibilities

  10. Single-shell tank interim stabilization project plan

    International Nuclear Information System (INIS)

    Ross, W.E.

    1998-01-01

    Solid and liquid radioactive waste continues to be stored in 149 single-shell tanks at the Hanford Site. To date, 119 tanks have had most of the pumpable liquid removed by interim stabilization. Thirty tanks remain to be stabilized. One of these tanks (C-106) will be stabilized by retrieval of the tank contents. The remaining 29 tanks will be interim stabilized by saltwell pumping. In the summer of 1997, the US Department of Energy (DOE) placed a moratorium on the startup of additional saltwell pumping systems because of funding constraints and proposed modifications to the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) milestones to the Washington State Department of Ecology (Ecology). In a letter dated February 10, 1998, Final Determination Pursuant to Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) in the Matter of the Disapproval of the DOE's Change Control Form M-41-97-01 (Fitzsimmons 1998), Ecology disapproved the DOE Change Control Form M-41-97-01. In response, Fluor Daniel Hanford, Inc. (FDH) directed Lockheed Martin Hanford Corporation (LNMC) to initiate development of a project plan in a letter dated February 25, 1998, Direction for Development of an Aggressive Single-Shell Tank (SST) Interim Stabilization Completion Project Plan in Support of Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement). In a letter dated March 2, 1998, Request for an Aggressive Single-Shell Tank (SST) Interim Stabilization Completion Project Plan, the DOE reaffirmed the need for an aggressive SST interim stabilization completion project plan to support a finalized Tri-Party Agreement Milestone M-41 recovery plan. This project plan establishes the management framework for conduct of the TWRS Single-Shell Tank Interim Stabilization completion program. Specifically, this plan defines the mission needs and requirements; technical objectives and approach; organizational structure, roles, responsibilities

  11. Interim process report for the safety assessment SR-Can

    Energy Technology Data Exchange (ETDEWEB)

    Sellin, Patrick (ed.)

    2004-08-01

    This report is a documentation of buffer processes identified as relevant to the long-term safety of a KBS-3 repository. The report is part of the interim reporting of the safety assessment SR-Can, see further the Interim main report. The final SR-Can reporting will support SKB's application to build an Encapsulation plant for spent nuclear fuel and is to be produced in 2006. The purpose of this report is to document the scientific knowledge of the processes to a level required for an adequate treatment in the safety assessment. The documentation is thus from a scientific point of not exhaustive since such a treatment is neither necessary for the purposes of the safety assessment nor possible within the scope of an assessment. The purpose is further to determine the handling of each process in the safety assessment and to demonstrate how uncertainties are taken care of, given the suggested handling. The process documentation in the SR 97 version of the Process report is a starting point for this SR-Can interim version. As further described in the Interim main report, the list of relevant processes has been reviewed and slightly extended by comparison to other databases. Furthermore, the backfill has been included as a system part of its own, rather than being described together with the buffer as in SR 97. Apart from giving an interim account of the documentation and handling of buffer processes in SR-Can, this report is meant to serve as a template for the forthcoming documentation of processes occurring in other parts of the repository system. A complete list of processes can be found in the Interim FEP report for the safety assessment SR-Can. All material presented in this document is preliminary in nature and will possibly be updated as the SR-Can project progresses.

  12. 10 CFR 431.401 - Petitions for waiver, and applications for interim waiver, of test procedure.

    Science.gov (United States)

    2010-01-01

    ... Renewable Energy, U.S. Department of Energy. Each Application for Interim Waiver must reference the Petition... Renewable Energy. (e) Provisions specific to interim waivers—(1) Disposition of application. If... 10 Energy 3 2010-01-01 2010-01-01 false Petitions for waiver, and applications for interim waiver...

  13. 78 FR 67442 - Congestion Mitigation and Air Quality Improvement Program Interim Guidance

    Science.gov (United States)

    2013-11-12

    ...] Congestion Mitigation and Air Quality Improvement Program Interim Guidance AGENCY: Federal Highway... Comment. SUMMARY: The FHWA is issuing Interim Guidance on the Congestion Mitigation and Air Quality.../environment/air_quality/cmaq/policy_and_guidance/2008_guidance/ guidance/. DATES: This Interim Guidance is...

  14. Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Lin YL

    2015-09-01

    Full Text Available Yu-Ling Lin,1,2,* Kai-Fu Chang,3,* Xiao-Fan Huang,3 Che-Lun Hung,4 Shyh-Chang Chen,5 Wan-Ru Chao,6,7 Kuang-Wen Liao,1,8 Nu-Man Tsai3,9 1College of Biological Science and Technology, 2Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, 3School of Medical Laboratory and Biotechnology, Chung Shan Medical University, 4Department of Computer Science and Communication Engineering, Providence University, 5Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, 6Institute of Medicine, Chung Shan Medical University, 7Department of Pathology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, 8Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, 9Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan *These authors contributed equally to this work Background: The natural compound n-butylidenephthalide (BP can pass through the blood–brain barrier to inhibit the growth of glioblastoma multiforme tumors. However, BP has an unstable structure that reduces its antitumor activity and half-life in vivo.Objective: The aim of this study is to design a drug delivery system to encapsulate BP to enhance its efficacy by improving its protection and delivery.Methods: To protect its structural stability against protein-rich and peroxide solutions, BP was encapsulated into a lipo-PEG-PEI complex (LPPC. Then, the cytotoxicity of BP/LPPC following preincubation in protein-rich, acid/alkaline, and peroxide solutions was analyzed by MTT. Cell uptake of BP/LPPC was also measured by confocal microscopy. The therapeutic effects of BP/LPPC were analyzed in xenograft mice following intratumoral and intravenous injections.Results: When BP was encapsulated in LPPC, its cytotoxicity was maintained following preincubation in protein-rich, acid/alkaline, and peroxide solutions. The cytotoxic activity of encapsulated BP was higher than

  15. Interim safety basis for fuel supply shutdown facility

    International Nuclear Information System (INIS)

    Brehm, J.R.; Deobald, T.L.; Benecke, M.W.; Remaize, J.A.

    1995-01-01

    This ISB in conjunction with the new TSRs, will provide the required basis for interim operation or restrictions on interim operations and administrative controls for the Facility until a SAR is prepared in accordance with the new requirements. It is concluded that the risk associated with the current operational mode of the Facility, uranium closure, clean up, and transition activities required for permanent closure, are within Risk Acceptance Guidelines. The Facility is classified as a Moderate Hazard Facility because of the potential for an unmitigated fire associated with the uranium storage buildings

  16. Interim guidance risk assessment of the device assembly facility at the Nevada test site

    International Nuclear Information System (INIS)

    Altenbach, T.J.

    1996-05-01

    The risks of plutonium dispersal and/or high explosive detonation from nuclear explosive operations at the Device Assembly Facility were examined in accordance with DOE Order 5610.11 and the Interim Guidance. The assessment consisted of a qualitative task and hazards analysis, and a quantitative risk screening. Results are displayed on risk matrices for the major types of operations. Most accident scenarios were considered to have Low risk; a few scenarios have Moderate risk; and none have High risk. The highest risk scenarios (Moderate category) consist of a high explosive detonation during assembly operations in a cell, with bare conventional high explosive surrounding the pit

  17. Unit cell modeling in support of interim performance assessment for low level tank waste disposal

    International Nuclear Information System (INIS)

    Kline, N.W.

    1996-01-01

    A unit cell model is used to simulate the base analysis case and related sensitivity cases for the interim performance assessment of low level tank waste disposal. Simulation case results are summarized in terms of fractional contaminant release rates to the vadose zone and to the water table at the unconfined aquifer. Results suggest that the crushed glass water conditioning layer at the top of the facility and the chemical retardation pad at the bottom of the facility can be important components of the facility. Results also suggest that the release rates to the water table are dominated by the release rate from the waste form

  18. 2. interim report on radiation situation in Finland from 5 to 16 May 1986

    International Nuclear Information System (INIS)

    1986-05-01

    This second interim report is a continuation of the first 'Fallout situation in Finland from April 26 to May 4' STUK-B-VALO-44. It deals with the results from external radiation measurements and analysis of environmental and foodstuff samples between 5 and 16 May, i.e. the development of the situation after the fallout peak. The whole-body counter measurements of tourists returning from the Soviet Union and from other countries in Eastern Europe after the accident are also reported

  19. Systemic approaches identify a garlic-derived chemical, Z-ajoene, as a glioblastoma multiforme cancer stem cell-specific targeting agent.

    Science.gov (United States)

    Jung, Yuchae; Park, Heejoo; Zhao, Hui-Yuan; Jeon, Raok; Ryu, Jae-Ha; Kim, Woo-Young

    2014-07-01

    Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and TGFβ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

  20. 18F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas

    International Nuclear Information System (INIS)

    Hirata, Kenji; Shiga, Tohru; Tamaki, Nagara; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Yamaguchi, Shigeru; Houkin, Kiyohiro; Hattori, Naoya; Magota, Keiichi; Tanaka, Shinya; Kuge, Yuji

    2012-01-01

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that 18 F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and 18 F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p ≤ 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 ± 0.60, range 1.71-3.81) than in non-GBM patients (1.22 ± 0.06, range 1.09-1.29, p ≤ 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also higher in GBM

  1. {sup 18}F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Kenji; Shiga, Tohru; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki; Yamaguchi, Shigeru; Houkin, Kiyohiro [Graduate School of Medicine, Hokkaido University, Department of Neurosurgery, Sapporo (Japan); Hattori, Naoya [Graduate School of Medicine, Hokkaido University, Department of Molecular Imaging, Sapporo (Japan); Magota, Keiichi [Hokkaido University Hospital, Department of Radiology, Sapporo (Japan); Tanaka, Shinya [Graduate School of Medicine, Hokkaido University, Department of Cancer Pathology, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan)

    2012-05-15

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that {sup 18}F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and {sup 18}F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p {<=} 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 {+-} 0.60, range 1.71-3.81) than in non-GBM patients (1.22 {+-} 0.06, range 1.09-1.29, p {<=} 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also

  2. Multifuntional Nanotherapeutics for the Combinatorial Drug and Gene Therapy in the Treatment of Glioblastoma Multiforme

    Science.gov (United States)

    Hourigan, Breanne

    Glioblastoma multiforme (GBM), a grade IV glioma, is the most common primary brain tumor, affecting about 3 out of 100,000 persons per year in the United States. GBM accounts for about 80% of primary malignant brain tumors, and is also the most aggressive of malignant brain tumors. With exhaustive treatment, survival only averages between 12 and 15 months, with a 2-year survival rate less than 25%. New therapeutic strategies are necessary to improve the outcomes of this disease. Chemotherapy with temozolomide (TMZ), a DNA alkylating agent, is used as a first-line of treatment for GBM. However, GBM tumors develop resistance to TMZ over time due to increased expression of O6-methylguanine-DNA methyltransferase (MGMT), a gene responsible for DNA repair. We previously developed cationic, amphiphilic copolymer poly(lactide-co-glycolide)-g-polyethylenimine (PgP) and demonstrated its utility for nucleic acid delivery. Here, we examine the ability of PgP polyplexes to overcome TMZ resistance and improve therapeutic efficacy through combination drug and gene therapy for GBM treatment. In this study, we evaluated the ability of PgP to deliver siRNA targeting to MGMT (siMGMT), a gene responsible for drug resistance in GBM. Our results demonstrated that PgP effectively forms stable complex with siRNA and protects siRNAs from heparin competition assay, serum- and ribonuclease-mediated degradation, confirming the potential of the polyplex for in vivo delivery. Results from MTT assays showed that PgP/siRNA polyplexes exhibited minimal cytotoxicity compared to untreated cells when incubated with T98G human GBM cells. We also demonstrated that PgP/siMGMT polyplexes mediate knockdown of MGMT protein as well as a significant ˜56% and ˜68% knockdown of MGMT mRNA in T98G GBM cells compared to cells treated with PgP complexed with non-targeting siRNA (siNT) at a 60:1 and 80:1 nitrogen:phosphate (N:P) ratio, respectively. Further, co-incubation of PgP/siMGMT polyplexes with TMZ

  3. Subsurface Interim Measures/Interim Remedial Action Plan/ Environmental Assessment and Decision Document, Operable Unit No. 2

    International Nuclear Information System (INIS)

    1992-01-01

    The subject Interim Measures/Interim Remedial Action plan/Environmental Assessment (IM/IRAP/EA) addresses residual free-phase volatile organic compound (VOC) contamination suspected in the subsurface within an area identified as Operable Unit No. 2 (OU2). This IM/IRAP/EA also addresses radionuclide contamination beneath the 903 Pad at OU2. Although subsurface VOC and radionuclide contamination on represent a source of OU2 ground-water contamination, they pose no immediate threat to public health or the environment. This volume contains five appendices

  4. Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review

    DEFF Research Database (Denmark)

    Henriksson, Roger; Asklund, Thomas; Poulsen, Hans Skovgaard

    2011-01-01

    The maintenance of quality of life (QoL) in patients with high-grade glioma is an important endpoint during treatment, particularly in those with glioblastoma multiforme (GBM) given its dismal prognosis despite limited advances in standard therapy. It has proven difficult to identify new therapies...... that extend survival in patients with recurrent GBM, so one of the primary aims of new therapies is to reduce morbidity, restore or preserve neurologic functions, and the capacity to perform daily activities. Apart from temozolomide, cytotoxic chemotherapeutic agents do not appear to significantly impact...... response or survival, but produce toxicity that is likely to negatively impact QoL. New biological agents, such as bevacizumab, can induce a clinically meaningful proportion of durable responses among patients with recurrent GBM with an acceptable safety profile. Emerging evidence suggests that bevacizumab...

  5. Maintenance of EGFR and EGFRvIII expressions in an in vivo and in vitro model of human glioblastoma multiforme

    DEFF Research Database (Denmark)

    Stockhausen, Marie-Thérése; Broholm, Helle; Villingshøj, Mette

    2011-01-01

    Glioblastoma multiforme (GBM) is the most common, and most aggressive primary brain tumor among adults. A vast majority of the tumors express high levels of the epidermal growth factor receptor (EGFR) as a consequence of gene amplification. Furthermore, gene amplification is often associated...... with mutation of EGFR, and the constitutive activated deletion variant EGFRvIII is the most common EGFR mutation found in GBM. Activated EGFR signaling, through overexpression and/or mutation, is involved in increased tumorigenic potential. As such, EGFR is an attractive target for GBM therapy. However......, clinical studies with EGFR inhibitors have shown inconsistent results, and as such, further knowledge regarding the role of EGFR and EGFRvIII in GBM is needed. For this, an appropriate in vivo/in vitro tumor model is required. Here, we report the establishment of an experimental GBM model in which...

  6. Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Coderre, J.A.; Chanana, A.D.; Joel, D.D.; Liu, H.B.; Slatkin, D.N.; Wielopolski, L. [Brookhaven National Lab., Upton, NY (United States); Bergland, R.; Elowitz, E. [Beth Israel Medical Center, New York, NY (United States). Dept. of Neurosurgery; Chadha, M. [Beth Israel Medical Center, New York, NY (United States). Dept. of Radiation Oncology

    1994-12-31

    The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report.

  7. Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

    International Nuclear Information System (INIS)

    Coderre, J.A.; Chanana, A.D.; Joel, D.D.; Liu, H.B.; Slatkin, D.N.; Wielopolski, L.; Bergland, R.; Elowitz, E.; Chadha, M.

    1994-01-01

    The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report

  8. Bilateral posterior RION after concomitant radiochemotherapy with temozolomide in a patient with glioblastoma multiforme: a case report

    International Nuclear Information System (INIS)

    Schreiber, Stefanie; Prox-Vagedes, Vanessa; Elolf, Erck; Brueggemann, Ines; Gademann, Guenther; Galazky, Imke; Bartels, Claudius

    2010-01-01

    Radiation induced optic neuropathy (RION) is a rare but severe consequence of radiation therapy that is associated with adjuvant chemotherapy, specifically therapy with vincristine or nitrosoureas. However, there is very little evidence regarding the occurrence of RION after concomitant radiochemotherapy with temozolomide. The case of a 63 year old woman with glioblastoma multiforme and concomitant radiochemotherapy with temozolomide is described. Due to a slight depressive episode the patient also took hypericum perforatum. Five months after cessation of fractionated radiation and adjuvant chemotherapy with temozolomide (cumulative dose of 11040 mg) the patient developed bilateral amaurosis due to RION. Tumor regrowth was excluded by magnetic resonance imaging. After the application of gadolinium a pathognomonic contrast enhancement of both prechiasmatic optic nerves could be observed. In this patient, the occurrence of RION may have been the result of radiosensitization by temozolomide, which could have been strengthened by hypericin. Consequently, physicians should avoid a concomitant application of hypericum perforatum and radiochemotherapy

  9. The use of positron emission tomography in BNCT treatment planning for metastatic malignant melanoma and glioblastoma multiforme

    International Nuclear Information System (INIS)

    Kabalka, G.; Nichols, T.; Smith, G.; Miller, L.; Kahn, M.

    2000-01-01

    Positron emission tomography (PET) evaluations of six glioblastoma multiforme (GBM) and one metastatic melanoma (MM) patient have been carried out utilizing fluorine-18 labeled p-boronophenylalanine. Four of the GBM patients were imaged both prior to and post BNCT. In one GBM patient, biopsy derived boron distribution data compared favorably to the PET derived data. The PET data have been used as input to dosimetry calculations and the results vary from those obtained using current protocols. In addition, PET images of the thorax would indicate that the utility of PET for staging tumors for BNCT may extend beyond the brain. However, higher than anticipated levels of activity in the lungs (as also seen in salivary glands) indicate the more effective BNCT agents will be required. (author)

  10. International Peer Review of Swedish Nuclear Fuel and Waste Management Company's SR-Can interim report

    International Nuclear Information System (INIS)

    Sagar, Budhi; Bailey, Lucy; Bennett, David G.; Egan, Mike; Roehlig, Klaus

    2004-12-01

    demonstration (e.g. allocation of safety to different barrier functions and the role of dilution); Basis and methods for scenario selection and evaluation; Assessment of model framework for consequence analysis and compliance evaluation (e.g. justification of models, and parameters); Methods for biosphere modelling including the transition zone from basement rock to quaternary deposits and ecosystems; Methods for risk analysis, including the use of probabilistic methods, uncertainty and sensitivity analysis, estimation of probabilities, averaging of risk; and Quality assurance measures including handling of expert judgments. Among its conclusions, the IRT considers that the SR-Can Interim Report describes a logical methodology for undertaking a safety assessment that could be used as a component of a safety case to support a licence application. SKB's assessment methodology also includes some innovative and positive components, such as the use of safety function indicators and analytical models. From the IRT's perspective, the main deficiencies in SKB's programme and approach relate less to the methodology and more to the rigour with which safety assessment needs to be conducted to support a formal licence application. There are a number of areas, for example in the development of scenarios and in the management and treatment of uncertainty, where current evidence suggests a need for greater clarity and traceability. More generally, it is recommended that SKB should ensure that all aspects of the safety assessment are conducted in accordance with auditable project-specific guidance and QA procedures. In view of the above, and the fact that SKB has acknowledged that some further development work remains to be done, the IRT believes that it could be a challenge for SKB to conduct and present a safety assessment of suitable quality within the currently proposed timescale for delivery of the SR-Can assessment and the 2006 licence application

  11. Safety report for Central Interim Storage facility for radioactive waste from small producers

    International Nuclear Information System (INIS)

    Zeleznik, N.; Mele, I.

    2004-01-01

    protection and remediation of minor defects in the facility. The safety report also incorporates the implementation projects for the inventory rearrangement and the projected waste quantities up to 2013, when the LILW repository should be available. The most important part of the safety report deals with safety analyses of all relevant operational conditions which could influence safety of the storage and its inventory, taking into account also the phase of reconstruction works. The Safety Report is prepared in accordance with the requirements of Regulation E2 (Pravilnik E2) and The Act on Ionising Radiation Protection and Nuclear Safety from 2002. After defining the objective of the safety report, the chapters deal with the following topics: The safety approach to the LILW storage, Description and location analysis of the Central interim storage, Technical characteristic of the Central interim storage, Safety analysis of the Central interim storage, Organizational measures for construction and pre-operational testing, Organizational measures for commissioning and normal operation of the Central interim storage, Operational conditions and limitations, Ionizing radiation protection service, its methods and equipment, Radioactive waste management and disposal, Review of the plans, measures and procedures to prevent radiological accidents, Quality assurance programme, Review of the measures for physical protection of the LILW storage and stored radioactive waste, Planned measures and necessary equipment for closure of the Central interim storage. The details on preparation of the Safety report, including the dilemmas and comments on different chapters, are presented in this paper. The most important findings of the safety analysis are also given.(author)

  12. Dose-escalated intensity-modulated radiotherapy and irradiation of subventricular zones in relation to tumor control outcomes of patients with glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Kusumawidjaja G

    2016-03-01

    Full Text Available Grace Kusumawidjaja,1 Patricia Zhun Hong Gan,1 Whee Sze Ong,2 Achiraya Teyateeti,3 Pittaya Dankulchai,3 Daniel Yat Harn Tan,1 Eu Tiong Chua,1 Kevin Lee Min Chua,1 Chee Kian Tham,4 Fuh Yong Wong,1 Melvin Lee Kiang Chua1,5 1Division of Radiation Oncology, National Cancer Centre, Singapore; 2Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore; 3Department of Radiology, Division of Radiation Oncology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand; 4Division of Medical Oncology, National Cancer Centre, Singapore; 5Duke-NUS Graduate Medical School, Singapore Background: Glioblastoma multiforme (GBM is the most aggressive primary brain tumor with high relapse rate. In this study, we aimed to determine if dose-escalated (DE radiotherapy improved tumor control and survival in GBM patients. Methods: We conducted a retrospective analysis of 49 and 23 newly-diagnosed histology-proven GBM patients, treated with DE radiotherapy delivered in 70 Gy (2.33 Gy per fraction and conventional doses (60 Gy, respectively, between 2007 and 2013. Clinical target volumes for 70 and 60 Gy were defined by 0.5 and 2.0 cm expansion of magnetic resonance imaging T1-gadolinium-enhanced tumor/surgical cavity, respectively. Bilateral subventricular zones (SVZ were contoured on a co-registered pre-treatment magnetic resonance imaging and planning computed tomography dataset as a 5 mm wide structure along the lateral margins of the lateral ventricles. Survival outcomes of both cohorts were compared using log-rank test. Radiation dose to SVZ in the DE cohort was evaluated. Results: Median follow-up was 13.6 and 15.1 months for the DE- and conventionally-treated cohorts, respectively. Median overall survival (OS of patients who received DE radiotherapy was 15.2 months (95% confidence interval [CI] =11.0–18.6, while median OS of the latter cohort was 18.4 months (95% CI =12.5–31.4, P=0.253. Univariate analyses of

  13. Connection between cell phone use, p53 gene expression in different zones of glioblastoma multiforme and survival prognoses

    Directory of Open Access Journals (Sweden)

    Reza Akhavan-Sigari

    2014-08-01

    Full Text Available The aim of this paper is to investigate p53 gene expression in the central and peripheral zones of glioblastoma multiforme using a real-time reverse transcription polymerase chain reaction (RT-PCR technique in patients who use cell phones ≥3 hours a day and determine its relationship to clinicopathological findings and overall survival. Sixty-three patients (38 males and 25 females, diagnosed with glioblastoma multiforme (GBM, underwent tumor resection between 2008 and 2011. Patient ages ranged from 25 to 88 years, with a mean age of 55. The levels of expression of p53 in the central and peripheral zone of the GBM were quantified by RT-PCR. Data on p53 gene expression from the central and peripheral zone, the related malignancy and the clinicopatholagical findings (age, gender, tumor location and size, as well as overall survival, were analyzed. Forty-one out of 63 patients (65% with the highest level of cell phone use (≥3 hours/day had higher mutant type p53 expression in the peripheral zone of the glioblastoma; the difference was statistically significant (P=0.034. Results from the present study on the use of mobile phones for ≥3 hours a day show a consistent pattern of increased risk for the mutant type of p53 gene expression in the peripheral zone of the glioblastoma, and that this increase was significantly correlated with shorter overall survival time. The risk was not higher for ipsilateral exposure. We found that the mutant type of p53 gene expression in the peripheral zone of the glioblastoma was increased in 65% of patients using cell phones ≥3 hours a day.

  14. Basis for Interim Operation for Fuel Supply Shutdown Facility

    International Nuclear Information System (INIS)

    BENECKE, M.W.

    2003-01-01

    This document establishes the Basis for Interim Operation (BIO) for the Fuel Supply Shutdown Facility (FSS) as managed by the 300 Area Deactivation Project (300 ADP) organization in accordance with the requirements of the Project Hanford Management Contract procedure (PHMC) HNF-PRO-700, ''Safety Analysis and Technical Safety Requirements''. A hazard classification (Benecke 2003a) has been prepared for the facility in accordance with DOE-STD-1027-92 resulting in the assignment of Hazard Category 3 for FSS Facility buildings that store N Reactor fuel materials (303-B, 3712, and 3716). All others are designated Industrial buildings. It is concluded that the risks associated with the current and planned operational mode of the FSS Facility (uranium storage, uranium repackaging and shipment, cleanup, and transition activities, etc.) are acceptable. The potential radiological dose and toxicological consequences for a range of credible uranium storage building have been analyzed using Hanford accepted methods. Risk Class designations are summarized for representative events in Table 1.6-1. Mitigation was not considered for any event except the random fire event that exceeds predicted consequences based on existing source and combustible loading because of an inadvertent increase in combustible loading. For that event, a housekeeping program to manage transient combustibles is credited to reduce the probability. An additional administrative control is established to protect assumptions regarding source term by limiting inventories of fuel and combustible materials. Another is established to maintain the criticality safety program. Additional defense-in-depth controls are established to perform fire protection system testing, inspection, and maintenance to ensure predicted availability of those systems, and to maintain the radiological control program. It is also concluded that because an accidental nuclear criticality is not credible based on the low uranium enrichment

  15. High Temperature Materials Interim Data Qualification Report FY 2011

    International Nuclear Information System (INIS)

    Lybeck, Nancy

    2011-01-01

    Projects for the very high temperature reactor (VHTR) Technology Development Office provide data in support of Nuclear Regulatory Commission licensing of the VHTR. Fuel and materials to be used in the reactor are tested and characterized to quantify performance in high temperature and high fluence environments. The VHTR program has established the Next Generation Nuclear Plant (NGNP) Data Management and Analysis System (NDMAS) to ensure that VHTR data are qualified for use, stored in a readily accessible electronic form, and analyzed to extract useful results. This document focuses on the first NDMAS objective. It describes the High Temperature Materials characterization data stream, the processing of these data within NDMAS, and reports the interim fiscal year (FY) 2011 qualification status of the data. Data qualification activities within NDMAS for specific types of data are determined by the data qualification category assigned by the data generator. The High Temperature Materials data are being collected under the Nuclear Quality Assurance (NQA)-1 guidelines and will be qualified data. For NQA-1 qualified data, the qualification activities include: (1) capture testing to confirm that the data stored within NDMAS are identical to the raw data supplied, (2) accuracy testing to confirm that the data are an accurate representation of the system or object being measured, and (3) documenting that the data were collected under an NQA-1 or equivalent Quality Assurance program. Currently, data from seven test series within the High Temperature Materials data stream have been entered into the NDMAS vault, including tensile tests, creep tests, and cyclic tests. Of the 5,603,682 records currently in the vault, 4,480,444 have been capture passed, and capture testing is in process for the remaining 1,123,238.

  16. LDEF materials: An overview of the interim findings

    International Nuclear Information System (INIS)

    Stein, B.A.

    1992-01-01

    The flight and retrieval of the National Aeronautics and Space Administration's Long Duration Exposure Facility (LDEF) provided an opportunity for the study of the low-Earth orbit (LEO) environment and long-duration space environmental effect (SEE) on materials that are unparalleled in the history of the U.S. space program. The 5.8-year flight of LDEF greatly enhanced the potential value of materials data from LDEF to the international SEE community, compared to that of the original 1-year flight plan. The remarkable flight attitude stability of LDEF enables specific analyses of various individual and combined effects of LEO environmental parameters on identical materials of the same space vehicle. NASA recognized the potential by forming the LDEF Space Environmental Effects on Materials Special Investigation Group (MSIG) to address the greatly expanded materials and LEO space environment parameter analysis opportunities available in the LDEF structure, experiment trays, and corollary measurements, so that the combined value of all LDEF materials data to current and future space missions will be assessed and documented. This paper provides an overview of the interim LDEF materials findings of the Principal Investigators and the Materials Special Investigation Group. These revelations are based on observations of LEO environmental effects on materials made in-space during LDEF retrieval and during LDEF tray deintegration at the Kennedy Space Center, and on findings of approximately 1.5 years of laboratory analyses of LDEF materials by the LDEF materials scientists. These findings were extensively reviewed and discussed at the MSIG-sponsored LDEF Materials Workshop '91. The results are presented in a format which categorizes the revelations as clear findings or confusing/unexplained findings and resultant needs for new space materials developments and ground simulation testing/analytical modeling

  17. New York State interim waste management cost evaluation

    International Nuclear Information System (INIS)

    Ma, M.S.; Watts, R.J.; Jorgensen, J.R.; Rochester Gas and Electric Corp., NY)

    1985-01-01

    The purpose of this study is to investigate and quantify the comparative costs associated with including or excluding Class A utility wastes at a centralized interim waste management facility in New York State. The objective of the study is to assess the unit costs and total statewide costs associated with two distinct scenarios: (1) the case where non-utility Class A LLRW is received, incinerated and stored at the centralized interim facility, and utility Class A wastes are held without incineration at respective nuclear power plant interim onsite facilities without incineration; and (2) the alternative case where both utility and non-utility Class A wastes are accepted, incinerated and stored at the centralized facility. Unit costs to waste generators are estimated for each of the two cases described. This is followed by an estimation of the statewide cost impact to the public. The cost impact represents the cost differential resulting from the exclusion of utility Class A waste from the centralized NYS interim waste management facility. The principal factors comprising the cost differential include (1) higher unit disposal fees charged to non-utility waste generators, which are passed along in the costs of products and services; and (2) costs to utilities due to construction of additional onsite storage capacity, which in turn are charged to electric rate payers

  18. Options for the interim storage of spent fuel

    International Nuclear Information System (INIS)

    Kromar, M.; Kurincic, B.

    1995-01-01

    Different concepts for the interim storage of spent fuel arising from operation of a NPP are discussed. We considered at reactor as well as away from reactor storage options. Included are enhancements of existing storage capabilities and construction of a new wet or dry storage facility. (author)

  19. Fuel supply shutdown facility interim operational safety requirements

    International Nuclear Information System (INIS)

    Besser, R.L.; Brehm, J.R.; Benecke, M.W.; Remaize, J.A.

    1995-01-01

    These Interim Operational Safety Requirements (IOSR) for the Fuel Supply Shutdown (FSS) facility define acceptable conditions, safe boundaries, bases thereof, and management or administrative controls to ensure safe operation. The IOSRs apply to the fuel material storage buildings in various modes (operation, storage, surveillance)

  20. 17 CFR 210.8-03 - Interim financial statements.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Interim financial statements... AND CONTENT OF AND REQUIREMENTS FOR FINANCIAL STATEMENTS, SECURITIES ACT OF 1933, SECURITIES EXCHANGE... ADVISERS ACT OF 1940, AND ENERGY POLICY AND CONSERVATION ACT OF 1975 Article 8 Financial Statements of...

  1. ASPECTS CONCERNING INTERIM FINANCIAL REPORTING IN ROMANIA: STANDARDS AND REGULATIONS

    Directory of Open Access Journals (Sweden)

    Aristita Rotila

    2014-12-01

    Full Text Available The mechanisms employed for the communication of accounting information that is necessary for users in their economic decision-making process consist of the financial statements of an entity. All legal entities, no matter the domain of their activity, have the obligation to draw up annual financial statements for every completed financial year. For certain categories of entities, reporting obligations are also required for periods other than the annual reporting, throughout the financial year. It is the case of interim financial reporting. At the level of the international accounting framework, the aspects related to interim financial reporting are the subject of a separate standard, namely, IAS 34 Interim Financial Reporting. In Romania, the current system of accounting regulations concerning the annual financial statements comprises accounting regulations that comply with the European directives and which apply to the various categories of entities, on the one hand and, on the other, accounting regulations in line with the IFRS, which are applicable to other classes of entities from certain activity sectors. The accounting regulations that apply to each category refer to, among other things, the contents and the format of financial statements that have to be presented. Analysing the system of norms and regulations, this article identifies the requirements concerning interim financial reporting in Romania, with reference to the different types of entities.

  2. 39 CFR 211.4 - Interim personnel regulations.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Interim personnel regulations. 211.4 Section 211.4... under the Postal Reorganization Act. (b) Continuation of Personnel Provisions of Former title 39, U.S.C... collective bargaining agreement under the Postal Reorganization Act, all provisions of former title 39, U.S.C...

  3. 46 CFR 308.303 - Amounts insured under interim binder.

    Science.gov (United States)

    2010-10-01

    ... 308.303 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE Second Seamen's War Risk Insurance § 308.303 Amounts insured under interim binder. The amounts insured are the amounts specified in the Second Seamen's War Risk Policy (1955) or as modified by shipping...

  4. System Specification for Immobilized High-Level Waste Interim Storage

    International Nuclear Information System (INIS)

    CALMUS, R.B.

    2000-01-01

    This specification establishes the system-level functional, performance, design, interface, and test requirements for Phase 1 of the IHLW Interim Storage System, located at the Hanford Site in Washington State. The IHLW canisters will be produced at the Hanford Site by a Selected DOE contractor. Subsequent to storage the canisters will be shipped to a federal geologic repository

  5. Guidelines for interim storage of low level waste

    International Nuclear Information System (INIS)

    Hornibrook, C.; Castagnacci, A.; Clymer, G.; Kelly, J.; Naughton, M.; Saunders, P.; Stoner, P.; Walker, N.; Cazzolli, R.; Dettenmeier, R.; Loucks, L.; Rigsby, M.; Spall, M.; Strum, M.

    1992-12-01

    This report presents an overview of on-site storage of Low Level Waste while providing guidelines for using the complete Interim On-Site Storage of Low Level Waste report series. Overall, this report provides a methodology for planning and implementing on-site storage

  6. Single-Shell Tank (SST) Interim Stabilization Project Plan

    International Nuclear Information System (INIS)

    VLADIMIROFF, D.T.; BOYLES, V.C.

    2000-01-01

    This project plan establishes the management framework for the conduct of the CHG Single-Shell Tank Interim Stabilization completion program. Specifically, this plan defines the mission needs and requirements; technical objectives and approach; organization structure, roles, responsibilities, and interfaces; and operational methods. This plan serves as the project executional baseline

  7. Single-shell tank interim stabilization project plan

    Energy Technology Data Exchange (ETDEWEB)

    Ross, W.E.

    1998-05-11

    This project plan establishes the management framework for conduct of the TWRS Single-Shell Tank Interim Stabilization completion program. Specifically, this plan defines the mission needs and requirements; technical objectives and approach; organizational structure, roles, responsibilities, and interfaces; and operational methods. This plan serves as the project executional baseline.

  8. 78 FR 70244 - Electronic Interim Assistance Reimbursement Program

    Science.gov (United States)

    2013-11-25

    ..., Social Security Online, at http://www.socialsecurity.gov . SUPPLEMENTARY INFORMATION: Background To be... SOCIAL SECURITY ADMINISTRATION 20 CFR Part 416 [Docket No. SSA-2011-0104] RIN 0960-AH45 Electronic Interim Assistance Reimbursement Program AGENCY: Social Security Administration. ACTION: Notice of...

  9. 14 CFR 136.41 - Interim operating authority.

    Science.gov (United States)

    2010-01-01

    ... AND NATIONAL PARKS AIR TOUR MANAGEMENT National Parks Air Tour Management § 136.41 Interim operating... terminate 180 days after the date on which an air tour management plan is established for the park and tribal lands; (6) Shall promote protection of national park resources, visitor experiences, and tribal...

  10. Public School Finance Problems in Texas. An Interim Report.

    Science.gov (United States)

    Texas Research League, Austin.

    The U.S. District Court ruling in Rodriguez vs San Antonio Independent School District, which struck down Texas' school finance system as inequitable and unconstitutional, provided the impetus for publishing this interim report. The report documents the growing cost of State-supported public school programs--the primary concern prior to the…

  11. Software Verification and Validation Report for the 244-AR Vault Interim Stabilization Ventilation System

    International Nuclear Information System (INIS)

    YEH, T.

    2002-01-01

    This document reports on the analysis, testing and conclusions of the software verification and validation for the 244-AR Vault Interim Stabilization ventilation system. Automation control system will use the Allen-Bradley software tools for programming and programmable logic controller (PLC) configuration. The 244-AR Interim Stabilization Ventilation System will be used to control the release of radioactive particles to the environment in the containment tent, located inside the canyon of the 244-AR facility, and to assist the waste stabilization efforts. The HVAC equipment, ducts, instruments, PLC hardware, the ladder logic executable software (documented code), and message display terminal are considered part of the temporary ventilation system. The system consists of a supply air skid, temporary ductwork (to distribute airflow), and two skid-mounted, 500-cfm exhausters connected to the east filter building and the vessel vent system. The Interim Stabilization Ventilation System is a temporary, portable ventilation system consisting of supply side and exhaust side. Air is supplied to the containment tent from an air supply skid. This skid contains a constant speed fan, a pre-filter, an electric heating coil, a cooling coil, and a constant flow device (CFD). The CFD uses a passive component that allows a constant flow of air to pass through the device. Air is drawn out of the containment tent, cells, and tanks by two 500-cfm exhauster skids running in parallel. These skids are equipped with fans, filters, stack, stack monitoring instrumentation, and a PLC for control. The 500CFM exhaust skids were fabricated and tested previously for saltwell pumping activities. The objective of the temporary ventilation system is to maintain a higher pressure to the containment tent, relative to the canyon and cell areas, to prevent contaminants from reaching the containment tent

  12. SLIGHTLY IRRADIATED FUEL (SIF) INTERIM DISPOSITION PROJECT

    International Nuclear Information System (INIS)

    Norton, S.H.

    2010-01-01

    CH2M HILL Plateau Remediation Company (CH2M HILL PRC) is proud to submit the Slightly Irradiated Fuel (SIF) Interim Disposition Project for consideration by the Project Management Institute as Project of the Year for 2010. The SIF Project was a set of six interrelated sub-projects that delivered unique stand-alone outcomes, which, when integrated, provided a comprehensive and compliant system for storing high risk special nuclear materials. The scope of the six sub-projects included the design, construction, testing, and turnover of the facilities and equipment, which would provide safe, secure, and compliant Special Nuclear Material (SNM) storage capabilities for the SIF material. The project encompassed a broad range of activities, including the following: Five buildings/structures removed, relocated, or built; Two buildings renovated; Structural barriers, fencing, and heavy gates installed; New roadways and parking lots built; Multiple detection and assessment systems installed; New and expanded communication systems developed; Multimedia recording devices added; and A new control room to monitor all materials and systems built. Project challenges were numerous and included the following: An aggressive 17-month schedule to support the high-profile Plutonium Finishing Plant (PFP) decommissioning; Company/contractor changeovers that affected each and every project team member; Project requirements that continually evolved during design and construction due to the performance- and outcome-based nature ofthe security objectives; and Restrictions imposed on all communications due to the sensitive nature of the projects In spite of the significant challenges, the project was delivered on schedule and $2 million under budget, which became a special source of pride that bonded the team. For years, the SIF had been stored at the central Hanford PFP. Because of the weapons-grade piutonium produced and stored there, the PFP had some of the tightest security on the Hanford

  13. SLIGHTLY IRRADIATED FUEL (SIF) INTERIM DISPOSITION PROJECT

    Energy Technology Data Exchange (ETDEWEB)

    NORTON SH

    2010-02-23

    CH2M HILL Plateau Remediation Company (CH2M HILL PRC) is proud to submit the Slightly Irradiated Fuel (SIF) Interim Disposition Project for consideration by the Project Management Institute as Project of the Year for 2010. The SIF Project was a set of six interrelated sub-projects that delivered unique stand-alone outcomes, which, when integrated, provided a comprehensive and compliant system for storing high risk special nuclear materials. The scope of the six sub-projects included the design, construction, testing, and turnover of the facilities and equipment, which would provide safe, secure, and compliant Special Nuclear Material (SNM) storage capabilities for the SIF material. The project encompassed a broad range of activities, including the following: Five buildings/structures removed, relocated, or built; Two buildings renovated; Structural barriers, fencing, and heavy gates installed; New roadways and parking lots built; Multiple detection and assessment systems installed; New and expanded communication systems developed; Multimedia recording devices added; and A new control room to monitor all materials and systems built. Project challenges were numerous and included the following: An aggressive 17-month schedule to support the high-profile Plutonium Finishing Plant (PFP) decommissioning; Company/contractor changeovers that affected each and every project team member; Project requirements that continually evolved during design and construction due to the performance- and outcome-based nature ofthe security objectives; and Restrictions imposed on all communications due to the sensitive nature of the projects In spite of the significant challenges, the project was delivered on schedule and $2 million under budget, which became a special source of pride that bonded the team. For years, the SIF had been stored at the central Hanford PFP. Because of the weapons-grade piutonium produced and stored there, the PFP had some of the tightest security on the Hanford

  14. The Safety Assessment of Long term Interim Storage at Sellafield

    International Nuclear Information System (INIS)

    Buchan, Andrew B.

    2014-01-01

    The Sellafield site comprises a wide range of nuclear facilities, including operating facilities associated with the Magnox reprocessing programme, the Thermal Oxide Reprocessing Plant (THORP) and a range of waste treatment plants. The operational life of some of the site facilities currently extends to 2120, requiring the retrieval, treatment, consolidation and safe extended storage of a variety of radioactive materials. Sellafield has utilised its existing safety assessment processes to inform and prioritise studies into beyond design basis events and resilience evaluation required following Fukushima by UK regulators and industry bodies such as WANO. There are significant differences between NPPs, for which the ENSREG 'stress tests' were originally intended, and the Sellafield site which is instead centered around two reprocessing facilities (Magnox and THORP), with a supporting infrastructure of waste processing and storage facilities, coupled with a legacy of high hazard older facilities. In the former case the consequences of a catastrophic failure are promptly realised, leading to significant problems such as fuel failure / meltdown in AGRs and LWRs respectively in the event of complete loss of cooling. At Sellafield, the processes are carried out at comparatively low temperatures and pressures with relatively low rates of change following any loss of cooling. Instead the consequences of catastrophic failure at Sellafield are more directly related to the very large inventories of radioactive materials, including high level liquid wastes and unprocessed fuels, present in specific plants and to the condition of the ageing assets, holding legacy wastes. The paper will consider how a number of analysis techniques have been used to establish a safety case for fault and accident conditions, i.e. design basis analysis (DBA), probabilistic safety analysis (PSA) and severe accident analysis (SAA) DBA is focused on the key safety measures for those initiating faults

  15. Subsurface Interim Measures/Interim Remedial Action Plan/Environmental Assessment and Decision Document, Operable Unit No. 2

    International Nuclear Information System (INIS)

    1992-01-01

    The subject Interim Measures/Interim Remedial Action plan/Environmental Assessment (IM/IRAP/EA) addresses residual free-phase volatile organic compound (VOC) contamination suspected in the subsurface within an area identified as Operable Unit No. 2 (OU2). This IM/IRAP/EA also addresses radionuclide contamination beneath the 903 Pad at OU2. Although subsurface VOC and radionuclide contamination on represent a source of OU2 ground-water contamination, they pose no immediate threat to public health or the environment. This IM/IRAP/EA identifies and evaluates interim remedial actions for removal of residual free-phase VOC contamination from three different subsurface environments at OU2. The term ''residual'' refers to the non-aqueous phase contamination remaining in the soil matrix (by capillary force) subsequent to the passage of non-aqueous or free-phase liquid through the subsurface. In addition to the proposed actions, this IM/IRAP/EA presents an assessment of the No Action Alternative. This document also considers an interim remedial action for the removal of radionuclides from beneath the 903 Pad

  16. The determination of the cesium distribution coefficient of the interim storage soil from Abadia de Goias, Go, Brazil

    International Nuclear Information System (INIS)

    Marumo, J.T.; Suarez, A.A.

    1989-01-01

    In September, 1987, an unauthorized removal of a cesium-therapy unit and its violation caused an accident, where several places of Goiania's city, capital of Goias, Brazil, were contaminated. The removal of the radioactive wastes generated from decontamination process, was made to Abadia de Goias city (near Goiania), where an interim storage was constructed. Soil samples collected from the 57th Street (Goiania) and from the interim storage permitted to determine, through static method, the cesium distribution coefficient for different cesium solution concentrations. Those results allows for some migration/retention evaluations in disposal site selection. Some soils parameters (water content, density, granulometric analysis, etc) as well as clay minerals constituents were also determined. (author) [pt

  17. A web-based endpoint adjudication system for interim analyses in clinical trials.

    Science.gov (United States)

    Nolen, Tracy L; Dimmick, Bill F; Ostrosky-Zeichner, Luis; Kendrick, Amy S; Sable, Carole; Ngai, Angela; Wallace, Dennis

    2009-02-01

    A data monitoring committee (DMC) is often employed to assess trial progress and review safety data and efficacy endpoints throughout a trail. Interim analyses performed for the DMC should use data that are as complete and verified as possible. Such analyses are complicated when data verification involves subjective study endpoints or requires clinical expertise to determine each subject's status with respect to the study endpoint. Therefore, procedures are needed to obtain adjudicated data for interim analyses in an efficient manner. In the past, methods for handling such data included using locally reported results as surrogate endpoints, adjusting analysis methods for unadjudicated data, or simply performing the adjudication as rapidly as possible. These methods all have inadequacies that make their sole usage suboptimal. For a study of prophylaxis for invasive candidiasis, adjudication of both study eligibility criteria and clinical endpoints prior to two interim analyses was required. Because the study was expected to enroll at a moderate rate and the sponsor required adjudicated endpoints to be used for interim analyses, an efficient process for adjudication was required. We created a web-based endpoint adjudication system (WebEAS) that allows for expedited review by the endpoint adjudication committee (EAC). This system automatically identifies when a subject's data are complete, creates a subject profile from the study data, and assigns EAC reviewers. The reviewers use the WebEAS to review the subject profile and submit their completed review form. The WebEAS then compares the reviews, assigns an additional review as a tiebreaker if needed, and stores the adjudicated data. The study for which this system was originally built was administratively closed after 10 months with only 38 subjects enrolled. The adjudication process was finalized and the WebEAS system activated prior to study closure. Some website accessibility issues presented initially. However

  18. Safety Consideration for a Wet Interim Spent Fuel Store at Conceptual Design Stage

    International Nuclear Information System (INIS)

    Astoux, Marion

    2014-01-01

    EDF Energy plans to build and operate two UK EPRs at the Hinkley Point C (HPC) site in Somerset, England. Spent fuel from the UK EPRs will need to be managed from the time it is discharged from the reactor until it is ultimately disposed of and this will involve storing the spent fuel for a period in the fuel building and thereafter in a dedicated interim facility until it can be emplaced within the UK Geological Disposal Facility. EDF Energy has proposed that this interim store should be located on the Hinkley Point site which is consistent with UK policy. This Interim Spent Fuel Store (ISFS) will have the capability to store for at least one hundred years the spent fuel arising from the operation of the two EPR units (sixty years operation). Therefore, specificities regarding the lifetime of the facility have to be accounted for its design. The choice of interim storage technology was considered in some depth for the HPC project and wet storage (pool) was selected. The facility is currently at conceptual design stage, although its construction will be part of main site construction phase. Safety functions and safety requirements for this storage facility have been defined, in compliance with WENRA 'Waste and Spent Fuel Storage - Safety Reference Level Report' and IAEA Specific Safety Guide no. 15 'Storage of Spent Nuclear Fuel'. EDF technical know-how, operational feedback on existing storage pools, UK regulatory context and Fukushima experience feedback have also been accounted for. Achievement of the safety functions as passively as reasonably practicable is a key issue for the design, especially in accident situations. Regarding lifetime aspects, ageing management of equipments, optimisation of the refurbishment, climate change, passivity of the facility, and long-term achievement of the safety functions are among the subjects to consider. Adequate Operational Limits and Conditions will also have to be defined, to enable the long-term achievement of the safety

  19. Initial care and outcome of glioblastoma multiforme patients in 2 diverse health care scenarios in Brazil: does public versus private health care matter?.

    Science.gov (United States)

    Loureiro, Luiz Victor Maia; Pontes, Lucíola de Barros; Callegaro-Filho, Donato; Koch, Ludmila de Oliveira; Weltman, Eduardo; Victor, Elivane da Silva; Santos, Adrialdo José; Borges, Lia Raquel Rodrigues; Segreto, Roberto Araújo; Malheiros, Suzana Maria Fleury

    2014-07-01

    The aim of this study was to describe the epidemiological and survival features of patients with glioblastoma multiforme treated in 2 health care scenarios--public and private--in Brazil. We retrospectively analyzed clinical, treatment, and outcome characteristics of glioblastoma multiforme patients from 2003 to 2011 at 2 institutions. The median age of the 171 patients (117 public and 54 private) was 59.3 years (range, 18-84). The median survival for patients treated in private institutions was 17.4 months (95% confidence interval, 11.1-23.7) compared with 7.1 months (95% confidence interval, 3.8-10.4) for patients treated in public institutions (P public setting (median of 64 days for the public hospital and 31 days for the private institution; P = .003). The patients at the private hospital received radiotherapy concurrent with chemotherapy in 59.3% of cases; at the public hospital, only 21.4% (P Brazil is critical.

  20. Andrographolide suppresses the migratory ability of human glioblastoma multiforme cells by targeting ERK1/2-mediated matrix metalloproteinase-2 expression

    OpenAIRE

    Yang, Shih-Liang; Kuo, Fu-Hsuan; Chen, Pei-Ni; Hsieh, Yi-Hsien; Yu, Nuo-Yi; Yang, Wei-En; Hsieh, Ming-Ju; Yang, Shun-Fa

    2017-01-01

    Glioblastoma multiforme (GBM) can be a fatal tumor because of difficulties in treating the related metastasis. Andrographolide is the bioactive component of the Andrographis paniculata. Andrographolide possesses the anti-inflammatory activity and inhibits the growth of various cancers; however, its effect on GBM cancer motility remains largely unknown. In this study, we examined the antimetastatic properties of andrographolide in human GBM cells. Our results revealed that andrographolide inhi...